Substituted pyrrolyl-cyanopyridines on the platform of acylethynylpyrroles via their 1 : 2 annulation with acetonitrile under the action of lithium metal

Abstract

A facile one-pot synthesis of 2-(pyrrolyl)-4-aryl(hetaryl)-5-cyano-6-methylpyridines in 63–87% yield via the cyclization of available acylethynylpyrroles with two molecules of acetonitrile under the action of lithium metal at room temperature has been developed.

Unexpected Decarbonylation of Acylethynylpyrroles under the Action of Cyanomethyl Carbanion: A Robust Access to Ethynylpyrroles

“…Also, it was reported that CH 2 CN − anion was added to ketones to form tertiary cyanomethyl alcohols [ 46 , 47 , 48 , 49 ]. Correspondingly, in the previous communication, we have shown that the intermediate propargyl alcohol 3 are actually adducts of acylethynylpyrroles and CH 2 CN − anion [ 36 ].…”

“…The major product, in this case, became tertiary propargylic alcohol 3a (content in the reaction mixture was 78%). Pyrrolylpyridine 2a , previously a major product [ 36 ], was also present in the reaction mixture but in a much smaller amount (10%). Almost the same results were obtained in the presence of 2 eq.…”

“…To verify this assumption, propargyl alcohols 3a , c , d , f , prepared from acylethynylpyrroles 1a , c , d , f and acetonitrile in the presence of t -BuONa according to the modified protocol ( Scheme 5 ) [ 36 ], were rapidly and quantitatively converted in the presence of t -BuOK into the corresponding ethynylpyrroles 4a , c , d , f ( Scheme 5 ).…”

“…Recently [ 36 ], we have disclosed the reaction of acylethynylpyrroles 1 with MeCN and metal lithium affording pyrrolyl-cyanopyridines 2 in up 87% yield ( Scheme 1 ).…”

Substituent-Dependent Divergent Synthesis of 2-(3-Amino-2,4-dicyanophenyl)pyrroles, Pyrrolyldienols and 3-Amino-1-acylethylidene-2-cyanopyrrolizines via Reaction of Acylethynylpyrroles with Malononitrile

“…Our assumption that one of the stages in the assembly of the aniline ring is the addition of acetonitrile to the carbonyl group, as we recently showed on the example of the formation of pyridines from acylethynylpyrroles [ 73 ], was not confirmed: when the reaction of acylethynylpyrrole 1d with malononitrile was carried out without acetonitrile in THF, the yield of pyrrole 3d was 38%.…”