Cu(I)-Catalyzed Intramolecular Tandem Cyclization of N-Indole-Tethered Cyclopropenes: Synthesis of Functionalized Hydrogenated Diazabenzo[a]cyclopenta[cd]azulene Derivatives

Abstract

A Cu(I)-catalyzed [3 + 2] intramolecular cycloaddition reaction of N-indole-tethered cyclopropenes is presented in this paper. This reaction starts from the formation of π-allyl cationic intermediate or its resonance-stabilized metal carbenoid intermediate upon activation of cyclopropene with Cu(I) catalyst and a Friedel−Crafts-type cyclization to give functionalized hydrogenated diazabenzo[a]cyclopenta[cd]azulenes in good to excellent yields along with moderate to good dr values. The asymmetric variant of this cycloaddition reaction can be realized, giving the desired products with moderate ee values.

Copper-catalyzed [3 + 1] cyclization of cyclopropenes/diazo compounds and bromodifluoroacetamides: facile synthesis of α,α-difluoro-β-lactam derivatives

“…The Cu( i )-complex reacted with cyclopropene 2a to form a ring-opened vinyl copper carbene intermediate A . 20 Compared with normally accepted copper carbene inserting into the N–H bond of aniline derivatives, 21 α-bromo-α,α-difluoroacetamide 1 with a relatively high acidity and low nucleophilicty 22 might be favoured to undergo a deprotonation in the presence of K 2 CO 3 to form nitrogen anion species B . Subsequently, the nitrogen anion species B attacked the copper carbene A , generating Cu( i ) species C , followed by an intramolecular nucleophilic substitution reaction to yield the expected product 3 and release the Cu( i ) catalyst.…”

C–C Bond Cleavages of Cyclopropenes: Operating for Selective Ring-Opening Reactions

“…To continue with their studies, Shi and co-workers modified the connectivity of both reactive centers synthesizing cyclopropenes 213 in which the tethering occurred at the N-atom of the indole (Scheme 33B). 160 Here, copper catalysts among other transition metals showed better performance to convert 213 into tetracyclic compounds 214 via formal [3 + 2]cycloaddition with dearomatization of the indole ring. A reasonable number of examples along with normally good yields proved the utility of this reaction, which included the possibility to use symmetrically 3,3-disubstituted cyclopropenes.…”

“…To continue with their studies, Shi and co-workers modified the connectivity of both reactive centers synthesizing cyclopropenes 213 in which the tethering occurred at the N -atom of the indole (Scheme B) . Here, copper catalysts among other transition metals showed better performance to convert 213 into tetracyclic compounds 214 via formal [3 + 2]-cycloaddition with dearomatization of the indole ring.…”

Construction of heterocyclic rings from cyclopropenes

“…The aza-azulene or cyclopenta-azepine motifs, which have been used in traditional medicine to treat carbuncle abscess in folk medicine and others as an insecticide, have been constructed through the Cu( i )-catalyzed [3 + 2] intramolecular cycloaddition reaction of N -indole-tethered cyclopropenes 18 . 7 In the first stage, the combination of the copper complex with cyclopropene gave a cyclopropyl copper intermediate, and then ring-opening provided the vinyl Cu( i ) carbenoid or π-allyl cationic intermediate. Subsequent electrophilic attack on the indole ring and vinyl group gave a tetracyclic compound diazabenzo[ a ]cyclopenta[ cd ]-azulenes 19 in high yields with good diastereomeric ratios (Scheme 5).…”