[112246-73-8]  · C20H34BCl  · (+)-B-Chlorodiisopinocampheylborane  · (MW 320.80) (-)


(chiral reducing agent for various prochiral ketones;1 reagent for asymmetric aldol condensation of methyl alkyl ketones;2 reacts with meso-epoxides to give nonracemic chlorohydrins3)

Alternate Name: (+)- and (-)-DIP-ChlorideTM.

Physical Data: mp 52-56 °C; (-)-DIP-Chloride [a]D -67.07° (c = 13.5, CH2Cl2); 11B NMR (diethyl ether) singlet at d = 74 ppm (with reference to BF3.OEt2).

Solubility: sol in both polar and nonpolar aprotic solvents like diethyl ether, THF, methylene chloride, pentane, hexane, etc.

Form Supplied in: white crystalline solid, available commercially.

Handling, Storage, and Precautions: the dry solid and its solutions are moisture and air sensitive. The reagent reacts instantaneously with water and protic solvents to liberate HCl. Containers of DIP-Chloride should be stored in the absence of moisture. Cans or bottles of DIP-Chloride should be flushed with N2 and kept tightly sealed to avoid contact of oxygen and moisture. The solid reagent should be crushed, transferred, or weighed only in glove bag or dry box under N2 atmosphere. The reagent can be stored for several years under N2 atmosphere below 25 °C. Use in a fume hood.

Asymmetric Reduction of Ketones.

The reagent, developed by Brown and co-workers, is used primarily for the asymmetric reduction of a variety of prochiral ketones to form secondary alcohols with high enantiomeric purity.1 It has been demonstrated that reduction of aryl alkyl ketones with DIP-Chloride proceeds with extraordinary consistency and predictable stereochemistry (eq 1).4,5 Reduction of a variety of substituted aryl alkyl ketones demonstrates that representative aromatic substituents do not affect the stereochemical outcome.1a The reagent shows poor enantioselectivity with unhindered aliphatic ketones; however, hindered aliphatic ketones like 3,3-dimethyl-2-butanone provide the corresponding alcohol in 95% ee.5,6 Bicyclic ketones like a-tetralone, 1-indanone, and 2-acetonaphthone are reduced by the reagent in 87%, 97%, and 98% ee, respectively.5 Substrates with heteroaromatic groups show some decrease in the enantioselectivity (e.g. 2-acetylthiophene and 3-acetylpyridine are reduced in 91% and 92% ee, respectively).5 The reagent has been recently applied to the reduction of fluoro ketones.7 It has been shown that good enantioselectivity can be obtained if the reduction of fluoro ketones are carried out neat (without solvent) (eq 2). The reagent shows poor selectivity in the reduction of unhindered alkynic ketones. However, hindered alkynic ketones are reduced in relatively good optical purity (eq 3).8 A variety of hindered alkynic ketones have been recently synthesized and converted by the reagent to the corresponding propargylic alcohol in high yields and in essentially optically pure form.8 It has also been demonstrated that DIP-Chloride is a remarkably effective reagent for the asymmetric reduction of acylsilanes to form corresponding a-silyl alcohols in 96-98% ee (eq 4).9

Chiral secondary alcohols are potentially of great importance in biological and medicinal science. For example, 3-chloro-1-phenyl-1-propanol, which is obtained in >99% ee via DIP-Chloride reduction of the corresponding ketone, provides access to a highly enantioselective synthesis of antidepressant agents such as Tomoxetine, Fluoxetine, and Nisoxetine.10 Another representative application of DIP-Chloride is found in the synthesis of (1R,3S)-1-aminomethyl-3,4-dihydro-5,6-dihydroxy-3-phenyl-1H-2-benzopyran, a potent and selective D1 agonist.11 The reagent has also been applied to the synthesis of a prostaglandin intermediate1a and for the synthesis of a dolaphenine intermediate which is the C-terminal unit of dolastatin (a promising anticancer agent).12

Enolboration of Ketones and Opening of meso-Epoxides.

Methyl alkyl ketones have been successfully enolized by Ipc2BX (X = OTf or Cl) in the presence of a tertiary amine. The corresponding enolborinates have been used in asymmetric aldol condensations (eq 5).2 The reagent has also been applied to the enantioselective opening of meso-epoxides to form the corresponding nonracemic chlorohydrins (eq 6).3

Related Reagents.

Diisopinocampheylboron Trifluoromethanesulfonate.

1. (a) Brown, H. C.; Ramachandran, P. V. ACR 1992, 25, 16. (b) Singh, V. K. S 1992, 7, 605. (c) Midland, M. M. CRV 1989, 89, 1553. (d) Brown, H. C.; Park, W. S.; Cho, B. T.; Ramachandran, P. V. JOC 1987, 52, 5406. (d) Dhar, R. K. Aldrichim. Acta 1994, 27, 43.
2. (a) Paterson, I.; Osborne, S. TL 1990, 31, 2213. (b) Paterson, I.; Goodman, J. M.; Lister, M. A.; Schumann, R. C.; McClure, C. K.; Norcross, R. D. T 1990, 46, 4663.
3. (a) Joshi, N. N.; Srebnik, M.; Brown, H. C. JACS 1988, 110, 6246. (b) Srebnik, M.; Joshi, N. N.; Brown, H. C. Isr. J. Chem. 1989, 29, 229.
4. Chandrasekharan, J.; Ramachandran, P. V.; Brown, H. C. JOC 1985, 50, 5446.
5. Brown, H. C.; Chandrasekharan, J.; Ramachandran, P. V. JACS 1988, 110, 1539.
6. Brown, H. C.; Chandrasekharan, J.; Ramachandran, P. V. JOC 1986, 51, 3394.
7. Ramachandran, P. V.; Teodorovic, A. V.; Brown, H. C. T 1993, 49, 1725.
8. Ramachandran, P. V.; Teodorovic, A. V.; Rangaishenvi, M. V.; Brown, H. C. JOC 1992, 57, 2379.
9. (a) Cirillo, P. F.; Panek, J. S. OPP 1992, 24, 555. (b) Soderquist, J. A.; Anderson, C. L.; Miranda, I. R.; Rivera, I.; Kabalba, G. W. TL 1990, 31, 4677. (c) Buynak, J. D.; Strickland, J. B.; Hurd, T.; Phan, A. CC 1989, 89.
10. Srebnik, M.; Ramachandran, P. V.; Brown, H. C. JOC 1988, 53, 2916.
11. DeNinno, M. P.; Schoenleber, R.; Asin, K. E.; Mackenzie, R.; Kebabian, J. W. JMC 1990, 33, 2948.
12. (a) Shioiri, T.; Hayashi, K.; Hamada, Y. T 1993, 49, 1913. (b) Irako, N.; Hamada, Y.; Shioiri, T. T 1992, 48, 7251.

Raj K. Dhar

Aldrich Chemical Company, Sheboygan Falls, WI, USA

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