Formaldehyde N,N-Dialkylhydrazones as Neutral Formyl Anion Equivalents in Iridium-Catalyzed Asymmetric Allylic Substitution

Transcription

1 Supporting Information for: Formaldehyde N,N-Dialkylhydrazones as Neutral Formyl Anion Equivalents in Iridium-Catalyzed Asymmetric Allylic Substitution Simon Breitler and Erick M. Carreira Table of Contents 1. Methods and Materials S2 2. Selected Optimization of Reaction Conditions S4 3. Experimental Procedures S5 3.1 Synthesis of Allyl Carbonates S5 3.2 Synthesis of Enantioenriched Hydrazones by Kinetic Resolution S8 3.3 Stereospecific Synthesis of Enantioenriched Hydrazones S Derivatizations of Hydrazones S19 4. References S25 5. Determination of Enantiomeric Excess (SFC/HPLC traces) S Hydrazones / Enantioenriched Carbonates by Kinetic Resolution S Hydrazones by Stereospecific Formylation S Derivatizations of Hydrazones S58 6. NMR Spectra S Hydrazones S Derivatizations of Hydrazones S85 7. X-Ray Crystallographic Data S X-Ray Crystallographic Data for Compound (R)-7 S X-Ray Crystallographic Data for Compound (2R,3R)-11 S X-Ray Crystallographic Data for (2R,3R)-12 S103 S1

2 1. Methods and Materials 1.1 General Methods. All non-aqueous reactions were performed under an inert atmosphere of dry argon or nitrogen in flame-dried glassware sealed with a rubber septum unless otherwise noted. Argon was passed over a column of CaCl 2 and supplied through a glass manifold. Reactions were stirred magnetically and monitored by thin layer chromatography (TLC) or 1 H-NMR. Analytical thin layer chromatography was performed using MERCK Silica Gel F 254 TLC glass plates and visualized by ultraviolet light (UV). Additionally, TLC plates were stained with aqueous potassium permanganate (KMnO 4 ) [3.0 g KMnO 4, 300 ml H 2 O, 20 g K 2 CO 3, 2.5 ml 1M NaOH aq.] or cerium ammonium molybdate (CAM) [0.5 g Ce(NH 4 ) 2 (NO 3 ) 6, 12 g (NH 4 ) 6 Mo 7 O 24 4H 2 O, 235 ml H 2 O, 15 ml conc. H 2 SO 4 ]. Chromatographic purification was performed as flash chromatography 1 on FLUKA silica gel 60 Å ( mesh) silica gel at bar over-pressure unless otherwise noted. After concentration on a rotary evaporator, purified compounds were dried further under high vacuum (0.05 to 0.1 torr). Yields refer to the purified compound. 1.2 Chemicals. All chemicals and solvents were purchased from ABCR, ACROS, ALDRICH, J. T. BAKER, FLUKA, MERCK, TCI, STREM, LANCASTER, COMBIBLOCKS or FLUOROCHEM and were used as received from the commercial supplier without further purification unless mentioned otherwise. THF, Et 2 O, CH 2 Cl 2, MeCN, toluene and DMF were dried on a LC Technology Solutions Inc. SP-1 Solvent Purification System under N 2. 1,2-Dichloroethane (puriss., p.a. >99.5%) was purchased from Fluka Analytics and used as received. Deuterated solvents were obtained from ARMAR CHEMICALS, Döttingen, Switzerland. Formyl hydrazones were prepared according to literature procedures either by LiAlH 4 -reduction of the corresponding commercially available nitroso compounds, followed by condensation with paraformaldehyde, 2 or, alternatively, from the commercially available hydrazines with formalin in water. 3 While purification by flash column chromatography afforded analytically pure formaldehyde hydrazones, their application in the iridiumcatalyzed allylic substitution required bulp-to-bulp vacuum distillation prior to use. Failure to redistill the formyl hydrazones resulted in sluggish reaction rates and variable results. Addition of trace amounts of Sc(OTf) 3 leads to reproducible results. 1.3 Analytics. Nuclear Magnetic Resonance (NMR) spectra were recorded on BRUKER AV and DRX (400 MHz), BRUKER DRX and DRXII (500 MHz). Measurements were carried out at ambient temperature (ca. 22 C). Chemical shifts (δ) are reported in ppm with the residual solvent signal as internal standard (chloroform at 7.26 and ppm for 1 H- and 13 C-NMR spectroscopy, respectively), unless otherwise noted. The data is reported as (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet or unresolved, br = broad signal, coupling constant(s) in Hz, integration). 13 C-NMR spectra were recorded with broadband 1 H-decoupling. Service measurements were performed by the NMR service team of the Laboratorium für Organische Chemie at ETH Zürich by Mr. René Arnold, Mr. Rainer Frankenstein and Mr. Philipp Zumbrunnen under direction of Dr. Marc-Olivier Ebert. Infrared (IR) spectra were recorded on a PERKIN ELMER Spectrum Two ATR-FT-IR as neat compounds. Absorptions are given in wavenumbers (cm 1 ). Enantiomeric excess was determined on a JASCO 2080Plus supercritical fluid chromatography system with the parameters given. Alternatively, HPLC analysis was carried out on a SHIMADZU LC-10A analytical HPLC (CHIRALCEL OH-J column) or a FISHER THERMOSCIENTIFIC DIONES ULTIMATE 3000 (CHIRALPAK IA, IB, IC, ID columns) was used. Optical rotations were measured on a JASCO P-2000 Polarimeter equipped with a 10 cm cell. Mass spectrometry (MS) analyses were performed as high resolution EI measurements on a WATERS MICROMASS AUTOSPEC ULTIMA at 70 ev, as high resolution ESI measurements on a BRUKER DALTONICS MAXIS (UHR-TOF) instrument or as high resolution MALDI measurements on a BRUKER ULTRAFLEX II (MALDI-TOF) by the mass spectrometry service of the Laboratorium für Organische Chemie at ETH Zürich by Mr. Louis Bertschi, Mr. Oswald Greter and Mr. Rolf Häfliger under direction of Dr. Xiangyang Zhang. Elemental analyses were performed by the Mikrolabor at ETH Zürich by Mr. Michael Schneider and Mr. René Kälin using a LECO CHNS 932 or TruSpec Micro Elemental Analyser. S2

3 X-ray diffraction experiments were carried out by Dr. Nils Trapp and Mr. Michael Solar on a BRUKER KAPPA APEX-II DUO system equipped with a graphite monochromator at the Laboratorium für Organische Chemie at ETH Zürich. The data obtained was deposited at the Cambridge Crystallographic Data Centre and can be obtained free of charge via Calculations. The s-factor for the kinetic resolution were calculated according to the method described by Kagan and Fiaud. 4 (C = conversion), s = k R /k S ( ) ( ) = = ( ) ( ) ( ) = ( ( ) ) ( ( ) ) S3

4 2. Selected Optimization of Reaction Conditions a 2a 1 additive conv. yield ee [equiv] [%] b [%] c [%] d 1 2 x Sc(OTf) 3 (1 equiv.) x (OBu) 2 PO 2 H (2 equiv.) x CSA (2.5 equiv.) e a a - f a - g a HCO 2 H (2 equiv) a citric acid (1 equiv.) a Citric acid (1 equiv.) Sc(OTf) 3 (1 mol%) 10 h 0.6 a Citric acid (0.3 equiv.) Sc(OTf) 3 (0.5 mol%) (a) Reaction conditions unless otherwise noted: 1 (0.1 mmol, 1.0 equiv), [Ir(cod)Cl] 2 (4 mol%), (S)-L1 (16 mol%), DCE (0.2 ml), 1 h. (b) Measured as consumption of starting material. (c) Determined by 1 H-NMR analysis versus an internal standard (1,4-dinitrobezene). (d) Determined by supercritical fluid chromatography (SFC) on chiral stationary phase. (e) impure mixture of α,β-unsaturated aldehyde products was obtained. (f) reaction time = 4 h. (g) reaction time = 24 h. (h) 2.5 mol% [Ir(cod)Cl] 2, 10 mol% (S)-L1 were used. Enantioenriched product (S)-3a could be subjected to the reaction conditions without loss of enantiomeric excess. Furthermore, no racemization of the hydrazone product was observed upon treatment with N-methlypyrrolidine in DCE or catalytic LiOtBu in THF at room temperature. S4

5 3. Experimental Procedures 3.1 Synthesis of Allyl Carbonates Allylic carbonates were prepared from commercially available aldehydes by the method of Kočovský and co-workers unless otherwise noted. 5 Spectral data for all compounds are given below. tert-butyl (1-phenylallyl) carbonate: TLC: R f = 0.54 (hexane/etoac, 10:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ (m, 5H), (m, 2H), (m, 2H), 1.47 (s, 9H); 13 C-NMR (101 MHz, CDCl 3 ): δ 152.7, 138.7, 136.2, (2x), 128.2, (2x), 117.1, 82.3, 79.2, 27.8 (3x); IR (neat, cm -1 ): 2981, 1738, 1272, 1250, 1157, 104, 862, 757, 699; Anal. Calcd. for C 14 H 18 O 3 : C, 71.77; H, 7.74; found C, 71.53; H, tert-butyl (1-(naphthalen-2-yl)allyl) carbonate: TLC: R f = 0.52 (hexane/etoac, 10:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ (m, 4H), (m, 3H), 6.19 (d, J = 6.1 Hz, 1H), 6.11 (ddd, J = 16.6, 10.3, 6.0 Hz, 1H), 5.37 (ddd, J = 17.0, 1.2, 1.1 Hz, 1H), 5.29 (ddd, J = 10.3, 1.2, 1.1 Hz, 1H), 1.48 (s, 9H); 13 C-NMR (101 MHz, CDCl 3 ): δ 152.8, 136.2, 136.1, , , 128.4, 128.1, 127.7, (2x), 126.1, 124.8, 117.4, 82.4, 79.3, 27.8 (3x); IR (neat, cm -1 ): 2985, 1733, 1273, 1248, 1155, 887, 846, 824, 750, 482; HRMS (ESI): required for C 18 H 2 NaO 3 [MNa] +, ; found tert-butyl (1-(3-methoxyphenyl)allyl) carbonate: TLC: R f = 0.43 (hexane/etoac, 10:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ 7.27 (t, J = 7.9 Hz, 1H), 6.96 (dt, J = 7.6, 1.0 Hz, 1H), (m, 1H), 6.84 (ddd, J = 8.2, 2.6, 0.9 Hz, 1H), (m, 2H), (m, 2H), 3.80 (s, 3H), 1.48 (s, 9H); 13 C-NMR (101 MHz, CDCl 3 ): δ 159.7, 152.7, 140.3, 136.1, 129.6, 119.2, 117.2, 113.8, 112.3, 82.4, 79.1, 55.2, 27.8 (3x); IR (neat, cm -1 ): 2981, 1739, 1269, 1249, 1156, 850, 790, 769, 698; HRMS (ESI): required for C 15 H 20 NaO 4 [MNa] +, ; found tert-butyl (1-(2-methoxyphenyl)allyl) carbonate: TLC: R f = 0.44 (hexane/etoac, 10:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ 7.37 (dd, J = 7.6, 1.7 Hz, 1H), 7.27 (ddd, J = 8.2, 7.6, 1.8 Hz, 1H), 6.96 (td, J = 7.5, 0.7 Hz, 1H), 6.88 (dd, J = 8.3, 1.1 Hz, 1H), 6.45 (d, J = 5.9 Hz, 1H), 6.03 (ddd, J = 17.2, 10.4, 5.8 Hz, 1H), 5.29 (ddd, J = 17.2, 1.4, 1.3 Hz, 1H), 5.19 (ddd, J = 10.4, 1.4, 1.3 Hz, 1H), 3.84 (s, 3H), 1.47 (s, 9H); 13 C-NMR (101 MHz, CDCl 3 ): δ 156.4, 152.8, 135.7, 129.1, 127.4, 127.1, 120.6, 116.2, 110.6, 82.1, 73.4, 55.5, 27.8 (3x); IR (neat, cm -1 ): 2981, 1739, 1493, 1272, 1242, 1157, 1029, 878, 753; HRMS (ESI): required for C 15 H 20 NaO 4 [MNa] +, ; found tert-butyl acetyl(4-(1-((tert-butoxycarbonyl)oxy)allyl)phenyl)carbamate: TLC: R f = 0.71 (hexane/etoac, 2:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ 7.39 (d, J = 8.3 Hz, 2H), 7.07 (d, J = 8.5 Hz, 2H), (m, 2H), (m, 2H), 2.56 (s, 3H), 1.47 (s, 9H), 1.36 (s, 9H); 13 C-NMR (101 MHz, CDCl 3 ): δ 172.8, (2x), 138.2, 135.9, (2x), (2x), 117.5, 83.3, 82.4, 78.6, (3x), (3x), 26.5; IR (neat, cm -1 ): 2980, 1734, 1696, 1368, 1275, 1253, 1156, 848; HRMS (ESI): required for C 21 H 33 N 2 O 6 [MNH 4 ] +, ; found (2-bromophenyl)allyl tert-butyl carbonate: TLC: R f = 0.62 (hexane/etoac, 10:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ 7.56 (dd, J = 8.0, 1.3 Hz, 1H), 7.47 (dd, J = 7.8, 1.7 Hz, 1H), 7.33 (td, J = 7.6, 1.2 Hz, 1H), 7.16 (ddd, J = 8.0, 7.4, 1.7 Hz, 1H), 6.40 (ddd, J = 5.8, 1.4, 1.2 Hz, 1H), 5.99 (ddd, J = 17.2, 10.5, 5.8 Hz, 1H), 5.34 (ddd, J = 17.3, 1.3, 1.2 Hz, 1H), 5.27 (ddd, J = 10.3, 1.3, 1.2 Hz, 1H), 1.47 S5

