Supporting Information

Transcription

1 Supporting Information Synthesis of Adjacent Quaternary Stereocenters by Catalytic Asymmetric Allylboration Rauful Alam, a Tobias Vollgraff, a Lars Eriksson b and Kálmán J. Szabó * a a Department of Organic Chemistry, b Department of Inorganic and Structural Chemistry, Stockholm University, SE Stockholm, Sweden. kalman@organ.su.se. Fax: Contents: General Information S2 Experimental Procedure and Spectral Data for 1c, 5a-q S2-S22 Montitoring of the mixture of 1a and 3c by 19 F NMR S23-24 Monitoring the reaction mixtures of 1a and i PrOH by 1 H NMR S24-25 References S26 1 H and 13 C NMR Spectra S27-S60 S1

2 General Information Allylboronic acids 1 (1a-b) and BINOL derivatives 2-4 (3b-c, 3e) were synthesized according to previously described literature. All other chemicals were obtained from commercial sources and used as received. Dry degassed CDCl 3 and activated molecular sieves (3Å pellets) were stored in an argon-filled glove box. 1 H NMR and 13 C NMR spectra were recorded in CDCl 3 (internal standard: 7.26 ppm, 1 H; ppm, 13 C), DMSO-d 6 (internal standard: 2.50 ppm, 1 H) and MeOD-d 4 using 400 MHz and 500 MHz spectrometers. High resolution mass data (HRMS) were obtained using ESI technique. For column chromatography, silica gel (35-70 microns) was used. TLC was performed on aluminium backed plates pre-coated (0.25 mm) with Silica Gel 60 F254 with a suitable solvent system and was visualized using UV fluorescence and/or developed with phosphomolybdic acid. Chiral HPLC was performed with a Chiralpak AD, Chiralcel OD-H and OJ-H column eluting with iproh/hexane at ambient temperature and monitored by DAD (Diode Array Detector). Chiral SFC was performed using Chiralpak IF column ( mm 5 μm) and monitored by DAD (Diode Array Detector). Retentions times (t R ) are quoted in minutes. Optical rotation was measured on a AUTOPOL IV polarimeter. Experimental Procedures and Spectral Data Synthesis of Allylboronic Acids 1: Allylboronic acids 1a-b were synthesized according to previously described literature methods 1 using toluene for extraction instead of CHCl 3. Procedure for the synthesis of prenyl boronic acid 1c (Figure 2): To a solution of the prenyl alcohol (2.0 mmol, 0.17 g) and DMSO/H 2 O (4:1), palladium catalyst 1 H 2 PdCl 4 (5 mol%) and diboronic acid B 2 (OH) 4 (2.4 mmol, 0.22 g) were successively added, and then the reaction mixture was stirred for 24 hours at room temperature. Completion of the starting material was confirmed by 1 H NMR. The reaction mixture was then kept without stirring for another 24 hours to allow sedimentation of black Pd(0). Then, the reaction mixture was filtered through a filtropur (0.2 µm, PES membrane) into an Ar-filled Schlenk tube containing a magnetic stir bar. Subsequently, toluene (2 ml) was added (Note 1) and the reaction mixture was S2

3 vigorously stirred with degassed brine (4 ml) for minutes. The toluene phase was then transferred to a Straus flask which was equipped with activated MS (3Å). Finally the naphthalene (10 mg) was added (as internal standard) and an aliquot was taken into CDCl 3 (0.5 ml) for 1 H NMR (Note 2). Using this procedure 1c was obtained in 32 % yield (Note 3). The Straus flask was stored inside the glove box and boronic acid was further used from there. 1 H NMR (400 MHz, CDCl 3 ): δ (m, 2H, internal standard), (m, 1H), 1.89 (s, 3H), (m, 5H). Note 1: The extraction was made with toluene, as this was the solvent of the allylboration. As we reported 1 allylboronic acids are very sensitive to oxidation and therefore have to be purified under oxygen free conditions. The above extraction procedure gave pure 1c. Note 2: As we used an aliquote of the toluene solution of 1c the signals of toluene appear in the 1 H NMR spectrum. Note 3: The relatively low yield of 1c (compared to 1a-b 1 ) is because of purification losses. Prenyl boronic acid 1c has a good solubility in both the water/brine and toluene phase, and therefore it could not be completely extracted to the toluene phase. General Procedure for Asymmetric Allylboration of Ketones: A Teflon coated screw capped glass vial (1.5 ml) was equipped with a magnetic stirrer and taken inside of an Ar-filled glove box. The vial was charged with molecular sieves (3 Å) ( g), catalyst 3-4 (0.02 mmol, 9.0 mg), boronic acid 1 (0.1 mmol, M solution in toluene) and tbuoh (0.3 mmol, 29 µl). Then, the reaction vial was taken out from the glove box and allowed to cool down at 0 o C under Ar. Ketone 2 (0.12 mmol) in toluene (20 µl) was added to the reaction mixture under Ar using a Hamilton syringe. Unless otherwise specified, the reaction mixture was stirred at 0 o C for 24 hours (Tables 2 and 3), then the reaction was quenched by the addition of MeOH (0.1 ml). Subsequently, the solvents were evaporated and the crude product was purified by silica gel chromatography. Separation of the diastereomers was not observed under the silica gel chromatography. This was ensured by the comparison of the 1 H NMR and the HPLC S3

