Asymmetric Palladium-Catalyzed Intramolecular α-Arylation of Aldehydes
Asymmetric Palladium-Catalyzed Intramolecular α-Arylation of Aldehydes
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DOI：
10.1002/anie.200803809
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Buchwald, Stephen L.
中科院分区：
文献类型：
--
作者：
Garcia-Fortanet, Jorge;Buchwald, Stephen L.
手性四元立体中心在许多天然产物中的普遍存在，引起了人们对其绝对立体控制构造方法发展的兴趣。[1,2]近年来，羰基化合物的α-芳基化受到了广泛关注尽管取得了很大的进展，但不对称金属催化羰基化合物的α芳基化仍然是一个巨大的挑战，而且很少有这样的例子被描述。[4-7]据我们所知，目前还没有不对称金属催化α-芳基化醛的报道在此，我们提出了第一个金属催化的醛类α芳基化反应，以高收率和对映选择性形成全碳取代的不对称中心（方案1）。醛的外消旋α-芳基化仍然具有挑战性，因为在反应条件下存在竞争性的醛缩反应在2007年，我们的小组描述了一种与ArBr和ArCl的醛的α-芳基化的一般方法。[9d]发现以Pd (OAc) 2/binap为基础的催化体系在使用芳基溴时效果最好。鉴于binap已被成功地用作相关α-芳基化方法中的配体[4-7]，我们决定研究这种配体在1a的不对称α-芳基化中的效用（表1）。经过对钯源、碱和溶剂的初步筛选，我们得到了所需的化合物2a
The prevalence of chiral quaternary stereocenters in many natural products has attracted a growing interest in the development of methods for their construction with absolute stereocontrol.[1, 2] In recent years, the α-arylation of carbonyl compounds has received a great deal of attention.[3] Despite substantial advances, the asymmetric metal-catalyzed αarylation of carbonyl compounds remains a formidable challenge, and few examples have been described.[4–7] To the best of our knowledge, no examples of asymmetric metalcatalyzed α-arylation of aldehydes have yet been reported.[8] Herein, we present the first asymmetric metal-catalyzed αarylation of aldehydes forming all-carbon-substituted asymmetric centers in high yields and enantioselectivities (Scheme 1).The racemic α-arylation of aldehydes remains challenging due to competing aldol condensation under the reaction conditions.[9] In 2007 our group described a general method for the α-arylation of aldehydes with both ArBr and ArCl.[9d] It was found that the catalytic system based upon Pd (OAc) 2/binap provided the best results when aryl bromides were used. Given that binap has been successfully used as a ligand in related α-arylation methodologies [4–7] we decided to examine the utility of this ligand for the asymmetric α-arylation of 1a (Table 1). After some initial screening of palladium sources, bases and solvents,[10] we obtained the desired compound 2a