Controlled Synthesis of Cis or Trans Isomers of 1,3-Disubstituted Tetrahydroisoquinolines and 2,5-Disubstituted Pyrrolidines

Abstract

[reactions: see text] The stereoselective outcome of Pd(II)- or Ag(I)-catalyzed intramolecular N-alkylation to afford 1,3-disubstituted 1,2,3,4-tetrahydroisoquinolines was examined. In the absence of additional substituents, Pd(II) allows a facile access to the cis isomers, while Ag(I) favors formation of the trans isomers. The same observation was made for the synthesis of 2,5-disubstituted pyrrolidines. Possible reasons for the observed stereoselectivities are discussed.

Diversity-oriented synthesis of medicinally important 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) derivatives and higher analogs

“…Eustache and co-workers 88 have reported a simple method for the synthesis of Tic derivatives 276 and 277 involving Ag(I)-catalyzed intramolecular N-alkylation (Scheme 48). The synthetic sequence began with the alkylation of the enolate derived from N-[bis(methylthio)methylene]glycine methyl ester 269 by 2-iodobenzyl bromide to give 2-iodophenylalanine derivative 270 which on treatment with hydrochloric acid gave 271 (71%) which upon N-protection using benzyl chloroformate provided 272 (71%).…”

Transition metals in organic synthesis: Highlights for the year 2005

“…A palladium-catalyzed decarboxylative amination of allyl carbamates was described [668]. (89) Palladium-catalyzed N-allylations were used to prepare novel carbocyclic nucleoside analogs [669], a polycyclic pyrazolo [3,4-d]pyrimidine [670], deoxymannojirimycin [671], (−)-norsecurine [672], gizzerosine [136] and tetrahydroisoquinolines [673].…”

Gold(I)-Catalyzed Intramolecular Amination of Allylic Alcohols With Alkylamines

“…8 Included in this family of transformations are a subset that employ simple alkylamines as nucleophiles. 2,4 The intramolecular amination of underivatized allylic alcohols has also attracted attention as a route to functionalized nitrogen heterocycles and methods employing Au(III), 9 Bi(III), 10 and Pd(II) 11,12,13 catalysts in combination with carbamate or sulfonamide nucleophiles have been documented. Of these, the Pd(II)-catalyzed methods are most highly developed and have been applied to the synthesis of a number of naturally-occurring nitrogen heterocycles.…”