Catalytic asymmetric addition of ZnPh2 to ketones:: Enantioselective formation of quaternary stereocenters
Catalytic asymmetric addition of ZnPh2 to ketones:: Enantioselective formation of quaternary stereocenters
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DOI：
10.1021/ja973169u
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发表时间：
1998-01-21
影响因子：
15
通讯作者：
Fu, GC
中科院分区：
文献类型：
--
作者：
Dosa, PI;Fu, GC
有机金属试剂与醛的对映选择性加成反应已发展出一系列高效的催化剂。1，2然而，据我们所知，还没有关于有机金属试剂对酮的有效催化不对称加成的报道。3在这篇文章中，我们提供了这样一个过程的例子，建立了3-exo-（二甲基氨基）异冰片（DAIB）1b用作ZnPh 2对映选择性加成到一系列芳基-烷基酮和二烷基酮的有效催化剂，从而产生具有良好至优异立体控制的季立构中心（等式1）。Noyori已经证明DAIB是ZnEt 2对醛的不对称加成的非常有效的催化剂。1b，d我们试图扩大DAIB催化过程的范围，以包括酮的反应，我们最初的努力集中在ZnPh 2 4加成到2-丙酮萘酮上。虽然我们观察到所需叔醇中有希望的对映体过量水平（64%ee），但产率令人失望（26%产率;等式2）。主要的反应产物是酮A，其通过醛醇-脱水共轭加成序列形成。5
A wide array of highly effective catalysts have been developed for the enantioselective addition of organometallic reagents to aldehydes. 1, 2 However, to the best of our knowledge there have been no reports of efficient catalytic asymmetric addition of organometallic reagents to ketones. 3 In this communication, we provide an example of such a process, establishing that 3-exo-(dimethylamino) isoborneol (DAIB) 1b serves as an effective catalyst for the enantioselective addition of ZnPh2 to a range of aryl-alkyl and dialkyl ketones, thereby producing a quaternary stereocenter with good to excellent stereocontrol (eq 1).In pioneering studies, Noyori has demonstrated that DAIB is a remarkably efficient catalyst for the asymmetric addition of ZnEt2 to aldehydes. 1b, d We sought to expand the scope of DAIB-catalyzed processes to include reactions of ketones, and we focused our initial efforts on the addition of ZnPh2 4 to 2-acetonaphthone. Although we observed a promising level of enantiomeric excess in the desired tertiary alcohol (64% ee), the yield was disappointing (26% yield; eq 2). The predominant reaction product was ketone A, which is formed via an aldol-dehydrationconjugate addition sequence. 5