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合成了香叶胺。在-60 ° C下，在二氯甲烷中用1.1当量的过氧乙酸氧化香叶胺，得到不稳定的烯丙基胺N-氧化物，其未经分离，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。在重排温度点上，较低的温度增加了羟胺的非对映体过量（de）。例如，C_2对称的吡咯烷（R^1 = EtO，R^2 = EtOCH_2）在80 ℃、25 ℃和-30 ℃下的脱乙酰度分别为35%、50%和60%。空间位阻较大的C_2对称的吡咯烷（R^1 = MeO，EtO ; R^2 = TBSOCH_2）有较好的结果（de =65 - 70%），而C_2对称的吡咯烷（R^1=MeO，EtO ; R^2 = MeOCH_2，EtOCH_2，Me）有较好的结果（de =60-65%）。最后，在乙酸中，在55 ° C下，通过超声辅助的N-O键与锌的还原断裂，在不进行外消旋的情况下得到叔烯丙醇（R）-芳樟醇。用气相色谱法在手性固定相上测定了芳樟醇的绝对构型和对映体过量。在类似条件下，橙花胺的氧化和重排反应得到了预期的反构型（S）。随后N-O键的还原裂解由香叶基吡咯烷提供（R）-里那布尔（利卡瑞醇）。类似地，（S）-芳樟醇（coriandrol）从橙花基吡咯烷获得。

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.