Modular Synthesis of a New Family of Tripodal Ligands all-cis-1,2,3-tris(diphenylphosphinomethyl)cyclopropane. Relatives

Transcription

1 Modular Synthesis of a New Family of Tripodal Ligands all-cis-1,2,3-tris(diphenylphosphinomethyl)cyclopropane and Relatives Supporting Information Heiko Schill and Armin de Meijere* Institut für Organische und Biomolekulare Chemie, Georg-August- Universität Göttingen, Tammannstraße 2, Göttingen armin.demeijere@chemie.uni-goettingen.de Dmitry S. Yufit University of Durham, Durham, South Rd., DM1 3LE, United Kingdom General: 1 H NMR: Bruker AM 250 (250 MHz), Varian UNITY-300 (300 MHz), Varian Inova 600 (600 MHz). Residual signals of solvents served as internal standards. Abbreviations for the assignment of signals: m c = centered multiplet, cpr-h = cyclopropylic, Ph-H = phenylic. 13 C NMR: Varian Mercury 200 (50.3 MHz), Bruker AM 250 (62.9 MHz), Varian UNITY-300 (75.5 MHz), Varian Inova 600 (150.8 MHz). Residual signals of solvents served as internal standards. The multiplicity of the signals was determined with the APT (attached proton test) technique and is given as: + = primary or tertiary (positive APT signal), = secondary or quaternary C atoms (negative APT signal). Abbreviations for the assignment of signals: cpr-c = cyclopropylic, Ph-C = phenylic. 31 P NMR: Bruker AVANCE 300 (121.5 MHz); δ = 0.0 ppm for 85% H 3 PO 4 solution in water (external standard). MS: DCI (NH 3 ): Finnigan MAT 95, ESI: Finnigan LCQ. Column chromatography: Merck silica gel 60 ( mm, mesh ASTM). Thin-layer chromatography: Macherey-Nagel precoated sheets: Alugram Sil G/UV 254, detection with UV light at 254 nm, molybdatophosphoric acid (5% solution in ethanol) M.p.: Büchi 510 capillary melting point apparatus, values are uncorrected. Elemental analyses were performed by the Mikroanalytisches Laboratorium des Instituts für Organische und Biomolekulare Chemie der Universität Göttingen with an elemental analyzer CHN-2000 (Leco). Solvents were dried according to standard laboratory procedures and degassed when necessary by freeze-andpump cycles. Reactions were run under argon. Organic solutions were dried over MgSO 4. all-cis-1-iodo-2,3-bis(benzyloxymethyl)cyclopropane (5) was prepared according to Charette S1

