Alkaline Earth Catalysis of Alkynyl Alcohol Hydroalkoxylation/Cyclization

Abstract

Heavier alkaline earth bis(trimethylsilyl)amides [Ae{N(SiMe3)2}2]2 (Ae = Ca, Sr, Ba) are shown to act as effective precatalysts for the regioselective intramolecular hydroalkoxylation/cyclization of a wide range of alkynyl and allenyl alcohols. In the majority of cases, cyclization of alkynyl alcohols produces mixtures of the possible endo- and exocyclic enol ether products, rationalized as a consequence of alkynylalkoxide isomerization to the corresponding allene derivatives. Cyclization rates for terminal alkynyl alcohols were found to be significantly higher than for substrates bearing internal alkynyl substituents, while the efficacy of cyclization was in general found to be determined by a combination of stereoelectronic influences and the thermochemical viability of the specific alkaline earth metal catalysis, which we suggest is determined by the individual M–O bond strengths. Kinetic studies have provided a rate law pertaining to a pronounced catalyst inhibition with increasing [substrate], indicating that turnover-limiting insertion of C–C unsaturation into the M–O bond requires the dissociation of substrate molecules away from the Lewis acidic alkaline earth center.