A three-component, one-pot synthesis of indolizidines and related heterocycles via the [3+2] cycloaddition of nonstabilized azomethine ylides.
Nonstabilized azomethine ylides (i.e. those bearing only hydrogens or alkyl groups) can be generated from (2-azaallyl)stannanes and (2-azaallyl)silanes through an intramolecular N-alkylation/demetalation cascade. The resulting ylides undergo [3+2] cycloaddition with electron-poor or electron-rich dipolarophiles yielding indolizidines and related 1-aza[m.3.0]bicycloalkane systems in good yield. An in situ protocol allows for a one-pot, three-component synthesis of indolizidines. The (2-azaallyl)stannanes tolerate enolizable hydrogens in these cycloadditions, while (2-azaallyl)silanes do not. The mechanism of the cycloaddition cascade is clarified by a series of control experiments. The same (2-azaallyl)stannanes may be transmetalated by n-butyllithium to generate 2-azaallyllithiums, which also may undergo a [3+2] cycloaddition/N-alkylation cascade to form indolizidines.
Pearson
William H
WH
Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055, USA. wpearson@berryassoc.com
Stoy
Patrick
P
Mi
Yuan
Y
D000447:Aldehydes / Q000737:chemistry; D000475:Alkenes / Q000737:chemistry; D000478:Alkylation; D001391:Azo Compounds / Q000737:chemistry*; D003500:Cyclization; D006572:Heterocyclic Compounds, Bridged-Ring / Q000138:chemical synthesis*; D006859:Hydrogen / Q000737:chemistry; D007212:Indolizines / Q000138:chemical synthesis*; D009947:Organotin Compounds / Q000737:chemistry; D012821:Silanes / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013237:Stereoisomerism; D013696:Temperature
D000447:Aldehydes; D000475:Alkenes; D001391:Azo Compounds; D006572:Heterocyclic Compounds, Bridged-Ring; D007212:Indolizines; D009947:Organotin Compounds; D012821:Silanes; D012997:Solvents; D006859:Hydrogen