Synthesis of Masked Vicinal Amino Aldehydes of Pyrrolizine and Pyrrolo [1,2-c]thiazole Series

Acylation of (1,3-dihydro-1,3-dimethyl-2H-benzimidazol-2-ylidene)acetonitrile with mixed anhydrides of N-Boc proline and 4-thiazolidinecarboxylic acid was found to proceed at the exocyclic carbon atom yielding the corresponding C-acyl derivatives. Removal of the protecting group with equimolar amount of hydrochloric acid effected simultaneous cyclization affording 2-(3-amino-5,6,7,7a-tetrahydro-1-oxo-1H-pyrrolizin-2-yl)- and 2-(5-amino-7,7a-dihydro-7-oxo-1H,3H-pyrrolo[1,2-c]thiazol-6-yl)-1,3-dimethylbenzimidazolium chlorides. Reduction of the prepared salts with sodium borohydride resulted in 3-amino-2-(2,3-dihydro-1,3-dimethyl-1H-benzimidazol-2-yl)-5,6,7,7a-tetrahydro-1H-pyrrolizin-1-one and 5-amino-6-(2,3-dihydro-1,3-dimethyl-1H-benzimidazol-2-yl)-1,7a-dihydro-3H,7H-pyrrolo[1,2-c]thiazol-7-one, respectively. These compounds were shown to be masked aldehydes. Their reactions with phenylhydrazine and hydroxylamine yielded corresponding hydrazones and oximes, whereas condensation with malononitrile furnished 2-amino-5a,6,7,8-tetrahydro-5-oxo-5H-pyrido[3,2-b]pyrrolizine-3-carbonitrile and 2-amino-5a,6-dihydro-5H,8H-thiazolo[3′,4′:1,5]pyrrolo[2,3-b]pyridine-3-carbonitrile.

Tverdokhlebov A. V.; Denisenko A. V.; Tolmachev A. A.; Volovenko Y. M.; Shishkina S. V.; Shishkin O. V.
Synthesis 2009, 08, 1265-1270
DOI: 10.1055/s-0028-1088029