Asymmetric synthesis of α,α-dibranched amines by the trimethylaluminum-mediated 1,2-addition of organolithiums to tert-butanesulfinyl ketimines
Asymmetric synthesis of α,α-dibranched amines by the trimethylaluminum-mediated 1,2-addition of organolithiums to tert-butanesulfinyl ketimines
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DOI：
10.1021/ja983217q
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发表时间：
1999-01-13
影响因子：
15
通讯作者：
Ellman, JA
中科院分区：
文献类型：
--
作者：
Cogan, DA;Ellman, JA
不对称诱导合成手性季铵中心一直是合成化学中的一个难题。事实上，直到最近才开发出实用和优雅的路线，以某些类别的四元中心。[1]然而，尽管胺官能团在天然产物、合成药物、催化剂和材料中普遍存在，但还没有报道用于不对称合成大类氮取代的季中心（R，R-二支链胺）的直接方法。为此，亲核试剂与酮亚胺的1，2-加成作为一种通用和直接的方法具有很大的潜力。2，3不幸的是，竞争性的R-去质子化已经禁止了芳基或烷基碳负离子的普遍使用。因此，R，R-二支化胺的不对称合成仅限于酮亚胺的烯丙基化2和R-吡啶基取代的酮亚胺的加成。5在此，我们报道了通过有机锂试剂与酮亚胺的前所未有的1，2-加成反应来不对称合成宽范围的R，R-二支链胺的第一个直接方法。具体地说，我们报道了有机锂试剂对N-叔丁基亚磺酰基酮亚胺的高非对映选择性1，2-加成，它们是由相应的酮在一步中高产率地制备的。虽然已经通过亲核试剂对N-亚磺酰基醛亚胺的非对映选择性加成制备了各种胺，但报道的N-亚磺酰基酮亚胺的转化少得多。7这可能是由于大多数N-亚磺酰基酮亚胺衍生物的不可用性，其传统上是通过手性亚磺酸酯与通过有机金属化合物与腈的1，2-加成原位制备的亚胺阴离子的反应来合成的。3，8这种方法受到容易获得的、不可烯醇化的腈的数量少的限制。
Asymmetric induction in the synthesis of chiral quaternary centers has been a formidable challenge in synthetic chemistry. In fact, only recently have practical and elegant routes to certain classes of quaternary centers been developed. 1 However, despite the prevalence of the amine functionality in natural products, synthetic pharmaceuticals, catalysts, and materials, no direct method has yet been reported for the asymmetric synthesis of the large class of nitrogen-substituted quaternary centers, the R, R-dibranched amines. To this end, the 1, 2-addition of nucleophiles to ketimines has great potential as a general and direct approach. 2, 3 Unfortunately, competitive R-deprotonation has prohibited the general use of aryl or alkyl carbanions. 2, 4 Thus, the asymmetric synthesis of R, R-dibranched amines has been limited to allylation of ketimines2 and additions to R-pyridyl-substituted ketimines. 5 Herein, we report the first direct method for the asymmetric synthesis of a broad range of R, R-dibranched amines by the unprecedented 1, 2-addition of organolithium reagents to ketimines. Specifically, we report the highly diastereoselective 1, 2-addition of organolithium reagents to N-tert-butanesulfinyl ketimines, which are prepared in high yield in one step from the corresponding ketones.Although a variety of amines have been prepared by the diastereoselective addition of nucleophiles to N-sulfinyl aldimines, 6 far fewer transformations of N-sulfinyl ketimines have been reported. 7 This is likely due to the unavailability of most N-sulfinyl ketimine derivatives, which have traditionally been synthesized by the reaction of chiral sulfinate esters with imine anions prepared in situ by the 1, 2-addition of organometallics to nitriles. 3, 8 This approach is limited by the small number of readily available, nonenolizable nitriles.