Evidence for a Morin Type Intramolecular Cyclization of an Alkene with a Phenylsulfenic Acid Group in Neutral Aqueous Solution

Abstract

Sulfenic acids (RSOH) are among the most common sulfur-centered reactive intermediates generated in biological systems. Given the biological occurrence of sulfenic acids, it is important to explore the reactivity of these intermediates under physiological conditions. The Morin rearrangement is a synthetic process developed for the conversion of penicillin derivatives into cephalosporins that proceeds via nucleophilic attack of an alkene on a sulfenic acid intermediate. In its classic form, the Morin reaction involves initial elimination of a sulfenic acid from a cyclic sulfoxide, followed by intramolecular cyclization of the resulting alkene and sulfenic acid groups to generate an episulfonium ion intermediate that undergoes further reaction to yield ring-expanded products. On the basis of the existing literature, it is difficult to assess whether the reaction between an alkene and a sulfenic group can occur under mild conditions because the conditions required to generate the sulfenic acid from the sulfoxide precursor in the Morin reaction typically involve high temperatures and strong acid. In the work described here, beta-sulfinylketone precursors were used to generate a "Morin type" sulfenic acid intermediate under mild conditions. This approach made it possible to demonstrate that the intramolecular cyclization of an alkene with a phenylsulfenic acid to generate an episulfonium ion intermediate can occur in neutral aqueous solution at room temperature.

Redox Regulation of Protein Tyrosine Phosphatases: Structural and Chemical Aspects

“…Low-molecular-weight sulfenic acids are typically quite unstable because they can decompose by a variety of pathways (79). Sulfenic acids have the potential to act as nucleophiles (23,62,76) and electrophiles (54,77,79,110), or to undergo dimerization to the corresponding thiosulfinate (34,79). On the other hand, only a few reactions are commonly available to cysteine sulfenic acid residues sequestered within the active site of proteins.…”

Phenyliodine(III) Diacetate/I2‐Mediated Domino Approach for Pyrrolo[1,4]Thiazines and 1,4‐Thiazines by a One‐Pot Morin Rearrangement of N,S‐Acetals

“…Regarding the mechanism, it is assumed now that the Morin reactionn eeds an oxidizing agent for the sulfoxidation and a base for the proton abstraction. [16][17][18] Contrary to the above two examples which need two steps, only one example using benzothiazolylacetates 12 and mCPBA was reported. It gives substituted benzo [1,4]thiazinesi naone-step procedure by an oxidative ring expansion.…”

“…(1)]. [17] On the other hand, the first chemical examples leading to fused 1,4-thiazines 11 were reported by Hart's group in 2001 [Scheme 1, Eq. (2)].…”