Department of Process Chemistry, Merck & Co. Inc. , Rahway, New Jersey 07065, United States.
J Am Chem Soc. 2015 Jan 21;137(2):999-1006. doi: 10.1021/ja511872a. Epub 2015 Jan 7.
We report a concise, enantio- and diastereoselective route to novel nonsymmetrically substituted N-protected β,β-diaryl-α-amino acids and esters, through the asymmetric hydrogenation of tetrasubstituted olefins, some of the most challenging examples in the field. Stereoselective generation of an E- or Z-enol tosylate, when combined with stereoretentive Suzuki-Miyaura cross-coupling and enantioselective hydrogenation catalyzed by (NBD)2RhBF4 and a Josiphos ligand, allows for full control over the two vicinal stereogenic centers. High yields and excellent enantioselectivities (up to 99% ee) were obtained for a variety of N-acetyl, N-methoxycarbonyl, and N-Boc β,β-diaryldehydroamino acids, containing a diverse and previously unreported series of heterocyclic and aryl substituted groups (24 examples) and allowing access to all four stereoisomers of these valuable building blocks.
我们报告了一种简洁、对映和非对映选择性的方法，通过不对称氢化四取代烯烃，合成新型非对称取代的 N-保护的β，β-二芳基-α-氨基酸及其酯，其中一些是该领域最具挑战性的例子。立体选择性地生成 E-或 Z-烯醇对甲苯磺酸盐，与立体保持的 Suzuki-Miyaura 交叉偶联以及（NBD）2RhBF4 和 Josiphos 配体催化的对映选择性氢化相结合，可完全控制两个相邻的立体中心。对于各种 N-乙酰基、N-甲氧基羰基和 N-Bocβ，β-二芳基脱氢氨基酸，获得了高产率和优异的对映选择性（高达 99%ee），其中包含了以前未报道的一系列杂环和芳基取代基的多种（24 个实例），并可获得这些有价值的构建块的所有四个立体异构体。