4 spectra of the crude and the purified products. Therefore, we give the d.r. values according to the HPLC chromatogram of the purified products. (2S,3S)-2-(4-bromophenyl)-3,7-dimethyl-3-vinyloct-6- en-2-ol (5a). The compound was prepared according to above general procedure. Product 5a was isolated in 75% yield (25.5 mg, mmol) as light yellow oil using toluene as eluent for silica gel chromatography. [α] 22 D 25.4 (c 0.41, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ): δ (m, 2H), (m, 2H), 5.85 (dd, J = 17.6, 10.9 Hz, 1H), 5.28 (dd, J = 10.9, 1.4 Hz, 1H), 5.08 (dd, J = 17.6, 1.4 Hz, 1H), (m, 1H), 1.93 (bs, 1H, OH), (m, 2H), 1.65 (s, 3H), 1.55 (s, 3H), 1.53 (s, 3H), (m, 2H), 0.93 (s, 3H); 13 C NMR (125 MHz, CDCl 3 ): δ 144.2, 143.3, 131.4, 130.3, 129.4, 124.9, 120.7, 116.8, 77.7, 48.0, 35.7, 25.8, 25.7, 23.5, 17.8, 16.7; HRMS (pos. ESI) m/z: Calcd for C 18 H 25 BrONa [M+Na] Found, Determination of dr and er: Chiral HPLC (Chiralcel OD-H 0.46 cm ϕ, 25 cm column, 1% i PrOH in n-hexane, flow rate: 1.0 ml/min; t R : 9.28 min (major diastereomer, major enantiomer), (minor diastereomer, major enantiomer), min (major diastereomer, minor enantiomer); dr = 98:2, er = 97:3. S4

5 (2R,3R)-2-(4-bromophenyl)-3,7-dimethyl-3-vinyloct-6- en-2-ol (5b). The compound was prepared according to above general procedure except that 0.03 mmol catalyst (4) was used. Product 5b was isolated in 89% yield (30.0 mg, mmol) as light yellow oil using toluene as eluent for silica gel chromatography. [α] 22 D (c 0.58, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ): δ (m, 2H), (m, 2H), 5.85 (dd, J = 17.6, 10.9 Hz, 1H), 5.28 (dd, J = 10.9, 1.4 Hz, 1H), 5.08 (dd, J = 17.6, 1.4 Hz, 1H), (m, 1H), 1.94 (s, 1H, OH), (m, 2H), 1.65 (s, 3H), 1.55 (s, 3H, overlapped with H 2 O peak), 1.53 (s, 3H), (m, 2H), 0.93 (s, 3H); 13 C NMR (125 MHz, CDCl 3 ): δ 144.2, 143.3, 131.4, 130.3, 129.4, 124.9, 120.8, 116.8, 77.7, 48.0, 35.7, 25.8, 25.7, 23.5, 17.8, 16.7; HRMS (pos. ESI) m/z: Calcd for C 18 H 25 BrONa [M+Na] Found, Determination of dr and er: Chiral HPLC (Chiralcel OD-H 0.46 cm ϕ, 25 cm column, 1% i PrOH in n-hexane, flow rate: 1.0 ml/min; t R : 9.21 min (major diastereomer, minor enantiomer), (major diastereomer, major enantiomer), min (minor diastereomer, major enantiomer); dr = >98:2, er = 95:5. S5

6 (2S,3R)-2-(4-bromophenyl)-3,7-dimethyl-3-vinyloct-6- en-2-ol (5c). The compound was prepared according to above general procedure except that 0.03 mmol catalyst (3b) was used and the reaction was stirred at room temperature for 18 hours. Product 5c was isolated in 80% yield (27.0 mg, 0.08 mmol) as light yellow oil using toluene as eluent for silica gel chromatography. [α] 23 D 16.0 (c 0.50, CHCl 3 ); 1 H NMR (500 MHz, DMSO-d 6 ): δ (m, 2H), (m, 2H), 5.92 (dd, J = 17.7, 10.9 Hz, 1H), 5.10 (dd, J = 10.9, 1.7 Hz, 1H), (m, 1H), 4.94 (s, 1H, OH), 4.82 (dd, J = 17.7, 1.7 Hz, 1H), (m, 6H), 1.47 (s, 3H), 1.41 (s, 3H), (m, 1H), 0.79 (s, 3H); 13 C NMR (125 MHz, CDCl 3 ): δ 144.7, 143.0, 131.3, 130.2, 129.3, 125.0, 120.7, 116.3, 77.9, 47.8, 34.9, 25.8, 25.3, 23.4, 17.8, 17.2; HRMS (pos. ESI) m/z: Calcd for C 18 H 25 BrONa [M+Na] Found, Determination of dr and er: Chiral HPLC (Chiralcel OD-H 0.46 cm ϕ, 25 cm column, 1% i PrOH in n-hexane, flow rate: 1.0 ml/min; t R : 9.32 min (minor diastereomer, major enantiomer), (major diastereomer, major enantiomer), min (major diastereomer, minor enantiomer); dr = >98:2, er = 97:3. S6

