Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.
J Am Chem Soc. 2021 Jun 16;143(23):8614-8618. doi: 10.1021/jacs.1c03903. Epub 2021 Jun 3.
Interest in unnatural α-amino acids has increased rapidly in recent years in areas ranging from protein design to medicinal chemistry to materials science. Consequently, the development of efficient, versatile, and straightforward methods for their enantioselective synthesis is an important objective in reaction development. In this report, we establish that a chiral catalyst based on nickel, an earth-abundant metal, can achieve the enantioconvergent coupling of readily available racemic alkyl electrophiles with a wide variety of alkylzinc reagents (1:1.1 ratio) to afford protected unnatural α-amino acids in good yield and ee. This cross-coupling, which proceeds under mild conditions and is tolerant of air, moisture, and a broad array of functional groups, complements earlier approaches to the catalytic asymmetric synthesis of this valuable family of molecules. We have applied our new method to the generation of several enantioenriched unnatural α-amino acids that have previously been shown to serve as useful intermediates in the synthesis of bioactive compounds.
近年来，从蛋白质设计到药物化学再到材料科学，人们对非天然α-氨基酸的兴趣迅速增加。因此，开发高效、通用和直接的方法来对其进行对映选择性合成是反应开发的重要目标。在本报告中，我们证明了基于镍的手性催化剂（一种丰富的地球金属）可以实现容易获得的外消旋烷基亲电试剂与各种烷基锌试剂（1:1.1 摩尔比）的对映选择性偶联，以高产率和对映选择性得到保护的非天然α-氨基酸。这种交叉偶联在温和条件下进行，并且耐受空气、水分和广泛的官能团，补充了以前的催化不对称合成这些有价值的分子家族的方法。我们已经将我们的新方法应用于几种对映体富集的非天然α-氨基酸的生成，这些氨基酸以前被证明是合成生物活性化合物的有用中间体。
