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With the adoption of a ring-strain-release strategy, iridium-catalyzed transannulations with norbornene derivatives are achieved in a diastereospecific and enantioselective manner. The first asymmetric transannulations of 1,2,3-thiadiazoles are reported.

A highly diastereoselective and chemoselective (3 + 2) transannulation of 1,2,3-thiadiazoles with cyanoepoxides has been discovered. The use of sterically larger DPEPhos allows the preparation of cis-epoxyl isothiazoles from cis-cyanoepoxides in up to 95% yields and 100 : 0 dr, while the use of sterically smaller DPPF allows the synthesis of trans-products from cis- or trans-cyanoepoxides in up to 95% yields and 100 : 0 dr. Bisphosphines and epoxides play dual roles. Bisphosphines serve not only as ligands, but also as catalysts to catalyze the isomerization of cis-epoxides to trans-isomers. The diastereoselectivity is controlled by the kinetic competition between the direct transannulation of cis-cyanoepoxides and the bisphosphine-catalyzed isomerization of cis-products. The epoxy group's large steric hindrance guarantees excellent chemoselectivity toward the (3 + 2) annulation, and its electron-withdrawing ability significantly improves the reactivity of the adjacent cyano group. To address the controversy over the organorhodium intermediates, we suggest the resonation between Lee's umpolung 1,3-dipoles, Bao's cyclometalated Rh(III) complexes, and our thioacyl-coordinated Rh(I) carbenes. Stereospecific access to isothiazole-fused γ-lactone is also developed.

Sulfocoumarins are key structural motifs in several bioactive molecules. Herein, we describe a simple, one-pot procedure for the synthesis of structurally diverse sulfonocoumarin-3-carboxylates by heating 2-hydroxyaryl aldehydes with an active sulfonyl chloride in the presence of pyridine. The process tolerates numerous functional groups including alkoxy, alkyl, halogen, nitro, and even nucleophilic phenolic hydroxy. Additionally, reactions of 2-hydroxyaryl ketones and 2-methylaminoaryl aldehydes give 4-substituted sulfocoumarins and 1-aza-2-sulfocoumarins, respectively. A gram-scale synthesis and further derivatizations are also reported. The ester group is easily removed via ­Happer’s decarboxylation.

A rhodium-catalyzed denitrogenative formal (3 + 3) transannulation of 1,2,3-thiadiazoles with alk-2-enals is achieved, producing 2,3-dihydrothiopyran-4-ones in moderate to excellent yields. An inverse KIE of 0.49 is obtained, suggesting the reversibility of the oxidative addition of thioacyl Rh(I) carbenes to alk-2-enals. The late-stage structural modifications of steroid compounds are realized. Moreover, our studies show that thioacyl carbenes have different reactivities to those of α-oxo and α-imino carbenes, and highlight the importance of heteroatoms in deciding the reactivities of heterovinyl carbenes.

A rhodium-catalyzed 1,1-hydroacylation of thioacyl carbenes with alkynyl and alkenyl aldehydes and subsequent 6- endo-trig/dig cyclization are realized, giving structurally diverse 4 H-thiopyran-4-ones and 2,3-dihydro-4 H-thiopyran-4-ones in moderate to good yields. The oxidative addition of Rh(I) to aldehydes is proposed to be the turnover-limiting step. Manipulations of estrones demonstrate the applications of our formal (3 + 3) transannulations in the structural modifications of natural products.