7 (2R,3S)-2-(4-bromophenyl)-3,7-dimethyl-3-vinyloct-6- en-2-ol (5d). The compound was prepared according to above general procedure except that 0.03 mmol catalyst (4) was used. Product 5d was isolated in 83% yield (28.0 mg, mmol) as light yellow oil using toluene as eluent for silica gel chromatography. [α] 21 D (c 0.46, CHCl 3 ); 1 H NMR (400 MHz, DMSO-d 6 ): δ (m, 2H), (m, 2H), 5.92 (dd, J = 17.7, 10.9 Hz, 1H), 5.10 (dd, J = 10.9, 1.7 Hz, 1H), (m, 1H), 4.94 (s, 1H, OH), 4.82 (dd, J = 17.7, 1.7 Hz, 1H), (m, 6H), 1.47 (s, 3H), 1.41 (s, 3H), (m, 1H), 0.79 (s, 3H); 13 C NMR (125 MHz, CDCl 3 ): δ 144.7, 143.0, 131.4, 130.2, 129.3, 125.0, 120.7, 116.3, 77.9, 47.8, 34.9, 25.8, 25.3, 23.4, 17.8, 17.2; HRMS (pos. ESI) m/z: Calcd for C 18 H 25 BrONa [M+Na] Found, Determination of dr and er: Chiral HPLC (Chiralcel OD-H 0.46 cm ϕ, 25 cm column, 1% i PrOH in n-hexane, flow rate: 1.0 ml/min; t R : min (major diastereomer, minor enantiomer), (minor diastereomer, major enantiomer), min (major diastereomer, major enantiomer); dr = >98:2, er = 97:3. S7

8 (2S,3S)-2-(3-bromophenyl)-3,7-dimethyl-3-vinyloct-6-en- 2-ol (5e). The compound was prepared according to above general procedure, except that the ketone (liquid) was added directly to the reaction vial using Hamilton syringe and stirred at room temperature for 18 hours. Product 5e was isolated in 89% yield (30.0 mg, mmol) as light yellow oil using toluene as eluent for silica gel chromatography. [α] 22 D 20.7 (c 0.55, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ): δ 7.61 (t, J = 1.9 Hz, 1H), 7.36 (ddd, J = 7.9, 1.9, 1.0 Hz, 1H), (m, 1H), 7.17 (t, J = 7.9, 1H), 5.87 (dd, J = 10.9, 17.6 Hz, 1H), 5.29 (dd, J = 10.9, 1.4 Hz, 1H), 5.09 (dd, J = 17.6, 1.4 Hz, 1H), (m, 1H), 1.96 (s, 1H, OH), (m, 2H), 1.66 (s, 3H), 1.55 (s, 3H), 1.53 (s, 3H), (m, 2H), 0.94 (s, 3H); 13 C NMR (125 MHz, CDCl 3 ): δ 147.6, 143.3, 131.5, 130.7, 129.7, 128.7, 126.2, 124.9, 121.7, 116.8, 77.7, 48.1, 35.6, 25.8, 25.7, 23.5, 17.8, 16.8; HRMS (pos. ESI) m/z: Calcd for C 18 H 25 BrONa [M+Na] Found, Determination of dr and er: Chiral HPLC (Chiralcel OD-H 0.46 cm ϕ, 25 cm column, 1% i PrOH in n- hexane, flow rate: 1.0 ml/min; t R : 8.08 min (major diastereomer, major enantiomer), (major diastereomer, minor enantiomer), min (minor diastereomer, major enantiomer); dr = 98:2, er = 97:3. S8

9 4-((2S,3S)-2-hydroxy-3,7-dimethyl-3-vinyloct-6- en-2-yl)phenyl acetate (5f). The compound was prepared according to above general procedure. Product 5f was isolated in 95% yield (30.0 mg, mmol) as colorless oil using cyclohexane:toluene:etoac (3:3:1) as eluent for silica gel chromatography. [α] 22 D 27.6 (c 0.54, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ): δ (m, 2H), (m, 2H), 5.86 (dd, J = 17.6, 10.9 Hz, 1H), 5.28 (dd, J = 10.9, 1.3 Hz, 1H), 5.08 (dd, J = 17.6, 1.4 Hz, 1H), (m, 1H), 3.91 (s, 3 H), 2.01 (s, 1H, OH), (m, 2H), 1.64 (s, 3H), 1.59 (s, 3H), 1.51 (s, 3H), (m, 2H), 0.94 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ): δ 167.3, 150.4, 143.2, 131.5, 128.4(9), 128.4(6), 127.6, 124.9, 116.9, 78.0, 52.2, 48.1, 35.7, 25.8, 25.6, 23.5, 17.7, 16.8; HRMS (pos. ESI) m/z: Calcd for C 20 H 28 O 3 Na [M+Na] Found, Determination of dr and er: Chiral HPLC (Chiralcel OD-H 0.46 cm ϕ, 25 cm column, 1% i PrOH in n-hexane, flow rate: 1.0 ml/min; t R : min (major diastereomer, minor enantiomer), (major diastereomer, major enantiomer), min (minor diastereomer, major enantiomer); dr = >98:2, er = 96:4. S9

