Monoisopinocampheylborane1

[64234-27-1]  · C10H19B  · Monoisopinocampheylborane  · (MW 150.10)

(asymmetric hydroboration of trans and trisubstituted alkenes;2 asymmetric reduction of ketones3)

Physical Data: a crystalline adduct with N,N,N,N-Tetramethylethylenediamine (2IpcBH2.TMEDA) has mp 140.5-141.5 °C; [a]23D +69.03° (c 9.33, THF).

Solubility: sol THF, Et2O.

Analysis of Reagent Purity: the optical purity of the reagent is assayed by oxidation (NaOH, H2O2) to give isopinocampheol, [a]27D -35.8° (c 0.9, benzene).

Handling, Storage, and Precautions: best used as prepared. Guidelines for the handling of air- and moisture-sensitive materials should be followed.1c

Preparation.

Hydroboration of alkenes with Borane-Tetrahydrofuran or Borane-Dimethyl Sulfide proceeds rapidly past the monoalkylborane stage with all but the most sterically demanding alkenes. Thus, attempts to prepare a solution of monoisopinocampheylborane (IpcBH2) by simple admixture of 1:1 (+)-a-pinene:borane result in an equilibrium mixture of IpcBH2, diisopinocampheylborane (Ipc2BH), and borane.4 Although several indirect methods for the preparation of IpcBH2 have been devised,5a-f the preparation of IpcBH2 by displacement of a-pinene from Ipc2BH with TMEDA is recommended (eq 1).5e,6 It is unique to this procedure that the crystalline adduct7 incorporates two IpcBH2 units which are of higher optical purity than the starting (+)-a-pinene used. Analysis of the mother liquor reveals that the minor enantiomer accumulates in the more soluble diastereomeric adduct.

IpcBH2 of essentially 100% ee is liberated from the TMEDA adduct by addition of Boron Trifluoride Etherate in THF. Filtration of the TMEDA.2BF3 adduct provides a solution of IpcBH2 in THF ready for subsequent hydroboration reactions (eq 2).

Asymmetric Hydroboration.

The steric requirements of IpcBH2 are such that hydroboration of trans and trisubstituted alkenes proceeds with little or no displacement of a-pinene from the reagent, a phenomenon which is observed with the more hindered Diisopinocampheylborane (Ipc2BH). Ipc2BH is most effective for the hydroboration of relatively unhindered cis alkenes, which are hydroborated with low asymmetric induction by IpcBH2 (eq 3). The two reagents are therefore complementary in this respect. (For a reagent which hydroborates cis, trans, and trisubstituted alkenes with excellent asymmetric induction, see also (R,R)-2,5-Dimethylborolane)

Representative trans alkenes are asymmetrically hydroborated by IpcBH2 derived from (+)-a-pinene to give (S)-alcohols in the range of 65-76% ee. With highly hindered trans alkenes, the enantioselectivity can be somewhat higher (eq 4).2

Aliphatic trisubstituted alkenes are likewise hydroborated to give (S)-alcohols in the range of 53-72% ee. When the trisubstituted alkene bears a phenyl substituent, a significant increase in enantioselectivity is observed (eq 5).2,8

In the asymmetric hydroboration of 1-heteroarylcycloalkenes,9 IpcBH2 exhibits enantioselectivities of 83-90% ee, comparable to the phenyl-substituted alkenes examined (eq 6).

Many intermediate dialkylboranes derived from hydroboration with IpcBH2 can be recrystallized to enantiomeric purities approaching 100%, thus giving alcohols of 98-99% ee upon oxidation.10 If, instead of being oxidized in situ, the dialkylborane intermediate is treated with Acetaldehyde,11 a-pinene is displaced for recovery and a chiral boronate bearing the R group of the alkene is obtained (eq 7).

This reaction is general, and these boronic esters are versatile synthetic intermediates in their own right.12

Asymmetric Reduction of Ketones.

The reduction of prochiral ketones with IpcBH2 is mechanistically complex. Although the secondary alcohols obtained are consistantly enriched in the (S) enantiomer when the reagent is prepared from (+)-a-pinene, the degree of asymmetric induction observed, 11-46% ee, varies with the reaction stoichiometry.3 This has been attributed to the ability of the 1:1 IpcBH2:ketone addition product to serve as a reducing agent for an additional equivalent of ketone (eq 8).


1. (a) Brown, H. C.; Jadhav, P. K.; Mandal, A. K. T 1981, 37, 3547. (b) Brown, H. C.; Jadhav, P. K. In Asymmetric Synthesis; Morrison, J. D., Ed.; Academic: New York, 1983; Vol. 2, Chapter 1. (c) Brown, H. C.; Kramer, G. W.; Levy, A. B.; Midland, M. M. In Organic Synthesis via Boranes; Wiley: New York, 1975. (d) Smith, K.; Pelter, A. COS 1991, 8, Chapter 3.10.
2. Brown, H. C.; Jadhav, P. K.; Mandal, A. K. JOC 1982, 47, 5074.
3. Brown, H. C.; Mandal, A. K. JOC 1984, 49, 2558.
4. Mandal, A. K.; Yoon, N. M. JOM 1978, 156, 183.
5. (a) Brown, H. C.; Yoon, N. M. JACS 1977, 99, 5514. (b) Singaram, B.; Schweir, J. R. JOM 1978, 156, C1. (c) Brown, H. C.; Mandal, A. K. S 1978, 146. (d) Pelter, A.; Ryder, D. J.; Sheppard, J. H.; Subrahmanyam, C.; Brown, H. C.; Mandal, A. K. TL 1979, 49, 4777. (e) Brown, H. C.; Mandal, A. K.; Yoon, N. M.; Singaram, B.; Schweir, J. R.; Jadhav, P. K. JOC 1982, 47, 5069. (f) Jadhav, P. K.; Desai, M. C. H 1982, 18, 233.
6. Brown, H. C.; Schweir, J. R.; Singaram, B. JOC 1978, 43, 4395.
7. X-ray crystal structure: Soderquist, J. A.; Hwang-Lee, S.-J.; Barnes, C. L. TL 1988, 29, 3385.
8. Mandal, A. K.; Jadhav, P. K., Brown, H. C. JOC 1980, 45, 3543.
9. Brown, H. C.; Gupta, A. K.; Vara Prasad, J. V. N. BCJ 1988, 61, 93.
10. Brown, H. C.; Singaram, B. JACS 1984, 106, 1797.
11. Brown, H. C.; Jadhav, P. K.; Desai, M. C. JACS 1982, 104, 4303.
12. Brown, H. C.; Jadhav, P. K.; Singaram, B. In Modern Synthetic Methods; Scheffold, R., Ed.; Springer: Berlin, 1986; Vol 4, pp 307-356.

Robert P. Short

Polaroid Corporation, Cambridge, MA, USA



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