2 et al. (Charette, A. B.; Gagnon, A.; Fournier, J.-F. J. Am. Chem. Soc. 2002, 124, ). All other chemicals are commercially available and were used without further purification. all-cis-bis(benzyloxymethyl)hydroxymethylcyclopropane (6): nbuli (1.85 ml, 4.48 mmol, 2.42 M in hexanes) was added dropwise within 12 min to a solution of all-cis-1- iodo-2,3-bis(benzyloxymethyl)cyclopropane 5 (1.84 g, 4.51 mmol) in anhydrous THF (40 ml) at 78 C. After stirring for 10 min, anhydrous DMF (500 μl, 6.46 mmol) was added within 5 min at the same temperature, and the reaction mixture was allowed to warm up to room temperature within 2 h. Water (10 ml) was added, and the resulting mixture was extracted with ether (3 20 ml). The organic extracts were washed with brine (2 20 ml) and dried before evaporation of the solvents. The crude product, obtained as a clear oil (1.49 g, quant.), was immediately dissolved in ethanol (15 ml) and treated with NaBH 4 (171 mg, 4.51 mmol) at room temperature. The reaction mixture was stirred for 18 h, the volatile components were removed in vacuo, and the residue taken up in water (10 ml). The suspension was extracted with ether (3 15 ml), and the organic extracts were dried before concentration. Column chromatography of the residue on silica gel (65 g, hexane/ether 1:5, R f = 0.26) afforded the alcohol 6 as a pale yellow oil (1.27 g, 4.07 mmol, 90% from 5). 1 H NMR (600 MHz, CDCl 3 ): δ = (m, 3 H, cpr-h), 2.60 (br s, 1 H, OH), (m, 2 H, CH 2 ), (m, 4 H, CH 2 ), 4.48 (s, 4 H, OCH 2 Ph), (m, 10 H, Ph-H). 13 C NMR (150.8 MHz, CDCl 3, APT): δ = 19.1 (+, cpr-c), 21.9 (+, cpr-c), 58.6 (, C-1), 66.2 (, CH 2 ), 73.0 (, OCH 2 Ph), (+, Ph-C), (+, Ph-C), (+, Ph-C), (, Ph- C). MS (DCI, NH 3 ), m/z (%): 642 (20) [2M+NH + 4 ], 420 (5), 330 (100) [M+NH + 4 ], 313 (23) [M+H + ], 295 (10), 205 (6), 108 (5). C 20 H 24 O 3 : calcd. C 76.89, H 7.74; found C 77.17, H all-cis-tris(methylsulfonyloxymethyl)cyclopropane (8): A suspension of 6 (2.36 g, 7.55 mmol) and 10% Pd on charcoal (100 mg, 1.24 mol%) in methanol (40 ml) was stirred under an atmosphere of H 2 (3 bar) at room temperature for 40 h. The reaction mixture was filtered through a pad of Celite, and the solvents were evaporated under reduced pressure. The crude product 7 (1.06 g, quant.) was taken up in a mixture of THF (20 ml) and CH 2 Cl 2 (40 ml), and the solution was cooled to 0 C. After addition of Et 3 N (6.30 ml, 45.2 mmol), mesyl chloride (2.70 ml, 34.8 mmol) was added dropwise at the same temperature. The reaction mixture was allowed to warm up to room temperature within 2 h under stirring before being poured into brine (40 ml). After extraction of the aqueous mixture with EtOAc (2 60 ml), S2

3 the combined organic phases were washed with NaHCO 3 soln. (40 ml) and brine/water (1:1, 2 25 ml), dried and concentrated under reduced pressure. Column chromatography of the preabsorbed crude product on silica gel (200 g, hexane/thf 2:1, R f = 0.31) afforded 8 as colorless crystals (2.34 g, 6.39 mmol, 85%). M.p C. 1 H NMR (600 MHz, [D 8 ]THF): δ = 1.76 (m c, 3 H, cpr-h), (m, 9 H, OSO 2 Me), 4.49 (m c, 6 H, CH 2 ). 13 C NMR (75.5 MHz, [D 8 ]THF, APT): δ = 20.0 (+, cpr-c), 37.1 (+, OSO 2 Me), 66.9 (, CH 2 ). MS (DCI, NH 3 ), m/z (%): 750 (<1) [2M+NH + 4 ], 384 (100) [M+NH + 4 ], 288 (13), 210 (13), 194 (6). C 9 H 18 O 9 S 3 : calcd. C 29.50, H 4.95; found C 29.50, H all-cis-tris(diphenylphosphinomethyl)cyclopropane trisborane complex 9: nbuli (3.10 ml, 7.50 mmol, 2.42 M in hexanes) was added dropwise at 5 C to a solution of PHPh 2 (1.30 ml, 7.54 mmol) in anhydrous and oxygen-free THF (10 ml). The reaction mixture was allowed to warm up to room temperature within 1 h under stirring. After cooling to 0 C, a solution of 8 (366 mg, 1.00 mmol) in anhydrous and oxygen-free THF (35 ml) was added dropwise. After stirring for 10 min, the cooling bath was removed, and the stirring continued for 18 h. The reaction mixture was cooled to 0 C again, a solution of BH 3 THF complex (10.0 ml, 10.0 mmol, 1.00 M) was added, and the stirring was continued for 15 min. The reaction mixture was poured into ice water and the mixture extracted with CH 2 Cl 2 (5 80 ml). The combined organic layers were washed with brine (150 ml), dried and concentrated under reduced pressure. Column chromatography on silica gel (55 g, toluene/hexane/ch 2 Cl 2 1:1:1, R f = 0.38) afforded the trisphosphine trisborane complex 9 as colorless crystals (629 mg, 927 μmol, 93%). M.p. >215 C. 1 H NMR (250 MHz, CDCl 3 ): δ = 0.98 (m c, 3 H, cpr-h), 2.41 (m c, 6 H, CH 2 ), (m, 18 H, Ph-H), (m, 12 H, Ph-H). 13 C NMR (50.3 MHz, CDCl 3, APT): δ = 15.1 (+, cpr-c), 20.8 (, d, 1 J C,P = 38 Hz, CH 2 ), (+, d, 3 J C,P = 10 Hz, Ph-C m ), (+, d, 1 J C,P = 55 Hz, Ph-C i ), (, d, 4 J C,P = 2.4 Hz, Ph-C p ), (+, d, 2 J C,P = 9.2 Hz, Ph-C o ). 31 P NMR (121.5 MHz, CDCl 3 ): δ = MS (ESI), positive mode, m/z (%): 1379 (73) [2M+Na + ], 701 (100) [M+Na + ]. all-cis-1,2,3-tris(diphenylphosphinomethyl)cyclopropane (TriCyp-PPP) 2: A solution of the trisborane complex 9 (101 mg, 149 μmol) in oxygen-free HEt 2 N (7 ml) was stirred at reflux for 1 d. Oxygen-free THF (5 ml) and silica gel (400 mg) were added to the reaction mixture, and the volatile components were removed in vacuo. Column chromatography of the preabsorbed crude product on silica gel under strict exclusion of oxygen (8 g, hexane/ether 20:1, R f = 0.18) yielded the free phosphine 2 as a colorless solid (88 mg, 138 μmol, 94%). S3

