Rapid assembly of complex cyclopentanes employing chiral, α,β-unsaturated acylammonium intermediates

Autor:	Morgan E. Shirley, Khoi N. Van, Rae Lynn McFarlin, Gang Liu, Daniel Romo
Rok vydání:	2013
Předmět:	Models Molecular Cyclopentanes Stereochemistry General Chemical Engineering Thiourea Stereoisomerism General Chemistry Combinatorial chemistry Article Catalysis Malonates Ammonium compounds chemistry.chemical_compound chemistry Ammonium Compounds
Zdroj:	Nature Chemistry. 5:1049-1057
ISSN:	1755-4349 1755-4330
DOI:	10.1038/nchem.1788
Popis:	With the intention of improving synthetic efficiency, organic chemists have turned to bioinspired organocascade or domino processes that generate multiple bonds and stereocentres in a single operation. However, despite the great importance of substituted cyclopentanes, given their prevalence in complex natural products and pharmaceutical agents, the rapid, enantioselective assembly of these carbocycles lags behind cyclohexanes. Here, we describe a Michael-aldol-β-lactonization organocascade process for the synthesis of complex cyclopentanes utilizing chiral α,β-unsaturated acylammonium intermediates, readily generated by activation of commodity unsaturated acid chlorides with chiral isothiourea catalysts. This efficient methodology enables the construction of two C-C bonds, one C-O bond, two rings and up to three contiguous stereogenic centres delivering complex cyclopentanes with high levels of relative and absolute stereocontrol. Our results suggest that α,β-unsaturated acylammonium intermediates have broad utility for the design of organocascade and multicomponent processes, with the latter demonstrated by a Michael-Michael-aldol-β-lactonization.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0b5a9155890eeb8d6887f7df68508091 https://doi.org/10.1038/nchem.1788 Zobrazit plný text záznamu Plný text ve formátu PDF