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

光氧化还原催化的单电子转移反应为有机合成开辟了一条新的途径。将光氧化还原催化与催化不对称催化相结合是一个新的、尚未开发的领域，它在合成那些具有挑战性但有价值的对映体纯的复合物分子方面具有巨大的潜力。非蛋白质对映体富集的氨基酸在设计具有增强的生物学性质的药物肽和蛋白质中发挥了核心作用。此外，它们作为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构件。传统的非天然氨基酸合成方法，如Strecker反应、脱氢氨基酸的氢化反应、Mannich型反应、亚氨基酯的烷基化反应等，都依赖于与双电子转移化学相关的极性键的断开，反应条件苛刻，合成过程冗长，底物缺乏通用性。手性硼酸及其衍生物在现代合成中是非常有价值的结构单元，因为它们可以很容易地立体特异性地转化为双功能基团。在过去的十年中，主持小组已经开发了一个广泛的研究计划，涉及硼化学，报告了合成复杂分子和天然产物的新方法。通过利用主机在硼化学的专业知识，在这个建议中，我们试图引入一种新的方法，通过合并不对称的光氧化还原反应和立体特异性的1，2-金属酸酯重排的对映体富集的硼官能化的非天然氨基酸衍生物的简便合成使用协同的手性磷酸/手性磷酸催化系统。

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.