4 1 H NMR (600 MHz, [D 8 ]THF): δ = 0.76 (m c, 3 H, cpr-h), (m, 6 H, CH 2 ), (m, 18 H, Ph-H), (m, 12 H, Ph-H). 13 C NMR (150.8 MHz, [D 8 ]THF, APT): δ = 17.1 (+, m c, cpr-c), 22.9 (, d, 1 J C,P = 12 Hz, CH 2 ), (+, d, 2 J C,P = 6.1 Hz, Ph-C o ), (+, Ph-C p ), (+, d, 3 J C,P = 19 Hz, Ph-C m ), (, d, 1 J C,P = 15 Hz, Ph-C i ). 31 P NMR (121.5 MHz, [D 8 ]THF): δ = all-cis-2,3-bis(benzyloxymethyl)-1-methoxymethylcyclopropane: To a suspension of sodium hydride (60% in mineral oil, 420 mg, 10.5 mmol) was added the alcohol 6 (1.56 g, 4.99 mmol), and the mixture was stirred for 30 min at room temperature. Methyl iodide (1.60 ml, 25.7 mmol) was added dropwise within 10 min, and the resulting suspension was stirred at 25 C for 18 h. After addition of H 2 O (20 ml), the reaction mixture was extracted with ether (35 ml). The organic phase was washed with water (3 20 ml), dried and concentrated under reduced pressure. Column chromatography on silica gel (100 g, hexane/ether 2:1, R f = 0.14) of the residue furnished the desired methyl ether (1.58 g, 4.84 mmol, 97%) as a colorless oil. 1 H NMR (300 MHz, CDCl 3 ): δ = (m, 3 H, cpr-h), 3.28 (s, 3 H, OCH 3 ), 3.42 (d, 3 J = 8 Hz, 2 H, 1'-H), (m, 4 H, 2',3'-H), 4.48 (s, 4 H, OCH 2 Ph), (m, 10 H, Ph-H). 13 C NMR (50.3 MHz, CDCl 3, APT): δ = 18.9 (+, cpr-c), 58.4 (+, OCH 3 ), 66.2 (, C-2',3'), 68.7 (, C-1'), 72.7 (, OCH 2 Ph), (+, Ph-C), (+, Ph-C), (+, Ph-C), (, Ph-C). MS (ESI), positive mode, m/z (%): 675 (100) [2M+Na + ], 349 (52) [M+Na + ]. all-cis-2,3-bis(methansulfonyloxymethyl)-1-methoxymethylcyclopropane: A suspension of all-cis-2,3-bis(benzyloxymethyl)-1-methoxymethylcyclopropane (1.13 g, 3.46 mmol) and 10% Pd on charcoal (50 mg, 1.36 mol%) in methanol (40 ml) was stirred under an atmosphere of H 2 (3 bar) at room temperature for 41 h. The reaction mixture was filtered through a pad of Celite, and the solvents were evaporated under reduced pressure. The crude product (506 mg, quant.) was taken up in a mixture of THF (10 ml) and CH 2 Cl 2 (20 ml), and the solution was cooled to 0 C. After addition of Et 3 N (2.00 ml, 14.3 mmol), mesyl chloride (820 μl, 10.6 mmol) was added dropwise at the same temperature. The reaction mixture was allowed to warm up to room temperature within 2 h under stirring before being poured into brine (20 ml). After extraction of the aqueous mixture with EtOAc (2 20 ml) the combined organic phases were washed with NaHCO 3 soln. (20 ml) and brine/water (1:1, 2 25 ml), dried and concentrated under reduced pressure. Column chromatography of the residue on silica gel (75 g, hexane/thf 1:1, R f = 0.17) afforded the bismesylate as a pale yellow oil S4

