Solvation and Structure of LiAlH 4 in Ethereal Solvents Damia ´ n E. Bikiel, Florencia Di Salvo, Mariano C. Gonza ´ lez Lebrero, Fabio Doctorovich,* and Darı ´o A. Estrin* Departamento de Quı ´mica Inorga ´ nica, Analı ´tica y Quı ´mica Fı ´sica - INQUIMAE-CONICET, Facultad de Ciencias Exactas y Naturales, UniVersidad de Buenos Aires, Ciudad UniVersitaria, Pabello ´ n 2, C1428EHA, Buenos Aires, Argentina Received March 3, 2005 The nature of the solute species present in ethereal solutions of LiAlH 4 is of crucial importance for understanding the mechanisms for the reduction of ketones and other functional groups by LiAlH 4 . We have employed a combination of theoretical and experimental techniques to investigate the structure of LiAlH 4 in ethereal solutions. Using complexation agents, we measured the IR spectra of LiAlH 4 and AlH 4 - in tetrahydrofuran (THF). Hybrid quantum- classical (QM-MM) simulations have also been carried out to compute the IR spectra of associated and dissociated LiAlH 4 species and the free-energy profile for the dissociation process in solution. Our experimental estimate of the dissociation constant in THF is 0.021 ± 0.002, while the predicted computational value corresponding to a model dimethyl ether solvent is 0.001. The free-energy profile shows only one minimum corresponding to a contact ion pair at a Li-Al separation distance of 3.0 Å. These results are consistent with the fact that LiAlH 4 is essentially associated in ethereal solutions forming contact ion pairs. I. Introduction The discovery of aluminum hydrides by Schlesinger and co-workers 1 in 1947 revolutionized organic synthesis by allowing the organic chemist to perform selective reductions that were not feasible previously. Since the early mechanistic proposals of Trevoy, 2 there have been several postulated reduction mechanisms involving different species. In some proposals, LiAlH 4 is supposed to remain associated, and in others, the reducing agent has been proposed to be a dimer. 3 Initially, it was suggested that the hydride was transferred from the free anion, 4 but later studies proposed that AlH 4 - is not the reducing agent. 5 In this sense, there have been several investigations that indicated that the cation played a significant role in the reaction. Several studies have been performed by sequestration of the cation; these studies were performed by adding various amounts of cations to the reaction mixture, changing the type of cation in the reaction mixture, or both. 5 It is still not clear if the reduction occurs prior to or in concert with the cation attack, but it is established that some sort of complexation of the carbonyl oxygen by lithium is necessary for the reaction to proceed. 6 The proposed mechanisms can be classified in two categories. In the first one (depicted in Scheme 1), the carbonyl oxygen is activated by the free-solvated cation, and then aluminum hydride (AlH 4 - ) attacks the carbonyl carbon. 7 The second mechanism (depicted in Scheme 2) proposes a concerted attack of the whole LiAlH 4 molecule with no activation via dissociation of the cation. 8 The relevance of both mechanisms is related to the dissociation equilibria between the associated (LiAlH 4 ) and * To whom correspondence should be addressed. Phone: 54-11-4576- 3378. Fax: 54-11-4576-3341. E-mail: dario@qi.fcen.uba.ar (D.A.E.); doctorovich@qi.fcen.uba.ar (F.D.). (1) Finholt, A. E.; Bond, A. C.; Schlesinger, H. I. J. Am. Chem. Soc. 1947, 69, 1199. (2) Trevoy, L. W.; Brown, W. G. J. Am. Chem. Soc. 1949, 71, 1675. (3) Wiegers, K. E.; Smith, S. G. J. Am. Chem. Soc. 1977, 99, 1480. (4) Brown, H. C.; McFarlin, R. F. J. Am. Chem. Soc. 1958, 80, 5372. (5) Wiegers, K. E.; Smith, S. G. J. Org. Chem. 1978, 43, 1126. (6) Ashby, E. C.; Boone, J. R.; Oliver, J. P. J. Am. Chem. Soc. 1973, 95, 5427. (7) Ashby, E. C.; Boone, J. R. J. Am. Chem. Soc. 1976, 98, 5524. (8) Luibrand, R. T.; Taigounov, I. R.; Taigounov, A. A. J. Org. Chem. 2001, 66, 7254. Scheme 1. Dissociative Mechanistic Scheme Inorg. Chem. 2005, 44, 5286-5292 5286 Inorganic Chemistry, Vol. 44, No. 15, 2005 10.1021/ic050330q CCC: $30.25 © 2005 American Chemical Society Published on Web 06/21/2005