One-Pot Synthesis of Unprotected 2-Acylpyrroles from 1,2,3-Triazoles and 2-Hydroxymethylallyl Carbonates

Abstract

An efficient, tandem one-pot approach to synthesize multisubstituted 2-acylpyrroles from readily prepared N-tosyl triazoles and 2-hydroxymethylallyl carbonates is reported. The reaction proceeds via Rh(II)-catalyzed O–H insertion, [3,3]-sigmatropic rearrangement, Pd(0)-catalyzed oxidative addition, intramolecular cyclization, DBU-promoted E1cB elimination, double bond isomerization, and aromatization, enabling the disconnection and formation of multiple bonds in one reactor. The approach represents a highly regioselective way to access di-, tri-, and tetra-substituted NH pyrroles with high efficiency.

Tandem One-Pot Synthesis of 2H- and 3H-Pyrroles Enabled by Dual Rh(II)/Pd(0) Catalysis

“…9 Considering that N-sulfonyl- Recently, we reported a tandem one-pot synthetic method for 2-acyl-substituted NH-pyrroles 4, involving tandem Rh(II)/Pd(0) catalysis using N-sulfonyl-1,2,3-triazoles 1 and hydroxymethylallyl carbonate 2 and a sequential DBU-promoted E1cB/aromatization (Scheme 1B). 10 In our continuing interest in dual Rh(II)/Pd(0)-catalyzed approaches toward valuable N-heterocycles, we wondered whether it would be possible to access 2H-pyrroles 5 and 3H-pyrroles 6 via a tandem one-pot operation starting from N-sulfonyl-1,2,3-triazoles 1 and R 2 -or R 3 -disubstituted hydroxymethylallyl carbonates 2a and 2b (Scheme 1C). Considering that 2H-and 3H-pyrroles undergo rapid isomerization into thermodynamically more stable 1H-pyrroles under acidic reaction conditions, 11 we anticipated that a dual catalytic approach involving the basic DBU-mediated process would be efficient for regioselective construction of 2H-and 3H-pyrroles.…”

“…Our previous studies have shown that the DBU-promoted E1cB elimination of prepared dimethyl-substituted N-tosylpyrrolidines and a double-bond isomerization cascade occur regioselectively, affording 2H-and 3H-pyrroles. 10 Based on previous work, tandem one-pot approaches involving dual Rh(II)/Pd(0) catalysis were attempted in this study using Rh 2 (OPiv) 4 , Pd(dba) 2 , bisphosphine ligand, and excess DBU in toluene, starting from N-tosyl-1,2,3-triazole 1a and dimethyl hydroxymethylallyl carbonate 2a or 2b. When using 2a with Rh 2 (OPiv) 4 , Pd(dba) 2 , and BINAP ligand L1, 2H-pyrrole 5a was isolated in 9% yield in a one-pot multistep operation (Table 1, entry 1).…”

“…Considering that N-sulfonyl triazoles 1 are reliable and easily accessible nitrogen-containing starting materials, developing a strategy to access valuable 2Hand 3H-pyrrole scaffolds via dual Rh(II)/Pd(0) catalysis from Nsulfonyl triazoles would be highly desirable. Recently, we reported a tandem one-pot synthetic method for 2-acyl-substituted NH-pyrroles 4, involving tandem Rh(II)/Pd(0) catalysis using N-sulfonyl-1,2,3-triazoles 1 and hydroxymethylallyl carbonates 2 and a sequential DBUpromoted E1cB/aromatization (Scheme 1B) [10] . In our continuing interest in dual Rh(II)/Pd(0)-catalyzed approaches toward valuable N-heterocycles, we wondered whether it would be possible to access 2H-pyrroles 5 and 3H-pyrroles 6 via a tandem one-pot operation starting from N-sulfonyl-1,2,3-triazoles 1 and R 2 -or R 3 -disubstituted hydroxymethylallyl carbonates 2a and 2b (Scheme 1C).…”

Recent Advances in Synthetic Methods for 2H‐Pyrroles

“…[30] Recently, the desulfonylative oxidations of N-tosyl pyrrolidine 36 utilizing DBU were accomplished by Kim group, affording the 2H-pyrrole, 37 (Scheme 10). [31] Initially, N-tosyl pyrrolidines 36 bearing an exo-cyclic double bond were synthesized over dual Rh(II)/Pd(0) catalysts. When dimethyl substituents were introduced to the C5-position of 36, the corresponding 2H-pyrrole product 37 was obtained in 83% yield.…”