Asmic Isocyanide [3 + 2] Cascade to Dihydrooxazoles and Dihydroimidazoles

The
versatile isocyanide building block Asmic, anisyl­sulfanyl­methyl­iso­cyanide,
reacts with aldehydes and ketones in a BF3·OEt2-mediated condensation to afford thioimidoyl-substituted 2,5-dihydrooxazoles.
The condensation is distinguished from related base and transition-metal-catalyzed
[3 + 2] processes in proceeding via the condensation of aldehydes
and ketones with 2 equiv of an isocyanide followed by a molecular
rearrangement that installs four new bonds. BF3·OEt2 mediates an analogous condensation of Asmic with imines to
generate N-substituted dihydroimidazoles. Mechanistically,
BF3·OEt2 activates the isocyanide to facilitate
deprotonation evolving to a zwitterion that traps π-electrophiles
in a formal [3 + 2] process. A second deprotonation–condensation
with Asmic initiates a structural rearrangement involving a sulfanyl
elimination–addition transposition sequence. The resulting
dihydrooxazoles and dihydroimidazoles contain a thioimidate that serves
as a diversification point for further elaboration.