6 (s, 9H); 13 C-NMR (101 MHz, CDCl 3 ): δ 152.4, 138.3, 134.6, 132.9, 129.5, 128.0, 127.8, 122.7, 117.7, 82.6, 77.6, 27.8 (3x); IR (neat, cm -1 ): 2981, 1742, 1269, 1249, 1155, 860, 753; HRMS (ESI): required for C 14 H 17 BrNaO 3 [MNa] +, and ; found and tert-butyl (1-(4-fluorophenyl)allyl) carbonate: TLC: R f = 0.66 (hexane/etoac, 5:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ (m, 2H), (m, 2H), (m, 2H), (m, 2H), 1.47 (s, 9H); 13 C-NMR (101 MHz, CDCl 3 ): δ (d, J = Hz), 152.6, 136.0, (d, J = 3.2 Hz), (d, J = 8.3 Hz, 2C), 117.3, (d, J = 21.5 Hz, 2C), 82.5, 78.4, 27.8 (3x); 19 F-NMR (377 MHz, CDCl 3 ): δ ; IR (neat, cm -1 ): 2983, 1739, 1510, 1273, 1251, 1224, 1154, 834; HRMS (ESI): required for C 14 H 17 FNaO 3 [MNa] +, ; found tert-butyl (1-(4-chlorophenyl)allyl) carbonate: TLC: R f = 0.57 (hexane/etoac, 10:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ (m, 4H), (m, 2H), (m, 2H), 1.47 (s, 9H); 13 C-NMR (101 MHz, CDCl 3 ): δ 152.6, 137.3, 135.8, 134.0, (2x), (2x), 117.6, 82.6, 78.4, 27.8 (3x); IR (neat, cm -1 ): 2982, 1739, 1271, 1250, 1157, 1089, 823; HRMS (ESI): required for C 14 H 17 ClNaO 3 [MNa] +, ; found tert-butyl (1-(4-iodophenyl)allyl) carbonate: TLC: R f = 0.60 (hexane/etoac, 10:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ 7.69 (d, J = 8.5 Hz, 2H), 7.11 (d, J = 8.2 Hz, 2H), (m, 2H), (m, 2H), 1.47 (s, 9H); 13 C-NMR (101 MHz, CDCl 3 ): δ 152.6, 138.5, (2x), 135.7, (2x), 117.6, 93.9, 82.6, 78.5, 27.8 (3x); IR (neat, cm -1 ): 2980, 1732, 1369, 1272, 1252, 1154, 935, 870, 822, 520; HRMS (ESI): required for C 14 H 17 INaO 3 [MNa] +, ; found tert-butyl (1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)allyl) carbonate: The corresponding allylic alcohol was prepared from the 3-bromo analogue according to Andrade and co-workers. 6 To a solution of 1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)prop-2- en-1-ol (0.90 g, 3.46 mmol) in THF (35 ml) at room temperature was added pyridine (0.42 ml, 5.19 mmol), Boc 2 O (0.91 g, 4.17 mmol) and DMAP (45 mg, 0.37 mmol). The resulting dark brown solution was stirred for 1.5 h before it was quenched with aq. sat. NH 4 Cl. The biphasic mixture was extracted with Et 2 O (3x), the combined organic layers washed with water and brine and dried over MgSO 4. Filtration and concentration afforded a brown wax which was purified by flash column chromatography (hexane/etoac 15:1 8:1 4:1) to afford unreacted starting material (128 mg, 14%) and the product as a yellowish wax which was pure by NMR but turned into a blueish-green solution in CDCl 3. Filtering through a plug of silica with hexane/etoac (5:1) afforded the product as a white solid upon extensive drying on high vacuum (628 mg, 52%, 61% brsm). TLC: R f = 0.38 (hexane/etoac, 10:1; CAM, KMnO 4 ); 1 H-NMR (600 MHz, CDCl 3 ): δ 7.80 (dd, J = 1.1, 0.5 Hz, 1H), 7.75 (dt, J = 7.3, 1.3 Hz, 1H), 7.47 (dddd, J = 7.7, 1.9, 1.3, 0.4 Hz, 1H), 7.36 (ddd, J = 7.8, 7.3, 0.6 Hz, 1H), (m, 2H), (m, 2H), 1.47 (s, 9H), 1.34 (s, 12H); 13 C-NMR (151 MHz, CDCl 3 ): δ 152.7, 138.0, 136.2, 134.7, 133.4, 129.9, (C-B, very broad), 128.0, 117.1, 83.9, 82.3, 79.4, 27.8 (3x), (2x), (2x); 11 B-NMR (160 MHz, CDCl 3 ): δ 30.7 (br); IR (neat, cm -1 ): 2980, 1738, 1361, 1342, 1272, 1254, 1140, 1107, 933, 852, 710; HRMS (ESI): required for C 20 H 29 BNaO 5 [MNa] +, ; found methyl 4-(1-((tert-butoxycarbonyl)oxy)allyl)benzoate: TLC: R f = 0.59 (hexane/etoac, 5:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ 8.03 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.4 Hz, 2H), (m, 2H), (m, 2H), 3.91 (s, 3H), 1.47 (s, 9H); 13 C-NMR (101 MHz, CDCl 3 ): δ 166.7, 152.6, 143.7, 135.6, (2x), (2x), 118.0, 82.7, 78.6, 52.2, (3x); IR (neat, cm -1 ): 2982, 1742, 1726, 1274, 1252, 1160, 1105, 857; HRMS (ESI): required for C 16 H 20 NaO 5 [MH] +, ; found tert-butyl (1-(4-(trifluoromethyl)phenyl)allyl) carbonate: TLC: R f = 0.58 (hexane/etoac, 10:1; KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ 7.62 (d, J = 8.1 Hz, 2H), 7.49 (d, J = 8.5 Hz, 2H), 6.06 (d, J = 6.4 Hz, 1H), (m, 1H), (m, 2H), 1.48 (s, 9H); 13 C-NMR (101 MHz, CDCl 3 ): S6

7 δ 152.5, (q, J = 1.5 Hz), 135.5, (q, J = 32.5 Hz), (2x), (q, J = 3.8 Hz, 2C), (q, J = Hz), 118.1, 82.8, 78.4, 27.7 (3x); 19 F-NMR (377 MHz, CDCl 3 ): δ 62.64; IR (neat, cm -1 ): 2975, 1743, 1518, 1347, 1310, 1272, 1251, 1153, 1074, 961, 931, 846, 826, 757, 706; HRMS (ESI): required for C 15 H 17 F 3 NaO 3 [MNa] +, ; found tert-butyl (1-(thiophen-3-yl)allyl) carbonate: TLC: R f = 0.52 (hexane/etoac, 10:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ (m, 2H), 7.08 (dd, J = 4.8, 1.5 Hz, 1H), 6.13 (d, J = 6.4 Hz, 1H), 6.06 (ddd, J = 16.7, 10.2, 6.2 Hz, 1H), 5.35 (ddd, J = 17.0, 1.1, 1.1 Hz, 1H), 5.28 (ddd, J = 10.3, 1.1, 1.1 Hz, 1H), 1.48 (s, 9H); 13 C-NMR (101 MHz, CDCl 3 ): δ 152.7, 139.6, 135.5, 126.5, 126.2, 126.1, 123.1, 117.4, 82.4, 75.1, 27.8 (3x); IR (neat, cm -1 ): 2981, 1737, 1270, 1250, 1154, 846, 790, 766; HRMS (ESI): required for C 12 H 16 NaO 3 S [MNa] +, ; found tert-butyl (1-(1-tosyl-1H-indol-3-yl)allyl) carbonate: The corresponding allylic alcohol was prepared from N-tosyl indole-3-carbaldehyde according to Jegelka and Plietker. 7 To a solution of 1-(1-tosyl-1Hindol-3-yl)prop-2-en-1-ol (2.24 g, 6.85 mmol) in THF (30 ml) at room temperature was added pyridine (0.83 ml, mmol), Boc 2 O (1.77 g, 8.11 mmol) and DMAP (42 mg, 0.34 mmol). The resulting dark brown solution was stirred for 45 min before it was quenched with water/1m HCl (1:1). The biphasic mixture was extracted with Et 2 O (3x), the combined organic layers washed with aq. sat. NaHCO 3 and dried over MgSO 4. Filtration and concentration afforded a brown wax which was purified by flash column chromatography (hexane/etoac 5:1 containing 1% v/v NEt 3 ) to afford the product as a slightly yellowish wax (2.56 mg, 87%). TLC: R f = 0.41 (hexane/etoac, 5:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ 7.96 (dd, J = 8.3, 0.9 Hz, 1H), (m, 2H), 7.60 (s, 1H), 7.58 (d, J = 7.9 Hz, 1H), 7.32 (ddd, J = 8.5, 7.2, 1.2 Hz, 1H), (m, 3H), 6.30 (dd, J = 6.0, 1.1 Hz, 1H), 6.12 (ddd, J = 17.2, 10.4, 6.0 Hz, 1H), 5.41 (ddd, J = 17.1, 1.2, 1.1 Hz, 1H), 5.33 (ddd, J = 10.4, 1.2, 1.1 Hz, 1H), 2.34 (s, 3H), 1.48 (s, 9H); 13 C-NMR (101 MHz, CDCl 3 ): δ 152.7, 145.0, 135.3, 135.1, 134.4, (2x), 128.7, (2x), 124.9, 124.6, 123.3, 120.4, 120.1, 118.2, 113.6, 82.5, 72.4, 27.7 (3x), 21.5; IR (neat, cm -1 ): 2981, 1737, 1368, 1271, 1251, 1168, 1120, 1086, 745, 663, 571, 537; HRMS (ESI): required for C 23 H 25 NNaO 5 S[MNa] +, ; found tert-butyl (1-(cyclopent-1-en-1-yl)allyl) carbonate: The corresponding aldehyde was prepared according to a literature procedure. 8 TLC: R f = 0.26 (hexane/etoac, 50:1; KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ 5.87 (ddd, J = 17.1, 10.4, 6.6 Hz, 1H), 5.70 (td, J = 2.1, 1.3 Hz, 1H), 5.58 (dq, J = 6.6, 1.2 Hz, 1H), 5.30 (ddd, J = 17.2, 1.3, 1.2 Hz, 1H), 5.21 (ddd, J = 10.4, 1.3, 1.2 Hz, 1H), (m, 4H), 1.89 (p, J = 7.6 Hz, 2H), 1.48 (s, 9H); 13 C-NMR (101 MHz, CDCl 3 ): δ 152.9, 141.3, 134.8, 128.2, 117.2, 82.0, 76.7, 32.4, 31.8, 27.8 (3x), 23.1; IR (neat, cm -1 ): 2959, 1738, 1369, 1270, 1250, 1158, 1101, 986, 929, 852; HRMS (EI): required for C 9 H 12 O 3 [M C 4 H 8 ] +, ; found S7

