Synthesis and Reactivity of α-Haloglycine Esters: Hyperconjugation in Action
Synthesis and Reactivity of α-Haloglycine Esters: Hyperconjugation in Action
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DOI：
10.1002/ejoc.201901033
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发表时间：
2019-09-17
影响因子：
2.8
通讯作者：
Roche, Stephane P.
中科院分区：
文献类型：
--
作者：
Samanta, Shyam S.;Roche, Stephane P.
报道了从市售原料化学品一步合成α-卤代甘氨酸酯的一般和有效的方法。研究了这些α-卤代甘氨酸酯与各种亲核试剂的反应性，作为α-亚氨基酯的替代物，在用氢键供体催化剂活化后。DFT计算上的α-卤代甘氨酸结构（X = F，Cl，Br）伴随着X-射线表征的α-溴甘氨酸酯支持存在的“广义”的异头效应所产生的hyperconjugation。这种特殊的超共轭效应被认为是负责增强卤素离核性，导致一个容易的卤素抽象的氢键供体催化剂。利用硫脲催化剂在几种催化转化（氮杂-Friedel-Crafts和Mannich反应）中的反应性，合成几种类型的非蛋白质α-氨基酯。
A general and efficient synthesis of alpha-haloglycine esters from commercially available feedstock chemicals, in a single step, is reported. The reactivity of these alpha-haloglycine esters with various nucleophiles was studied as surrogates of alpha-iminoesters upon activation with hydrogen-bond donor catalysts. DFT calculations on the alpha-haloglycine structures (X = F, Cl, Br) accompanied by an X-ray characterization of the alpha-bromoglycine ester support the existence of a "generalized" anomeric effect created by hyperconjugation. This peculiar hyperconjugative effect is proposed to be responsible for the enhanced halogen nucleofugality leading to a facile halogen abstraction by hydrogen-bond donor catalysts. This reactivity was exploited with thiourea catalysts on several catalytic transformations (aza-Friedel-Crafts and Mannich reactions) for the synthesis of several types of non-proteinogenic alpha-amino esters.