Organocatalytic Asymmetric Cyclization Reaction of 2‐Alkynyl‐3,3‐Difluoro‐3H‐Indoles and 2‐Mercaptoimidazoles: Access to gem‐Difluorinated C2‐Spiro Indolines

Abstract

We reported a cupreidine catalyzed enantioselective cascade cyclization reaction of 2alkynyl-3,3-difluoro-3H-indole and 2-mercaptoimidazole under simple and mild conditions. The corresponding chiral gem-difluorinated C2-spiro indolines were obtained in moderate to good yields and enantioselectivities, which could be interesting compounds from synthetic and medicinal chemistry points of view. This work represents the first catalytic enantioselective example of utilizing 2alkynyl-3,3-difluoro-3H-indoles as the bis-electrophiles in a cyclization reaction.

Enantioselective construction of chiral gem-difluorinated C2-quaternary indoline via dual MgSO4–CPA-catalyzed asymmetric Mannich reactions

“…3 In particular, the chiral derivatives bearing a quaternary stereocenter at the C2 position are valuable structural skeletons for numerous natural biologically active compounds. 4 Given the unique chemical properties of the gem -difluoromethylene (CF 2 ) unit, the incorporation of gem -difluoromethylene into chiral indole derivatives could significantly affect their solubility, lipophilicity, biological potency, and metabolic stability 5 (Scheme 1a).…”

Base-Controlled Divergent Synthesis of Fluorine-Containing Benzo[4,5]imidazo[2,1-b][1,3]thiazines from 2-Mercaptobenzimidazoles and β-CF3-1,3-Enynes

“…Annulation of 2-mercaptobenzoimidazoles and their derivatives is a straightforward approach to accessing benzo­[4,5]­imidazo­[2,1- b ]­[1,3]­thiazines . However, to the best of our knowledge, conventional methods allowing for the formation of fluorine-containing benzo­[4,5]­imidazo­[2,1- b ]­[1,3]­thiazines are rare . Accordingly, the development of new methods for the preparation of these fluorine-containing polyheterocyclic systems employing inexpensive and readily available fluorinated building blocks is still highly desirable.…”

Selective 5‐Exo‐Dig versus 6‐Endo‐Dig Cyclization of Benzoimidazole Thiols with Propargyl Alcohols

“…Benzothiazole derivatives show a large range of biological activities, such as antimicrobial, [28] antifungal, [29] antioxidant, [30] antiinflammatory [31] antidepressant, [32] anticonvulsant, [33] antitumor, [34] and anticancer [35] . To date, the most powerful and versatile processes for the synthesis of benzothiazolo imidazole are the cyclocondensation of N ‐(propynyl)‐o‐phenylenediamines with phenyl isothiocyanate, [36] NHC‐catalyzed [3+3] annulation of mercaptobenzimidazoles with alkynyl acylazoliums, [37] palladium‐catalyzed cyclocarbonylation of 2‐(propynylthio)‐1 H ‐benzo[ d ]imidazoles, [38,39] copper‐catalyzed cyclization of 2‐alkynyl‐3,3‐difluoro‐3 H ‐indole and mercaptoimidazole, [40] organocatalytic cyclizations of 2‐alkynyl‐3,3‐difluoro‐3 H ‐indoles with mercaptoimidazole, [41] palladium‐catalyzed multicomponent reactions of 2,4‐dichloroquinazoline, terminal alkynes, secondary amines, and mercaptoimidazole [42] . We can anticipate that the main features of our methodology are the high chemo‐ and regioselectivity, and the possibility of obtaining two important classes of heterocycles using the same substrates making a small change in the solvent.…”