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

以香叶基溴和各种手性吡咯烷衍生物为原料制备香叶胺。在-60℃的过氧化氢条件下，用1.1当量的过氧乙酸在二氯甲烷中氧化香叶胺，得到了不稳定的烯丙胺n -氧化物，这些烯丙胺n -氧化物未经分离就被重排为三取代的羟胺。不对称诱导依赖于重排温度和取代基R^1和R^2，在重排温度上，较低的温度增加了羟胺的非对映异构体过量（de）。例如，c_2对称吡咯烷（R^1 = EtO, R^2 = EtOCH_2）在80、25和-30的温度下分别有35%、50%和60%的脱氢率。此外，空间位阻更强的c_2对称吡咯烷（R^1=MeO, EtO; R^2 = TBSOCH_2）得到了较好的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de =60 ~ 65%。最后，用超声辅助zn - o键还原裂解法制备了未消旋的叔烯丙醇-芳樟醇。吡咯烷助剂在加工过程中被分离并回收。用手性固定相气相色谱法测定了合成芳樟醇的绝对构型和对映体过量。在类似的条件下，氧化后的神经胺重排导致了新的立体中心的反构型(S)。总之，描述了一种新的c_2对称吡咯烷助剂的不对称[2,3]符号位重排。随后N-O键的还原裂解从香叶基吡咯烷中得到(R)-linabool （licareol）。类似地，(S)-芳樟醇（香菜醇）也可从奈基吡咯烷中得到。

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.