Simple Thiazocine-2-acetic Acid Derivatives via Ring-Closing Metathesis

Abstract

A new protocol for synthesis of 2-heterocylylacetic acid derivatives involving conjugate addition of allyl mercaptan to an acrylate containing a tethered olefinic site followed by RCM (ring-closing metathesis) is described. In this series, sulfanyl derivatives were unreactive, while sulfoxide and sulfone analogues provided the corresponding thiazocines in fair to excellent yields. Use of the sulfoxide oxidation state as a protecting group for sulfides inert to RCM is demonstrated also. Thus, oxidation of sulfide 9 [N-allyl-N-[2-(allylthio)-4-(1H-indol-1-yl)-4-oxobutyl]-4-methylbenzenesulfonamide] followed by cyclization yielded the corresponding thiazocine sulfoxide 12. Deprotection (deoxygenation) of 12 was accomplished using Lawesson's reagent, producing 1-[[4-[4-(methylphenyl)sulfonyl]-3,4,5,8-tetrahydro-2H-1,4-thiazocin-2-yl]acetyl]-1H-indole (21) in 67% unoptimized yield.

C2‐Symmetric Chiral Disulfoxide Ligands in Rhodium‐Catalyzed 1,4‐Addition: From Ligand Synthesis to the Enantioselection Pathway

“…This path allows an indirect yet elegant determination of the purity of each homochiral diastereoisomers, as well as the (DNHS)-disulfoxides. By adapting literature procedures, [31] and by making sure that racemization of the atropisomeric backbone does not occur, [32] quantitative reduction of all disulfoxide ligand isomers gave their corresponding disulfides 24-31 (Scheme 7). Table 1 summarizes the HPLC results obtained for the respective disulfides and the isomeric purity of our disulfoxide ligands.…”

Stereoselective synthesis of new glycooxathiecinone using vic-cyclic thionocarbonate haloalkylation and ring closing metathesis as key steps

“…7 Such an effect has been described in the literature and attributed to catalyst inactivation of the metal by S-coordination. The second challenge would be to avoid possible ring-opening metathesis polymerisation due to the ring strain generated upon macrocyclisation.…”

Synthesis of Benzimidazole‐Fused Medium‐Sized N,S‐Heterocycles via Palladium‐Catalyzed Cyclizations

“…From an organic synthesis point of view, the access to medium‐sized rings is particularly difficult because of the high degree of transannular strain and unfavorable entropic factors involved . Several methods to access 8‐ and 9‐membered N,S ‐heterocycles have been published, including inter or intramolecular cyclizations of N/S‐nucleophiles, ring‐closing metathesis, intramolecular Friedel‐Crafts, and carbonylation reactions . However, compared to the numerous syntheses of 5 to 7‐membered N,S ‐heterocyclic counterparts, they remain rather limited.…”