A safe, scaleable method for the oxidation of carbon-boron bonds with Oxone

Article abstract of DOI:10.1016/S0040-4039(00)00978-3

A new procedure for the oxidation of carbon-boron bonds to the corresponding alcohol with Oxone is described. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00978-3

Tetrahedron Letters 41 (2000) 5817±5819
A safe, scaleable method for the oxidation of carbon±boron
bonds with Oxone1
David H. Brown Ripin,* Weiling Cai and Steven J. Brenek
Process Research and Development, Central Research Division, P®zer Inc., Eastern Point Road, Groton,
Connecticut 06340, USA
Received 27 April 2000; accepted 22 May 2000
Abstract
A new procedure for the oxidation of carbon±boron bonds to the corresponding alcohol with Oxone1 is
described. # 2000 Elsevier Science Ltd. All rights reserved.
Keywords: hydroboration; organoborane; carbon±boron bond; oxidation; Oxone1.
The oxidation of carbon±boron bonds to the corresponding alcohol can be achieved with a
wide range of oxidants.1 The most common method used is hydrogen peroxide in a basic medium,
although trimethylamine N-oxide (TMANO),2 peracids,3 chromium reagents,4 sodium perbo-
rate,5 sodium percarbonate,6 and many others can be used. Most of these methods are of limited
utility on a large-scale due to safety, reproducibility, or reagent waste concerns. Herein, we report
a general, safe, and reproducible method for the oxidation of carbon±boron bonds with Oxone1
.
(2KHSO5 KHSO4 K2SO4).
.
While investigating the hydroboration of 7, we encountered diculty in the oxidative workup
of the reaction. In order to fully convert the alkyl±borane to the secondary alcohol, the reaction
had to be heated to re¯ux with 30% hydrogen peroxide and NaOH for 2 full hours. From this
procedure, an 88% yield of material could be isolated after column chromatography. This sub-
strate is particularly slow to oxidize, possibly because of intramolecular coordination of the tertiary
amine to the alkyl±borane intermediate. This procedure is not optimal for large-scale work for a
number of reasons, including the inherent instability of the hydrogen peroxide solution.7 Accel-
erating Rate Calorimetry (ARCTM) revealed a primary exotherm that was sucient to raise the
reaction temperature to the onset of a secondary exothermic decomposition occurring near
110ꢀC, which could contribute to potential runaway conditions on scale.
We found that working this reaction up with Oxone1 (3 equivalents, 5 volumes water) provided
the corresponding alcohol in 92% yield and higher purity than any of the other procedures
* Corresponding author.
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00978-3

5818
investigated.8 Oxone1, in direct comparison, has a higher onset of decomposition than 30%
hydrogen peroxide and liberates less energy. This reaction is performed at lower temperature,
which provides a larger margin of safety, and is dose-rate controlled by addition of Oxone1
solution, providing a better overall safety pro®le for the oxidation.9 Additionally, Oxone1 is a
solid, allowing for the addition of precisely weighed amounts of reagent to be used in the reaction.
A minimum of 3 equivalents of Oxone1 are necessary to drive the oxidation to completion.
This reaction is general and works on a range of organoboranes to provide the alcohol products
in good yield (Table 1).10 11
Table 1a
References
1. Pelter, A.; Smith, K. In Comprehensive Organic Synthesis; Trost, B. M., Ed.; Pergamon: Oxford, 1991; Vol. 7, p.
593.
2. (a) Koster, R.; Morita, Y. Justus Leibigs Ann. Chem. 1967, 704, 70; (b) Kabalka, G. W.; Hedgecock, H. C. J. Org.
Chem. 1986, 40, 1776.
3. Johnson, J. R.; van Campen, M. G. J. Am. Chem. Soc. 1938, 60, 121.
4. (a) Pappo, R. J. Am. Chem. Soc. 1959, 81, 1010; (b) Brown, H. C.; Garg, C. P. J. Am. Chem. Soc. 1961, 83, 2951;
(c) Ware, J. C.; Traylor, T. G. J. Am. Chem. Soc. 1963, 85, 3036.
5. Matteson, D. S.; Moody, R. J. J. Org. Chem. 1980, 45, 1091.
6. Kabalka, G. W.; Wadgoonkar, P. P.; Shoup, T. M. Tetrahedron Lett. 1989, 30, 5103.
7. DSC for 30% aqueous H2O2: Exothermic decomposition from 31 to 100ꢀC liberating 747 J/g of energy. Reaction
calorimetry was performed in an Accelerating Rate Calorimeter (ARCTM).
8. No chromatography was necessary. A variety of methods were investigated including TMANO, MCPBA, and
sodium perborate. These methods all su€ered from either safety concerns (TMANO), incomplete reaction
(perborate), or side reactions (MCPBA).
9. DSC for 30% aqueous Oxone1: Exothermic decomposition from 56 to 127ꢀC liberating 86 J/g of energy. Reaction
calorimetry was performed in a CRC90eTM reaction calorimeter.
10. A typical procedure is as follows: To a solution of alkene 7 (18.7 g, 100 mmol) in THF (150 mL) was added
ꢀ
.
NaBH4 (6.5 g, 170 mmol) at room temperature under N2. The slurry was cooled to 0 C, and BF3 OEt2 (15 mL,
16.8 g, 118.3 mmol) in THF (25 mL) was slowly added through an addition funnel. The addition was kept slow
enough to keep the temperature of the reaction mixture below 0ꢀC. After the addition the reaction mixture was
stirred at 0ꢀC for 1 h and at room temperature for 1.5 h. The reaction was re-cooled to 0ꢀC and water (50 mL) was

5819
added slowly to destroy the excess borane. The reaction was stirred at rt for 2 h, followed by the addition of
Oxone1 (110 g, 342.8 mmol) in water (500 mL) at 0ꢀC. The reaction mixture was allowed to warm to room
temperature and stirred overnight. The reaction was quenched by adding NaHSO3 (solid) until all excess oxidant
was destroyed (KI/starch test paper). The pH of the reaction mixture was 1±2. The reaction mixture was extracted
with ethyl acetate (3Â50 mL), and the aqueous layer was adjusted to pH 12 with 6 N NaOH and extracted with
ethyl acetate (4Â100 mL). The organic layer was washed with brine, dried over NaSO4, and concentrated in
vacuo. The residue obtained is pure alcohol (19.0 g, 92%).
11. Compounds 2, 4 and 10 were compared to authentic samples purchased from Aldrich. Compounds 6, 8 and 12
were compared to data reported in the literature. Compound (6): J. Am. Chem. Soc. 1989, 111, 6749; compound
(8): Tetrahedron 1970, 26, 5519; compound (12): J. Org. Chem. 1982, 47, 4692.