Ionic or radical α-amino Schiff base methods are well known for the synthesis of α,α-disubstituted α-amino acids. However, the incorporation of sterically demanding groups is challenging with ionic methods, and radical methods require prefunctionalization of the substrates. Now we have developed a dehydrogenative coupling process of α-amino acid Schiff bases with hydrocarbon feedstocks for the synthesis of α,α-disubstituted α-amino acid derivatives. These α-amino acid derivatives were transformed into C- and N-protected amino acids, which could be easily incorporated into peptide synthesis. A range of α-amino acid derivatives could be readily accessed, which includes, notably, those that bear contiguous quaternary centres. Circular dichroism measurements show that the helical peptide structure is stabilized by the highly sterically congested unnatural α-amino acid. Mechanistic studies revealed that deprotonation of the α-amino acid Schiff base is a turnover-limiting step and the use of an enhanced Brønsted basic copper(I) tert-butoxide complex produced a superior catalytic performance. Photoinduction of the catalytic reaction, using blue light-emitting diode radiation, allowed the reaction to proceed without external heating.

离子或自由基 α-氨基席夫碱方法对于合成 α,α-二取代的 α-氨基酸是众所周知的。然而，离子方法难以引入空间要求高的基团，而自由基方法需要对底物进行预功能化。现在我们开发了一种α-氨基酸席夫碱与烃类原料的脱氢偶联工艺，用于合成α，α-二取代的α-氨基酸衍生物。这些α-氨基酸衍生物被转化为C-和N-保护的氨基酸，可以很容易地结合到肽合成中。可以很容易地获得一系列 α-氨基酸衍生物，其中尤其包括那些带有连续四元中心的衍生物。圆二色性测量显示螺旋肽结构被高度空间拥挤的非天然α-氨基酸稳定。机理研究表明，α-氨基酸席夫碱的去质子化是一个限制周转的步骤，并且使用增强的布朗斯台德碱式铜 (I)叔丁醇络合物产生了优异的催化性能。使用蓝色发光二极管辐射的催化反应的光诱导允许反应在没有外部加热的情况下进行。