STEREOSELECTIVE CYCLOADDITIONS OF 8-AZAHEPTAFULVENES WITH SULFENES AND WITH KETENES; AND THE BASE INITIATED REARRANGEMENTS OF THE RESPECTIVE GAMMA-SULTAMS AND GAMMA-LACTAMS
Abstract
The dipolar cycloaddition reactions between 8-aryl-8-azaheptafulvenes and monosubstituted sulfenes results in the formation of substituted (gamma)-sultams. Both reacting species are generated in situ. The reaction proceeds in a stereoselective manner with only one isomer being isolated. The cycloaddition proceeds such that the cis (endo) isomer is initially formed and isolated, except when the sulfene substituent is capable of significant charge delocalization and post isomerization results in the isolation of the trans-(gamma)-sultam. The (gamma)-sultams derived from alkyl- or arylsulfenes undergo a base-induced rearrangement to only the Z-(alpha)-substituted styrenesulfonamides. The rearrangement proceeds through a norcaradiene intermediate and is influenced by both the anion stabilizing capacity of the sulfene substituent and the delocalization of the lone pair of electrons on nitrogen. The (gamma)-sultams also serve as excellent precursors to 1,2-disubstituted indoles. A one pot conversion of the (gamma)-sultam to the appropriately substituted indole can be achieved through the oxidation of the (gamma)-sultam anion followed by rearrangement through a norcaradiene intermediate. The oxidation is accomplished at low temperature with MoO(,5)(.)HMPA(.)(3 equivalents) LDA, while rearrangement of the (gamma)-sultam to the indole requires higher temperatures (45(DEGREES)C). The dipolar cycloaddition reactions of 8-azaheptafulvenes with monosubstituted ketenes as well as disubstituted ketenes (bearing a sulfone substituent) proceed stereoselectivity. The cycloaddition process involves the orthogonal approach of ketene to the azaheptafulvene with cyclization occurring in a concerted manner. Cycloaddition involving the monosubstituted ketenes results in exclusive formation of the trans-(gamma)-lactams, while the disubstituted ketenes give (gamma)-lactams with the sulfonyl unit exo. The trans-(gamma)-lactams and the disubstituted (gamma)-lactams undergo base-induced rearrangement through a norcaradiene intermediate to (Z)-(alpha)-substituted cinnamanilides (cinnamamides) and E vinylic sulfones, respectively.
Degree
Ph.D.
Subject Area
Organic chemistry
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