title: Synthesis of indolizidines and pyrrolizidines through the [2 + 2]cycloaddition of five-membered endocyclic enecarbamates to alkyl ketenes. Unusual regioselectivity of Baeyer-Villiger ring expansions of alkyl aza-bicyclic cyclobutanones.
abstract: The total syntheses of two indolizidine skeletons and of the necine base (+/-)-platynecine were accomplished in a concise manner with good overall yields starting from a common five-membered endocyclic enecarbamate. These syntheses feature a [2 + 2]cycloaddition of the five-membered endocyclic enecarbamate 5 to alkylketenes that proceeded in high yields and with high stereoselectivity to provide an endo alkyl cycloadduct as the major or only product. The minor exo alkyl cycloadducts, which can be observed in some [2 + 2]cycloadditions, seem to derive from the endo cycloadduct, the putative kinetic product, by epimerization. An unusual regioselectivity was observed for the Baeyer-Villiger oxidation of 7-alkyl-2-azabicyclic cyclobutanones. Endo-7-alkyl cycloadducts ring-expanded exclusively to a gamma-lactone in which oxygen is inserted into the C6-C7 bond in preference to the bridgehead C5-C6 bond. With the exo-7-alkyl cycloadduct the regioselectivity of the Baeyer-Villiger oxidation is drastically reduced, leading to mixtures of regioisomeric lactones in a ratio of approximately 1.5 to 1. It is hypothesized that the steric strain built into the Criegee cyclobutane intermediate is the regioselective controlling factor in these oxidations, overriding any stereoelectronic bias for ring expansion. A rationale for the mechanism of the [2 + 2]cycloaddition involving enecarbamates and ketenes is presented, which seems to involve the participation of an N-acyliminium-enolate intermediate.
authors.affiliation: Instituto de Química, Universidade Estadual de Campinas, P.O. Box 6154, Campinas, SP, 13083-970 São Paulo, Brazil.
authors.forename: Antonio R
authors.initials: AR
authors.lastname: de Faria
authors.forename: Elias L
authors.initials: EL
authors.lastname: Salvador
authors.forename: Carlos Roque D
authors.initials: CR
authors.lastname: Correia
mesh_terms: D002219:Carbamates / Q000737:chemistry*; D003503:Cyclobutanes / Q000737:chemistry*; D005030:Ethylenes / Q000737:chemistry; D026121:Indole Alkaloids / Q000138:chemical synthesis*; D007212:Indolizines / Q000138:chemical synthesis*; D007659:Ketones / Q000737:chemistry; D011763:Pyrrolizidine Alkaloids / Q000138:chemical synthesis*
chemical_list: D002219:Carbamates; D003503:Cyclobutanes; D005030:Ethylenes; D026121:Indole Alkaloids; D007212:Indolizines; D007659:Ketones; D011763:Pyrrolizidine Alkaloids; C008223:ketene