Diastereoselective domino reactions of chiral 2-substituted 1-(2′,2′,3′,3′-tetramethylcyclopropyl)-alkan-1-ols under Friedel-crafts conditions

(Chemical Equation Presented) The 2-substituted 1-(2′,2′, 3′,3′-tetramethylcyclopropyl)-alkan-1-ols 3-7 were prepared by carbonyl addition of tetramethylcyclopropyl lithium to the respective aldehydes or by addition of the respective substituted carbanions to tetramethylcyclopropyl carbaldehyde 16. Under Brønsted acidic conditions (HBF₄·OEt₂), the alcohols served as substrates in Friedel-Crafts alkylation reactions with 2-methylthiophene (8) and N-tosylpyrrole (9). The alkanols 3-6 carrying the groups ^tBu, Ph, CN, PO(OEt)₂ in 2-position delivered the rearranged substitution products 17-20 in very good chemical yields (9 examples, 81-97%). The products were formed presumably via ring-opening of the tetramethylcyclopropyl- substituted cation, which rearrange by a Wagner-Meerwein shift to allylic cations I. The latter cations are eventually attacked by the arene nucleophile. The diastereoselectivity of this process is good (anti-preference for Ph, CN, PO(OEt)₂) to excellent (syn-preference for ^tBu). The esters 7, carrying a methoxycarbonyl group in 2-position, yielded under the same reaction conditions products 25 and 26, which are formed by an intermolecular Friedel-Crafts reaction followed by a subsequent intramolecular Friedel-Crafts alkylation (3 examples, 80-93%).