Stereoselective isomerization of 10-arylsulfenate-11,12-dehydroretinoids to 9-cis-retinoids

Functions, Therapeutic Applications, and Synthesis of Retinoids and Carotenoids

“…A pericyclic cascade was proposed to explain the stereoselective formation to 9- cis -retinoids 475 from the reaction of alkenynol 471 with arylsulfenyl chloride (Scheme ) . The process comprises an ordered sequence of sigmatropic rearrangements: a reversible [2,3]-allyl sulfenate to allyl sulfoxide shift, which interconverts the isomers E - 472 and Z - 472 , followed by a [2,3]-rearrangement of the propargyl sulfenate with Z geometry to allenyl sulfoxide Z - 474 , and a final stereodifferentiating [1,5]-H sigmatropic migration leading to polyene 475 .…”

“…Two torquoselective electrocyclic ring closure reactions, first a 8πe − conrotatory cyclization from the s-cis conformer of 468 to give cyclooctatriene 469, and second a 6πe − disrotatory cyclization of the latter, could mechanisti- A pericyclic cascade was proposed to explain the stereoselective formation to 9-cis-retinoids 475 from the reaction of alkenynol 471 with arylsulfenyl chloride (Scheme 58). 443 The process comprises an ordered sequence of sigmatropic rearrangements: a reversible [2,3]-allyl sulfenate to allyl sulfoxide shift, which interconverts the isomers E-472 and Z-472, followed by a [2,3]-rearrangement of the propargyl sulfenate with Z geometry to allenyl sulfoxide Z-474, and a final stereodifferentiating [1,5]-H sigmatropic migration leading to polyene 475. 444 The migration of hydrogen from C7 to C11 was demonstrated by labeling experiments.…”

From Allylic Sulfoxides to Allylic Sulfenates: Fifty Years of a Never-Ending [2,3]-Sigmatropic Rearrangement

“…310 Another interesting application directed toward the synthesis of retinoids was developed by de Lera and co-workers. 311,312 This approach starts from racemic α-ionone and involves a reversible [2,3]-sigmatropic rearrangement of the E-allylic sulfenate derived from alcohol 512, which promotes E/Z double-bond isomerization at C-9, followed by [2,3]-sigmatropic rearrangement of the propargylic sulfenate to an allenyl sulfoxide 513, which undergoes an irreversible and diastereoselective [1,5]sigmatropic hydrogen shift to finally generate Z vinyl sulfoxide intermediate 514, which is transformed into (9Z)-4,6-retroretinoic acid 515 in a three-step sequence (Scheme 88). Finally, Okamura and co-workers have extensively studied the reactivity of allenyl sulfoxides, obtained through Mislow− Braverman−Evans rearrangement, in a search for approaches to the synthesis of drimanes, retinoids, and vitamin D derivatives.…”

A Pericyclic Cascade to the Stereocontrolled Synthesis of 9-cis-Retinoids

“…Within this context, we became interested in the study of the effect that heteroatoms attached to the internal position (C4 in 11 , vide infra) might have on the thermal behavior of divinylallenes. In a preliminary communication we described the unprecedented isomerization of alkenynol 10 to polyene 13a upon treatment with phenylsulfenyl chloride and Et 3 N (Scheme ), which was suspected to involve a divinylallene sulfoxide . We report here a detailed mechanistic study of this remarkable approach to 9- cis -retinoic acid, the native ligand of the RXR nuclear receptors, and its extension to the stereocontrolled synthesis of retinoids with 9 Z geometry.…”