Benzosultam Synthesis by Gold(I)-Catalyzed Ammonium Formation/Nucleophilic Substitution

Abstract

The synthesis of benzosultams has been achieved through a gold(I)-catalyzed ammonium formation strategy. Starting from easily available N-(2-alkynyl)phenylsulfonyl azetidine derivatives, a cyclization reaction generated a spiroammonium gold intermediate which was ring-opened by nucleophilic alcohol or indole. This new methodology is compatible with large variation on the substrates and nucleophiles, and allowed to form benzosultams in high yield (18-98%, 20 examples). This strategy also allowed the preparation of benzosultam analogs via iododeauration and subsequent cross-coupling reactions.

Gold-Catalyzed Conversion of Highly Strained Compounds

“…159 More recently, Blanc and co-workers explored an alternative substrate (622) where the pendant alkyne was tethered through the Nsulfonyl protecting group (Scheme 100, eq 4). 160 In this case, spiroammonium intermediate 626 was formed via a goldcatalyzed 6-endo-dig cyclization. Subsequent nucleophilic ringopening of this intermediate gave a range of medicinally relevant benzosultams in generally high yield.…”

“…Blanc and co-workers have reported a series of gold-catalyzed reactions involving azetidines that proceed via formation of a key vinyl gold ammonium intermediates. − These reactive species were formed by intramolecular nucleophilic attack of an azetidine nitrogen onto a gold-activated pendant alkyne (Scheme ). The 1-( N -sulfonylazetidin-2-yl) ynones 615 could form vinyl gold ammonium intermediate 618 in the presence of a gold­(I) catalyst, which then underwent ring-opening by an external nucleophile to yield a range of multisubstituted pyrrolin-4-ones 617 (Scheme , eq 1) .…”

A Ag2CO3/TFA-catalyzed intramolecular annulation approach to imidazo[1,2-c][1,3]oxazin-5-one derivatives

“…In order to prepare a library of new imidazo[1,2- c ][1,3]oxazin-5-one heterocycles, N -Boc-4-bromo-5-methyl-2-phenylethynylimidazole 1a was studied as a model substrate and subjected to some annulation process conditions which have been already described in the literature. 25,37,46,49,50,57–64 Compound 1a , which is a suitable substrate for undergoing intramolecular annulation, was prepared following our recent procedure involving the regioselective Sonogashira cross coupling reaction of N -Boc-2,5-dibromo-4-methylimidazole. 48 Initially, the zinc catalyst (ZnCl 2 ) was used in dichloromethane at 40 °C but it was found to be totally inert since the starting material was completely recovered after 48 h (Table 1, entry 1).…”

Recent Advances in Catalytic Synthesis of Benzosultams

“…Very recently, Blanc and co-workers developed a convenient approach to benzosultams from N -(2-alkynyl)-phenylsulfonyl azetidines and nucleophilic alcohols through a gold(I)-mediated cyclization/nucleophilic substitution process ( Scheme 14 ) [ 91 ]. A variety of alkyl alcohols were compatible with this catalytic system.…”