5 (352 mg, 1.16 mmol, 34%). A sample of this quite sensitive compound decomposed upon removal of the last traces of solvents under reduced pressure (p = mbar). 1 H NMR (250 MHz, CDCl 3 ): δ = 1.66 (m c, 3 H, cpr-h), 3.04 (s, 6 H, OSO 2 CH 3 ), 3.33 (s, 3 H, OCH 3 ), (m, 2 H, 1'-H), (m, 2 H, 2',3'-H a ), (m, 2 H, 2',3'-H b ). 13 C NMR (62.9 MHz, CDCl 3, DEPT): δ = 18.7 (+, C-1), 20.1 (+, C-2,3), 37.6 (+, OSO 2 CH 3 ), 58.7 (+, OCH 3 ), 66.8 (, C-2',3'), 67.7 (, C-1'). MS (ESI), positive mode, m/z (%): 627 (25) [2M+Na + ], 325 (100) [M+Na + ], 303 (69) [M+H + ], 223 (48), 207 (45). all-cis-1-methoxymethyl-2,3-bis(diphenylphosphinomethyl)cyclopropane bisborane complex 10: nbuli (1.05 ml, 2.54 mmol, 2.42 M in hexanes) was added dropwise at 5 C to a solution of PHPh 2 (440 μl, 2.55 mmol) in anhydrous and oxygen-free THF (10 ml). The reaction mixture was allowed to warm up to room temperature within 1 h under stirring. After cooling to 0 C, a solution of all-cis-2,3-bis(methansulfonyloxymethyl)-1-methoxymethylcyclopropane (150 mg, 496 μmol) in anhydrous and oxygen-free THF (10 ml) was added dropwise. After stirring for 10 min, the cooling bath was removed, and the stirring continued for 18 h. The reaction mixture was cooled to 0 C again, a solution of BH 3 THF complex (4.00 ml, 4.00 mmol, 1.00 M) was added, and the stirring was continued for 15 min. The reaction mixture was poured into ice water and the mixture extracted with CH 2 Cl 2 (5 25 ml). The combined organic layers were washed with brine (40 ml), dried and concentrated under reduced pressure. Column chromatography of the residue on silica gel (30 g, CH 2 Cl % MeOH, R f = 0.78) afforded the bisphosphine bisborane complex 10 as a waxy solid (132 mg, 259 μmol, 52%). 1 H NMR (250 MHz, CDCl 3 ): δ = 1.08 (m c, 2 H, cpr-h), (m, 1 H, cpr-h), (m, 4 H, 2',3'-H), 3.27 (s, 3 H, OCH 3 ), (m, 12 H, Ph-H), (m, 8 H, Ph-H). The protons at the 1' position could not be detected. 13 C NMR (62.9 MHz, CDCl 3, DEPT): δ = 14.2 (+, cpr-c), 19.2 (+, cpr-c), 21.0 (, d, 1 J C,P = 37 Hz, C-2',3'), 58.7 (+, OCH 3 ), 69.2 (, C-1'), (+, d, 3 J C,P = 9.8 Hz, Ph C m ), (C quart, d, 1 J C,P = 55 Hz, Ph C i ), (+, d, 4 J C,P = 2.4 Hz, Ph C p ), (+, d, 2 J C,P = 9.1 Hz, Ph C o ). 31 P-NMR (121.5 MHz, CDCl 3 ): δ = all-cis-1-methoxymethyl-2,3-bis(diphenylphosphinomethyl)cyclopropane (TriCyp-PPO): A solution of the bisborane complex 10 (128 mg, 251 μmol) in oxygen-free HEt 2 N (10 ml) was stirred at reflux for 15 h. Oxygen-free THF (5 ml) and silica gel (500 mg) were added to the reaction mixture, and the volatile components were removed in vacuo. Column chromatography of the preabsorbed crude product on silica gel under strict exclusion of S5