10 (2S,3S)-3,7-dimethyl-2-(4-(methylsulfonyl)phenyl)-3- vinyloct-6-en-2-ol (5g). The compound was prepared according to above general procedure, except that the ketone was added inside the glove box. Product 5g was isolated in 60% yield (20.0 mg, 0.06 mmol) as white solid using toluene:thf(6:1) as eluent for silica gel chromatography. The reaction was also performed in 0.5 mmol scale and isolated in 72% yield. mp: o C; [α] 22 D 24.5 (c 0.34, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ): δ (m, 2H), (m, 2H), 5.85 (dd, J = 17.6, 10.9 Hz, 1H), 5.32 (dd, J = 10.9, 1.3 Hz, 1H), 5.10 (dd, J = 17.7, 1.4 Hz, 1H), (m, 2H), 3.06 (s, 3H), 2.07 (s, 1H, OH), (m, 2H), 1.65 (s, 3H), 1.59 (s, 3H), 1.52 (s, 3H), (m, 2H), 0.93 (s, 3H); 13 C NMR (125 MHz, CDCl 3 ): δ 151.6, 142.8, 138.7, 131.7, 128.6, 126.3, 124.7, 117.3, 77.9, 48.1, 44.7, 35.7, 25.8, 25.7, 23.5, 17.8, 16.7; HRMS (pos. ESI) m/z: Calcd for C 19 H 28 O 3 SNa [M+Na] Found, Determination of dr and er: Chiral HPLC (Chiralpak AD 0.46 cm ϕ, 25 cm column, 10% i PrOH in iso-hexane, flow rate: 0.5 ml/min; t R : min (major diastereomer, minor enantiomer), (major diastereomer, major enantiomer); dr = >99:1, er = 97:3. S10

11 Absolute stereochemistry of compound 5g: The absolute stereochemistry of compound 5g was determined by X-ray crystallographic analysis. Figure 1. Chem3D diagram of compound 5g from the X-ray diffraction data. This crystal structure has been deposited with the Cambridge Crystallographic Database (CCDC), the deposition number is CCDC The.cif file is available as a separate file under the supporting information section (cif file name: compound 5g.cif). S11

12 (2S,3S)-3,7-dimethyl-2-(naphthalen-2-yl)-3-vinyloct- 6-en-2-ol (5h). The compound was prepared according to above general procedure. Product 5h was isolated in 65% yield (20.0 mg, mmol) as colorless oil by two consecutive silica gel chromatography eluting with toluene and then pentane:ehter(10:1). [α] 22 D 28.4 (c 0.45, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ): δ (m, 3H), 7.77 (d, J = 8.7 Hz 1H), 7.60 (dd, J = 8.7, 1.8 Hz, 1H), (m, 2H), 5.94 (dd, J = 17.6, 10.9 Hz, 1H), 5.30 (dd, J = 10.8, 1.4 Hz, 1H), 5.12 (dd, J = 17.6, 1.4 Hz, 1H), (m, 1H) 2.08 (s, 1H, OH), (m, 2H), 1.69 (s, 3H), 1.64 (s, 3H), (m, 5H), 1.01 (s, 3H); 13 C NMR (125 MHz, CDCl 3 ): δ 143.7, 142.7, 132.6, 132.2, 131.2, 128.4, 127.4, 126.3, 126.2, 126.1, 125.8, 125.7, 125.0, 116.4, 78.0, 48.3, 35.7, 25.9, 25.7, 23.5, 17.7, 16.8; HRMS (pos. ESI) m/z: Calcd for C 22 H 28 ONa [M+Na] Found, Determination of dr and er: Chiral HPLC (Chiralpak OJ-H 0.46 cm ϕ, 25 cm column, 1% i PrOH in n-hexane, flow rate: 1.0 ml/min; t R : min (major diastereomer, minor enantiomer), (major diastereomer, major enantiomer); dr = >99:1, er = 96:4. S12

13 (2S,3S)-2-(furan-2-yl)-3,7-dimethyl-3-vinyloct-6-en-2-ol (5i). The compound was prepared according to above general procedure, except that the ketone (liquid) was added directly to the reaction vial using Hamilton syringe. Product 5i was isolated in 81% yield (20.0 mg, mmol) as colorless oil using petroleum ether:et 2 O (10:1) as eluent for silica gel chromatography. [α] 22 D 42.5 (c 0.28, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ): δ 7.34 (dd, J = 1.8, 0.9 Hz, 1H), 6.33 (dd, J = 3.3, 1.8 Hz, 1H), 6.18 (dd, J = 3.2, 0.9 Hz, 1H), 5.84 (dd, J = 17.6, 10.9 Hz, 1H), 5.23 (dd, J = 10.9, 1.5 Hz, 1H), (m, 2H), 2.19 (s, 1H, OH), (m, 2H), 1.66 (s, 3H), 1.55 (s, 3H), 1.49 (s, 3H), (m, 2H), 1.01 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ): δ 158.7, 142.9, 141.1, 131.3, 125.1, 115.9, 110.2, 106.6, 76.4, 48.3, 35.2, 25.8, 23.7, 23.4, 17.8, 17.0; HRMS (pos. ESI) m/z: Calcd for C 16 H 24 O 2 Na [M+Na] Found, Determination of dr and er: Chiral HPLC (Chiralcel OD-H 0.46 cm ϕ, 25 cm column, 2% i PrOH in n-hexane, flow rate: 1.0 ml/min; t R : 5.70 min (major diastereomer, minor enantiomer), 6.59 (minor diastereomer, major enantiomer), 7.83 min (major diastereomer, major enantiomer); dr = >98:2, er = 95:5. S13