8 3.2 Synthesis of Enantioenriched Hydrazones by Kinetic Resolution General Procedure: A non-dried 5 ml-flask was charged with [Ir(cod)Cl] 2 (0.025 equiv), (R)-L1 (0.10 equiv) open to air, the atmosphere exchanged with argon and DCE (2.0 ml) was added. The resulting deep red solution was stirred at room temperature for 15 min. To this solution was then sequentially added carbonate 1 (1.0 mmol), hydrazone 2a (0.6 mmol, 0.60 equiv), citric acid (0.3 mmol, 0.3 equiv) and Sc(OTf) 3 (5 µmol, equiv) open to air. The vial was purged with argon and the resulting yellow suspension was stirred at room temperature for the indicated time. The mixture was diluted with hexane, concentrated under reduced pressure at 30 C and the residue purified by flash column chromatography with the indicated eluent to afford enantioenriched hydrazones. In addition, enantioenriched carbonates were recovered which were spectroscopically identical to the racemic starting material unless otherwise noted. The calculated s-factor is given. The hydrazone products are colorless to yellow oils which are moderately stable to ambient atmosphere and temperature. For prolonged storage, they were dissolved in benzene and stored at 20 C in the dark. (R)-N-(2-phenylbut-3-en-1-ylidene)pyrrolidin-1-amine: 234 mg carbonate 1a, 64 µl hydrazone 2a, 58 mg citric acid and 2.5 mg Sc(OTf) 3 were reacted for 2 h. Purification by flash column chromatography (hexane/etoac 20:1 10:1) afforded (R)-3a (92 mg, 43%, >99% ee) and (S)-1a (110 mg, 47%, >99% ee), s = TLC: R f = 0.31 (hexane/etoac, 10:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ (m, 5H), 6.61 (d, J = 6.5 Hz, 1H), 6.14 (ddd, J = 17.1, 10.3, 6.6 Hz, 1H), 5.18 (ddd, J = 10.3, Hz, 1H), 5.13 (ddd, J = 17.3, 1.5, 1.5 Hz, 1H), 4.25 (ddd, J = 6.5, 1.5, 1.4 Hz, 1H), (m, 4H), (m, 4H); 13 C-NMR (101 MHz, CDCl 3 ): δ 141.8, 139.0, 137.7, (2x), (2x), 126.5, 115.7, 52.7, 51.3 (2x), 23.0 (2x); IR (neat, cm -1 ): 2970, 2825, 1600, 1491, 1452, 1339, 1132, 913, 759, 699; Anal. Calcd. for C 14 H 18 N 2 : C, 78.46; H, 8.47; N, 13.07; found C, 78.34; H, 8.58; N, 13.11; HRMS (ESI): required for C 14 H 19 N 2 [MH] +, ; found ; [α] 26 D = (c = 1.54, CHCl 3 ); SFC: Daicel CHIRALPAK AS-H, 99% CO 2, 1% MeOH, 2.0 ml/min, 25 C, 247 nm: t R (major) = 3.62 min, t R (minor) = 4.07 min. (S)-tert-butyl (1-phenylallyl) carbonate: [α] 26 D = 37.8 (c = 1.68, CHCl 3 ) [lit. for (R)-enantiomer [α] D = (c = 0.94, CHCl 3, >99% ee) 4 ]; HPLC: (CHIRALCEL OJ-H, 99% hexane, 1% i PrOH, 0.5 ml/min, 25 C, 210 nm): t R (minor) = min, t R (major) = min. The deviation in magnitude of the optical rotation could be explained by contamination with trace amounts of ligand (R)-L1. Large-scale reaction: The same reaction was repeated on a 10 mmol scale, wherein carbonate 1a (2.38 g, mmol), hydrazone 2a (0.64 ml, 6.00 mmol), citric acid (576 mg, 3.00 mmol) and Sc(OTf) 3 (25 mg, 0.05 mmol) were added to a catalyst solution of [Ir(cod)Cl] 2 (67 mg, 1 mol%) and (R)-L1 (203 mg, 4 mol%) in DCE (20 ml). After 1 h, the mixture was diluted with hexane, concentrated in vacuo and purified by flash column chromatography (hexane/etoac 25:1 9:1) to afford (R)-3a (0.95 g, 44%, 98% ee) and (S)-1a (1.16 g, 49%, 99% ee), s = 663. S8

9 (R)-N-(2-(naphtalen-2-yl)but-3-en-1-ylidene)pyrrolidin-1-amine: 284 mg carbonate 1b, 64 µl hydrazone 2a, 58 mg citric acid and 2.5 mg Sc(OTf) 3 were reacted for 2 h. Purification by flash column chromatography (hexane/etoac 20:1 10:1) afforded (R)-3b (123 mg, 47%, 97% ee) and (S)-1b (120 mg, 42%, >99% ee), s = TLC: R f = 0.26 (hexane/etoac, 10:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ (m, 3H), 7.71 (s, 1H), (m, 3H), 6.68 (d, J = 6.6 Hz, 1H), 6.25 (dddd, J = 16.9, 10.3, 6.5, 1.0 Hz, 1H), 5.24 (ddd, J = 10.3, 1.5, 1.4 Hz, 1H), 5.18 (ddd, J = 17.2, 1.5, 1.4 Hz, 1H), 4.43 (dd, J = 6.6, 6.5 Hz, 1H), (m, 4H), (m, 4H); 13 C-NMR (101 MHz, CDCl 3 ): δ 139.3, 138.9, 137.4, 133.6, 132.3, 128.2, 127.7, 127.6, 126.7, 126.2, 126.0, 125.5, 116.0, 52.7, 51.4 (2x), 23.1 (2x); IR (neat, cm -1 ): 2969, 2826, 1632, 1599, 1506, 1339, 1126, 913, 855, 817, 744; Anal. Calcd. for C 18 H 20 N 2 : C, 81.78; H, 7.62; N, 10.60; found C, 81.50; H, 7.71; N, 10.53; HRMS (ESI): required for C 18 H 21 N 2 [MH] +, ; found ; [α] 25 D = (c = 1.50, CHCl 3 ); SFC: Daicel CHIRALPAK AS-H, 99% CO 2, 1% MeOH, 2.0 ml/min, 25 C, 255 nm: t R (major) = 9.57 min, t R (minor) = min. 25 (S)-tert-butyl (1-(naphthalen-2-yl)allyl) carbonate: [α] D = 36.6 (c = 1.47, CHCl 3 ); HPLC: (CHIRALCEL OJ-H, 99% hexane, 1% i PrOH, 0.5 ml/min, 25 C, 210 nm): t R (minor) = min, t R (major) = min. (R)-N-(2-(3-methoxyphenyl)but-3-en-1-ylidene)pyrrolidin-1-amine: 265 mg carbonate 1c, 64 µl hydrazone 2a, 58 mg citric acid and 2.5 mg Sc(OTf) 3 were reacted for 2 h. The mixture was triturated with hexane, the solids (ligand) filtered off over celite and the filtrate concentrated and purified by flash column chromatography (hexane/etoac 10:1 5:1) to afford (R)-3c (109 mg, 45%, 99% ee) and (S)-1c (119 mg, 45%, 99% ee), s = TLC: R f = 0.36 (hexane/etoac, 5:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ 7.24 (t, J = 8.4 Hz, 1H), 6.87 (d, J = 7.6 Hz, 1H), 6.83 (td, J = 2.1, 1.0 Hz, 1H), 6.77 (ddd, J = 8.2, 2.6, 0.9 Hz, 1H), 6.59 (d, J = 6.7 Hz, 1H), 6.13 (ddd, J = 17.1, 10.3, 6.6 Hz, 1H), 5.18 (ddd, J = 10.4, 1.5, 1.5 Hz, 1H), 5.14 (ddd, J = 17.2, 1.5, 1.5 Hz, 1H), 4.22 (t, J = 6.6 Hz, 1H), 3.80 (s, 3H), (m, 4H), (m, 4H); 13 C-NMR (101 MHz, CDCl 3 ): δ 159.7, 143.4, 138.8, 137.5, 129.5, 120.3, 115.7, 113.8, 111.7, 55.2, 52.7, 51.3 (2x), 23.0 (2x); IR (neat, cm -1 ): 2966, 2834, 1598, 1584, 1486, 1260, 1149, 1046, 782, 700; Anal. Calcd. for C 15 H 20 N 2 O: C, 73.74; H, 8.25; N, 11.47; found C, 73.58; H, 8.51; N, 11.63; HRMS (ESI): required for C 15 H 21 N 2 O[MH] +, ; found ; [α] 24 D = (c = 1.41, CHCl 3 ); SFC: Daicel CHIRALPAK IB, 98% CO 2, 2% MeOH, 2.0 ml/min, 25 C, 250 nm: t R (major) = 6.49 min, t R (minor) = 7.23 min. (S)-tert-butyl (1-(3-methoxyphenyl)allyl) carbonate: [α] 24 D = 41.6 (c = 1.54, CHCl 3 ); HPLC: (CHIRALPAK IC, 99.5% hexane, 0.5% i PrOH, 0.6 ml/min, 25 C, 210 nm): t R (minor) = 8.80 min, t R (major) = 9.01 min. (R)-N-(2-(2-methoxyphenyl)but-3-en-1-ylidene)pyrrolidin-1-amine: 264 mg carbonate 1d, 64 µl hydrazone 2a, 58 mg citric acid and 2.5 mg Sc(OTf) 3 were reacted for 70 min. The mixture was triturated with hexane, the solids (ligand) filtered off over celite and the filtrate concentrated and purified by flash column chromatography (hexane/etoac 10:1 7:1) to afford (R)-3d (110 mg, 45%, 98% ee) and (S)-1d (122 mg, 46%, >99% ee), s = 611. TLC: R f = 0.34 (hexane/etoac, 5:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ (m, 2H), 6.93 (td, J = 7.5, 1.2 Hz, 1H), 6.88 (dd, J = 8.6, 1.1 Hz, 1H), 6.72 (d, J = 6.2 Hz, 1H), 6.17 (ddd, J = 17.2, 10.3, 6.4 Hz, 1H), 5.10 (ddd, J = 10.5, 1.7, 1.7 Hz, 1H), 5.05 (ddd, J = 17.2, 1.7, 1.7 Hz, 1H), 4.64 (ddd, J = 7.9, 6.3, 1.6 Hz, 1H), 3.82 (s, 3H), S9

10 (m, 4H), (m, 4H); 13 C-NMR (101 MHz, CDCl 3 ): δ 156.9, 139.1, 138.3, 130.2, 128.9, 127.6, 120.6, 114.8, 110.9, 55.4, 51.4 (2x), 46.5, 22.9 (2x); IR (neat, cm -1 ): 2966, 1597, 1585, 1490, 1460, 1339, 1241, 1028, 911, 751; Anal. Calcd. for C 15 H 20 N 2 O: C, 73.74; H, 8.25; N, 11.47; found C, 73.56; H, 8.28; N, 11.35; HRMS (ESI): required for C 15 H 21 N 2 O [MH] +, ; found ; [α] 24 D = 55.1 (c = 2.36, CHCl 3 ); SFC: Daicel CHIRALCEL OJ-H, 99% CO 2, 1% MeOH, 2.0 ml/min, 25 C, 246 nm: t R (major) = min, t R (minor) = min. 24 (S)-tert-butyl (1-(2-methoxyphenyl)allyl) carbonate: [α] D = 29.6 (c = 2.12, CHCl 3 ); HPLC: (CHIRALPAK IB, 99.5% hexane, 0.5% i PrOH, 0.5 ml/min, 25 C, 210 nm): t R (minor) = min, t R (major) = min. (R)-tert-butyl acetyl(4-(1-(pyrrolidin-1-ylimino)but-3-en-2-yl)phenyl)carbamate: 391 mg carbonate 1e, 64 µl hydrazone 2a, 58 mg citric acid and 2.5 mg Sc(OTf) 3 were reacted for 1.5 h. Purification by flash column chromatography (hexane/etoac 5:1 2:1) afforded (R)-3e (173 mg, 47%, 98% ee) and (S)-1e (192 mg, 47%, >99% ee), s = 744. TLC: R f = 0.30 (hexane/etoac, 3:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ (m, 2H), (m, 2H), 6.56 (d, J = 6.6 Hz, 1H), 6.11 (ddd, J = 17.0, 10.3, 6.5 Hz, 1H), 5.16 (ddd, J = 10.3, 1.5, 1.4 Hz, 1H), 5.08 (ddd, J = 17.2, 1.5, 1.4 Hz, 1H), 4.25 (t, J = 6.6 Hz, 1H), (m, 4H), 2.53 (s, 3H), (m, 4H), 1.37 (s, 9H); 13 C-NMR (101 MHz, CDCl 3 ): δ 172.8, 152.7, 141.2, 138.6, 137.1, 137.1, (2x), (2x), 115.9, 83.1, 52.1, 51.2 (2x), 27.7 (3x), 26.4, 23.0 (2x); IR (neat, cm -1 ): 2976, 1734, 1708, 1369, 1269, 1253, 1153, 1095, 848; Anal. Calcd. for C 21 H 29 N 3 O 3 : C, 67.90; H, 7.87; N, 11.31; found C, 67.61; H, 8.16; N, 10.84; HRMS (ESI): required for C 21 H 30 N 3 O 3 [MH] +, ; found ; [α] 27 D = +0.5 (c = 1.21, CHCl 3 ); SFC: Daicel CHIRALPAK IB, 98% CO 2, 2% MeOH, 2.0 ml/min, 25 C, 251 nm: t R (major) = min, t R (minor) = min. 28 (S)-tert-butyl acetyl(4-(1-((tert-butoxycarbonyl)oxy)allyl)phenyl)carbamate: [α] D = 21.1 (c = 1.31, CHCl 3 ); HPLC: (CHIRALPAK IB, 99.5% hexane, 0.5% i PrOH, 0.6 ml/min, 25 C, 210 nm): t R (minor) = min, t R (major) = min. (R)-N-(2-(2-bromophenyl)but-3-en-1-ylidene)pyrrolidin-1-amine: 314 mg carbonate 1f, 64 µl hydrazone 2a, 58 mg citric acid and 2.5 mg Sc(OTf) 3 were reacted for 3 h. Purification by flash column chromatography (hexane/etoac 20:1 10:1) afforded (R)-3f (131 mg, 45%, 98% ee) and (S)-1f (141 mg, 45%, >99% ee), s = 933. TLC: R f = 0.56 (hexane/etoac, 5:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ 7.56 (d, J = 7.7 Hz, 1H), (m, 2H), 7.08 (ddd, J = 8.0, 5.6, 3.4 Hz, 1H), 6.61 (d, J = 5.6 Hz, 1H), 6.13 (ddd, J = 17.3, 10.3, 6.1 Hz, 1H), 5.18 (ddd, J = 10.3, 1.5, 1.6 Hz, 1H), 5.06 (ddd, J = 17.3, 1.6, 1.5 Hz, 1H), 4.76 (dd, J = 5.8, 1.6 Hz, 1H), (m, 4H), (m, 4H); 13 C-NMR (101 MHz, CDCl 3 ): δ 141.0, 138.1, 136.0, 133.1, 129.7, 128.0, 127.5, 124.6, 115.9, 51.3 (2x), 51.1, 23.1 (2x); IR (neat, cm -1 ): 2969, 2827, 1589, 1468, 1339, 1137, 1021, 914, 751; Anal. Calcd. for C 14 H 17 BrN 2 : C, 57.35; H, 5.84; N, 9.55; found C, 57.63; H, 6.05; N, 9.49; HRMS (ESI): required for C 14 H 18 BrN 2 [MH] +, ; found ; [α] 25 D = 83.8 (c = 1.35, CHCl 3 ); SFC: Daicel CHIRALPAK IB, 98% CO 2, 2% MeOH, 2.0 ml/min, 25 C, 251 nm: t R (major) = 7.68 min, t R (minor) = 8.67 min. (S)-tert-butyl (1-(2-bromophenyl)allyl) carbonate: [α] 25 D = 3.3 (c = 1.19, CHCl 3 ); HPLC: (CHIRALPAK IA, 99% hexane, 1% i PrOH, 0.5 ml/min, 25 C, 210 nm): t R (minor) = min, t R (major) = min. S10

