A one-pot stereoselective synthesis of trans-1-aryl- 2-aminotetralins from 2-arylethyl styrenes Saumen Hajra * , Biswajit Maji, Debarshi Sinha, Sukanta Bar Department of Chemistry, Indian Institute of Technology, Kharagpur 721 302, India Received 25 January 2008; revised 5 April 2008; accepted 10 April 2008 Available online 12 April 2008 Abstract An efficient stereoselective synthesis of trans-1-aryl-2-aminotetralins has been achieved via Cu(OTf) 2 catalyzed one-pot aziridination and regioselective intramolecular arylation of in situ generated aziridines from 2-arylethyl styrenes and PhINSO 2 (4-NO 2 C 6 H 4 ) [PhINNs]. Reaction of a mixture of E/Z-styrenes (685:15) provided trans-N-protected-1-aryl-2-aminotetralins with high diastereoselec- tivity (dr > 95:5), which are important synthons for many artificial pharmaceuticals. Ó 2008 Elsevier Ltd. All rights reserved. 1-Aryl-2-aminotetralin 1 is the key precursor to many biologically active compounds, in particular, artificial pharmaceuticals such as dihydrexidine, A-86929 and Sch39166. 1–3 Concise stereoselective synthesis of trans-tetr- alin 1 is, therefore, highly desirable in organic and medici- nal chemistry. A straightforward synthetic approach towards 1 is the stereoselective intramolecular arylation of tethered aziridines (Scheme 1). In contrast to the exten- sive study on aziridine ring opening with a number of nucleophiles, 4 intramolecular electrophilic arylation with tethered aziridines has not been explored. 5 Our efforts 6 towards electrophilic arylation with alkenes via reactive intermediates led us to investigate this chemistry. Herein, we report our preliminary results on the stereoselective one-pot synthesis of trans-1-aryl-2-aminotetralins via Cu(OTf) 2 catalyzed intramolecular arylation of in situ gen- erated aziridines. Cu(I) and Cu(II) are excellent catalysts for the aziridin- ation of alkenes with PhINSO 2 Ar. 4 Thus, we began our studies on the reactions of 2-phenylethyl styrene 3a with PhINSO 2 (4-MeC 6 H 4 ) [PhINTs] and PhINSO 2 (4- NO 2 C 6 H 4 ) [PhINNs] in the presence of commonly avail- able Cu-catalysts (Table 1). The CuCl, CuCl 2 and Cu(OAc) 2 catalyzed reactions with PhINTs as a nitrenoid source produced traces of products after 12 h (entries 2, 4 and 6). In the case of PhINNs, the CuCl catalyzed reac- tion afforded exclusively aziridine 2a, no cyclized product 1a was obtained even after a prolonged reaction time (entry 3). With CuCl 2 and Cu(OAc) 2 as catalysts, mixtures of 1a and 2a were obtained (entries 5 and 7). The Cu(OTf) 2 cata- lyzed reactions both with PhINTs and with PhINNs pro- vided directly 1a in 40% and 56% yields, respectively (entries 8 and 9). The catalytic reaction of 3a with PhINNs to produce 1a was found to be better in CH 2 Cl 2 (56%) com- pared to dichloroethane (51%), benzene (41%) and aceto- nitrile (45%), and there was no reaction in THF, DMF 0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2008.04.056 * Corresponding author. Tel.: +91 3222 283340; fax: +91 3222 255303. E-mail address: shajra@chem.iitkgp.ernet.in (S. Hajra). NH HO HO NH RO RO S NMe Dihydrexidine R = H: A-86929 R = Ac: ABT-431 Sch 39166 HO Cl Ar NHR Ar NR Ar Z Z Z 1 2 3 Scheme 1. Available online at www.sciencedirect.com Tetrahedron Letters 49 (2008) 4057–4059