title: New Regio- and Stereoselective Cascades via Unstabilized Azomethine Ylide Cycloadditions for the Synthesis of Highly Substituted Tropane and Indolizidine Frameworks.
abstract: Multisubstituted tropanes and indolizidines have been prepared with high regio- and stereoselectivity by the [3+2] cycloaddition of unstabilized azomethine ylides generated from readily prepared trimethylsilyl-substituted 1,2-dihydropyridines via protonation or alkylation followed by desilylation. Starting from 1,2-dihydropyridines bearing a ring trimethylsilyl substituent at the 6-position, an intermolecular alkylation/desilylation provides endocyclic unstabilized ylides that successfully undergo cycloaddition with a range of symmetrical and unsymmetrical alkyne and alkene dipolarophiles to afford densely substituted tropanes incorporating quaternary carbons in good yields and with high regio- and stereoselectivity. Additionally, an intramolecular alkylation/desilylation/cycloaddition sequence provides convenient and rapid entry to bridged tricyclic tropane skeletons, allowing for five contiguous carbon stereocenters to be set in a single experimental operation and under mild conditions. Starting from 1,2-dihydropyridines with trimethylsilylmethyl groups on nitrogen, protonation followed by desilylation generates exocyclic unstabilized ylides that undergo cycloaddition with unsymmetrical alkynes to give indolizidines with good regio- and stereoselectivity. N-Trimethylsilylmethyl-1,2-dihydropyridines can also be alkylated and subsequently desilylated to give endocyclic unstabilized ylides that undergo intermolecular cycloadditions with carbonyl compounds to give bicyclic oxazolidine products in good overall yields. Moreover, an intramolecular alkylation/desilylation/cycloaddition sequence with the N-trimethylsilylmethyl-1,2-dihydropyridines affords tricyclic indolizidines that incorporate quaternary carbons and up to five stereocenters with good to excellent regio- and diastereoselectivity.
authors.affiliation: Department of Chemistry, Yale University , New Haven, Connecticut 06520, United States.
authors.forename: Shuming
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Chemistry, Yale University , New Haven, Connecticut 06520, United States.
authors.forename: Vlad
authors.initials: V
authors.lastname: Bacauanu
authors.affiliation: Department of Chemistry, Yale University , New Haven, Connecticut 06520, United States.
authors.forename: Tobias
authors.initials: T
authors.lastname: Knecht
authors.affiliation: Department of Chemistry, Yale University , New Haven, Connecticut 06520, United States.
authors.forename: Brandon Q
authors.initials: BQ
authors.lastname: Mercado
authors.affiliation: Division of Chemical Sciences, Lawrence Berkeley National Laboratory, and Department of Chemistry, University of California , Berkeley, California 94720, United States.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Bergman
authors.affiliation: Department of Chemistry, Yale University , New Haven, Connecticut 06520, United States.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Ellman