Nucleophilic Metal Complexes as Acylation Catalysts: Solvent-Dependent “Switch” Mechanisms Leading to the First Catalyzed Staudinger Reaction Harald Wack, William J. Drury, III, Andrew E. Taggi, Dana Ferraris, and Thomas Lectka* Department of Chemistry, Johns Hopkins UniVersity, Baltimore, Maryland 21218 lectka@jhunix.hcf.jhu.edu Received October 14, 1999 ABSTRACT Catalytic acylation using complex transition metal salts MCo(CO) 4 is demonstrated. Surprisingly, a solvent-dependent mechanistic “switch” results in a Lewis acid-based acylation mechanism in nonpolar media and a nucleophilic mechanism in polar organic media. These observations lead to the first example of a catalyzed Staudinger reaction to form -lactams. The remarkable diversity and specificity of catalyzed reac- tions underpin much of modern organic chemistry. For example, many catalysts operate as Lewis acids, as Lewis bases, or less commonly as a combination of the two. 1 Almost unheard of is the scenario in which a change in solvent fundamentally transforms a catalyst from acting primarily as a Lewis acid to a Lewis base or vice versa. For example, complex transition metal salts X m Y n , in which both X and Y are metal-centered units, are potentially bifunctional species wherein X +n may act as a Lewis acid and counterion Y -m as a nucleophile or Lewis base. 2 In this report, we present catalyzed acylations in which the solVent determines whether a soluble transition metal salt functions mainly as a Lewis acid-based or, alternatively, as a nucleophile-based catalyst. We found that salts, such as NaCo(CO) 4 (1a), provide the first examples of metal complexes acting as nucleophiles to catalyze standard acylation reactions in polar aprotic solvents including CH 3 CN (path a, Scheme 1). 3 Most interestingly, in nonpolar solvents it is the Lewis acidic counterion that becomes primarily responsible for catalysis (path b, Scheme 1), resulting in an unusual mechanistic “switch”. We also demonstrate that the lessons learned from (1) Jencks, W. P. Catalysis in Chemistry and Enzymology; Dover: New York, 1987; Chapter 3. (2) We have previously reported a novel reaction pathway divergence in the Lewis acid-catalyzed reactions of acylaziridines, see: Ferraris, D.; Drury, III.; W. J.; Cox, C.; Lectka, T. J. Org. Chem. 1998, 63, 4568. (3) Complexes MCo(CO)4 (1) react with alkyl halides through nucleo- philic displacement followed by carbonyl insertion, see: Kerr, W. J. In Encyclopedia of Reagents for Organic Synthesis; Paquette, L. A., Ed.; John Wiley & Sons: New York, 1995; p 4633. Acylcobalt intermediates react with alcohols stoichiometrically to afford esters: Tkatchenko, I. In ComprehensiVe Organometallic Chemistry; Wilkinson, G., Stone, F. G. A., Abel, E. W., Eds.; Pergamon: Oxford, 1982; Vol. 8, p 101. Scheme 1 ORGANIC LETTERS 1999 Vol. 1, No. 12 1985-1988 10.1021/ol9903234 CCC: $18.00 © 1999 American Chemical Society Published on Web 11/12/1999