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.

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Rearrangements O 0140Mechanistically Diverse Copper-, Silver-, and Gold-Catalyzed Acyloxy and Phosphatyloxy Migrations: Efficient Synthesis of Heterocycles via Cascade Migration/Cycloisomerization Approach. -The synthetic application of the phosphatyloxy-substituted heterocycles is demonstrated in the Kumada cross-coupling reaction with Grignard reagents. -(SCHWIER, T.; SROMEK, A. W.; YAP, D. M. L.; CHERNYAK, D.; GEVORGYAN*, V.; J. Am. Chem. Soc. 129 (2007) 32, p9868-p9878; Dep. Chem., Univ. Ill., Chicago, IL 60607, USA; Eng.) -Bartels 50-043

Cycloisomerization Approach. -The cycloisomerization of alkynyl ketones and cyclic imines proceeds with concurrent migration of acyloxy and phosphatyloxy groups, respectively, to produce multisubstituted furans and fused pyrroles (to be continued). -(SCHWIER, T.; SROMEK, A. W.; YAP, D. M. L.; CHERNYAK, D.; GEVORGYAN*, V.; J. Am. Chem. Soc. 129 (2007) 32, 9868-9878; Dep. Chem., Univ. Ill., Chicago, IL 60607, USA; Eng.) -Bartels 50-120

Significance: An efficient synthesis of tri-and tetrasubstituted furans and indolizines via cycloisomerization of alkynyl ketones and pyridines is reported. 17 O-labeling experiments (as shown) were employed to demonstrate plausible mechanisms, which indicate that, for the substrates of conjugated alkynyl ketones and alkynyl pyridines, the cycloisomerization proceeds via 1,3-phosphatyloxy migration to A or 1,2-acyloxy migration to B, respectively. For the skipped alkynyl ketone substrates C, other reaction routes were suggested.Comment: The present work represents an expansion of efforts from the Gevorgyan laboratories aimed to provide new synthetic routes to substituted furan and pyrrole derivatives. Previous cycloisomerization of conjugated alkynyl ketones and alkynyl imines to furans and pyrroles were reported, via double hydride migrations (V. J. Gevorgyan and co-workers J. P OEt OEt O X R 2 O R 1 P EtO EtO O 17 CuCl (5 mol%) DMA, 110-130 °C 67-75% 3 examples for furans 68-96% 5 examples for indolizines CuCl (5 mol%) Et 3 N (20 mol%) DMA, 130 °C 69-90% 8 examples cat. (5 mol%) CH 2 Cl 2 , r.t. 60% to >99% (10 of 11 examples) R 1 = Me, C 5 H 11 , n-Pr, t-Bu, s-Bu, Bn; R 2 = Me, Ph X = O, N R 3 = Me, C 5 H 11 , R 4 = Ph, t-Bu R 5 = Ph, Me, Et, i-Pr, t-Bu R 6 = t-Bu, TMS, Ph; R 7 = Ph, Me; R 8 = Ph, Me cat. = AgBF 4 , TMSOTf, Cu(OTf) 2 , AuCl 3