Rh(iii)-catalyzed regioselective C–H activation/[3 + 2] cyclization of KHAs with iodonium ylides accessing pyrimido[1,2-a]indole derivatives

Abstract

Herein, we present a protocol for the regioselective construction of two kinds of functionalized pyrrole derivatives, i.e., pyrimido[1,2-a]indole derivatives (PIIDOs) 3–4 from HKAs with iodonium ylides promoted by AgSbF₆ (Lewis acid) vs. NaSbF₆ (Lewis base) additives in different solvents (acetone vs. DCE). This strategy incorporated the regioselective cascade reaction promoted by different additives in different solvents, entailing the simple heating of a mixture of substrates 1 with 2 and a solvent catalyzed by [Cp*RhCl₂]₂ (conducive to C–H bond activation) and HOAc (facilitating the elimination of the hydroxyl group as water), promoted by different anion exchange agents (AgSbF₆vs. NaSbF₆). The nitro-substituted HKA exhibited the highest nucleophilicity at the α-carbon as a result of the significant electron-withdrawing nature of the nitro group. Consequently, this substitution produced products analogous to those in the 3 series when reacted in both acetone and DCE. Moreover, the strong electron-withdrawing effect of the nitro group facilitated the dehydrogenation of the cyclohexenone backbone in the products, leading to the formation of the target compound 5 at the elevated boiling point of DCE. As a result, a series of PIIDOs 3–5 were produced via the formation of two bonds (C–C and C–N) in a single step. This protocol can be used to synthesize functionalized PIIDOs for the combinatorial and parallel syntheses of PIIDOs in a one-pot reaction.