ASYMMETRIC SYNTHESIS OF TERTIARY ALLYLIC ALCOHOLS AND EPOXIDES USING TETRASUBSTITUTED PYRROLIDINE AUXILIARIES.

1998 Fiscal Year Final Research Report Summary

• Project/Area Number: 09650950
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Synthetic chemistry
• Research Institution: YOKOHAMA NATIONAL UNIVERSITY
• Principal Investigator: HONDA Kiyoshi FACULTY OF ENGINEERING,ASSOCIATE PROFESSOR, 工学部, 助教授 (60231578)
• Project Period (FY): 1997 – 1998
• Keywords: ALLYLAMINE N-OXIDE / [2,3] SIGMATROPIC REARRANGEMENT / ASYMMETRIC INDUCTION / DIASTEREOFACIAL SELECTIVE REACTION / OPTICALLY ACTIVE TERTIARY ALCOHOL / OPTICALLY ACTIVE INALOOL / C_2-SYMMETRIC PYRROLIDINE / ASYMMETRIC EPOXIDE

Research Abstract

Geranylamines were prepared from geranyl bromide and various chiral pyrrolidine derivertives. Oxidation of the geranylamines with 1.1 equivalent of peracetic acid in dichioromethane at -60ﾟC led to labile allylamine N-oxides, which were, without isolation, rearranged to the trisubstituted hydroxyamines. Asymmetric inductions were dependent upon the rearrangement temperature and substituents R^1 and R^2, On the point of rearrangement temperature, lower temperature increased diastereomeric excess (de) of the hydroxyamines. For example, C_2-symmetrical pyrrolidine (R^1 = EtO, R^2 = EtOCH_2) gave 35%, 50% and 60% de at 80ﾟC, 25ﾟC and -30ﾟC, respectively. Furthermore, sterically more hindered C_2-symmetrical pyrrolidine (R^1 = MeO, EtO ; R^2 = TBSOCH_2) gave good result (de =65 - 70%) and fairly good results (de =60-65%) were obtained when using C_2-symmetrical pyrrolidine (R^1=MeO, EtO ; R^2 = MeOCH_2, EtOCH_2, Me). Finally, the tertiary allylic alcohol (R)-linalool was obtained without racemization by ultrasound-assisted reductive cleavage of N-O bond with zinc in acetic acid at 55ﾟC.The pyrrolidine auxiliary was separated during the work-up procedure and recycled. The absolute configuration and enantiomeric excess were determined by gas chromatography of synthetic linalool on a chiral stationary phase. The oxidation followed by rearrangement of nerylamine under similar conditions led to the inverse configuration (S) of the new stereogenic center as expected.
In summary, the asymmetric [2,3]sigmatropic rearrangement using a new C_2-symmetrical pyrrolidine auxiliary is described. Subsequent reductive cleavage of N-O bond provides (R)-linabool (licareol) from geranylpyrrolidine. Similary, (S)-linalool (coriandrol) is obtained from nerylpyrrolidine.