Pyrrolo[2,1-b]thiazole Derivatives by Asymmetric 1,3-Dipolar Reactions of Thiazolium Azomethine Ylides to Activated Vinyl Sulfoxides

Abstract

1,3-Dipolar reactions of thiazolium azomethine ylides to enantiopure cyclic and acyclic vinyl sulfoxides provide an efficient access to polyfunctionalized pyrrolo[2,1-b][1,3]thiazoles in a highly regio- and stereoselective manner. Regioselectivity can be inverted by modifying the position of the sulfinyl group at the double bond of the sulfinylfuranones. The sulfoxide is the main controller of the endo selectivity of these processes as well as of the pi-facial selectivity in reactions of (Z)-3-p-tolylsulfinylacrylonitriles. In contrast, the pi-facial selectivity in reactions of 5-alkoxy-3-p-tolylsulfinyl furan-2(5H)-ones is mainly controlled by the configuration at C-5, affording the anti adducts with respect to the alkoxy group as the major or exclusive adducts.

2-Azaallyl Anions, 2-Azaallyl Cations, 2-Azaallyl Radicals, and Azomethine Ylides

“…As outlined in Scheme , there are several different synthetic strategies for the generation of N-protonated azomethine ylides ( 289 ) and their N-alkylated cousins ( 290 ) including (1) ring-opening reactions, (2) deprotonation, (3) 1,2-prototropic rearrangement, (4) decarboxylation, (5) disilylation/destannylation, and (6) via carbenes and carbenoids. The most classical method involves the thermal (or photochemical) retro -pericyclic ring opening of aziridines ( 291 ). − The mechanism of this ring-opening process and the ensuing 1,3-dipolar cycloaddtions have been investigated thoroughly. − More recent innovations include the use of Lewis acids to mediate the ring-opening of aziridines to azomethine ylides at lower temperatures. − Dihydrooxazoles ( 292 , X = O), ,− dihydrothiazoles ( 292 , X = S), and related heterocycles ,, also can produce N -alkyl azomethine ylide dipoles via ring-opening processes.…”

“…For example, She and co-workers described the rapid construction of the [6-6-6-5] tetracyclic skeleton of daphenylline (248) starting from the acyclic stannyl imine 245 (Scheme 78). 161 Treatment of stannyl imine 245 with n-BuLi generated the corresponding 2-azaallyl anion (246) which rapidly underwent intramolecular cycloaddition to form, after aqueous workup, the desired pyrrolidine 247 as a single diastereomer in 60% isolated yield. Hydrolysis of the silyl ether following intramolecular N-alkylation via the corresponding bromide generated the desired tetracyclic core 248.…”

Enantiopure sulfoxides: recent applications in asymmetric synthesis

“…Recently, enantiopure p-tolylsulfinylfuran-2(5H)-one 152 have been reported 82 to react with dipole 153, generated in situ from ethyl pent-2,3-dienoate (AE)-154 and PPh 3 (Lu reaction), furnishing 155 as the sole adduct, with a total control of the regio-and the stereochemistry (Scheme 30). Compound 155 could be transformed into the enantiopure tetrasubstituted cyclopentane derivative 156 after desulfinylation, hydrogenation, protection as dithiane and methyl ester formation.…”

The Crucial Role of S‐oxidation State on the Selectivity and Reaction Rate of the 1,3‐Dipolar Cycloaddition of Azomethine Ylides and Homochiral Thiazolines

“…[22] The reaction between azomethine ylides and sulfinyl or sulfonyl groups has been reported in the past, with diverse results. [23][24][25][26][27][28][29][30] Among those references, it is interesting to mention two publications in which different strategies were developed starting from 1,2 diactivated sulfonyl acrylates to obtain exo adducts with a regiochemistry controlled by the sulfonyl group [30] or endo adducts with the opposite regiochemistry, so controlled by the ester moiety. [26] The origin of these switch on diastereo-and regioselectivity relies on the use of a copper or silver catalyst, respectively, and different ligands.…”