11 (R)-N-(2-(4-fluorophenyl)but-3-en-1-ylidene)pyrrolidin-1-amine: 254 mg carbonate 1g, 64 µl hydrazone 2a, 58 mg citric acid and 2.5 mg Sc(OTf) 3 were reacted for 2 h. Purification by flash column chromatography (hexane/etoac 20:1 10:1) afforded (R)-3g (98 mg, 42%, >99% ee) and (S)-1g (116 mg, 46%, >99% ee), s = TLC: R f = 0.58 (hexane/etoac, 5:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ (m, 2H), (m, 2H), 6.55 (d, J = 6.6 Hz, 1H), 6.10 (ddd, J = 17.0, 10.3, 6.6 Hz, 1H), 5.18 (ddd, J = 10.3, 1.5, 1.4 Hz, 1H), 5.10 (ddd, J = 17.2, 1.5, 1.4 Hz, 1H), 4.23 (dd, J = 6.6, 6.6 Hz, 1H), (m, 4H), (m, 4H); 13 C-NMR (101 MHz, CDCl 3 ): δ (d, J = Hz), 138.9, (d, J = 3.3 Hz), 137.2, (d, J = 7.9 Hz, 2C), 115.8, (d, J = 21.2 Hz, 2C), 51.8, 51.3 (2x), 23.0 (2x); 19 F-NMR (377 MHz, CDCl 3 ): δ ; IR (neat, cm -1 ): 2971, 2827, 1600, 1506, 1340, 1220, 1157, 916, 833; Anal. Calcd. for C 14 H 17 FN 2 : C, 72.39; H, 7.38; N, 12.06; found C, 72.28; H, 7.62; N, 11.99; HRMS (ESI): required for C 14 H 18 FN 2 [MH] +, ; found ; [α] 25 D = (c = 1.50, CHCl 3 ); SFC: Daicel CHIRALCEL OJ-H, 99% CO 2, 1% MeOH, 2.0 ml/min, 25 C, 247 nm: t R (major) = 8.43 min, t R (minor) = min. 25 (S)-tert-butyl (1-(4-fluorophenyl)allyl) carbonate: [α] D = 33.8 (c = 1.52, CHCl 3 ); HPLC: (CHIRALPAK IA, 99.5% hexane, 0.5% i PrOH, 0.6 ml/min, 25 C, 210 nm): t R (minor) = 5.65 min, t R (major) = 6.45 min. (R)-N-(2-(4-chlorophenyl)but-3-en-1-ylidene)pyrrolidin-1-amine: 273 mg carbonate 1h, 64 µl hydrazone 2a, 58 mg citric acid and 2.5 mg Sc(OTf) 3 were reacted for 3 h. Purification by flash column chromatography (hexane/etoac 20:1 10:1) afforded (R)-3h (100 mg, 40%, >99% ee) and(s)-1h (114 mg, 42%, 99% ee), s = TLC: R f = 0.31 (hexane/etoac, 10:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ (m, 2H), (m, 2H), 6.53 (d, J = 6.6 Hz, 1H), 6.09 (ddd, J = 17.0, 10.3, 6.6 Hz, 1H), 5.18 (ddd, J = 10.3, 1.5, 1.4 Hz, 1H), 5.11 (ddd, J = 17.2, 1.5, 1.4 Hz, 1H), 4.22 (t, J = 6.6 Hz, 1H), (m, 4H), (m, 4H); 13 C-NMR (101 MHz, CDCl 3 ): δ 140.3, 138.6, 136.6, 132.3, (2x), (2x), 116.0, 52.0, 51.2 (2x), 23.0 (2x); IR (neat, cm -1 ): 2971, 1488, 1339, 1089, 1014, 916, 823, 525; Anal. Calcd. for C 14 H 17 ClN 2 : C, 67.60; H, 6.89; N, 11.26; found C, 67.56; H, 7.11; N, 11.29; HRMS (ESI): required for C 14 H 18 ClN 2 [MH] +, ; found ; [α] 24 D = (c = 1.25, CHCl 3 ); SFC: Daicel CHIRALCEL OJ-H, 97% CO 2, 3% MeOH, 2.0 ml/min, 25 C, 250 nm: t R (major) = 7.39 min, t R (minor) = 9.35 min. 24 (S)-tert-butyl (1-(4-chlorophenyl)allyl) carbonate: [α] D = 27.5 (c = 1.55, CHCl 3 ); HPLC: (CHIRALPAK IA, 99.5% hexane, 0.5% i PrOH, 0.6 ml/min, 25 C, 210 nm): t R (minor) = 4.92 min, t R (major) = 5.75 min. (R)-N-(2-(4-iodophenyl)but-3-en-1-ylidene)pyrrolidin-1-amine: 361 mg carbonate 1i, 64 µl hydrazone 2a, 58 mg citric acid and 2.5 mg Sc(OTf) 3 were reacted for 1.5 h. Purification by flash column chromatography (hexane/etoac 25:1 10:1) afforded (R)-3i (146 mg, 43%, >99% ee) and(s)-1i (176 mg, 49%, 98% ee), s = TLC: R f = 0.33 (hexane/etoac, 10:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ (m, 2H), (m, 2H), 6.52 (d, J = 6.5 Hz, 1H), 6.08 (ddd, J = 17.0, 10.3, 6.6 Hz, 1H), 5.18 (ddd, J = 10.3, 1.5, 1.4 Hz, 1H), 5.11 (ddd, J = 17.3, 1.5, 1.4 Hz, 1H), 4.19 (t, J = 6.6 Hz, 1H), (m, 4H), (m, 4H); 13 C-NMR (101 MHz, CDCl 3 ): δ 141.6, 138.4, (2x), 136.4, (2x), 116.1, 91.8, 52.1, 51.2 (2x), 23.0 (2x); IR (neat, cm -1 ): 2968, 1482, 1339, 1133, 1005, 915, 816, 519; Anal. Calcd. for C 14 H 17 IN 2 : C, 49.43; H, 5.04; N, 8.23; found C, 49.29; H, 5.22; N, 8.26; HRMS (ESI): required for C 14 H 18 IN 2 [MH] +, ; found ; [α] 27 D = +5.7 (c = 1.42, CHCl 3 ); S11

12 SFC: Daicel CHIRALPAK IB, 98% CO 2, 2% MeOH, 2.0 ml/min, 25 C, 230 nm: t R (major) = 9.43 min, t R (minor) = min. 27 (S)-tert-butyl (1-(4-iodophenyl)allyl) carbonate: [α] D = 26.3 (c = 1.39, CHCl 3 ); HPLC: (CHIRALPAK ID, 99.5% hexane, 0.5% i PrOH, 0.6 ml/min, 25 C, 210 nm): t R (minor) = 5.87 min, t R (major) = 6.01 min. (R)-N-(2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)but-3-en-1-ylidene)pyrrolidin-1- amine: 360 mg carbonate 1j, 64 µl hydrazone 2a, 58 mg citric acid and 2.5 mg Sc(OTf) 3 were reacted for 1 h. Purification by flash column chromatography (hexane/etoac 12:1 6:1) afforded (R)-3j (149 mg, 44%, 97% ee) and (S)-1j (164 mg, 45%, >99% ee), s = 603. TLC: R f = 0.37 (hexane/etoac, 5:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ 7.70 (dq, J = 1.9, 0.6 Hz, 1H), 7.68 (dt, J = 7.0, 1.4 Hz, 1H), 7.36 (dt, J = 7.7, 1.6 Hz, 1H), 7.32 (ddd, J = 7.7, 7.0, 0.7 Hz, 1H), 6.62 (d, J = 6.6 Hz, 1H), 6.16 (ddd, J = 17.3, 10.3, 6.5 Hz, 1H), 5.16 (ddd, J = 10.3, 1.6, 1.5 Hz, 1H), 5.12 (ddd, J = 17.2, 1.6, 1.5 Hz, 1H), 4.26 (t, J = 6.5 Hz, 1H), 3.15 (ddt, J = 7.7, 5.9, 1.9 Hz, 4H), (m, 4H), 1.34 (s, 12H); 13 C-NMR (101 MHz, CDCl 3 ): δ 141.2, 139.2, 137.9, 134.2, 133.1, 131.1, (C-B, very broad), 128.0, 115.7, 83.8, 52.9, 51.4 (2x), (2x), (2x), 23.1 (2x); 11 B NMR (160 MHz, CDCl 3 ) δ = 30.9 (br); IR (neat, cm -1 ): 2976, 1354, 1321, 1142, 1078, 965, 854, 709; Anal. Calcd. for C 20 H 29 N 2 O 2 B: C, 70.60; H, 8.59; N, 8.23; found C, 70.23; H, 8.43; N, 8.01; HRMS (ESI): required for C 20 H 30 N 2 O 2 B [MH] +, ; found ; [α] 24 D = +4.8 (c = 3.42, CHCl 3 ); SFC: Daicel CHIRALPAK IB, 99% CO 2, 1% MeOH, 2.0 ml/min, 25 C, 220 nm: t R (major) = min, t R (minor) = min. (S)-tert-butyl (1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)allyl) carbonate: [α] 24 D = 42.5 (c = 1.68, CHCl 3 ); HPLC: (CHIRALPAK ID, 99.5% hexane, 0.5% i PrOH, 0.5 ml/min, 25 C, 210 nm): t R (minor) = 7.07 min, t R (major) = 7.48 min. (R)-methyl 4-(1-(pyrrolidin-1-ylimino)but-3-en-2-yl)benzoate: 310 mg carbonate 1k, 70 µl hydrazone 2a, 64 mg citric acid and 4.0 mg Sc(OTf) 3 were reacted for 6 h. Purification by flash column chromatography (hexane/etoac 10:1 5:1) afforded (R)-3k (82 mg, 28%, 99% ee) and(s)-1k (143 mg, 46%, >99% ee), s = TLC: R f = 0.37 (hexane/etoac, 5:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ (m, 2H), (m, 2H), 6.55 (d, J = 6.6 Hz, 1H), 6.12 (ddd, J = 17.0, 10.3, 6.6 Hz, 1H), 5.20 (ddd, J = 10.3, 1.4, 0.6 Hz, 1H), 5.12 (ddd, J = 17.2, 1.4, 0.6 Hz, 1H), 4.30 (t, J = 6.6 Hz, 1H), 3.90 (s, 3H), (m, 4H), (m, 4H); 13 C-NMR (101 MHz, CDCl 3 ): δ 167.0, 147.2, 138.3, 136.1, (2x), 128.4, (2x), 116.3, 52.6, 52.0, 51.2 (2x), 23.1 (2x); IR (neat, cm -1 ): 2961, 1719, 1609, 1435, 1275, 1179, 1105, 1019, 779, 709; Anal. Calcd. for C 16 H 20 N 2 O 2 : C, 70.56; H, 7.40; N, 10.29; found C, 70.45; H, 7.41; N, 10.12; HRMS (ESI): required for C 16 H 21 N 2 O 2 [MH] +, ; found ; [α] 24 D = (c = 2.96, CHCl 3 ); SFC: Daicel CHIRALPAK AS-H, 98% CO 2, 2% MeOH, 2.0 ml/min, 25 C, 235 nm: t R (major) = 5.17 min, t R (minor) = 9.26 min. (S)-methyl 4-(1-((tert-butoxycarbonyl)oxy)allyl)benzoate: [α] 24 D = 23.0 (c = 1.95, CHCl 3 ); HPLC: (CHIRALPAK IC, 99% hexane, 1% i PrOH, 0.8 ml/min, 25 C, 230 nm): t R (minor) = min, t R (major) = min. S12

