Reações de Heck da N-Boc-3-pirrolina com sais de diazonio. Aplicações na sintese de arilcainatos, arilaspartatos, lactamas ariladas e do baclofeno e analogos

AUTOR(ES)
DATA DE PUBLICAÇÃO

2001

RESUMO

Heck Reaction of N-Boc-3-pyrroline with aryldiazonium salts reemerged as a very practical alternative to the "traditional" Heck protocols, which use mostly aryl triflates or aryl halides. The lactamols obtained in the Heck reaction were employed with success at the synthesis of important pharmacologically active compounds. The dehydration of the lactamols produced the 4-aryl enecarbamates in good overall yields (68-83%). A second Heck arylation of the endocyclic enecarbamates with aryldiazonium salts provided the 2,4-diaryl 3-pyrrolines in reasonable yields (20-60%). The 4-aryl enecarbamates were also applied in the synthesis of aminoacids acting as neurotransmitters analogues of the arylkainoids, as well as in the synthesis of conformationally constrained arylaspartates. The arylaspartates were synthesized through a reaction sequence that involved a [2+2] cycloaddition with dichloroketene as the key step. This reaction led to dichlorocyclobutanones in a stereocontrolled manner, and in excellent yields (85-95%). The diesters arylaspartates were obtained through of an oxidative cleavage of the dichlorocyclobutanones in good overall yields (40-60%). The arylkainoids were obtained through a regioselective cycloexpansion of the cyclobutanones, producing the desired dichlorocyclopentanones. The cyclopentanones underwent oxidative cleavage providing the corresponding diesters in yields of 40-48% from the diclorocyclobutanone. The lactamols in the presence of oxidizers such as PCC and RuCl3, gave the arylated lactams in good overall yields (70-90% ). The acidic hydrolysis of the lactams led to GABA neurotransmitters analogues baclofen and homobaclofen as well as to other new analogues.

ASSUNTO(S)

pirrolizidinas lactonas quimica organica oxidação aminoacidos

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