Single-Electon-Transfer-Mediated Asymmetric Synthesis of Boron-Functionalised Amino Acids and Peptides Empowered by Synergistic Photocatalysis

光氧化还原催化下的单电子转移介导转化为有机合成开辟了一条很有前途的途径。将光氧化还原催化与催化不对称催化相结合代表了一个新的、很大程度上尚未开发的领域，它在合成那些本质上具有挑战性但有价值的对映不纯复杂分子方面具有巨大的潜力。非蛋白质原性对映体富集氨基酸在设计具有增强生物学特性的药用肽和蛋白质中发挥了核心作用。此外，它们是手性助剂和手性催化剂的重要前体，是构建生物分子的关键组成部分。传统的获取对映纯非天然氨基酸的方法，如Strecker反应、脱氢氨基酸的氢化反应、mannich型反应和亚胺酯的烷基化反应等，依赖于与双电子转移化学相关的极性键的断开，并且常常受到苛刻的反应条件和冗长的合成序列的影响，或者缺乏底物的共性。手性硼酸及其衍生物在现代合成中具有很高的价值，因为它们可以很容易地立体特异性转化为各种功能基团。在过去的十年中，该小组已经开发了一个涉及硼化学的广泛研究项目，报告了合成复杂分子和天然产物的新方法。利用宿主在硼化学方面的专业知识，在本提案中，我们试图引入一种新的方法，将不对称光氧化还原反应和立体定向1,2-金属重排结合起来，利用协同光催化/手性磷酸催化体系，轻松合成对映体富集硼功能化的非天然氨基酸衍生物。

Single-electron transfer-mediated transformation enabled by photoredox catalysis has opened up a promising avenue in organic synthesis. Merging photoredox catalysis with catalytic asymmetric catalysis represents a new and largely unexplored field which possesses significant potential for the synthesis of those essentially challenging-to-synthesise but valuable enantiopure complex molecules. Nonproteinogenic enantioenriched amino acids have played a central role in the design of pharmaceutical peptides and proteins with enhanced biological properties. Furthermore, they act as significant precursors for chiral auxiliaries and chiral catalysts, and are key building blocks for the construction of biomolecules. Traditional strategies to access enantiopure unnatural amino acids, such as Strecker reactions, hydrogenation of dehydroamino acids, Mannich-type reactions, and alkylation of iminoesters etc, lie on the disconnection of polar bonds associated with two-electron transfer chemistry, and often suffer from harsh reaction conditions and lengthy synthetic sequences, or lack of substrate generality. Chiral boronic acids and related derivatives are highly valuable building blocks in modern synthesis as they can be easily transformed stereospecifically into diversely functional groups. Over the last decade, the host group have developed a broad research programme involving boron chemistry, reporting novel methods for the synthesis of complex molecules and natural products. By taking advantage of the host's expertise in boron chemistry, in this proposal, we seek to introduce a new methodology by merging asymmetric photoredox reactions and stereospecific 1,2-metallate rearrangements for the facile synthesis of enantiomerically enriched boron-functionalised unnatural amino acid derivatives using a synergistic photocatalysis/chiral phosphoric acid catalysis system.