Practical Synthesis of anti‐β‐Hydroxy‐α‐Amino Acids by PdII‐Catalyzed Sequential C(sp3)H Functionalization |
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| Authors: | Kai Chen Shuo‐Qing Zhang Huai‐Zhi Jiang Jing‐Wen Xu Prof?Dr Bing‐Feng Shi |
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| Affiliation: | 1. Department of Chemistry, Zhejiang University, Hangzhou 310027 (China);2. State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institution of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032 (China) |
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| Abstract: | An improved and practical procedure for the stereoselective synthesis of anti‐β‐hydroxy‐α‐amino acids (anti‐βhAAs), by palladium‐catalyzed sequential C(sp3)?H functionalization directed by 8‐aminoquinoline auxiliary, is described. followed by a previously established monoarylation and/or alkylation of the β‐methyl C(sp3)?H of alanine derivative, β‐acetoxylation of both alkylic and benzylic methylene C(sp3)?H bonds affords various anti‐β‐hydroxy‐α‐amino acid derivatives. As an example, the synthesis of β‐mercapto‐α‐amino acids, which are highly important to the extension of native chemical ligation chemistry beyond cysteine, is described. The synthetic potential of this protocol is further demonstrated by the synthesis of diverse β‐branched α‐amino acids. The observed diastereoselectivities are strongly influenced by electronic effects of aromatic AAs and steric effects of the linear side‐chain AAs, which could be explained by the competition of intramolecular C?OAc bond reductive elimination from PdIV intermediates vs. intermolecular attack by an external nucleophile (AcO?) in an SN2‐type process. |
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| Keywords: | acetoxylation amino acids C H activation homogeneous catalysis palladium |
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