14 (2R,3S)-2-cyclopropyl-3,7-dimethyl-3-vinyloct-6-en-2-ol (5j). The compound was prepared according to above general procedure, except that the ketone (liquid) was added directly to the reaction vial using Hamilton syringe. Product 5j was isolated in 62% yield (14.0 mg, mmol) as colorless oil using petroleum ether:et 2 O (10:1) as eluent for silica gel chromatography. [α] 24 D 24.7 (c 0.20, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ): δ 5.95 (dd, J = 10.9, 17.7 Hz, 1H), 5.21 (dd, J = 11.0, 1.6 Hz, 1H), (m, 1H), 5.04 (dd, J = 17.7, 1.6 Hz, 1H), (m, 4H), 1.68 (s, 3H), (m, 4H), (m, 1H), 1.18 (s, 1H, OH), (m, 2H), (m, 1H), (m, 2H), (m, 1H) ; 13 C NMR (125 MHz, CDCl 3 ): δ 144.1, 131.2, 125.3, 115.3, 74.6, 48.7, 35.3, 25.9, 23.5, 22.2, 17.8, 17.3, 17.1, 2.0, 1.3; HRMS (pos. ESI) m/z: Calcd for C 15 H 26 ONa [M+Na] Found, Determination of dr and er: Chiral SFC (Diacel IF, 40 bar, 25 o C, 0.46 cm ϕ, 25 cm column, 5% MeOH in CO 2, flow rate: 2.0 ml/min; t R : 7.23 min (major diastereomer, minor enantiomer), 8.92 (major diastereomer, major enantiomer), dr = >99:1, er = 95:5. S14

15 (2S,3R)-2-cyclopropyl-3,7-dimethyl-3-vinyloct-6-en-2-ol (5k). The compound was prepared according to above general procedure, except that the ketone (liquid) was added directly to the reaction vial using Hamilton syringe. Product 5k was isolated in 54% yield (12.0 mg, mmol) as light yellow oil using petroleum ether/et 2 O (10:1) as eluent for silica gel chromatography. [α] 22 D (c 0.24, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ): δ 5.95 (dd, J = 17.8, 11.0 Hz, 1H), 5.21 (dd, J = 10.9, 1.6 Hz, 1H), (m, 1H), 5.04 (dd, J = 17.8, 1.6 Hz, 1H), (m, 2H), 1.68 (s, 3H), (m, 5H, overlapped with H 2 O peak), 1.18 (bs, 1H, - OH), 1.09 (s, 3H), (m, 4H), (m, 1H), (m, 3H); 13 C NMR (101 MHz, CDCl 3 ): δ 144.1, 131.3, 125.3, 115.3, 77.4, 74.6, 35.3, 25.9, 23.5, 22.2, 17.8, 17.3, 17.1, 2.01, 1.30; HRMS (pos. ESI) m/z: Calcd for C 15 H 26 ONa [M+Na] Found, Determination of dr and er: Chiral SFC (Diacel IF, 40 bar, 25 o C, 0.46 cm ϕ, 25 cm column, 5% MeOH in CO 2, flow rate: 2.0 ml/min; t R : 6.27 min (major diastereomer, major enantiomer), 7.58 (major diastereomer, minor enantiomer) ; dr = >99:1, er = 95:5. S15

16 4-((2S,3R)-2-hydroxy-3,7-dimethyl-3-vinyloct-6- en-2-yl)phenyl acetate (5l). The compound was prepared according to above general procedure. Product 5l was isolated in 76% yield (24.2 mg, mmol) as light yellow oil using Cyclohexane/Toluene/EtOAc (3:3:1) as eluent for silica gel chromatography. [α] 22 D 8.12 (c 0.48, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ): δ (m, 2H), (m, 2H), 5.75 (dd, J = 17.6, 10.9 Hz, 1H), 5.25 (dd, J = 10.9, 1.5 Hz, 1H), (m, 3H), 2.29 (s, 3H), 1.97 (bs, 1H, -OH), (m, 2H), 1.64 (s, 3H), 1.55 (s, 3H), (m, 4H), (m, 1H), 1.01 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ): δ 169.6, 149.4, 143.3, 131.2, 128.5, 125.1, 120.1, 116.0, 78.0, 47.9, 34.9, 25.8, 25.5, 23.4, 21.3, 17.8, 17.2; HRMS (pos. ESI) m/z: Calcd for C 20 H 28 O 3 Na [M+Na] Found, Determination of dr and er: Chiral HPLC (Chiralcel OD-H 0.46 cm ϕ, 25 cm column, 1% i PrOH in n-hexane, flow rate: 1.0 ml/min); t R : min (minor diastereomer, major enantiomer), (major diastereomer, major enantiomer), min (major diastereomer, minor enantiomer); dr = 98:2, er = 95:5. S16

