Diastereoselective Access to Polyoxygenated Polycyclic Spirolactones through a Rhodium‐Catalyzed [3+2] Cycloaddition Reaction: Experimental and Theoretical Studies

Abstract

The synthetic utility of γ-alkylidenebutenolides is demonstrated as highly competent dipolarophile partners in both intra- and intermolecular rhodium(II)-catalyzed 1,3-dipolar cycloaddition reactions. The strength of this approach lies in the formation of spiro[6,4]lactone moieties with the concomitant construction of quaternary spiro stereocenters. Typically, the construction of spirolactones involves an esterification step, which has often been reported as a "biosynthetic pathway", and often occurs either as or near to the final step of a total synthesis. Furthermore, a convergent and versatile route is reported for the formation of the (5,7) skeleton of molecules that were isolated from the Schisandra genus. Computational studies were performed to provide an overall picture of the mechanism of the intermolecular [3+2] cycloaddition between 2-diazo-1,3-ketoester and protoanemonin and to rationalize the empirical observations. In particular, we have demonstrated for the first time that the rhodium center plays an important role during the cyclization step itself and reacts with the dipolarophile as a complex with the ylide.

Transition-Metal-Catalyzed Synthesis of Spirolactones

“…This reaction proceeds through initial carbonyl-ylide formation 108, followed by a chemo-, regio-, and diastereoselective intramolecular cycloaddition reaction on the exocyclic double bond of the dipolarophile (Scheme 29). 56 The computational study, which incorporated the rhodium complex for the first time, served not only to corroborate the experimental results of this report, but also to elucidate the reaction mechanism.…”

Modern Organic Synthesis with α-Diazocarbonyl Compounds

“…656 Very recently, Chouraqui and Commeiras have demonstrated intermolecular cycloaddition reactions of alkylidene butenolides with carbonyl ylides, affording adducts with complete chemoand diastereoselectivity, in yields of 43−62% (Scheme 286). 657 Harwood and co-workers described the reactions of chiral mesoionic isomunchnone dipoles with dipolarophiles, using chiral auxiliaries derived from phenylgycinol (Scheme 287). Moderate diastereofacial selectivity and good endo selectivity were observed in reactions with maleimides or dimethyl acetylenedicarboxylate, while excellent diastereofacial and exo selectivity were obtained in reactions with aldehydes, but with slightly lower yields.…”

“…The diastereoselectivity was found to depend on the length of the tether, although extending the tether beyond four carbon atoms leads to formation of 4H-pyran products due to 1,4-shift (Scheme 297). 657 Extensive investigations by the Padwa group describe the intramolecular cyclizations of a variety of isomunchnones 704−707 and carbonyl ylides. 708−714 Some representative examples are illustrated in Scheme 298.…”

Control of Chemoselectivity by Coordinated Water and Relative Size of Ligands to Metal Cations of Lewis Acid Catalysts for Cycloaddition of an Oxirane Derivative to an Aldehyde: Theoretical and Experimental Study

“…For those complicated reactions beyond the control of a simple FMO picture, density functional theory (DFT) was widely used to gain a more quantitative picture of reaction paths and corresponding activation energy barriers . The catalytic effects of noble metals (for instance, the complexes of Rh, Pt, et al) and Lewis acids (such as the metallic salts and BF 3 ) have been addressed theoretically. Despite these advances in the rationalization of chemo- and stereoselectivities, there are still some open questions for understanding all of the experiments.…”