Mechanistically Diverse Copper-, Silver-, and Gold-Catalyzed Acyloxy and Phosphatyloxy Migrations:  Efficient Synthesis of Heterocycles via Cascade Migration/Cycloisomerization Approach

Abstract

A set of cycloisomerizaton 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 17 O-labelled 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/S N 1' isomerization to the allene, followed by cycloisomerization to the furan, while 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.

Metal-catalyzed Furan Synthesis. A Review

“…71,72 The mechanism proceeds through a propargyl-allenyl isomerization followed by intramolecular conjugate addition of the acyl group to form a dioxolenylium intermediate. Cyclization to the furan re-generates the copper catalyst.…”

Transition Metal‐Catalyzed Synthesis of Monocyclic Five‐Membered Aromatic Heterocycles

“…In the case of conjugated acyloxy-substituted ketones, the prerequisite of base for the selective formation of the observed regioisomer 62 supported possible involvement of an allene intermediate 66 via a prototropic rearrangement (Scheme 8.27). According to the mechanism proposed by the authors, this mode of cycloisomerization most likely occurred with the involvement of a dioxolenylium intermediate 67 [140].…”

“…Thus, it was [3,3]-phosphatyloxy shift [140]. In the case of conjugated acyloxy-substituted ketones, the prerequisite of base for the selective formation of the observed regioisomer 62 supported possible involvement of an allene intermediate 66 via a prototropic rearrangement (Scheme 8.27).…”

“…Thus, syntheses of 3-acyloxyfurans 69 from alkynyl acetates 68 occurred with a formal 1,2-migration in the presence of 5 mol% of Ag-catalyst at room temperature (Scheme 8.28) [139,140]. Several other transition metals such as Cu(II), Pd(II), Pt(II), and Au(III) were also found to catalyze this transformation.…”

“…It is then followed by a subsequent 1,2-migration through competitive oxirenium and dioxolenylium pathways (Scheme 8.31). The mechanism for the cycloisomerization of skipped alkynyl ketones containing an acyloxy group (76, Y ¼ CR 4 ) was found to follow either a Rautenstrauch-type 1,2-migration of the acyloxy group followed by cycloisomerization to the furan 78 directly or, alternatively, two 1,2-migrations of the acyloxy group to form the postulated allenyl intermediate 77, which cycloisomerizes to the furan via another 1,2-acyloxy shift (Scheme 8.31) [140].…”