Stereoselective Cascade Formal Nucleophilic Substitution and Mannich Reaction of Ethyl 2‑Aroyl-1-chlorocyclopropanecarboxylates

A highly
regio- and diastereoselective cascade formal nucleophilic substitution
and Mannich reaction of ethyl 2-aroyl-1-chlorocyclopropanecarboxylates
with salicylaldimines is described. Under basic conditions, ethyl
2-aroyl-1-chlorocyclopropanecarboxylate is easily converted into a
cyclopropene intermediate via simple 1,2-elimination of hydrogen chloride.
The highly reactive cyclopropene quickly combines with salicylaldimine
through regioselective oxa-addition to the strained CC bond
and subsequent diastereoselective addition to CN bond, constructing
C–O and C–C bonds at one time. This provides a highly
stereoselective novel methodology for synthesis of conformationally
constrained cis-tetrahydrocyclopropa­[b]­chromene derivatives.