Enantiomerically enriched allylglycine derivatives through the catalytic asymmetric allylation of iminoesters and iminophosphonates with allylsilanes
Enantiomerically enriched allylglycine derivatives through the catalytic asymmetric allylation of iminoesters and iminophosphonates with allylsilanes
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DOI：
10.1002/anie.200504196
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发表时间：
2006-01-01
影响因子：
16.6
通讯作者：
Kobayashi, S
中科院分区：
文献类型：
--
作者：
Kiyohara, H;Nakamura, Y;Kobayashi, S
α-氨基酸的合成是现代药物化学的重要课题之一。[1]在迄今报道的各种合成方法中，亚氨基酯的不对称碳-碳键形成反应为光学活性α-氨基酸提供了一条有效的途径。虽然N-保护的亚氨基酯的催化不对称曼尼希型反应已经被几个小组报道[2]，但亚氨基酯的催化不对称烯丙基化的例子很少，尽管它们在有机合成中的用途。[3]Lectka及其同事报道了N，O-缩醛与β-苯基烯丙基三甲基硅烷在CuI/binap（binap= 2，2 '-双（二苯基膦基）-1，1'-联萘）络合物存在下反应[3a]，他们还公开了N-甲苯磺酰基亚氨基酯与β-芳基烯丙基三甲基硅烷以及未取代的烯丙基三甲基硅烷在类似条件下的反应。[3d]然而，只有β-芳基烯丙基硅烷得到具有高对映体纯度的所需产物，而其它烯丙基三烷基硅烷得到中等选择性（高达72%ee）。Jørgensen及其同事报道了N-甲苯磺酰基亚氨基酯与烯丙基三丁基锡的高度对映选择性反应。[3b它们表明使用烯丙基硅烷导致低收率和低选择性。另外，从合成实用性的观点来看，与酰胺或烷氧基羰基相比，氮中心处的磺酰基有时对于脱保护是有问题的。因此，强烈期望开发环境友好、高效和实用的方法。在这里，我们报告了一个铜催化的，高对映选择性的烯丙基化的N-酰基和N-烷氧羰基亚胺酯使用环境友好的烯丙基硅烷作为亲核试剂。报道了亚氨基膦酸酯催化烯丙基化反应合成α-氨基膦酸及其膦酸酯的第一个实例，考察了N-酰基亚氨基酯1与几种烯丙基化试剂在Cu（OTf）_2与二胺3形成的铜配合物（10mol%）存在下的烯丙基化反应，该配合物对亚氨基酯与烯醇化硅的Mannich型反应是一种有效的催化剂。[2f发现相对反应性的烯丙基三丁基锡烷（2a）得到所需产物，尽管产率低，选择性低（方案1，Eq.① ①）。另一方面，当使用在硅原子的β-位上带有硫取代基的烯丙基硅烷2b时[4]，以高产率和高选择性获得烯丙基化产物[方案1，Eq.②]。
The synthesis of α-amino acids is one of the most important topics in modern medicinal chemistry.[1] Among the variety of synthetic methods so far reported, asymmetric carbon–carbon bond-forming reactions of iminoesters provide an efficient route to optically active α-amino acids. While catalytic asymmetric Mannich-type reactions of N-protected iminoesters have already been reported by several groups,[2] few examples of catalytic asymmetric allylations of iminoesters are known despite their utility in organic synthesis.[3] Lectka and co-workers reported that N, O-acetals react with βphenylallyltrimethylsilane in the presence of a CuI/binap (binap= 2, 2’-bis (diphenylphosphino)-1, 1’-binaphthyl) complex,[3a] and they also disclosed reactions of N-tosyl iminoesters with β-arylallyltrimethylsilanes as well as nonsubstituted allyltrimethylsilane under similar conditions.[3d] However, only β-arylallylsilane gave the desired product with high enantiomeric purity while other allyltrialkylsilanes gave moderate selectivities (up to 72% ee). Jørgensen and coworkers reported highly enantioselective reactions of N-tosyl iminoesters with allyltributyltin.[3b, c] They showed that the use of allylsilanes resulted in low yields with low selectivity. Additionally, from a viewpoint of synthetic utility, a sulfonyl group at the nitrogen center is sometimes problematic for deprotection compared to amide or alkoxycarbonyl groups. Hence, the development of environmentally friendlier, efficient, and practical methods is strongly desired. Herein, we report a CuII-catalyzed, highly enantioselective allylation of N-acyl and N-alkoxycarbonyl iminoesters using environmentally benign allylsilanes as nucleophiles. The first example of catalytic enantioselective allylations of iminophosphonates for the synthesis of α-aminophosphonic acids and their phosphonate esters is also described.Allylation reactions of N-acyliminoester 1 with several allylating reagents were examined in the presence of a copper complex (10 mol%) prepared from Cu (OTf) 2 and diamine 3, which was an efficient catalyst for Mannich-type reactions of iminoesters with silicon enolates.[2f, g] Relatively reactive allyltributylstannane (2a) was found to give the desired product, albeit in low yield with low selectivity (Scheme 1, Eq.(1)). On the other hand, when allylsilane 2b, which bears a sulfur substituent at the β-position to the silicon atom, was employed [4] the allylated product was obtained in high yield with high selectivity [Scheme 1, Eq.(2)].