Stereochemistry of the Triazollinedione-Alkene Ene Reaction: A Stereospecific Suprafacial Transformation Georgios Vassilikogiannakis, Yiannis Elemes, ² and Michael Orfanopoulos* Department of Chemistry, UniVersity of Crete 71409 Iraklion, Crete, Greece ReceiVed April 5, 2000 ReVised Manuscript ReceiVed June 29, 2000 Triazolinedione (RTAD, R ) methyl or phenyl), one of the most reactive electrophiles, 1 reacts with conjugated dienes to give Diels-Alder products 2-4 and with olefins to produce ene or [2+2] adducts. 4-6 The ene reaction has attracted considerable mechanis- tic 5-12 and theoretical attention. 13,14 Most of the experimental studies 5-12 and to a lesser extent computational work 13 support a stepwise mechanism with formation of an aziridinium imide, AI, intermediate in the rate determinig step. AI intermediates also have been observed spectroscopically and reported independently by a number of investigators. 15-17 The stereoselectivity of this synthetically useful transforma- tion 18-21 has received conciderable attention. For example, RTAD adds to various alkenes and shows a number of regioselectivi- ties 5,7,22,23 depending on the double bond substitution. It also adds to allylic alcohols showing a remarkable diastereoselectivity, 12,24,25 and to allyl silanes affording cis ene products. 26 In this paper we report the stereochemistry of this reaction with simple alkenes and discuss mechanistic possibilities in the light of the present results. This stereochemistry has not been previously recognized and may hold important implications for the mech- anism of this reaction. The optically active, by virtue of deuterium substitution, and isomerically pure olefin, (R,R)-cis-3-hexene-2,5-d 2 (1), is well suited to test the stereochemical requirements of this classical ene reaction. This olefin has three distinctive characteristics: (a) asymmetry at the two reactive allylic carbons C 2 and C 2′ , by virtue of stereospecific deuteration, (b) distinguishable groups at both ends of the double bond such that the ene adducts will contain a new stereogenic center, and (c) a C 2 symmetry axis such that the two faces of the double bond are equally accessible. The preparation 27 of (R,R)-cis-3-hexene-2,5-d 2 (1) from (S)- (-)-ethyl lactate is shown in Scheme 1. The reaction of this olefin with PTAD at -40 °C in dicloromethane quantitatively gave product 2 with only the trans stereochemistry. For convenience, we present here mechanistic possibilities considering only one of the two equivalent faces of the double bond. Approach of PTAD from the top face would abstract H and form an S stereogenic center, whereas abstraction of D would form the R stereogenic center (Scheme 2). We define the new stereogenic ² Permanent address: Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece. (1) Moody, C. J. AdV. Heterocycl. Chem. 1982, 30, 1 and references therein. (2) Jensen, F.; Foote, C. S. J. Am. Chem. Soc. 1987, 109, 6376-6385. (3) Chen, S. C.; Houk, K. N.; Foote, C. S. J. Am. Chem. Soc. 1998, 120, 12303-12309. (4) Clennan, E. L.; Earlywine, A. D. J. Am. Chem. Soc. 1987, 109, 7104- 7110. (5) Cheng, C. C.; Seymour, C. A.; Petti, M. A.; Greene, F. D.; Blount, J. F. J. J. Org. Chem. 1984, 49, 2910-2916. (6) Orfanopoulos, M.; Smonou, I.; Foote, C. S. J. Am. Chem. Soc. 1990, 112, 3607-3614. (7) Orfanopoulos, M.; Stratakis, M.; Elemes, Y.; Jensen, F. J. Am. Chem. Soc. 1991, 113, 3180-3181 (8) Elemes, Y.; Foote, C. S. J. Am. Chem. Soc. 1992, 114, 6044-6050. (9) Clennan, E. L.; Koola, J. J. J. Am. Chem. Soc. 1993, 115, 3802-3803. (10) Smonou, I.; Khan, S.; Foote, C. S.; Elemes, Y.; Mavridis, I. M.; Pantidou, A.; Orfanopoulos, M. J. Am. Chem. Soc. 1995, 117, 7081-7087. (11) Stratakis, M.; Orfanopoulos, M.; Foote, C. S. J. Org. Chem. 1998, 63, 1315-1318. (12) Vassilikogiannakis, G.; Stratakis, M.; Orfanopoulos, M.; Foote C. S. J. Org. Chem. 1999, 64, 4130-4139. (13) Chen, J. S.; Houk, K. N.; Foote, C. S. J. Am. Chem. Soc. 1997, 119, 9852-9855. (14) Singleton, D. A.; Hang, C. J. Am. Chem. Soc. 1999, 121, 11885- 11893. (15) . Poon, T. H. W.; Park, S.; Elemes, Y.; Foote, C. S. J. Am. Chem. Soc. 1995, 117, 10468-10473. (16) Squillacote, M.; Mooney, M.; De Felipis, J. J. Am. Chem. Soc. 1990, 112, 5364-5365. (17) Nelsen, S. F.; Kapp, D. L. J. Am. Chem. Soc. 1985, 107, 5548-5549. (18) Gau, A. H.; Lin, G. L.; Uang, B. J.; Liao, F. L.; Wang, S. L. J. Org. Chem. 1999, 64, 2194-2201 and references therein. (19) Corey, E. J.; Snider, B. B. Tetrahedron Lett. 1973, 3091-3094 (20) Breslow, R.; Corcoran, R. J.; Snider, B. B.; Doll, R. J.; Khanna, P. L.; Kaleya, R. J. Am. Chem. Soc. 1977, 99, 905-915. (21) Adam, W.; Pastor, A.; Wirth, T. Org. Lett. 2000, 2, 1295-1297. (22) Elemes, Y.; Stratakis, M.; Orfanopoulos, M. Tetrahedron Lett. 1997, 38, 6437-6440. (23) Orfanopoulos, M.; Elemes, Y.; Stratakis, M. Tetrahedron Lett. 1990, 31, 5775-5778. (24) Prein, M.; Adam, W. Angew. Chem., Int. Ed. Engl. 1996, 35, 477- 494 and references therein. (25) Stratakis. M.; Vassilikogiannakis, G.; Orfanopoulos. M. Tetrahedron Lett. 1998, 39, 2393-2396. (26) Adam, W.; Schwarm, M. J. Org. Chem. 1988, 53, 3129-3130. (27) The synthesis proceeds through the key intermediate 1-propanol-2- d 1 , a compound whose chirooptical properties have been well documented: Green, M. M.; Moldowan, J. M.; McGrew, J. G., II J. Org. Chem. 1974, 39, 2166-2171 Scheme 1. Preparation of (R,R)-cis-3-hexene-2,5-d 2 from (S)-(-)-Ethyl Lactate Scheme 2. PTAD Ene Addition to Olefin 1 9540 J. Am. Chem. Soc. 2000, 122, 9540-9541 10.1021/ja001190g CCC: $19.00 © 2000 American Chemical Society Published on Web 09/16/2000