Hydroboration. 92. Investigation of Practical Methods for the Synthesis of Optically Pure Isopinocampheylchloroborane for the Asymmetric Hydroboration of Representative Prochiral Alkenes

Abstract

A quantitative study was made of the preparation of the optically pure borane reagent, isopinocampheylchloroborane (IpcBHCl), potentially valuable for asymmetric hydroboration. IpcBHCl (87−90%) in equilibrium with 5−6.5% of IpcBCl2 and IpcBH2, respectively, can be prepared conveniently by a number of relatively simple operations: (1) the reaction of isopinocampheylborane (IpcBH2) with anhydrous hydrochloric acid (HCl) in ethyl ether (EE); (2) the reaction of stoichiometric amounts of IpcBH2 with isopinocampheyldichloroborane (IpcBCl2) in EE; and (3) the reduction of IpcBCl2 with trimethylsilane (Me3SiH) or lithium aluminum hydride (LAH) in EE. The reduction of IpcBCl2 with Me3SiH in pentane proceeds extremely slowly to provide the desired reagent, IpcBHCl. However, in EE, the reduction proceeds much faster, providing an equilibrium mixture of 90% IpcBHCl, 5% IpcBH2, and 5% IpcBCl2. We also investigated the reduction of IpcBCl2 with Me3SiH in pentane and dichloromethane (CH2Cl2) in the presence of known amounts of EE, tetrahydrofuran (THF), and dimethyl sulfide (SMe2), solvents which coordinate with the dichloroboranes. A comparative study of the rate of hydroboration of the alkene, 2-methyl-2-butene, with IpcBH2 and IpcBHCl, obtained as described above, was made in representative solvents, such as pentane, CH2Cl2, EE, and THF, at 0 °C and, in many cases, also at 25 °C. This study revealed that the rate of hydroboration is faster in THF for IpcBH2, while for IpcBHCl, the rate is faster in EE. Asymmetric hydroboration of prochiral alkenes was achieved by two methods, viz., IpcBHCl, produced by the reaction of IpcBH2 with HCl in EE (method A), and the reduction−hydroboration reaction of IpcBCl2 with LAH (0.25 equiv) in the presence of the prochiral alkene (method B) in EE. In both methods, the temperature of the reaction mixture was maintained at −25 °C. Almost identical results were realized in these two procedures, with the enantiomeric excess (ee) realized with IpcBHCl, in some cases, considerably better than that achieved with IpcBH2. Although, IpcBHCl was obtained in only 87−90% purity along with IpcBH2 and IpcBCl2 as side products, the presence of the latter compound had no observable effect on the chiral outcome of the asymmetric hydroboration.