17 4-((2S,3R)-2-hydroxy-3,7-dimethyl-3-vinyloct-6-en-2- yl)benzonitrile (5m). The compound was prepared according to above general procedure. Product 5m was isolated in 81% yield (23.0 mg, mmol) as light yellow oil using Pentane/Diethylether (5:1) as eluent for silica gel chromatography. [α] 22 D 13.7 (c 0.30, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ): δ (m, 2H), (m, 2H), 5.70 (dd, J = 17.7, 10.9 Hz, 1H), 5.28 (dd, J = 10.9, 1.3 Hz, 1H), (m, 3H), 2.02 (bs, 1H, OH), (m, 2H), 1.65 (s, 3H), 1.57 (s, 3H), (m, 4H), (m, 1H), 0.99 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ): δ 151.1, 142.5, 131.6, 131.0, 128.3, 124.7, 119.1, 116.8, 110.5, 78.1, 47.9, 34.9, 25.8, 25.2, 23.3, 17.7, 17.2; HRMS (pos. ESI) m/z: Calcd for C 19 H 25 NONa [M+Na] Found, Determination of dr and er: Chiral HPLC (Chiralcel OJ-H 0.46 cm ϕ, 25 cm column, 2% i PrOH in iso-hexane, flow rate: 0.5 ml/min); t R : min (minor diastereomer, major enantiomer), (major diastereomer, minor enantiomer), min (major diastereomer, major enantiomer); dr 98:2, er = 96:4. S17

18 (S)-2-(4-bromophenyl)-3,3-dimethylpent-4-en-2-ol (5n). The compound was prepared according to above general procedure. Product 5n was isolated in 71% yield (19.0 mg, mmol) as light yellow oil using Hexane/EtOAc (15:1) as eluent for silica gel chromatography. [α] 22 D 22.1 (c 0.32, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ): δ (m, 2H), (m, 2H), 5.92 (dd, J = 17.6, 10.9 Hz, 1H), 5.12 (dd, J = 10.9, 1.5 Hz, 1H), 5.05 (dd, J = 17.6, 1.5 Hz, 1H), 1.88 (bs, 1H, OH), 1.55 (s, 3H, overlapped with H 2 O peak), 1.00 (s, 3H), 0.96 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ): δ 144.8, 144.5, 130.3, 129.1, 120.8, 114.4, 77.4, 44.5, 25.4, 22.8, 22.4; HRMS (pos. ESI) m/z: Calcd for C 13 H 17 BrNaO [M+Na] Found, Determination of er: Chiral HPLC (Chiralcel OD-H 0.46 cm ϕ, 25 cm column, 1% i PrOH in n-hexane, flow rate: 1.0 ml/min); t R : min (major enantiomer), (minor enantiomer); er = 97:3. S18

19 (R)-2-(4-bromophenyl)-3,3-dimethylpent-4-en-2-ol (5o). The compound was prepared according to above general procedure except that 0.03 mmol catalyst (4) was used. Product 5o was isolated in 78% yield (21.0 mg, mmol) as light yellow oil using Hexane/EtOAc (15:1) as eluent for silica gel chromatography. [α] 22 D (c 0.42, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ): δ (m, 2H), (m, 2H), 5.92 (dd, J = 17.6, 10.9 Hz, 1H), 5.12 (dd, J = 10.9, 1.5 Hz, 1H), 5.05 (dd, J = 17.6, 1.5 Hz, 1H), 1.88 (bs, 1H, OH), 1.55 (s, 3H, overlap with H 2 O peak), 1.00 (s, 3H), 0.96 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ): δ 144.8, 144.5, 130.3, 129.1, 120.8, 114.4, 77.5, 44.5, 25.4, 22.8, 22.4; HRMS (pos. APCI) m/z: Calcd for C 13 H 17 BrO [M-OH] Found, Determination of er: Chiral HPLC (Chiralcel OD-H 0.46 cm ϕ, 25 cm column, 1% i PrOH in n-hexane, flow rate: 1.0 ml/min); t R : min (minor enantiomer), min (major enantiomer); er = 94:6. S19

20 (S)-3,3-dimethyl-2-(4-(methylsulfonyl)phenyl)pent-4-en- 2-ol (5p). The compound was prepared according to above general procedure, except that the ketone was added inside the glove box. Product 5p was isolated in 69% yield (18.5 mg, mmol) as white solid using Toluene:Cyclohexane:MeCN (3:3:1) as eluent for silica gel chromatography. mp: o C; [α] 22 D 34.7 (c 0.34, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ): δ (m, 2H), (m, 2H), 5.91 (dd, J = 17.5, 10.8 Hz, 1H), 5.16 (dd, J = 10.8, 1.3 Hz, 1H), 5.07 (dd, J = 17.5, 1.3 Hz, 1H), 3.06 (s, 3H), 2.00 (bs, 1H, OH), 1.60 (s, 3H), 1.02 (s, 3H), 0.98 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ): δ 151.9, 144.2, 138.7, 128.3, 126.3, 115.1, 77.7, 44.7, 44.6, 25.5, 22.8, 22.4; HRMS (pos. ESI) m/z: Calcd for C 14 H 20 O 3 SNa [M+Na] Found, Determination of er: Chiral HPLC (Chiralpak AD 0.46 cm ϕ, 25 cm column, 10% i PrOH in iso-hexane, flow rate: 0.5 ml/min); t R : min (minor enantiomer), (major enantiomer); er = 95:5. S20

