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Download fileMechanistically Diverse Copper-, Silver-, and Gold-Catalyzed Acyloxy and Phosphatyloxy Migrations: Efficient Synthesis of Heterocycles via Cascade Migration/Cycloisomerization Approach
journal contribution
posted on 15.08.2007, 00:00 authored by Todd Schwier, Anna W. Sromek, Dahrika M. L. Yap, Dmitri Chernyak, Vladimir GevorgyanA set of cycloisomerization methodologies of alkynyl ketones and imines with concurrent acyloxy,
phosphatyloxy, or sulfonyloxy group migration, which allow for the efficient synthesis of multisubstituted
furans and N-fused heterocycles, has been developed. Investigation of the reaction course by way of
employing 17O-labeled substrates allowed for elucidation of the mechanisms behind these diverse
transformations. It was found that, while the phosphatyloxy migration in conjugated alkynyl imines in their
cycloisomerization to N-fused pyrroles proceeded via a [3,3]-sigmatropic rearrangement, the analogous
cycloisomerization of skipped alkynyl ketones proceeds through two consecutive 1,2-migrations, resulting
in an apparent 1,3-shift, followed by a subsequent 1,2-migration through competitive oxirenium and
dioxolenylium pathways. Investigations of the 1,2-acyloxy migration of conjugated alkynyl ketones en route
to furans demonstrated the involvement of a dioxolenylium intermediate. The mechanism of cycloisomerization of skipped alkynyl ketones containing an acyloxy group was found to be catalyst dependent; Lewis
and Brønsted acid catalysts caused an ionization/SN1‘ isomerization to the allene, followed by cycloisomerization to the furan, whereas transition metal catalysts evoked a Rautenstrauch-type mechanistic pathway.
Furthermore, control experiments in the cycloisomerization of skipped alkynyl ketones under transition metal
catalysis revealed that, indeed, these reactions were catalyzed by transition metal complexes as opposed
to Brønsted acids resulting from hydrolysis of these catalysts with eventual water. Further synthetic utility
of the obtained phosphatyloxy-substituted heterocycles was demonstrated through their efficient employment
in the Kumada cross-coupling reaction with various Grignard reagents.