Synthesis of the 3-(3,4,5-Trimethoxyphenyl)- pyrrolidine: A New Conformationally Constrained Mescaline Analogue Ricardo de L. Barreto, Laura B. L. R. Nascimbem, and Carlos R. D. Correia Chemistry Institute, State University of Campinas (UNICAMP), Campinas, Sa ˜o Paulo, Brazil Abstract: The total synthesis of the 3-(3,4,5-trimethoxyphenyl)-pyrrolidine, a new and conformationally constrained mescaline analogue, was accomplished in a concise and efficient manner. The synthetic route encompassed only 4 steps from the starting N- Cbz-3-pyrrolidine, in 46% overall yield. The route features a highly effective Heck arylation of the non-activated olefin N-Cbz-3-pyrrolidine with the 3,4,5- trimethoxybenzene diazonium tetrafluoroborate. The hemiaminal (lactamol) Heck adduct was converted to the mescaline analogue in a sequence of reactions: (a) dehy- dration of the intermediate hemiaminal 3 with trifluoroacetic acid anhydride, (b) hydro- genation/hydrogenolysis of the endocyclic enecarbamate 6 with H2-Pd/C, and (c) formation of the rather stable mescaline analogue in the form of a hydrochloride salt. The target molecule constitutes a new mescaline analogue with potential activity towards 5-HT2 dopamine receptors. Keywords: arenediazonium tetrafluoroborates, 3-aryl pyrrolidines, heck arylation, mescaline analogues INTRODUCTION Mescaline, an important hallucinogenic alkaloid, was discovered in 1896 by Heffer. [1] Mescaline is found in the small cactus peyote Lophophora williamsii (Cactaceae), and its structure corresponds to the rather simple alkaloid Received in the USA November 7, 2006 Address correspondence to Carlos Roque Duarte Correia, Instituto de Quı ´mica, UNICAMP, P. O. Box 6154, Campinas, Sa ˜o Paulo, 13084-971 Brazil. E-mail: roque@ iqm.unicamp.br Synthetic Communications w , 37: 2011–2018, 2007 Copyright # Taylor & Francis Group, LLC ISSN 0039-7911 print/1532-2432 online DOI: 10.1080/00397910701356504 2011