21 Absolute stereochemistry of compound 5p: The absolute stereochemistry of compound 5p was determined by X-ray crystallographic analysis. Figure 2. Chem3D diagram of compound 5p from the X-ray diffraction data. This crystal structure has been deposited with the Cambridge Crystallographic Database (CCDC), the deposition number is CCDC The.cif file is available as a separate file under the supporting information section (cif file name: compound 5p.cif). S21

22 (1r,4S)-1-((S)-3,7-dimethylocta-1,6-dien-3-yl)-4- phenylcyclohexan-1-ol (5q). The compound was prepared according to above general procedure except that 0.03 mmol catalyst (3a) was used. Product 5q was isolated in 93% yield (29.0 mg, 0.09 mmol) as colorless oil using petroleum ether:et 2 O (20:1) as eluent for silica gel chromatography. [α] 21 D 8.4 (c 0.50, CHCl 3 ); 1 H NMR (400 MHz, MeOD-d 4 ): δ (m, 4H), (m, 1H), 5.93 (dd, J = 17.7, 11.0 Hz, 1H), (m, 2H), 5.00 (dd, J = 17.7, 1.7 Hz, 1H), 2.39 (tt, J = 12.2, 3.3 Hz, 1H), (m, 6H), (m, 13H), 1.04 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ): δ 147.5, 143.8, 131.4, 128.4, 127.0, 126.1, 125.2, 115.9, 74.3, 47.7, 44.1, 35.1, 32.3, 31.5, 29.7, 29.6, 25.8, 23.6, 17.8, 16.4; HRMS (pos. ESI) m/z: Calcd for C 22 H 32 ONa [M+Na] Found, Determination of er: Chiral HPLC (Chiralpak OJ-H 0.46 cm ϕ, 25 cm column, 1% i PrOH in n-hexane, flow rate: 1.0 ml/min); t R : min (minor enantiomer), (major enantiomer); er = 90:10. S22

23 Monitoring of the mixture of 1a and 3c by 19 F NMR. In order to get information on the nature of the interactions between the allylboronic acids and the chiral BINOL ligand, we monitored the mixture of 1a and fluoro- BINOL 3c by 19 F NMR (Scheme 1). Although, 3c catalyzed the allylboration with poor selectivity (Table 1, entry 11), the 19 F NMR shifts are expected to change significantly in case of interactions between 1a and 3c. Scheme 1. Reaction between geraniol boronic acid 1a and 3c. Figures 3a-e. Comparison of the 19 F NMR spectra of 1a + 3c under various reaction conditions (see Scheme 1) In an Ar filled glovebox a mixture of boronic acid 1a (0.015 mmol) and 3c (7.5 µmol, 2.40 mg) in CDCl 3 (0.40 ml) was stirred in a vial at room temperature for 2 hours. The 19 F NMR of this reaction mixture (Figure 3b) showed two peaks at ppm (1aD) and at ppm (1a *** 3c), which are both upfield to the shift value of free 3c at ppm (Figure 3a). When molecular sieves (MS) 3Å were added to S23

24 this mixture, the intensity of 1aD was considerably increased and the intensity of 1a *** 3c was decreased (Figure 3c). These changes of the 19 F NMR shifts suggest that by mixing of 1a and 3c at least two new species are formed. The first one resonating at ppm is probably an associative complex (1a *** 3c) between 1a and 3c, which is kept together by secondary interactions, such as electrostatic forces and/or hydrogen bonds. The relatively small change of the 19 F shift of (free) 3c also suggests a non-covalent interaction. The second peak at ppm was tentatively assigned to 1aD (Scheme 1), which is probably the diester of 1a and 3c. Addition of MS (Scheme 3c) is supposed to lead to increase of the amount of 1aD at the expense of decreasing of 1a *** 3c (Figure 3c). When 3 equivalent of i PrOH (0.045 mmol) was added to the mixture of 1a, 3c and MS, the peak of 1aD disappeared and the concentration of 1a *** 3c was increased (Figure 3d). As mentioned in the paper i PrOH inhibited the allylboration reaction (Table 1, entry 7), probably because formation of the diester of the allylboronic acid and the BINOL derivatives (such as 1aD) was hindered (see also Scheme 2 and Figures 4a-c). Interestingly, when t BuOH (0.045 mmol) was added to the mixture of 1a, 3c and MS, the concentration of 1aD was decreased but it was still present in the reaction mixture (Figure 3e). This is in line with our observation that addition of t BuOH did not inhibit the reaction, as the active species (Table 1, entry 1), such as 1aD, is still available for allylboration. Monitoring the reaction mixtures of 1a and i PrOH by 1 H NMR. As mentioned in the paper allylation of 2a with 1a proceeds with high selectivity with BINOL catalyst 3a in the presence of 3 equivalent of t BuOH (Table 1, entry 1). However, no reaction takes place, when the t BuOH is replaced by i PrOH (Table 1, entry 7). We hypothesized that i PrOH may react with allylboronic acids to give ester compounds such as, 1a(OiPr) and 1a(OiPr) 2 (Scheme 2) and thus inhibit the reaction. As shown above (Figure 3d) formation of 1aD (Scheme 1) did not proceed either. S24

