Carbonylation of Silylated Hydroxymethyl Aziridines to -Lactams Paolo Davoli, † Irene Moretti, ‡ Fabio Prati, ‡ and Howard Alper* ,† Department of Chemistry, University of Ottawa, 10 Marie Curie, Ottawa, Ontario K1N 6N5, Canada, and Dipartimento di Chimica, Universita ` di Modena, Via Campi 183, 41100 Modena, Italy Received August 4, 1998 Functionalized -lactams are synthesized by carbonylative ring expansion of silylated hydroxymethyl aziridines catalyzed by dicobalt octacarbonyl, a process that proceeds with inversion of configuration. Ring opening and elimination occurs on attempted carbonylation of aziridine carboxylates. Introduction Carbonylative ring expansion using carbon monoxide in the presence of a transition-metal catalyst is a useful reaction for the synthesis of a variety of heterocyclic compounds. 1 In this process, carbon monoxide is inserted into a ring carbon-heteroatom bond, thus affording a carbonyl-containing ring-expanded product. For instance, -lactams can be obtained by this methodology from aziridines. N-alkyl phenylaziridines give -lactams in quantitative yields using [Rh(CO) 2 Cl] 2 and CO pressure by regiospe- cific insertion into the most substituted ring carbon- nitrogen bond. 2 This reaction is limited to aziridines bearing an activating group at the 2-position, such as a phenyl or vinyl. Carbonylation of alkylaziridines has been also performed, in moderate yields, using excess quanti- ties of the highly toxic Ni(CO) 4 , with CO insertion occurring into the less substituted ring C-N bond with net retention of configuration. 3 A significant advance in the carbonylation of simple N-alkylaziridines resulted when catalytic amounts of Co 2 (CO) 8 were used: 4 the reaction proceeded in excellent yields and CO insertion occured into the less substituted carbon-nitrogen bond by a S N 2 like mechanism (inversion of configuration). The application of the Co 2 (CO) 8 -catalyzed reaction to the synthesis of more functionalized -lactams by the carbonylative ring expansion of aziridines was a desirable goal: our attention was focused on cis- and trans-2- alkoxycarbonyl- and silylated 2-hydroxymethyl-3-alky- laziridines as possible substrates for carbonylation. In fact, the presence of a carboxylic ester group may be of use in a subsequent step of an extended synthesis, since it can be easily transformed into different functionalities. An alternative ring substituent can be a hydroxymethyl group, acting as a “masked” ester function. Therefore, aziridinecarboxylates and hydroxy-methylated aziridines represent interesting substrates for carbonylation, taking into account the fact that they can be obtained in optically active form by several methods. 5 We now wish to report that the cobalt-catalyzed carbonylation is applicable to different carbon-ring func- tionalized aziridines. In particular, silylated hydroxym- ethyl aziridines can be successfully carbonylated to -lactams in excellent yields. Results and Discussion Synthesis and Attempted Carbonylation of Aziri- dinecarboxylates 3a,b. Addition of bromine to com- mercial ethyl crotonate (1) in carbon tetrachloride readily afforded ethyl 2,3-dibromobutanoate (2) (98% yield) (Scheme 1). Cyclization of 2 with benzylamine in absolute ethanol gave a mixture of cis- and trans-1-benzyl-2- ethoxycarbonyl-3-methylaziridines, 3a and 3b, respec- tively, in a 73:27 ratio and in 86% total yield. 6,7a On the basis of 1 H NMR spectral analysis ( 3 J H-Hcis > 3 J H-Htrans ), the cis stereochemistry was assigned to aziridine 3a ( 3 J 2,3 6.8 Hz) and trans stereochemistry to 3b ( 3 J 2,3 2.6-2.9 Hz). Treatment of 3a with carbon monoxide and Co 2 (CO) 8 in 1,2-dimethoxyethane (DME) for 18 h at 110 °C and 500 psi of CO gave only the elimination product, ethyl 3-benzylamino-2-butenoate (3e), in 73% yield (Scheme 2). The 1 H NMR spectrum shows two singlets, one for the methyl group and the other for the proton attached to the double bond, and 13 C NMR spectroscopy confirms the presence of two unsaturated carbons. This result indi- cates that the aziridine 3a undergoes nucleophilic ring opening by the in situ-generated tetracarbonylcobaltate anion [Co(CO) 4 ] - with attack at the C 2 ring carbon atom. Formation of the four-membered -lactam ring requires CO insertion into the C-Co bond and subsequent ring closure by nucleophilic attack on the new carbonyl by the † University of Ottawa. ‡ Universita ` di Modena. (1) Khumtaveeporn K.; Alper H. Acc. Chem. Res. 1995, 28, 414. (2) Calet S.; Urso F.; Alper H. J. Am. Chem. Soc. 1989, 111, 931. (3) Chamchaang W.; Pinhas A. R. J. Org. Chem. 1990, 55, 2943. (4) Piotti M. E.; Alper H. J. Am. Chem. Soc. 1996, 118, 111. (5) Tanner D. Angew. Chem., Int. Ed. Engl. 1994, 33, 599 and references therein. Bucciarelli M.; Forni A.; Moretti I.; Prati F.; Torre G. J. Chem Soc., Perkin Trans. 1 1993, 3041. (6) (a) Stolberg M. A.; O’Neill J. J.; Wagner-Jauregg T. J. Am. Chem. Soc. 1953, 75, 5045. (b) v. Capeller R.; Griot R.; Ha ¨ ring M.; Wagner- Jauregg T. Helv. Chim. Acta 1957, 40, 1652. (7) (a) Andersson P. H.; Guijarro D.; Tanner D. J. Org. Chem. 1997, 62, 7364. (b) Deyrup J. A.; Moyer C. L. J. Org. Chem. 1970, 35, 3424. A slightly modified procedure was adopted, using THF instead of ether as solvent. Scheme 1 518 J. Org. Chem. 1999, 64, 518-521 10.1021/jo981568h CCC: $18.00 © 1999 American Chemical Society Published on Web 01/05/1999