Organocatalytic Route to Dihydrocoumarins and Dihydroquinolinones in All Stereochemical Configurations

A straightforward
stereodivergent route to dihydrocoumarins and
dihydroquinolinones based on cinchona alkaloid catalyzed addition
reactions of monothiomalonates (MTMs) to functionalized nitroolefins
followed by deprotection and chemoselective cyclization has been developed.
The synthesis proceeds under mild conditions and yields heterocycles
with adjacent quaternary and tertiary stereogenic centers in very
high yields and stereoselectivities. Moreover, full control over the
relative and absolute configuration is achieved by the use of (pseudo)­enantiomeric
catalysts and the difference in reactivity of thioester versus oxoester
moieties.

本研究开发了一条简便的立体发散合成路径，可用于制备二氢香豆素（dihydrocoumarins）与二氢喹啉酮（dihydroquinolinones）类化合物：该路径以金鸡纳生物碱催化单硫代丙二酸单酯（monothiomalonates，MTMs）与功能化硝基烯烃的加成反应为基础，后续依次经过脱保护与化学选择性环化两步完成。合成反应在温和条件下即可进行，所得杂环化合物带有相邻的季碳与叔碳手性中心，且产物收率与立体选择性均极高。此外，通过采用（假）对映异构催化剂，并借助硫酯与氧酯基团间的反应活性差异，可实现对产物相对构型与绝对构型的完全调控。