Catalytic asymmetric synthesis of tertiary alkyl chlorides
Catalytic asymmetric synthesis of tertiary alkyl chlorides
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DOI：
10.1002/anie.200604312
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发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
Fu, Gregory C.
中科院分区：
文献类型：
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作者：
Lee, Elaine C.;McCauley, Kevin M.;Fu, Gregory C.
对映体富集的卤代烷的生物活性和合成用途为立体选择性合成它们的方法的发展提供了强大的动力。[1]近年来，许多报道描述了在发现这类化合物（特别是α-卤代羰基化合物[2，3]）的催化不对称方法方面的显著进展;几乎所有这些过程都产生仲烷基卤化物。[1]相比之下，在用于叔卤化物的对映选择性合成的催化剂的开发方面取得了有限的成功。[4-6]在这里，我们描述了解决这一挑战的进展，特别是从烯酮催化不对称合成叔α-氯酯[7-9]的方法[Eq.①]。[10在早期的研究中，我们检查了苯基乙基乙烯酮与各种氯化剂在一系列条件下的反应（例如，表1的条目1-4）。在PPY*（4-（吡咯烷基）吡啶（PPY）的平面手性衍生物）的存在下，[12]向烯酮添加试剂如N-氯琥珀酰亚胺、[3b] 2、[5d]和3 [10a]，产率和/或对映选择性较差（条目1和2，表1）。另一方面，与六氯丙酮[13]的反应干净地消除了
The bioactivity and the synthetic utility of enantioenriched alkyl halides provide a strong impetus for the development of stereoselective methods for their synthesis.[1] In recent years, a number of reports have described remarkable progress in the discovery of catalytic asymmetric approaches to this family of compounds (particularly, α-halocarbonyls [2, 3]); nearly all of these processes generate secondary alkyl halides.[1] In contrast, there has been limited success in the development of catalysts for the enantioselective synthesis of tertiary halides.[4–6] Here, we describe progress toward addressing this challenge, specifically, a method for the catalytic asymmetric synthesis of tertiary α-chloroesters [7–9] from ketenes [Eq.(1)].[10, 11]In early studies, we examined the reaction of phenyl ethyl ketene with various chlorinating agents under a range of conditions (eg, entries 1–4 of Table 1). In the presence of PPY*, a planar-chiral derivative of 4-(pyrrolidino) pyridine (PPY),[12] additions of reagents such as N-chlorosuccinimide,[3b] 2,[5d] and 3 [10a] to the ketene proceed in poor yield and/or enantioselectivity (entries 1 and 2, Table 1). On the other hand, reaction with hexachloroacetone [13] cleanly furnishes