cis-4-Alkoxydialkyl- and cis-4-Alkoxydiarylprolinol Organocatalysts: High Throughput Experimentation (HTE)-Based and Design of Experiments (DoE)-Guided Development of a Highly Enantioselective aza-Michael Addition of Cyclic Imides to α,β-Unsaturated Aldehydes
cis-4-Alkoxydialkyl- and cis-4-Alkoxydiarylprolinol Organocatalysts: High Throughput Experimentation (HTE)-Based and Design of Experiments (DoE)-Guided Development of a Highly Enantioselective aza-Michael Addition of Cyclic Imides to α,β-Unsaturated Aldehydes
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DOI：
10.1002/adsc.201700120
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发表时间：
2017-07-17
影响因子：
5.4
通讯作者：
Pericas, Miquel A.
中科院分区：
文献类型：
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作者：
Arenas, Ismael;Ferrali, Alessandro;Pericas, Miquel A.
首次制备了多种顺式-4-烷氧基二有机脯氨醇衍生物家族（37 种化合物）并在有机催化中进行了评估。高通量实验 (HTE) 技术与高效分析方法的结合使用，鉴定出两种用于琥珀酰亚胺对映选择性加成到 α,β-不饱和醛的优异催化剂。通过实验设计 (DoE) 技术进一步优化反应条件，确定了所考虑的氮杂迈克尔反应的催化剂选择，相应的加合物（12 个实例）以良好的产率和优异的对映选择性（琥珀酰亚胺和马来酰亚胺供体）获得。这些迈克尔加合物的合成多功能性通过产生对映体纯 1,3-氨基醇的两步序列来说明。
A diverse family (37 compounds) of cis-4-alkoxydiorganylprolinol derivatives has been prepared and evaluated in organocatalysis for the first time. The combined use of high throughput experimentation (HTE) techniques with efficient analytical methods has led to the identification of two superior catalysts for the enantioselective addition of succinimide to alpha,beta-unsaturated aldehydes. Further optimization of the reaction conditions with design of experiments (DoE) techniques established the catalyst of choice for the considered aza-Michael reaction, the corresponding adducts (12 examples) being obtained in good yields and excellent enantioselectivities (succinimide and maleimide donors). The synthetic versatility of these Michael adducts is illustrated by a two-step sequence leading to enantiopure 1,3-amino alcohols.