25 Scheme 2. Reaction between geraniol boronic acid 1a and iproh. Monitoring the reaction mixture of 1a in the presence of i PrOH indicates formation of at least two types of esterified products of the B(OH) 2 group (Figure 4a-c). Spectrum 4a was recorded in the absence of i PrOH. When 3 equivalent of iproh (0.3 mmol) was added to 1a (0.1 mmol), three new peaks appeared between 4-5 ppm (Figure 4b). The highest peak (4.08 ppm) is assigned to the -OCH(Me) 2 proton of free i PrOH. The two additional new peaks (4.56 and 4.47 ppm) were tentatively assigned to the same proton in isopropoxy esters 1a(OiPr) and 1a(OiPr) 2. When molecular sieves (MS) 3Å were added to the mixture of 1a and iproh, the intensity of the peak at 4.47 ppm was remarkably increased (Figure 4c) and the peak intensity at 4.56 ppm was decreased. This change in the 1 H NMR also suggest that the septet at 4.47 ppm most likely corresponds the compound 1a(OiPr) 2. Figures 4a-c. Comparison of the 1 H NMR spectra of 1a in the absence and presence of iproh and MS (see Scheme 2). S25

26 References: (1) Raducan, M.; Alam, R.; Szabó, K. J. Angew. Chem. Int. Ed. 2012, 51, (2) Zhang, Y.; Li, N.; Qu, B.; Ma, S.; Lee, H.; Gonnella, N. C.; Gao, J.; Li, W.; Tan, Z.; Reeves, J. T.; Wang, J.; Lorenz, J. C.; Li, G.; Reeves, D. C.; Premasiri, A.; Grinberg, N.; Haddad, N.; Lu, B. Z.; Song, J. J.; Senanayake, C. H. Org. Lett. 2013, 15, (3) Brenet, S.; Baptiste, B.; Philouze, C.; Berthiol, F.; Einhorn, J. Eur. J. Org. Chem. 2013, 2013, (4) Le, P. Q.; Nguyen, T. S.; May, J. A. Org. Lett. 2012, 14, S26

27 H NMR of compound 5a (CDCl 3, 500 MHz) Br ppm S27

28 C NMR of compound 5a (CDCl 3, 125 MHz) Br ppm S28

29 H NMR of compound 5b (CDCl 3, 400 MHz) Br ppm S29

30 C NMR of compound 5b (CDCl 3, 125 MHz) Br ppm S30

31 H NMR of compound 5c (DMSO-d 6, 500 MHz) Br ppm S31

32 C NMR of compound 5c (CDCl 3, 125 MHz) Br ppm S32

33 H NMR of compound 5d (DMSO-d 6, 400 MHz) Br ppm S33

34 C NMR of compound 5d (CDCl 3, 125 MHz) Br ppm S34

35 H NMR of compound 5e (CDCl 3, 500 MHz) Br ppm S35

36 C NMR of compound 5e (CDCl 3, 125 MHz) Br ppm S36

37 H NMR of compound 5f (CDCl 3, 400 MHz) O O ppm S37

38 C NMR of compound 5f (CDCl 3, 101 MHz) O O ppm S38

39 H NMR of compound 5g (CDCl 3, 500 MHz) S O O ppm S39

40 C NMR of compound 5g (CDCl 3, 125 MHz) S O O ppm S40

41 H NMR of compound 5h (CDCl 3, 400 MHz) ppm S41

42 C NMR of compound 5h (CDCl 3, 125 MHz) ppm S42

43 H NMR of compound 5i (CDCl 3, 400 MHz) O ppm S43

44 C NMR of compound 5i (CDCl 3, 101 MHz) O ppm S44

45 H NMR of compound 5j (CDCl 3, 400 MHz) ppm S45

46 C NMR of compound 5j (CDCl 3, 125 MHz) ppm S46

47 H NMR of compound 5k (CDCl 3, 400 MHz) ppm S47

48 C NMR of compound 5k (CDCl 3, 101 MHz) ppm S48

49 H NMR of compound 5l (CDCl 3, 400 MHz) O O ppm S49

50 C NMR of compound 5l (CDCl 3, 101 MHz) O O ppm S50

51 H NMR of compound 5m (CDCl 3, 400 MHz) 4 4 NC ppm S51

52 C NMR of compound 5m (CDCl 3, 101 MHz) NC ppm S52

53 H NMR of compound 5n (CDCl 3, 400 MHz) Br ppm S53

54 C NMR of compound 5n (CDCl 3, 101 MHz) Br ppm S54

55 H NMR of compound 5o (CDCl 3, 400 MHz) Br ppm S55

56 C NMR of compound 5o (CDCl 3, 101 MHz) Br ppm S56

57 H NMR of compound 5p (CDCl 3, 400 MHz) S O O ppm S57

58 C NMR of compound 5p (CDCl 3, 101 MHz) S O O ppm S58

59 H NMR of compound 5q (MeOD-d 4, 400 MHz) OH Ph ppm S59

60 C NMR of compound 5q (CDCl 3, 101 MHz) OH Ph ppm S60

61 H NMR of compound 1c (CDCl 3, 400 MHz) see also Note 2 in page S3. B(OH) ppm S61