13 (R)-N-(2-(4-trifluoromethylphenyl)but-3-en-1-ylidene)pyrrolidin-1-amine: To a solution of 33.6 mg [Ir(cod)Cl] 2 (0.05 equiv) and mg (R)-L1 (0.20 equiv) in 2.0 ml DCE which was stirred at room temperature for 15 min, was added sequentially 304 mg carbonate 1l, 64 µl hydrazone 2a, 58 mg citric acid and 5.0 mg Sc(OTf) 3 and stirring was continued for 3 h. Purification by flash column chromatography (hexane/etoac 25:1 10:1 5:1) afforded (R)-3l (75 mg, 26%, 99% ee) and(s)-1l (130 mg, 43%, 99% ee). Additionally, some hydrazine product (see below) was obtained (20 mg, 5%), s = 883. TLC: R f = 0.30 (hexane/etoac, 10:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ 7.57 (d, J = 8.1 Hz, 2H), 7.38 (d, J = 8.3 Hz, 2H), 6.55 (d, J = 6.5 Hz, 1H), 6.12 (ddd, J = 17.1, 10.3, 6.6 Hz, 1H), 5.22 (ddd, J = 10.3, 1.5, 1.4 Hz, 1H), 5.13 (ddd, J = 17.3, 1.5, 1.4 Hz, 1H), 4.31 (t, J = 6.5 Hz, 1H), (m, 4H), (m, 4H); 13 C-NMR (101 MHz, CDCl 3 ): δ (q, J = 1.5 Hz), 138.2, 135.8, (q, J = 32.4 Hz), (2x), (q, J = 3.8 Hz, 2C), (q, J = Hz), 116.4, 52.4, 51.2 (2x), 23.1 (2x); 19 F-NMR (377 MHz, CDCl 3 ): δ 62.40; IR (neat, cm -1 ): 2973, 1618, 1323, 1162, 1118, 1067, 1018, 919, 838; Anal. Calcd. for C 15 H 17 F 3 N 2 : C, 63.82; H, 6.07; N, 9.92; found C, 63.79; H, 6.32; N, 10.19; HRMS (ESI): required for C 15 H 18 F 3 N 2 [MH] +, ; found ; [α] 25 D = (c = 1.17, CHCl 3 ); SFC: Daicel CHIRALPAK IB, 99.5% CO 2, 0.5% MeOH, 2.0 ml/min, 25 C, 251 nm: t R (major) = 5.99 min, t R (minor) = 6.63 min. (S)-tert-butyl (1-(4-trifluoromethylphenyl)allyl) carbonate: [α] 25 D = 12.4 (c = 2.04, CHCl 3 ); HPLC: (CHIRALPAK IA, 99.5% hexane, 0.5% i PrOH, 0.5 ml/min, 25 C, 217 nm): t R (minor) = 5.60 min, t R (major) = 6.47 min. N-(2-(pyrrolidin-1-ylimino)ethyl)-N-(1-(4-(trifluoromethyl)phenyl)allyl)pyrrolidin-1-amine: TLC: R f = 0.32 (hexane/etoac, 5:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ 7.53 (s, 4H), 6.37 (t, J = 5.5 Hz, 1H), 6.09 (ddd, J = 17.7, 9.6, 8.7 Hz, 1H), (m, 2H), 4.30 (d, J = 8.7 Hz, 1H), 3.52 (dd, J = 13.8, 4.8 Hz, 1H), 3.39 (dd, J = 13.8, 6.2 Hz, 1H), 3.02 (tdd, J = 6.9, 5.3, 2.7 Hz, 4H), 2.74 (ddt, J = 8.7, 6.5, 3.3 Hz, 4H), (m, 4H), (m, 4H); 13 C-NMR (101 MHz, CDCl 3 ): δ (q, J = 1.4 Hz), 138.5, 135.5, (q, J = 32.1 Hz), (2x), (q, J = 3.8 Hz, 2C), (q, J = Hz), 116.5, 70.5, 51.1 (2x), 49.4, 48.1 (2x), 23.0 (2x), 22.1 (2x); 19 F-NMR (377 MHz, CDCl 3 ): δ 62.23; IR (neat, cm -1 ): 2968, 2830, 1617, 1416, 1324, 1161, 1121, 1066, 1018, 923, 834; HRMS (ESI): required for C 20 H 28 F 3 N 4 [MH] +, ; found ; [α] 24 D = 46.5 (c = 1.10, CHCl 3 ). (R)-N-(2-(thiophen-3-yl)but-3-en-1-ylidene)pyrrolidin-1-amine: 250 mg carbonate 1m, 64 µl hydrazone 2a and 58 mg citric acid were reacted for 2 h. Purification by flash column chromatography (hexane/etoac 20:1 10:1) afforded (R)-3m (103 mg, 45%, 96% ee) and (S)-1m (93 mg, 37%, 97% ee), s = 232. TLC: R f = 0.52 (hexane/etoac, 5:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ 7.28 (dd, J = 5.0, 3.0 Hz, 1H), 7.04 (ddd, J = 3.0, 0.9 Hz, 1H), 7.00 (ddd, J = 5.0, 1.3, 0.4 Hz, 1H), 6.57 (d, J = 6.8 Hz, 1H), 6.11 (ddd, J = 17.2, 10.3, 6.9 Hz, 1H), 5.17 (ddd, J = 6.3, 1.5, 1.4 Hz, 1H), 5.14 (ddd, J = 13.0, 1.5, 1.4 Hz, 1H), 4.31 (ddd, J = 6.9, 6.8, 1.2 Hz, 1H), (m, 4H), (m, 4H); 13 C-NMR (101 MHz, CDCl 3 ): δ 142.4, 138.4, 137.0, 127.6, 125.6, 120.8, 115.7, 51.3 (2x), 48.5, 23.1 (2x); IR (neat, cm -1 ): 2969, 2826, 1636, 1592, 1458, 1411, 1339, 1132, 915, 860, 838, 782, 747, 677; Anal. Calcd. for C 12 H 16 N 2 S: C, 65.41; H, 7.32; N, 12.71; found C, 65.55; H, 7.40; N, 12.50; HRMS (ESI): required for C 23 H 26 N 3 O 2 S [MH] + 26, ; found ; [α] D = (c = 1.58, CHCl 3 ); SFC: Daicel CHIRALCEL OJ-H, 98% CO 2, 2% MeOH, 2.0 ml/min, 25 C, 244 nm: t R (major) = 9.86 min, t R (minor) = min. (S)-tert-butyl (1-(thiophen-3-yl)allyl) carbonate: [α] 26 D = 34.9 (c = 1.60, CHCl 3 ); HPLC: (CHIRALCEL OJ-H, 99% hexane, 1% i PrOH, 0.5 ml/min, 25 C, 234 nm): t R (minor) = min, t R (major) = min. S13

14 (R)-N-(2-(1-tosyl-1H-indol-3-yl)but-3-en-1-ylidene)pyrrolidin-1-amine: 458 mg carbonate 1n, 70 µl hydrazone 2a, 62 mg citric acid and 2.5 mg Sc(OTf) 3 were reacted for 20 min. Purification by flash column chromatography (hexane/etoac 5:1 3:1 containing 1% v/v NEt 3 ) afforded (R)-3n (212 mg, 49%, 96% ee) and (S)-1n (204 mg, 45%, 96% ee), s = 218. TLC: R f = 0.31 (hexane/etoac, 4:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ 7.96 (dt, J = 8.4, 1.0 Hz, 1H), (m, 2H), 7.57 (dt, J = 8.0, 1.1 Hz, 1H), 7.40 (d, J = 1.3 Hz, 1H), 7.29 (ddd, J = 8.4, 7.2, 1.3 Hz, 1H), (m, 3H), 6.54 (d, J = 6.7 Hz, 1H), 6.14 (ddd, J = 17.0, 10.3, 6.5 Hz, 1H), 5.19 (ddd, J = 10.3, 1.5, 1.5 Hz, 1H), 5.15 (ddd, J = 17.3, 1.5, 1.5 Hz, 1H), 4.43 (ddd, J = 6.7, 6.5, 1.4 Hz, 1H), (m, 4H), 2.33 (s, 3H), (m, 4H); 13 C-NMR (101 MHz, CDCl 3 ): δ 144.8, 137.2, 135.4, 135.3, 135.3, 130.1, (2x), (2x), 124.6, 123.0, 122.9, 122.9, 120.5, 116.2, 113.5, 51.3 (2x), 44.3, 23.0 (2x), 21.5; IR (neat, cm -1 ): 2969, 1446, 1368, 1171, 1122, 1093, 977, 745, 660, 574, 537; HRMS (ESI): required for C 23 H 26 N 3 O 2 S[MH] +, ; found ; [α] 27 D = 29.3 (c = 3.56, CHCl 3 ); HPLC: (CHIRALPAK ID, 95% hexane, 5% i PrOH, 1.0 ml/min, 25 C, 250 nm): t R (major) = min, t R (minor) = min. (S)-tert-butyl (1-(1-tosyl-1H-indol-3-yl)allyl) carbonate: [α] 26 D = 27.9 (c = 2.14, CHCl 3 ); HPLC: (CHIRALPAK ID, 90% hexane, 10% i PrOH, 1.0 ml/min, 25 C, 250 nm): t R (minor) = 5.23 min, t R (major) = 6.36 min. (((S,E)-2-allylidenecyclopentyl)methylene)pyrrolidin-1-amine: 116 mg carbonate 1o, 34 µl hydrazone 2a, 30 mg citric acid and 1.3 mg Sc(OTf) 3 were reacted for 1 h. Purification by flash column chromatography (hexane/etoac 20:1 10:1) afforded (E,S)-3o (39 mg, 37%, 98% ee, 95:5 regioselectivity). In addition, 48 mg of an inseparable mixture of 1o and 1o (1:1, 41%) was recovered. The diene stereochemistry is assigned based on a strong NOE-signal between H1 and H6 and between H3(a,b) and H7. The absolute stereochemistry is assigned by analogy to the aromatic substrates, wherein 1o and the Ir-catalyst from (R)-L1 affords putative allyliridium species II. Assuming the diene geometry is set during the impending nucleophile attack, S N 2 -substitution then produces (E,S)-3o. TLC: R f = 0.43 (hexane/etoac, 5:1; UV, KMnO 4 ); 1 H-NMR (500 MHz, CDCl 3 ): δ 6.44 (dddd, J = 16.9, 10.9, 10.2, 0.7 Hz, 1H), 6.37 (dd, J = 7.0, 0.6 Hz, 1H), 5.90 (dd, J = 10.9, 2.3 Hz, 1H), 5.09 (ddd, J = 16.9, 1.3, 0.5 Hz, 1H), 4.99 (ddd, J = 10.2, 1.9, 1.1 Hz, 1H), 3.21 (dd, J = 7.8, 7.8 Hz, 1H), (m, 4H), (m, 1H), 2.37 (dddd, J = 17.1, 12.7, 8.3, 1.6 Hz, 1H), (m, 1H), (m, 5H), (m, 1H), (m, 1H); 13 C-NMR (126 MHz, CDCl 3 ): δ 148.6, 140.5, 134.5, 123.0, 114.9, 51.7 (2x), 48.9, 32.6, 29.7, 24.8, 22.9 (2x); IR (neat, cm -1 ): 2956, 2870, 2829, 1600, 1459, 1339, 1135, 990, 894; Anal. Calcd. for C 13 H 20 N 2 : C, 76.42; H, 9.87; N, 13.71; found C, 76.47; H, 10.05; N, 13.92; HRMS (ESI): required for C 13 H 21 N 2 [MH] +, ; found ; [α] 23 D = (c = 0.50, CHCl 3 ); SFC: Daicel CHIRALPAK IC, 99% hexane, 1% MeOH 2.0 ml/min, 25 C, 230 nm: t R (major) = 5.72 min, t R (minor) = 7.42 min. (S)-2-(methoxymethyl)-N-((R)-2-phenylbut-3-en-1-ylidene)pyrrolidin-1-amine: 238 mg carbonate 1a, 85 mg hydrazone (S)-2b, 58 mg citric acid and 2.5 mg Sc(OTf) 3 were reacted for 1 h. Purification by flash column chromatography (hexane/etoac 25:1 7:1) afforded (R)-10 (100 mg, 38%, 99% de) and(s)-1a (119 mg, 50%, 99% ee). TLC: R f = 0.45 (hexane/etoac, 5:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ (m, 5H), 6.67 (d, J = 6.5 Hz, 1H), 6.16 (ddd, J = 17.1, 10.3, 6.5 Hz, 1H), 5.18 (ddd, J = 10.3, 1.5, 1.5 Hz, 1H), 5.12 (ddd, J = 17.3, 1.5, 1.5 Hz, 1H), 4.26 S14

