Supporting Information S1 Optical Resolution via Catalytic Generation of Chiral Auxiliary Hiroki Kiyama, Tsubasa Inokuma, Yusuke Kuroda, Yousuke Yamaoka, Kiyosei Takasu, and Ken-ichi Yamada* Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Kyoto 606-8501, Japan. Graduate School of Pharmaceutical Sciences, Tokushima University, Shomachi, Tokushima 770-8505, Japan E-mail: [email protected]Table of Contents Experimental Section General Information .............................................................................................................. S2 Starting Materials .................................................................................................................. S2 General Procedure for the Catalytic Asymmetric Addition of Alcohol 1 to Imine 2............ S2 Hydrolysis of 4a and 5a ........................................................................................................ S4 NMR Spectra and HPLC Traces 4a ........................................................................................................................................... S5 5a ........................................................................................................................................... S8 4b ......................................................................................................................................... S11 5b ......................................................................................................................................... S13 4c ......................................................................................................................................... S16 5c ......................................................................................................................................... S18 1a ......................................................................................................................................... S21
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Optical Resolution via Catalytic Generation of Chiral ... · S2 Experimental Section General. All melting points are uncorrected. Silica gel was used for column chromatography. NMR
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Supporting Information �
S1�
Optical Resolution via Catalytic Generation of Chiral Auxiliary
Experimental Section General Information .............................................................................................................. S2 Starting Materials .................................................................................................................. S2 General Procedure for the Catalytic Asymmetric Addition of Alcohol 1 to Imine 2 ............ S2 Hydrolysis of 4a and 5a ........................................................................................................ S4
(m/z): [M + H]+ calcd for C27H28NO2, 398.2125; found, 398.2127. The absolute configuration of the aminal moiety
was assigned based on the reported selectivity of the asymmetric addition.5 The absolute configuration of the
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1. Hazmi, A. M. A.; Sheikh, N. S.; Bataille, C. J. R.; Al-Hadedi, A. A. M.; Watkin, S. V.; Luker, T. J.; Camp, N. P.; Brown, R. C. D. Org. Lett. 2014, 16, 5104. 2. Alexakis, A.; Jachiet, D.; Normant, J. F. Tetrahedron 1986, 42, 5607. 3. (a) Cowen, B. J.; Saunders, L. B.; Miller, S. J. J. Am. Chem. Soc. 2009, 131, 6105. (b) Murry, J. A.; Frantz, D. E.; Soheili, A.; Tillyer, R.; Grabowski, E. J. J.; Reider, P. J. J. Am. Chem. Soc. 2001, 123, 9696. 4. (a) Uraguchi, D.; Sorimachi, K.; Terada, M. J. Am. Chem. Soc. 2005, 127,9360. (b) Hoffmann, S.; Seayad, A. M.; List, B. Angew. Chem. Int. Ed. 2005, 44, 7424. (c) Akiyama, T.; Tamura, Y.; Itoh, J.; Morita, H.; Fuchibe, K. Synlett 2006, 141. 5. Nimmagadda, S. K.; Zhang, Z.; Antilla, J. C. Org. Lett. 2014, 16, 4098.
Bn
Ph NHBz
O H
Supporting Information �
S3�
cyclohexanol moiety was determined after hydrolysis to (1R,2S)-1a (vide infra).
N-((R)-((1S,2R)-2-Benzylcyclohexyloxy)(phenyl)methyl)benzamide (5a): Purified by silica
gel column chromatography (hexane/EtOAc 40:1 to 10:1). 94% ee (Daicel Chiralpak IA; 254
nm; hexane/i-PrOH 95:5, 1.0 mL/min; tr major 11.9 min, minor 17.9 min). Colorless