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

以溴化香叶基和各种手性吡咯烷衍生物为原料合成了香叶胺类化合物。在-60ﾟC下，用1.1当量的过氧乙酸在二氯甲烷中氧化香叶胺得到不稳定的烯丙胺N-氧化物，这些氧化物在没有分离的情况下重排成三取代羟胺。不对称诱导依赖于重排温度和取代基R^1和R^2，在重排温度下，温度越低，羟胺的非对映异构体过量(De)越大。例如，C2-对称吡咯烷(R^1=ETO，R^2=EtOCH2)在80ﾟC、25ﾟC和-30ﾟC时分别得到35%、50%和60%的De。空间位阻较大的C_2-对称吡咯烷(R^1=MeO，ETO；R^2=TBSOCH_2)得到了较好的结果(De=65-70%)，而使用C_2-对称吡咯烷(R^1=MeO，ETO；R^2=MeOCH_2，EtOCH_2，Me)得到了较好的结果(De=60-65%)。最后，在55ﾟC的条件下，利用超声波辅助的N-O键与锌在醋酸中还原裂解得到未消旋的叔烯丙醇(R)-芳樟醇。合成芳樟醇在手性固定相上用气相色谱测定了绝对构型和对映体过量。在类似的条件下，橙花胺的氧化和重排导致了新的立体合成中心的逆构型(S)。综上所述，我们描述了一个新的C2对称的吡咯烷辅助剂的不对称[2，3]Sigma重排反应。随后N-O键的还原裂解从香叶基吡咯烷中得到(R)-芳香醇(利卡瑞醇)。类似地，(S)-芳樟醇也是从甲基吡咯烷中得到的。

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.