15 (dd, J = 6.5, 6.5 Hz, 1H), 3.59 (dd, J = 8.9, 3.6 Hz, 1H), (m, 1H), 3.43 (dd, J = 8.9, 6.8 Hz, 1H), 3.37 (s, 3H), (m, 1H), 2.82 (q, J = 8.2 Hz, 1H), (m, 3H), (m, 1H); 13 C-NMR (101 MHz, CDCl 3 ): δ 141.7, 139.1, 137.6, (2x), (2x), 126.4, 115.5, 74.7, 63.1, 59.1, 52.5, 50.0, 26.6, 22.1; IR (neat, cm -1 ): 2975, 2877, 1451, 1196, 1116, 914, 759, 700; Anal. Calcd. for C 16 H 22 N 2 O: C, 74.38; H, 8.58; N, 10.84; found C, 74.21; H, 8.58; N, 10.75; HRMS (ESI): required for C 16 H 23 N 2 O[MH] +, ; found ; [α] 23 D = 63.0 (c = 1.30, CHCl 3 ); SFC: Daicel CHIRALCEL OJ-H, 99% CO 2, 1% MeOH, 2.0 ml/min, 25 C, 248 nm: t R (major) = min, t R (minor) = min. (S)-2-(methoxymethyl)-N-((S)-2-phenylbut-3-en-1-ylidene)pyrrolidin-1-amine: (S)-L1 was used instead of (R)-L mg carbonate 1a, 86 mg hydrazone (S)-2b, 58 mg citric acid and 2.5 mg Sc(OTf) 3 were reacted for 1 h. Purification by flash column chromatography (hexane/etoac 25:1 7:1) afforded (S)-10 (93 mg, 36%, 99% de) and (R)-1a (116 mg, 50%, 99% ee). TLC: R f = 0.47 (hexane/etoac, 5:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ (m, 5H), 6.70 (d, J = 6.5 Hz, 1H), 6.15 (ddd, J = 17.1, 10.3, 6.7 Hz, 1H), 5.16 (ddd, J = 10.3, 1.5, 1.4 Hz, 1H), 5.10 (ddd, J = 17.3, 1.5, 1.4 Hz, 1H), 4.25 (dd, J = 6.7, 6.5 Hz, 1H), (m, 1H), (m, 2H), 3.38 (s, 3H), (m, 1H), 2.78 (q, J = 8.3 Hz, 1H), (m, 4H); 13 C-NMR (101 MHz, CDCl 3 ): δ 141.9, 139.2, 137.6, (2x), (2x), 126.5, 115.5, 74.7, 63.2, 59.2, 52.6, 50.0, 26.6, 22.1; IR (neat, cm -1 ): 2975, 2877, 1451, 1196, 1116, 913, 758, 699; Anal. Calcd. for C 16 H 22 N 2 O: C, 74.38; H, 8.58; N, 10.84; found C, 74.51; H, 8.46; N, 10.72; HRMS (ESI): required for C 16 H 23 N 2 O[MH] +, ; found ; [α] 23 D = 86.1 (c = 1.84, CHCl 3 ); SFC: Daicel CHIRALCEL OJ-H, 99% CO 2, 1% MeOH, 2.0 ml/min, 25 C, 248 nm: t R (minor) = min, t R (major) = min. S15

16 3.3 Stereospecific Synthesis of Enantioenriched Hydrazones General Procedure: A stock solution of the catalyst was prepared as follows: A 5 ml-flask was charged with [Ir(cod)Cl] 2 (3.4 mg, 5.0 µmol) and L2 (8.4 mg, 20 µmol), the atmosphere exchanged with argon and DCE (1.0 ml) was added. The resulting orange solution was stirred at room temperature for 15 min. Part of this solution (0.5 ml, corresponding to 1 mol% [Ir(cod)Cl] 2 ) was then added via syringe to a 2 ml-vial with a Teflon-lined screw cap containing the carbonate (S)-1 (0.25 mmol) and hydrazone 2a (0.30 mmol, 1.20 equiv). Sc(OTf) 3 (2 mol%) was added, the vial purged with argon and the resulting yellow suspension was stirred at room temperature for the indicated time. The mixture was directly purified by flash column chromatography with the indicated eluent to afford enantioenriched hydrazones which were spectroscopically identical to the products from the kinetic resolution with the exception of the sign of the optical rotation. SFC traces with the same conditions as for the (R)-enantiomers (cf. chapter 3.2) can be found in chapter 5.2. (S)-N-(2-phenylbut-3-en-1-ylidene)pyrrolidin-1-amine: 58 mg carbonate (S)-1a (99% ee), 32 µl hydrazone 2a and 2.5 mg Sc(OTf) 3 were reacted for 1 h. Purification by flash column chromatography (hexane/etoac 10:1) afforded (S)-3a (43 mg, 81%, 98% ee, 99% es). (S)-N-(2-(naphtalen-2-yl)but-3-en-1-ylidene)pyrrolidin-1-amine: 71 mg carbonate (S)-1b (99% ee), 32 µl hydrazone 2a and 2.5 mg Sc(OTf) 3 were reacted for 1 h. Purification by flash column chromatography (hexane/etoac 10:1) afforded (S)-3b (58 mg, 88%, 99% ee, >99% es). (S)-N-(2-(3-methoxyphenyl)but-3-en-1-ylidene)pyrrolidin-1-amine: 66 mg carbonate (S)-1c (99% ee), 32 µl hydrazone 2a and 2.5 mg Sc(OTf) 3 were reacted for 1 h. Purification by flash column chromatography (hexane/etoac 5:1) afforded (S)-3c (49 mg, 80%, 98% ee, 99% es). (S)-N-(2-(2-methoxyphenyl)but-3-en-1-ylidene)pyrrolidin-1-amine: 66 mg carbonate (S)-1d (>99% ee), 32 µl hydrazone 2a and 2.5 mg Sc(OTf) 3 were reacted for 1 h. Purification by flash column chromatography (hexane/etoac 5:1) afforded (S)-3d (51 mg, 83%, 97% ee, 97% es). S16

17 (S)-tert-butyl acetyl(4-(1-(pyrrolidin-1-ylimino)but-3-en-2-yl)phenyl)carbamate: 98 mg carbonate (S)-1e (>99% ee), 32 µl hydrazone 2a and 2.5 mg Sc(OTf) 3 were reacted for 1 h. Purification by flash column chromatography (hexane/etoac 4:1 3:1) afforded (S)-3e (81 mg, 87%, 99% ee, 99% es). (S)-N-(2-(2-bromophenyl)but-3-en-1-ylidene)pyrrolidin-1-amine: 78 mg carbonate (S)-1f (>99% ee), 32 µl hydrazone 2a and 2.5 mg Sc(OTf) 3 were reacted for 1 h. Purification by flash column chromatography (hexane/etoac 10:1) afforded (S)-2a (51 mg, 70%, 97% ee, 97% es). (S)-N-(2-(4-fluorophenyl)but-3-en-1-ylidene)pyrrolidin-1-amine: 65 mg carbonate (S)-1g (>99% ee), 32 µl hydrazone 2a and 2.6 mg Sc(OTf) 3 were reacted for 1 h. Purification by flash column chromatography (hexane/etoac 10:1 5:1) afforded (S)-3g (50 mg, 84%, 99% ee, 99% es). (S)-N-(2-(4-chlorophenyl)but-3-en-1-ylidene)pyrrolidin-1-amine: 67 mg carbonate (S)-1h (>99% ee), 32 µl hydrazone 2a and 2.5 mg Sc(OTf) 3 were reacted for 1 h. Purification by flash column chromatography (hexane/etoac 10:1) afforded (S)-3h (49 mg, 79%, 98% ee, 99% es). (S)-N-(2-(4-iodophenyl)but-3-en-1-ylidene)pyrrolidin-1-amine: 90 mg carbonate (S)-3i (98% ee), 32 µl hydrazone 2a and 2.5 mg Sc(OTf) 3 were reacted for 1 h. Purification by flash column chromatography (hexane/etoac 10:1) afforded (S)-3i (67 mg, 79%, 98% ee, 99% es). (S)-N-(2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)but-3-en-1-ylidene)pyrrolidin-1- amine: 92 mg carbonate (S)-1j (>99% ee), 32 µl hydrazone 2a and 2.5 mg Sc(OTf) 3 were reacted for 1.5 h. Purification by flash column chromatography (hexane/etoac 5:1) afforded (S)-3j (71 mg, 82%, 97% ee, 97% es). (S)-methyl 4-(1-(pyrrolidin-1-ylimino)but-3-en-2-yl)benzoate: 74 mg carbonate (S)-1k (>99% ee), 32 µl hydrazone 2a and 2.5 mg Sc(OTf) 3 were reacted with 0.5 ml of a catalyst solution consisting of 7.7 mg [Ir(cod)Cl] 2 and 18.7 mg L2 in 0.75 ml DCE (corresponding to 3 mol% [Ir(cod)Cl] 2 ) for 1 h. Purification by flash column chromatography (hexane/etoac 5:1) afforded (S)-3k (46 mg, 67%, 98% ee, 98% es). S17

18 (S)-N-(2-(4-trifluoromethylphenyl)but-3-en-1-ylidene)pyrrolidin-1-amine: 78 mg carbonate (S)-1l (99% ee), 32 µl hydrazone 2a and 2.5 mg Sc(OTf) 3 were reacted with a catalyst solution consisting of 5.1 mg [Ir(cod)Cl] 2 and 12.3 mg L2 in 0.5 ml DCE (corresponding to 3 mol% [Ir(cod)Cl] 2 ) for 1.5 h. Purification by flash column chromatography (hexane/etoac 10:1) afforded (S)-3l (39 mg, 54%, 96% ee, 96% es) along with hydrazine byproduct (cf. chapter 3.2, 18 mg, 18%). (S)-N-(2-(thiophen-3-yl)but-3-en-1-ylidene)pyrrolidin-1-amine: 61 mg carbonate (S)-1m (97% ee), 32 µl hydrazone 2a and 2.5 mg Sc(OTf) 3 were reacted for 1 h. Purification by flash column chromatography (hexane/etoac 10:1) afforded (S)-3m (49 mg, 88%, 96% ee, 99% es). (S)-N-(2-(1-tosyl-1H-indol-3-yl)but-3-en-1-ylidene)pyrrolidin-1-amine: 107 mg carbonate (S)-1n (96% ee), 32 µl hydrazone 2a and 2.5 mg Sc(OTf) 3 were reacted for 45 min. Purification by flash column chromatography (hexane/etoac 4:1) afforded (S)-3n (86 mg, 84%, 95% ee, 99% es). S18

19 3.4 Derivatizations of Hydrazones (R)-2-phenylbut-3-enenitrile: To a vigorously stirred suspension of MMPP 6H 2 O (2.00 g, 4.04 mmol) in MeOH/pH 7 phosphate buffer (1:1, 40 ml) at 0 C open to air was added a solution of hydrazone (R)-3a (433 mg, 2.02 mmol) in MeOH (9.0 ml). The reaction was instantaneous and after 9 min the mixture was diluted with Et 2 O and washed with aq. sat. NaHCO 3. The layers were separated, the aqueous layer extracted with Et 2 O (3x) and the combined organic layers washed with water and brine and dried over Na 2 SO 4. Purification by flash column chromatography (pentane/et 2 O 5:1) and careful concentration (volatile material) afforded the product (R)-5 as a clear oil (268 mg, 93%, 98% ee). TLC: R f = 0.55 (hexane/etoac, 5:1; KMnO 4 ); 1 H-NMR (400 MHz, CD 2 Cl 2 ): δ (m, 2H), 7.36 (ddd, J = 6.9, 3.1, 1.4 Hz, 3H), 5.92 (ddd, J = 16.9, 10.0, 5.8 Hz, 1H), 5.52 (dd, J = 16.9, 1.6 Hz, 1H), 5.37 (dd, J = 9.9, 1.4 Hz, 1H), 4.58 (dd, J = 5.9, 1.7 Hz, 1H); 13 C-NMR (101 MHz, CD 2 Cl 2 ): δ 135.0, 132.9, 129.6, 128.7, 127.9, 119.0, 118.5, 41.1; IR (neat, cm -1 ): 3033, 2245, 1495, 1454, 985, 931, 754, 697, 674; HRMS (EI): required for C 10 H 9 N[M H] +, ; found ; [α] 25 D = (c = 3.41, CHCl 3 ); SFC: Daicel CHIRALCEL AS-H, 99.5% CO 2, 0.5% MeOH, 2.0 ml/min, 25 C, 205 nm: t R (minor) = 4.39 min, t R (major) = 4.71 min. (R)-2-phenylbutanenitrile: To a 10 ml flask containing a suspension of magnesium MMPP 6H 2 O (222 mg, 0.45 mmol) in MeOH/pH 7 phosphate buffer (1:1, 4.0 ml) at 0 C was added a solution of hydrazone (R)-3a (48 mg, 0.22 mmol) in MeOH (1.3 ml). After 5 min, TLC showed complete conversion and the mixture was diluted with Et 2 O, washed with aq. sat. NaHCO 3 and the layers separated. The aq. layer was extracted with Et 2 O (2x) and the combined organic phases were washed with water and brine and dried over MgSO 4. Filtration and careful concentration afforded crude (R)-5 (39 mg) which was used without further purification. A suspension of crude (R)-5 and Pd/C (10 weight% Pd, 23 mg, 0.02 mmol) in MeOH (1.1 ml) was stirred under an atmosphere of hydrogen for 45 min. The mixture was filtered through celite with Et 2 O and the filtrate concentrated. Purification by flash column chromatography (pentane/et 2 O 10:1) afforded the nitrile (R)-6 as a colorless oil (20.2 mg, 63% over 2 steps, 94% ee). TLC: R f = 0.50 (hexane/etoac, 4:1; KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ (m, 5H), 3.74 (t, J = 7.2 Hz, 1H), 1.95 (dq, J = 7.3, 7.2 Hz, 2H), 1.08 (t, J = 7.4 Hz, 3H); 13 C-NMR (101 MHz, CDCl 3 ): δ 135.7, (2x), 128.0, (2x), 120.7, 38.9, 29.2, 11.5; IR (neat, cm -1 ): 2971, 2936, 2879, 2240, 1493, 1454, 1384, 759, 698; HRMS (EI): required for C 10 H 11 N [M] +, ; found ; SFC: Daicel CHIRALPAK AS-H, 99.5% CO 2, 0.5% MeOH, 2.0 ml/min, 25 C, 203 nm: t R (minor) = 2.96 min, t R (major) = 3.18 min; [α] 26 D = (c = 0.70, CH 3 OH) [lit. [α] 25 D = (c = 7.08, CH 3 OH, er = 99:1) 9 and for (S)-enantiomer [α] 25 D = 27 (c = 1.1, CH 3 OH, er = 93:7) 10 ]. S19