6 oxygen (25 g, hexane/ether 20:1 hexane/ether/thf 10:1:1, R f = 0.32) yielded the free bisphosphine TriCyp-PPO as a viscous grey oil (99 mg, 205 μmol, 82%). 1 H NMR (300 MHz, [D 8 ]THF): δ = (m c, 2 H, cpr-h), 1.07 (m c, 1 H, cpr-h), (m, 4 H, 2',3'-H), 3.24 (s, 3 H, OCH 3 ), 3.37 (d, 3 J = 7 Hz, 1'-H), (m, 12 H, Ph-H), (m, 8 H, Ph-H). 13 C NMR (75.5 MHz, [D 8 ]THF, APT): δ = 16.9 (+, m c, cpr-c), 19.8 (+, cpr-c), 23.1 (, d, 1 J C,P = 13 Hz, C-2',3'), 58.3 (+, OCH 3 ), 69.3 (, C-1'), (+, m, Ph C o ), (+, m, Ph C p ), (+, m, Ph C m ), (, m, Ph C i ). 31 P NMR (121.5 MHz, [D 8 ]THF): δ = MS (ESI), positive mode, m/z (%): 515 (100) [M+Na + ], 483 (5), [M+H + ]. all-cis-2,3-bis(benzyloxymethyl)cyclopropylmethyl methanesulfonate: A solution of 6 (196 mg, 627 μmol) and Et 3 N (265 μl, 1.90 mmol) in anhydrous CH 2 Cl 2 was treated dropwise with mesyl chloride (75.0 μl, 968 μmol) at 0 C. The resulting mixture was stirred for 10 min at this temperature and then allowed to warm up to 25 C within 1 h while stirring was continued. Brine (6 ml) was added and the emulsion extracted with EtOAc (15 ml). The extract was washed with aqueous NaHCO 3 (6 ml) and brine/water (1:1, 2 4 ml), dried and concentrated under reduced pressure. The yellow residue (236 mg, 604 μmol, 96%) was used for further transformations without purification. 1 H NMR (250 MHz, CDCl 3 ): δ = 1.57 (m c, 3 H, cpr-h), 2.91 (s, 3 H, OSO 2 CH 3 ), (m, 4 H, 2''',3'''-H), 4.36 (d, 3 J = 7.5 Hz, 3 H, 1'-H), 4.87 (s, 4 H, OCH 2 Ph), (m, 10 H, Ph-H). 13 C NMR (62.9 MHz, CDCl 3, DEPT): δ = 17.6 (+, C-1''), 19.4 (+, C-2'',3''), 37.4 (+, OSO 2 CH 3 ), 65.5 (, C-2''',3'''*), 67.8 (, C-1*), 72.7 (, OCH 2 Ph), (+, Ph-C), (+, Ph-C), (+, Ph-C), (C quart, Ph-C). all-cis-2,3-bis(benzyloxymethyl)cyclopropylmethyldiphenylphosphan borane complex: A solution of lithium diphenylphosphide (4.30 ml, 4.00 mmol, 0.93 M in THF; prepared according to: Laurenti, D.; Feuerstein, M.; Pèpe, G.; Doucet, H.; Santelli, M. J. Org. Chem. 2001, 66, ) was added slowly to a solution of all-cis-2,3-bis(benzyloxymethyl)- cyclopropylmethyl methanesulfonate (805 mg, 2.00 mmol) in anhydrous and oxygen-free THF (10 ml) at 0 C. The reaction mixture was allowed to warm up to 25 C within 16 h, cooled again to 0 C and treated with BH 3 THF (1.0 M in THF, 5.00 ml, 5.00 mmol). After 15 min of stirring, the reaction mixture was poured into ice water (30 ml) and the resulting emulsion was extracted with CH 2 Cl 2 (5 35 ml). The combined organic extracts were dried and concentrated in vacuo. Column chromatography of the residue on silica gel (100 g, S6

