Protective Groups in Organic Chemistry

Abstract

Palladium and Raney nickel were found to catalyze the methanolysis of borane−amine adducts. Hence, strongly complexed amines can now be liberated by simple treatment with Pd/C or Raney Ni in methanol. The method is applicable to primary, secondary, tertiary, and aromatic amines, and the mildness of the reaction conditions allows preservation of otherwise labile functional groups. Borane-amine adducts are widely encountered in modern synthetic organic chemistry 1 and industrial processes. 2 Notable examples of their applications include aqueous reductions of aldehydes and ketones, 3 reductive aminations, 4 olefin hydroborations, 5 and amide reductions. 5b,c Recently, borane-amine adducts were employed in palladium-catalyzed systems such as epoxide openings, 6 aryl triflate reductions, 7 and N-alloc deprotections. 8 Complexes of amine-boranes have also been utilized as chiral transfer agents, 9 as activators for R-deprotonation of benzylamines, 10 and as a protective device against nitrogen lone pair oxidation. 11 Usually, borane-amine complexes are readily formed by reduction of amides, imides, and imines or by treatment of the corresponding amine with diborane or borane carriers such as THF, 12 DMS, 13 and amines. 5,14 Tertiary amine-boranes have also been prepared from benzyl halides and lithium aminoborane (LAB) reagents. 15 An attractive feature of these complexes is they are usually air-stable, crystalline compounds, and therefore are easily handled. 16 A limitation is they can be difficult to cleave (vide infra). In the course of developing a drug candidate, we required † Coop international trainee from Université de Sherbrooke (Canada). (1) For reviews, see: (a) Carboni, B.; Monnier, L. Tetrahedron 1999, 55, 1197. (b) Hutchins, R. O.; Learn, K.; Nazer, B.; Pytlewski, D.; Pelter, A.) (a) Bomann, M. D.; Guch, I. C.; DiMare, M. J. Org. Chem. 1995, 60, 5995. (b) Pelter, A.; Rosser, R. M. J. Chem. Soc., Perkin Trans. 1 1984, 718. (5) (a) Brown, H. C.; Kanth, J. V. B.; Dalvi, P. V.; Zaidlewicz, M. J. Org. Chem. 2000, 65, 4655. (b) Brown, H. C.; Kanth, J. V. B.; Dalvi, P. V.; Zaidlewicz, M. (9) (a) Ferey, V.; Veddrenne, P.; Toupet, L.; Le Gall, T.; Mioskowski, C.