20 (R)-2-(1-(naphthalen-2-yl)allyl)-1,3-dithiolane: To a solution of hydrazone (R)-3b (104 mg, 0.39 mmol) in anhydrous CH 2 Cl 2 (2.0 ml) at 0 C was added ethane-1,2-dithiol (0.07 ml, 0.83 mmol) followed by freshly distilled BF 3 OEt 2 (0.20 ml, 1.58 mmol). The resulting yellowish solution was refluxed for 56 h. After cooling to room temperature, the reaction mixture was poured into aq. sat. NaHCO 3. After extraction with EtOAc (2x), the combined organic layers were washed with additional aq. sat. NaHCO 3 and dried over MgSO 4 to afford an off-white solid which was purified by flash column chromatography (hexane/etoac 20:1). The product (R)-7 (84 mg, 78%, 96% ee) was obtained as a white crystalline solid which could be recrystallized from hexane for X-ray crystallographic analysis. Melting point: C (hexane); TLC: R f = 0.53 (hexane/etoac, 10:1; KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ 7.82 (dd, J = 7.4, 2.9 Hz, 3H), 7.73 (s, 1H), (m, 2H), 7.42 (dd, J = 8.5, 1.8 Hz, 1H), 6.22 (ddd, J = 17.6, 10.0, 7.9 Hz, 1H), 5.22 (dt, J = 5.3, 1.3 Hz, 1H), 5.19 (d, J = 1.0 Hz, 1H), 5.03 (d, J = 8.8 Hz, 1H), 3.76 (dd, J = 8.8, 7.9 Hz, 1H), (m, 2H), (m, 2H); 13 C-NMR (101 MHz, CDCl 3 ): δ 139.5, 139.3, 133.4, 132.6, 128.1, 127.9, 127.6, 126.9, 126.2, 126.0, 125.7, 117.0, 58.5, 58.0, 38.9, 38.8; IR (neat, cm -1 ): 3054, 2922, 1633, 1599, 1508, 1419, 1276, 989, 920, 855, 820, 751; HRMS (EI): required for C 16 H 16 S 2 [M] +, ; found ; [α] 25 D = 52.9 (c = 1.33, CHCl 3 ); SFC: Daicel CHIRALCEL OJ-H, 80% CO 2, 20% MeOH, 2.0 ml/min, 25 C, 223 nm: t R (major) = min, t R (minor) = min. (R)-tert-butyl acetyl(4-(1-(pyrrolidin-1-ylimino)butan-2-yl)phenyl)carbamate: To a solution of hydrazone (R)-3e (38 mg, 0.10 mmol, stored over long period in benzene at 20 C, repurified by flash column chromatography, 96% ee) in anhydrous MeOH (1.0 ml) was added PtO 2 (83% w/w Pt, 5.6 mg, 0.02 mmol). 11 The atmosphere was exchanged with H 2 and the suspension was stirred vigorously at room temperature. After 20 min, the reaction mixture was filtered over celite with Et 2 O and concentrated. The crude material was purified by flash column chromatography (pentane/et 2 O2:1 1:1) to afford the desired product (R)-3e (30 mg, 79%, 94% ee). In addition, a minor byproduct arising from N-deacetylation was obtained (3 mg, 9%). TLC: R f = 0.30 (pentane/et 2 O, 1:1; UV, KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ 7.24 (d, J = 8.3 Hz, 2H), 7.00 (d, J = 8.4 Hz, 2H), 6.58 (d, J = 6.8 Hz, 1H), 3.37 (q, J = 7.3 Hz, 1H), (m, 4H), 2.54 (s, 3H), (m, 6H), 1.37 (s, 9H), 0.87 (t, J = 7.3 Hz, 3H); 13 C-NMR (101 MHz, CDCl 3 ): δ 172.9, 152.8, 142.9, 140.5, 137.0, (2x), (2x), 83.1, 51.4 (2x), 50.5, 27.8 (3x), 27.5, 26.5, 22.9 (2x), 11.9; IR (neat, cm -1 ): 2968, 1737, 1710, 1370, 1303, 1273, 1157, 1097; HRMS (ESI): required for C 21 H 32 N 3 O 3 [MH] +, ; found ; [α] 23 D = 2.8 (c = 1.00, CHCl 3 ); SFC: Daicel CHIRALPAK IB, 98% CO 2, 2% MeOH, 2.0 ml/min, 25 C, 204 nm: t R (major) = min, t R (minor) = min. S20

21 (R)-tert-butyl acetyl(4-(1-oxobutan-2-yl)phenyl)carbamate: Prepared by the method of Lassaletta et al. 12 To a solution of hydrazone (R)-3e (28 mg, 0.06 mmol, 94% ee) in Et 2 O (2.0 ml) at 0 C under vigorous stirring was added 3M HCl (0.66 ml) dropwise. The aqueous phase turned bright yellow, while the organic layer remained colorless. After 10 min, the phases were separated, the aqueous phase extracted with Et 2 O (4x) and the combined organic layers basified with solid NaHCO 3 (57 mg) and then dried over Na 2 SO 4. The crude aldehyde was purified by flash column chromatography over SiliCycle SiliaFlash F60 (40 63 µm) (pentane/et 2 O2:1 3:2) to afford aldehyde (R)-8 (18 mg, 79%). TLC: R f = 0.47 (hexane/etoac, 2:1; KMnO 4 ); 1 H-NMR (400 MHz, CD 2 Cl 2 ): δ 9.68 (d, J = 2.0 Hz, 1H), 7.22 (d, J = 8.2, 0.4 Hz, 2H), 7.08 (d, J = 8.5 Hz, 2H), 3.44 (ddd, J = 8.4, 6.5, 2.0 Hz, 1H), 2.54 (s, 3H), 2.10 (dqd, J = 14.0, 7.4, 6.6 Hz, 1H), 1.75 (ddq, J = 13.8, 8.1, 7.4 Hz, 1H), 1.35 (s, 9H), 0.88 (t, J = 7.4 Hz, 3H); 13 C-NMR (101 MHz, CD 2 Cl 2 ): δ 201.0, 173.2, 153.0, 138.9, 136.5, (2x), (2x), 83.6, 60.7, 27.9 (3x), 26.8, 23.5, 11.8; IR (neat, cm -1 ): 2793, 1736, 1512, 1370, 1303, 1273, 1255, 1157, 1098; HRMS (EI): required for C 17 H 23 NO 4 [M] +, ; found ; [α] 23 D = 63.6 (c = 0.78, CH 2 Cl 2 ). (R)-tert-butyl acetyl(4-(1-hydroxybutan-2-yl)phenyl)carbamate: To a solution of aldehyde (R)-8 (15 mg, 0.05 mmol) in anhydrous CH 2 Cl 2 (0.32 ml) and anhydrous MeOH (0.16 ml) at 78 C under nitrogen was added NaBH 4 (3.7 mg, 0.10 mmol). The mixture was stirred at 78 C for 15 min and then quenched by addition of aq. sat. NH 4 Cl. After extraction with Et 2 O (3x), the combined organic layers were dried over MgSO 4 and the crude material was purified by flash column chromatography (pentane/et 2 O1:1 1:3) to afford alcohol (R)-9 (14 mg, 93%, 94% ee). TLC: R f = 0.31 (hexane/etoac, 1:1; KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ 7.22 (d, J = 8.3 Hz, 2H), 7.04 (d, J = 8.4 Hz, 2H), 3.74 (q, J = 6.8 Hz, 2H), (m, 1H), 2.57 (s, 3H), 1.77 (dqd, J = 12.9, 7.4, 5.4 Hz, 1H), (m, 1H), 1.43 (s, 1H), 1.37 (s, 9H), 0.82 (t, J = 7.4 Hz, 3H); 13 C-NMR (101 MHz, CDCl 3 ): δ 173.0, 152.8, 141.9, 137.4, (2x), (2x), 83.1, 67.2, 50.1, 27.8 (3x), 26.5, 24.9, 11.9; IR (neat, cm -1 ): 3449, 2962, 2929, 1738, 1709, 1370, 1275, 1255, 1157, 1098; HRMS (ESI): required for C 17 H 29 N 2 O 4 [MNH 4 ] +, ; found ; [α] 24 D = 8.6 (c = 0.80, CHCl 3 ); SFC: Daicel CHIRALPAK IB, 98% CO 2, 2% MeOH, 2.0 ml/min, 25 C, 205 nm: t R (major) = min, t R (minor) = min. S21

22 2,2,2-trifluoro-N-((S)-2-(methoxymethyl)pyrrolidin-1-yl)-N-((2R,3R)-3-phenylpent-4-en-2-yl)acetamide: To a solution of LaCl 3 2LiCl (0.5M in THF, 2.9 ml, 1.45 mmol) in additional anhydrous THF (3.6 ml) at 78 C was added MeLi (freshly titrated, 1.80M in Et 2 O, 0.81 ml, 1.46 mmol). The resulting brown suspension was stirred at 90 C C for 15 min before a solution of hydrazone (R)-10 (94 mg, 0.36 mmol) in anhydrous THF (1.8 ml) precooled to 78 C was added dropwise via cannula. Additional THF (2x0.4 ml) was used to complete the transfer and the resulting brown suspension was let come to 78 C and stirred at this temperature for 1 h before it was allowed to warm to room temperature overnight. After 14 h, the dark brown solution was cooled to 0 C and quenched with TFAA (0.26 ml, 1.84 mmol). Stirring was continued for 45 min at 0 C before aq. sat. NaHCO 3 was added and the mixture extracted with Et 2 O (3x). The combined organic layers were washed with brine and dried over MgSO 4 to afford a yellow oil. Crude NMR showed only a single diastereomer. Purification by flash column chromatography (hexane/etoac 8:1 5:1) afforded the product (2R,3R)-11 as a yellow oil which solidified upon drying (119 mg, 88%). X-ray quality grade crystals could be obtained by slow evaporation of a solution in hexane/ch 2 Cl 2. TLC: R f = 0.44 (hexane/etoac, 5:1; KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ (m, 2H), (m, 3H), 6.02 (ddd, J = 16.8, 10.3, 9.9 Hz, 1H), 5.15 (ddd, J = 16.8, 1.7, 0.8 Hz, 1H), 5.02 (dd, J = 10.0, 1.7 Hz, 1H), 4.23 (t, J = 10.3 Hz, 1H), 3.66 (q, J = 6.7 Hz, 1H), 3.62 (dd, J = 8.3, 3.0 Hz, 1H), 3.37 (s, 3H), (m, 1H), 3.13 (td, J = 8.8, 1.1 Hz, 1H), 3.05 (ddd, J = 7.3, 5.4, 3.1 Hz, 1H), 2.93 (q, J = 8.2 Hz, 1H), (m, 1H), (m, 3H), 1.26 (d, J = 6.6 Hz, 3H); 13 C-NMR (101 MHz, CDCl 3 ): δ (q, J = 33.7 Hz), 141.9, 138.8, (2x), (2x), 127.0, 117.0, (q, J = Hz), 74.7 (q, J = 2.1 Hz), 59.2, 58.0, 57.1, 53.2, 52.9, 27.9, 21.1, 16.8; 19 F NMR (376 MHz, CDCl 3 ): δ 70.24; IR (neat, cm -1 ): 2981, 1697, 1450, 1162, 1125, 923, 758, 736, 702; HRMS (ESI): required for C 19 H 26 F 3 N 2 O 2 [MH] +, ; found ; [α] 25 D = (c = 3.62, CHCl 3 ). 2,2,2-trifluoro-N-((S)-2-(methoxymethyl)pyrrolidin-1-yl)-N-((2R,3S)-3-phenylpent-4-en-2-yl)acetamide: To a solution of LaCl 3 2LiCl (0.5M in THF, 3.0 ml, 1.50 mmol) in additional anhydrous THF (3.5 ml) at 78 C was added MeLi (freshly titrated, 1.80M in Et 2 O, 0.83 ml, 1.49 mmol). The resulting brown suspension was stirred at 90 C C for 15 min before a solution of hydrazone (S)-10 (97 mg, 0.37 mmol) in anhydrous THF (1.8 ml) precooled to 78 C was added dropwise via cannula. Additional THF (2x0.4 ml) was used to complete the transfer and the resulting brown suspension was let come to 78 C and stirred at this temperature for 1 h before it was allowed to warm to room temperature overnight. After 14 h, the dark brown solution was cooled to 0 C and quenched with TFAA (0.27 ml, 1.91 mmol). Stirring was continued for 1 h at 0 C before aq. sat. NaHCO 3 was added and the mixture extracted with Et 2 O (3x). The combined organic layers were washed with brine and dried over MgSO 4 to afford a yellow oil. Crude NMR showed a 10:1 ratio of diastereomers which were separable on silica. Purification by flash column chromatography (hexane/etoac 5:1) afforded the diastereomerically pure syn-product (2R,3S)-11 as a dark yellow oil which solidified upon drying (123 mg, 88%). S22