7 hexane/ether 2:1, R f = 0.18) afforded the phosphine borane complex as a colorless solid (775 mg, 1.57 mmol, 78%). M.p C. 1 H NMR (250 MHz, CDCl 3 ): δ = (m, 3 H, cpr-h), 2.28 (dd, 2 J = 11 Hz, 3 J = 6.4 Hz, 2 H, 1'-H), (m, 4 H, 2''',3'''-H), 4.43 (s, 4 H, CH 2 OPh), (m, 10 H, Ph-H), (m, 6 H, Ph-H), (m, 4 H, Ph-H). 13 C NMR (62.9 MHz, CDCl 3, DEPT): δ = 13.7 (+, C-1''), 18.8 (+, C-2'',3''), 21.0 (, d, 1 J C,P = 37 Hz, C-1'), 66.4 (, C-2''',3'''), 72.7 (, OCH 2 Ph), (+, Ph-C), (C quart, d, 1 J C,P = 53 Hz, Ph C i ), (+, Ph-C), (+, Ph-C), (+, d, 3 J C,P = 9.8 Hz, Ph C m ), (+, d, 4 J C,P = 3.0 Hz, Ph C p ), (+, d, 2 J C,P = 8.9 Hz, Ph C o ), (C quart, Ph-C). MS (DCI, NH 3 ), m/z (%): 512 (46) [M+NH + 4 ], 493 (60), [M+NH + 4 ], 481 (12) 314 (20), 297 (15), 202 (33), 187 (100). all-cis-1,2,3-tris(azidomethyl)cyclopropane (12): CAUTION: Polyazides are generally explosive compounds! They should not be handled as neat compounds but only in solutions and further transformed as soon as possible! Sodium azide (650 mg, 10.0 mmol) was added to a solution of the trismesylate 8 (733 mg, 2.00 mmol) in anhydrous DMSO (7.5 ml), the resulting mixture was stirred at 65 C for 17 h and poured into water (15 ml). The emulsion was extracted with CH 2 Cl 2 (3 10 ml), and the combined organic extracts were washed with water (3 10 ml), dried and concentrated under reduced pressure. The trisazide 12 was obtained as a pale yellow oil (482 mg, 1.94 mmol, 97%) which was immediately dissolved in THF and further transformed to prevent decomposition. all-cis-1,2,3-tris(aminomethyl)cyclopropane trishydrochloride (13): Triphenylphosphine (2.50 g, 9.53 mmol) and water (1 ml) were added to a solution of 12 (482 mg, 1.94 mmol) in THF (15 ml). The mixture was stirred at 25 C for 18 h before being treated with 2 M aqueous HCl (5.00 ml, 10.0 mmol). The aqueous phase was washed with ether (2 5 ml) and concentrated under reduced pressure. The trishydrochloride 13 crystallized from the yellowish oil as colorless crystals (463 mg,1.94 mmol, quant.) M.p. >255 C. 1 H NMR (250 MHz, D 2 O): δ = 1.33 (br s, 3 H, cpr-h), 2.95 (br s, 6 H, 1',2',3'-H). 13 C NMR (62.9 MHz, D 2 O): δ = 18.3 (cpr-c), 36.9 (C-1',2',3'). Preparation of catalyst solutions (general procedure GP1): π-allylpalladium chloride dimer (7.4 mg, 20.2 μmol) and the respective ligand (40.4 μmol) were dissolved in anhydrous and oxygen-free THF (40.0 ml), and the resulting solution was stirred for 1 h at room S7

