Chiral Bisphosphine-Catalyzed Asymmetric Staudinger/aza-Wittig Reaction: An Enantioselective Desymmetrizing Approach to Crinine-Type Amaryllidaceae Alkaloids.

An unprecedented chiral bisphosphine-catalyzed asymmetric Staudinger/aza-Wittig reaction of 2,2-disubstituted cyclohexane-1,3-diones is reported, enabling the facile access of a broad range of cis-3a-arylhydroindoles in high yields with excellent enantioselectivities. The key to the success of this work relies on the first application of chiral bisphosphine DuanPhos to the asymmetric Staudinger/aza-Wittig reaction. An effective reductive system has been established to address the challenging PV═O/PIII redox cycle associated with the chiral bisphosphine catalyst. In addition, comprehensive experimental and computational investigations were carried out to elucidate the mechanism of the asymmetric reaction. Leveraging the newly developed chemistry, the enantioselective total syntheses of several crinine-type Amaryllidaceae alkaloids, including (+)-powelline, (+)-buphanamine, (+)-vittatine, and (+)-crinane, have been accomplished with remarkable conciseness and efficiency.

Enantioselective Total Synthesis of Dysiherbols A, C, and D.

Herein, we report the enantioselective total synthesis of dysiherbols A, C, and D, a unique group of 6/6/5/6/6 pentacyclic quinone/hydroquinone sesquiterpenes, featuring a photo-induced quinone-alkene [2 + 2] cycloaddition and a tandem [1,2]-anionic rearrangement/cyclopropane fragmentation as key elements. Based on our total synthesis, the originally proposed structures of dysiherbols C and D have been revised. Detailed computational studies were carried out to gain deep insight into the unprecedented [1,2]-anionic rearrangement, which revealed that the transformation, albeit a symmetry-forbidden process, proceeded through a concerted manner owing to the release of high ring-strain energy and the evolution of local aromaticity in the transition state. Taking all, the present work offers a mechanistically interesting and synthetically useful approach to accessing dysiherbols and related congeners.

Strain-Driven Dyotropic Rearrangement: A Unified Ring-Expansion Approach to α-Methylene-γ-butyrolactones.

An unprecedented strain-driven dyotropic rearrangement of α-methylene-ß-lactones has been realized, which enables the efficient access of a wide range of α-methylene-γ-butyrolactones displaying remarkable structural diversity. Several appealing features of the reaction, including excellent efficiency, high stereospecificity, predictable chemoselectivity and broad substrate scope, render it a powerful tool for the synthesis of MBL-containing molecules of either natural or synthetic origin. Both experimental and computational evidences suggest that the new variant of dyotropic rearrangements proceed in a dualistic pattern: while an asynchronous concerted mechanism most likely accounts for the reactions featuring hydrogen migration, a stepwise process involving a phenonium ion intermediate is favored in the cases of aryl migration. The great synthetic potential of the title reaction is exemplified by its application to the efficient construction of several natural products and relevant scaffolds.