23 TLC: R f = 0.35 (hexane/etoac, 5:1; KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ (m, 2H), (m, 3H), 6.02 (ddd, J = 16.9, 10.0, 9.5 Hz, 1H), 5.22 (ddd, J = 17.0, 1.6, 0.9 Hz, 1H), 5.16 (dd, J = 10.2, 1.5 Hz, 1H), 4.32 (dd, J = 10.5, 10.0 Hz, 1H), 3.51 (dq, J = 10.5, 6.6 Hz, 1H), 2.99 (s, 3H), (m, 2H), 2.59 (tt, J = 8.7, 3.7 Hz, 1H), 2.35 (tq, J = 9.5, 1.3 Hz, 1H), (m, 1H), 1.73 (dd, J = 8.3, 3.6 Hz, 1H), (m, 3H), 1.56 (d, J = 6.6 Hz, 3H); 13 C-NMR (101 MHz, CDCl 3 ): δ (q, J = 33.6 Hz), 141.9, 138.6, (2x), (2x), 126.8, 117.7, (q, J = Hz), 73.2 (q, J = 1.8 Hz), 58.2, 57.2, 57.1, 53.4, 52.5, 27.0, 20.9, 17.7; 19 F NMR (376 MHz, CDCl 3 ): δ 70.41; IR (neat, cm -1 ): 2980, 1694, 1451, 1162, 1126, 922, 759, 736, 704; HRMS (ESI): required for C 19 H 26 F 3 N 2 O 2 [MH] +, ; found ; [α] 25 D = 93.4 (c = 3.71, CHCl 3 ). 2,2,2-trifluoro-N-((2R,3R)-3-phenylpent-4-en-2-yl)acetamide: To a solution of (2R,3R)-11 (43 mg, 0.12 mmol) in anhydrous HMPA (0.23 ml) was added freshly prepared SmI 2 (0.1M in THF, 3.5 ml, 0.35 mmol). The resulting solution was stirred at room temperature for 10 min. The flask was opened to air and stirring continued. After discoloration of the solution, it was concentrated in vacuo and purified by flash column chromatography (hexane/etoac 7:1) to afford the product (2R,3R)-12 as a colorless crystalline solid (22 mg, 74%, 99% ee). X-ray quality grade crystals could be obtained by slow evaporation of a solution in hexane/ch 2 Cl 2. TLC: R f = 0.50 (hexane/etoac, 5:1; KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ (m, 2H), (m, 1H), (m, 2H), 6.12 (br, 1H), (m, 1H), 5.17 (d, J = 0.8 Hz, 1H), 5.14 (ddd, J = 6.9, 1.4, 0.9 Hz, 1H), (m, 1H), 3.30 (t, J = 8.8 Hz, 1H), 1.10 (d, J = 6.6 Hz, 3H); 13 C-NMR (101 MHz, CDCl 3 ): δ (q, J = 36.7 Hz), 139.9, 137.9, (2x), (2x), 127.3, 117.5, (q, J = Hz), 56.4, 49.6, 18.1; 19 F NMR (376 MHz, CDCl 3 ): δ 76.05; IR (neat, cm -1 ): 3312, 1700, 1562, 1212, 1179, 1151, 919, 699; HRMS (ESI): required for C 13 H 14 F 3 NO [MH] +, ; found ; [α] 23 D = 48.4 (c = 0.80, CHCl 3 ); SFC: Daicel CHIRALCEL OJ-H, 100% CO 2, 1.0 ml/min, 40 C, 200 nm: t R (minor) = min, t R (major) = min. 2,2,2-trifluoro-N-((2R,3S)-3-phenylpent-4-en-2-yl)acetamide: To a solution of (2R,3S)-11 (55 mg, 0.15 mmol) in anhydrous HMPA (0.23 ml) was added freshly prepared SmI 2 (0.08M in THF, 5.6 ml, 0.45 mmol). The resulting solution was stirred at room temperature for 10 min. The flask was opened to air and stirring continued. After discoloration of the solution, it was concentrated in vacuo and purified by flash column chromatography (hexane/etoac 10:1 5:1) to afford the product (2R,3S)-12 as a colorless solid (31mg, 82%, 99% ee). TLC: R f = 0.51 (hexane/etoac, 5:1; KMnO 4 ); 1 H-NMR (400 MHz, CDCl 3 ): δ (m, 2H), (m, 1H), (m, 2H), (m, 2H), 5.26 (dd, J = 10.4, 2.0 Hz, 1H), 5.22 (dd, J = 17.1, 1.2 Hz, 1H), 4.40 (dd, J = 9.0, 6.8 Hz, 1H), 3.47 (dd, J = 8.9, 6.7 Hz, 1H), 1.21 (d, J = 6.7 Hz, 3H); 13 C-NMR (101 MHz, CDCl 3 ): δ (q, J = 36.7 Hz), 139.6, 136.1, (2x), (2x), 127.2, 118.6, (q, J = Hz), 54.7, 49.2, 17.4; 19 F NMR (376 MHz, CDCl 3 ): δ 76.24; IR (neat, cm -1 ): 3316, 1698, 1560, 1202, 1179, 1154, 923, 759, 702, 668; HRMS (MALDI, 3-HPA): required for S23

24 C 13 H 14 F 3 NO [MH] +, ; found ; [α] 23 D = (c = 1.40, CHCl 3 ); SFC: Daicel CHIRALCEL OJ-H, 99.5% CO 2, 0.5% MeOH, 1.5 ml/min, 40 C, 200 nm: t R (minor) = 9.70 min, t R (major) = 10.77min. The racemic reference sample for SFC analysis was prepared analogously from rac-3a by nucleophilic addition (91%, d.r. = 5:1, anti:syn) and reductive N,N-cleavage with SmI 2 (66%). (2R,3R)-3-phenylpent-4-en-2-amine: Trifluoroacetamide (2R,3R)-12 (23.4 mg, 0.09 mmol) was dissolved in MeOH (0.78 ml). Deionized water (0.13 ml) and K 2 CO 3 (63 mg, 0.46 mmol) were added and the mixture was heated to 50 C for 18 h. After cooling to room temperature, the mixture was partitioned between 1M HCl and CH 2 Cl 2. The phases were separated, the aqueous phase washed with CH 2 Cl 2 (2x) and then basified with solid NaOH. Extraction with CH 2 Cl 2 (5x) was followed by drying of the combined organic layers over Na 2 SO 4. After filtration and concentration to <5 ml, 2M HCl in Et 2 O (0.5 ml) was added and the volatiles removed to afford pure amine hydrochloride as a white solid (85%, single diastereomer). 1 H-NMR (400 MHz, MeOD-d 4 ) δ 7.37 (ddt, J = 7.8, 6.6, 1.0 Hz, 2H), 7.28 (tt, J = 8.0, 1.4 Hz, 3H), 6.08 (dt, J = 17.0, 9.8 Hz, 1H), 5.34 (ddd, J = 16.9, 1.3, 0.7 Hz, 1H), 5.27 (dd, J = 10.1, 1.4 Hz, 1H), 3.61 (ddd, J = 10.1, 6.6, 6.5 Hz, 1H), 3.36 (t, J = 9.8 Hz, 1H), 1.12 (d, J = 6.5 Hz, 3H), (NH 3 not observed in MeOD-d 4 ); 13 C-NMR (101 MHz, MeOD-d 4 ): δ 141.0, 138.7, (2x), (2x), 128.6, 119.6, 57.2, 51.8, 17.4; IR (neat, cm -1 ): (broad, strong), 1599, 1510, 1491, 1196, 1014, 986, 933, 757, 698; HRMS (MALDI, 3-HPA): required for C 11 H 16 N [MH] +, ; found ; [α] 22 D = (c = 0.73, MeOH). (2R,3S)-3-phenylpent-4-en-2-amine: Trifluoroacetamide (2R,3S)-12 (23.1 mg, 0.09 mmol) was dissolved in MeOH (0.77 ml). Deionized water (0.13 ml) and K 2 CO 3 (62 mg, 0.46 mmol) were added and the mixture was heated to 50 C for 18 h. After cooling to room temperature, the mixture was partitioned between 1M HCl and CH 2 Cl 2. The phases were separated, the aqueous phase washed with CH 2 Cl 2 (2x) and then basified with solid NaOH. Extraction with CH 2 Cl 2 (5x) was followed by drying of the combined organic layers over Na 2 SO 4. After filtration and concentration to <5 ml, 2M HCl in Et 2 O (0.5 ml) was added and the volatiles removed to afford pure amine hydrochloride as a white solid (88%, single diastereomer). 1 H-NMR (400 MHz, MeOD-d 4 ) δ (m, 2H), (m, 3H), 6.10 (ddd, J = 16.9, 10.2, 9.2 Hz, 1H), (m, 1H), (m, 1H), 3.67 (dd, J = 8.6, 6.6 Hz, 1H), 3.49 (t, J = 9.0 Hz, 1H), 1.34 (d, J = 6.6 Hz, 3H), (NH 3 not observed in MeOD-d 4 ); 13 C-NMR (101 MHz, MeOD-d 4 ): δ 140.6, 137.4, (2x), (2x), 128.8, 119.4, 56.0, 52.2, 16.8; IR (neat, cm -1 ): 2933, 2169, 2105, 1165, 928, 757, 701; HRMS (MALDI, 3-HPA): required for C 11 H 16 N [MH] +, ; found ; [α] 22 D = (c = 0.75, MeOH). S24

25 4. References 1 Still, W. C.; Kahn, M.; Mitra, A. J. J. Org. Chem. 1978, 43, Pareja, C.; Martín-Zamora, E.; Fernández, R.; Lassaletta, J. M. J. Org. Chem. 1999, 64, Nakao, A.; Suzuki, H.; Tatsumi, R. et al. US2012/ A1, p Kagan, H. B.; Fiaud, J. C. Top. Stereochem. 1988, 18, Štambaský, J.; Malkov, A. V.; Kočovský, R. J. Org. Chem. 2008, 73, Barcellos, T.; Tauber, K.; Kroutil, W.; Andrade, L. H. Tetrahedron: Asymmetry 2011, 22, Jegelka, M.; Plietker, B. ChemCatChem 2012, 4, Ohfusa, T.; Nishida, A. Tetrahedron 2011, 67, Kosjek, B.; Fleitz, F. J.; Dormer, P. G.; Kuethe, J. T.; Devine, P. N. Tetrahedron: Asymmetry 2008, 19, Guin, J.; Varseev, G.; List, B. J. Am. Chem. Soc. 2013, 135, The use of palladium-based hydrogenation catalysts (e.g. Pd/C, Pd(OH) 2 /C) leads to appreciable epimerization (80 85% ee), presumably due to double bond isomerization prior to hydrogenation. 12 Díez, E.; Fernández, R.; Gasch, C.; Lassaletta, J. M.; Llera, J. M.; Martín-Zamora, E.; Vázquez, J. J. Org. Chem. 1997, 62, S25

26 5. Determination of Enantiomeric Excess (SFC/HPLC traces) 5.1 Hydrazones / Enantioenriched Carbonates S26

27 S27

28 S28

29 S29

30 S30

31 S31

32 S32

33 S33

34 S34

35 S35

36 S36

37 S37

38 S38

39 S39

40 S40

41 S41

42 S42

43 S43

44 5.2 Hydrazones by Stereospecific Formylation The enantioenriched carbonate starting materials correspond to the recovered carbonates from the kinetic resolution. For their HPLC traces, see chapter 5.1. S44

45 S45

46 S46

47 S47

48 S48

49 S49

50 S50

51 S51

52 S52

53 S53

54 S54

55 S55

56 S56

57 S57