Diisopinocampheylborane is an organoborane that is useful for asymmetric synthesis. This colourless solid is the precursor to a range of related reagents. The compound was reported in 1961 by Zweifel and Brown in a pioneering demonstration of asymmetric synthesis using boranes. The reagent is mainly used for the synthesis of chiral secondary alcohols. The reagent is often depicted as a monomer but like most hydroboranes, it is dimeric with B-H-B bridges.
Diisopinocampheylborane was originally prepared by hydroboration of excess ñ-pinene with borane, but it is now more commonly generated from borane-methyl sulfide (BMS).
The compound can be isolated as a solid, but because it is quite sensitive to water and air, it is often generated in situ and used as a solution. The synthesis is complicated by a number of factors, including the tendency of the compound to eliminate pinene.
Diisopinocampheylborane is often represented as a monomer (including in this article), but X-ray crystallography establishes a dimeric structure.
Oxidation of diisopinocampheylborane with basic hydrogen peroxide gives isopincampheol. Methanolysis gives methoxydiisopinocampheylborane
Because of the large size of the ñ-pinenyl substituents, diisopinocampheylborane only hydroborates unhindered alkenes. These reactions proceed with high enantioselectivity. 2-Butene, 2-pentene, 3-hexene are converted to the respective chiral alcohols in high ee's. Norbornene under the same conditions gave an 83% ee. Heterocycles (dihydrofuran, dihydrothiophene, dihydropyrrole, tetrahydropyran) give the alcohols in âÂÂ¥99% ee; the high ee's reflect their constrained conformations.
It adds to alkynes to form the corresponding vinyldiisopinocampheylboranes
In a highly stereoselective reaction, allyldiisopinocampheylboranes converts aldehydes to the homologated alcohols, rapidly even at -100 ðC. The alkyldiisopinocampheylboranes, which result from the addition to alkenes, usefully react with a range of different reagents. Hydroxylamine-O-sulfonic acid provides 3-pinanamine.
Also useful is the reaction of diisopinocampheylborane with an aldehyde (RCHO) to give the chiral boronic ester, (isopinocampheyl)<sub>2</sub>BOCH<sub>2</sub>(R), which can be further used is a number of reactions e.g. Suzuki reaction.
Treatment of diisopinocampheylborane with TMEDA give the crystalline adduct of monoisopinocampheylborane. This adduct reacts with boron trifluoride to liberate the monoisopinocampheylborane (IpcBH<sub>2</sub>) in 100% ee. Monoisopinocampheylborane reacts with a variety of alkenes. Two other reagents have been developed for the hydroboration of ketones:
In the above mechanism where G=O and R is Ipc and Cl or 9-Borabicyclononane. Diisopinocampheylchloroborane (Ipc<sub>2</sub>BCl) is produced by treating diisopinocampheylborane with hydrogen chloride. The chloride is reported to be more stable that the trialkyl boranes, it works well with aryl alkyl ketones and tert-butyl alkyl ketones. Diisopinocampheylchloroborane is often complementary with diisopinocampheylborane, where one provides the R enantiomer and the other the S, the enantioselectivity is typically very high.
Alpine-borane is produced by hydroborating ñ-pinene with 9-borabicyclononane. Both of these reagents can be improved upon by using 2-ethylapopinene in place of ñ-pinene, 2-ethylapopinene has an ethyl group in place of the methyl in ñ-pinene. The additional steric bulk improves the stereoselectivity of the reduction.
Diisopinocampheylborane reacts with methanol to give diisopinocampheylmethoxyborane, which in turn reacts with an allyl or crotyl Grignard reagent to give B-allyldiisopinocampheylborane. This can then undergo an asymmetric allylboration to give a chiral homologated alcohol, which is a useful building block in a chiral synthesis.