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

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 IpcBCl 2 and IpcBH 2, respectively, can be prepared conveniently by a number of relatively simple operations: (1) the reaction of isopinocampheylborane (IpcBH 2 ) with anhydrous hydrochloric acid (HCl) in ethyl ether (EE); (2) the reaction of stoichiometric amounts of IpcBH 2 with isopinocampheyldichloroborane (IpcBCl 2 ) in EE; and (3) the reduction of IpcBCl 2 with trimethylsilane (Me 3 SiH) or lithium aluminum hydride (LAH) in EE. The reduction of IpcBCl 2 with Me 3 SiH 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% IpcBH 2, and 5% IpcBCl 2 . We also investigated the reduction of IpcBCl 2 with Me 3 SiH in pentane and dichloromethane (CH 2 Cl 2 ) in the presence of known amounts of EE, tetrahydrofuran (THF), and dimethyl sulfide (SMe 2 ), solvents which coordinate with the dichloroboranes. A comparative study of the rate of hydroboration of the alkene, 2-methyl-2-butene, with IpcBH 2 and IpcBHCl, obtained as described above, was made in representative solvents, such as pentane, CH 2 Cl 2, 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 IpcBH 2, 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 IpcBH 2 with HCl in EE (method A), and the reduction−hydroboration reaction of IpcBCl 2 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 IpcBH 2 . Although, IpcBHCl was obtained in only 87−90% purity along with IpcBH 2 and IpcBCl 2 as side products, the presence of the latter compound had no observable effect on the chiral outcome of the asymmetric hydroboration.