8 temperature before use. If necessary, an aliquot of the stock solution was further diluted with anhydrous and oxygen-free THF. Allylation of diethyl methyl malonate (general procedure GP2): Diethyl methylmalonate 14 (1.75 ml, 10.1 mmol) was added dropwise to a suspension of sodium hydride (400 mg, 10.0 mmol, 60% suspension in mineral oil) in anhydrous and oxygen-free THF (25.0 ml) at room temperature. The resulting solution was stirred for 30 min before allyl acetate (545 μl, 5.01 mmol) and the respective amount of catalyst solution (GP 1) were added. The reaction mixture was stirred for the indicated time at 55 C. After addition of water (5 ml) and Et 2 O (50 ml), the phases were separated, and the aqueous layer was extracted with Et 2 O (15 ml). The combined organic extracts were dried and concentrated in vacuo. The residue was purified by column chromatography on silica gel (35 g, hexane/et 2 O 20:1 5:1, R f (5:1) = 0.52) to give diethyl allylmethylmalonate 15 as a colorless oil, the physical constants and spectral data of which were identical to those reported in the literature (Uenishi, J.; Kobayashi, N.; Komine, S.; Okadai, T.; Yonemitsu, O.; Sasaki, T.; Yamada, Y. Chem. Pharm. Bull. 1999, 47, ). S8

9 OBn HO 6 OBn 600 MHz CDCl3 S9

10 OBn HO 6 OBn MHz CDCl3 S10

11 OMs MsO 8 OMs 600 MHz [D8]THF S11

12 OMs MsO 8 OMs 75.5 MHz [D8]THF S12

13 Ph 2 P PPh 2 3BH 3 9 PPh MHz CDCl3 S13

14 PPh 2 Ph 2 P 3BH 3 9 PPh MHz CDCl3 S14

15 Ph 2 P PPh 2 2 PPh MHz [D8]THF S15

16 PPh 2 Ph 2 P 2 PPh MHz [D8]THF S16

17 OMe BnO OBn all-cis-2,3-bis(benzyloxymethyl)- 1-methoxymethylcyclopropane 300 MHz CDCl3 S17

18 OMe BnO OBn all-cis-2,3-bis(benzyloxymethyl)- 1-methoxymethylcyclopropane 50.3 MHz CDCl3 S18

19 OMe MsO OMs all-cis-2,3-bis(methansulfonyloxymethyl)- 1-methoxymethylcyclopropane 250 MHz CDCl3 S19

20 OMe MsO OMs all-cis-2,3-bis(methansulfonyloxymethyl)- 1-methoxymethylcyclopropane 62.9 MHz CDCl3 S20

21 OMe Ph 2 P 2BH 3 PPh MHz CDCl3 S21

22 OMe Ph 2 P 2BH 3 PPh MHz CDCl3 S22

23 OMe Ph 2 P TriCyp-PPO PPh MHz [D8]THF S23

24 OMe Ph 2 P TriCyp-PPO PPh MHz [D8]THF S24

25 OMs BnO OBn all-cis-2,3-bis(benzyloxymethyl)cyclopropylmethyl methanesulfonate 250 MHz CDCl3 S25

26 OMs BnO OBn all-cis-2,3-bis(benzyloxymethyl)cyclopropylmethyl methanesulfonate 62.9 MHz CDCl3 S26

27 PPh 2 BH 3 BnO 11 OBn 250 MHz CDCl3 S27

28 PPh 2 BH 3 BnO 11 OBn 250 MHz CDCl3 S28

29 NH 2 H 2 N 3 HCl 13 NH MHz D2O S29

30 NH 2 H 2 N 3 HCl 13 NH MHz D2O S30