Simple two-step synthesis of 2,4-disubstituted pyrroles and 3,5-disubstituted pyrrole-2-carbonitriles from enones

Abstract

SummaryThe cyclocondensation of enones with aminoacetonitrile furnishes 3,4-dihydro-2H-pyrrole-2-carbonitriles which can be readily converted to 2,4-disubstituted pyrroles by microwave-induced dehydrocyanation. Alternatively, oxidation of the intermediates produces 3,5-disubstituted pyrrole-2-carbonitriles.

Regioselective Synthesis of 2,4-Differentially Arylated Pyrroles and Its Application to The Synthesis of Lamellarins

“…The successful cyclization of the alcohol (19) to 13 in the presence of NaH supports this mechanism (Scheme 6). phenolic aldehyde (12) was converted to the lactone (22) by palladium-catalyzed Tamaru oxidation. 21,23 Bromination of 22 with NBS gave regioselectively brominated compound (11) in 93% yield.…”

“…4 In the last decade, several strategies for the synthesis of 2,4-differentially arylated pyrroles have been reported. They involve the interesting key reactions such as ring formation from 1,3-diaryl-4-nitrobutan-1-ones, 5 carbanion induced pyrrole synthesis from azirines and ketones, 6 ozonolysis of homoallylic ketones followed by Paal-Knorr condensation, 7 gold-catalyzed reaction with N-tosyl alkynyl aziridines, 8 rhodium-catalyzed transannulation of N-tosyl-1,2,3-triazoles with terminal alkynes 9 or alkenyl alkyl ethers, 10 copper-catalyzed denitrogenative annulation of vinyl azides with aryl acetaldehydes, 11 cyclocondensation of enones with aminoacetonitriles, 12 selenium-catalyzed reaction of γ-nitro substituted carbonyl compounds with carbon monoxide, 13 and gold-catalyzed reaction of N- (2,2-dimethoxyethyl)benzamide with terminal alkynes. 14 All of these approaches consist of de novo ring construction of the pyrrole core This paper is dedicated to Professor Dr. Lutz F. Tietze on the occasion of his 75 th birthday and some of them suffer from drawbacks such as hard accessibility of starting materials, multiple synthetic steps, and harsh reaction conditions.…”

2-Aminoacetonitrile

“…25, 27 In the presence of formic acid, the same reaction furnishes N-7H-imidazo [1,5-a]imidazol-2-ylmethanimidate (eq 11). 29 Furthermore, pyrrolizidines can be formed from 3,5-diphenyl-3,4-dihydro-2H-pyrrole-2-carbonitriles by reaction with enones under basic conditions and following reduction with sodium cyanoborohydride (eq 14). Aminoacetonitrile hydrochloride reacts with chalcones under basic conditions to 3,5-diphenyl-3,4-dihydro-2Hpyrrole-2-carbonitriles.…”

Heterocycles from α‐Aminonitriles

“…[61] However, heating to 250 8C under microwave irradiation transforms compounds 108 to 2,4-disubstituted pyrroles 109 in a thermal de-hydrocyanation. [62] This represents the hitherto most efficient entry to this compound class.…”