Bull Steven D, Davies Stephen G, Nicholson Rebecca L, Sanganee Hitesh J, Smith Andrew D
Dyson Perrins Laboratory, University of Oxford, South Parks Road, Oxford, UK OX1 3 QY.
Org Biomol Chem. 2003 Aug 21;1(16):2886-99. doi: 10.1039/b305623f.
The proclivity of alpha-branched N-2'-benzyl-3'-phenylpropionyl derivatives of (S)-4-benzyl-5,5-dimethyl-, (S)-4-phenyl-5,5-dimethyl-, (S)-4-isopropyl-5,5-dimethyl-, (S)-4-benzyl- and (S)-4-benzyl-5,5-diphenyl-oxazolidin-2-ones to generate directly 2-benzyl-3-phenylpropionaldehyde upon hydride reduction with DIBAL is investigated. The (S)-4-benzyl-5,5-dimethyl-derivative proved optimal for inhibition of endocyclic nucleophilic attack, giving 2-benzyl-3-phenylpropionaldehyde in good yield upon reduction. Application of this methodology for the asymmetric synthesis of chiral aldehydes via diastereoselective enolate alkylation of a range of (S)-N-acyl-4-benzyl-5,5-dimethyloxazolidin-2-ones to afford and array of alpha-substituted-N-acyl-5,5-dimethyloxazolidin- 2-ones (85-94% de) and subsequent reduction with DIBAL afforded directly non-racemic alpha-substituted aldehydes without loss of stereochemical integrity (87-94% ee). The extension of this protocol for the asymmetric synthesis of beta-substituted aldehydes is demonstrated, via the diastereoselective conjugate addition of a range of organocuprates to (S)-N-acyl-4-phenyl-5,5-dimethyloxazolidin-2-ones which proceeds with high diastereoselectivity (generally > 95% de). Reduction of the conjugate addition products with DIBAL gives non-racemic beta-substituted aldehydes in high yields and in high ee (generally > 95% ee). This methodology is exemplified by the asymmetric synthesis of (R)-3-isopropenylhept-6-enal, which has previously been used in the synthesis of (3Z,6R)-3-methyl-6-isopropenyl-3,9-decadien-1-yl acetate, a component of the sex pheromones of the California red scale.
研究了(S)-4-苄基-5,5-二甲基-、(S)-4-苯基-5,5-二甲基-、(S)-4-异丙基-5,5-二甲基-、(S)-4-苄基-和(S)-4-苄基-5,5-二苯基-恶唑烷-2-酮的α-支链N-2'-苄基-3'-苯基丙酰衍生物在用二异丁基氢化铝进行氢化物还原时直接生成2-苄基-3-苯基丙醛的倾向。(S)-4-苄基-5,5-二甲基衍生物被证明是抑制环内亲核进攻的最佳选择，还原时能以良好的产率得到2-苄基-3-苯基丙醛。通过一系列(S)-N-酰基-4-苄基-5,5-二甲基恶唑烷-2-酮的非对映选择性烯醇盐烷基化反应进行手性醛的不对称合成，得到一系列α-取代的-N-酰基-5,5-二甲基恶唑烷-2-酮（非对映体过量85 - 94%），随后用二异丁基氢化铝还原，直接得到非外消旋的α-取代醛，且立体化学完整性无损失（对映体过量87 - 94%）。展示了该方法用于β-取代醛不对称合成的扩展，即通过一系列有机铜酸盐与(S)-N-酰基-4-苯基-5,5-二甲基恶唑烷-2-酮的非对映选择性共轭加成反应，该反应具有高非对映选择性（通常非对映体过量>95%）。用二异丁基氢化铝还原共轭加成产物，以高产率和高对映体过量（通常对映体过量>95%）得到非外消旋的β-取代醛。(R)-3-异丙烯基庚-6-烯醛的不对称合成举例说明了该方法，(R)-3-异丙烯基庚-6-烯醛先前已用于合成(3Z,6R)-3-甲基-6-异丙烯基-3,9-癸二烯-1-基乙酸酯，它是加州红圆蚧性信息素的一个成分。
