Hydroboration–oxidation reaction

In organic chemistry, the hydroboration–oxidation reaction is a two-step organic reaction that converts an alkene into a neutral alcohol by the net addition of water across the double bond.[1] The hydrogen and hydroxyl group are added in a syn addition leading to cis stereochemistry. Hydroboration–oxidation is an anti-Markovnikov reaction, with the hydroxyl group attaching to the less-substituted carbon. The reaction was first reported by Herbert C. Brown in the late 1950s[2] and it was recognized in his receiving the Nobel Prize in Chemistry in 1979.

The general form of the reaction is as follows:

Hydroboration–oxidation

where THF is tetrahydrofuran, the archetypal solvent used for hydroborations.

Contents

Mechanism and scope

Hydroboration step

Main article: hydroboration

In the first step, borane (BH3) adds to the double bond, transferring one hydrogen from itself to the adjacent carbon. This reaction, hydroboration is repeated two additional times so that three alkenes add to each BH3. The resulting trialkylborane is treated with hydrogen peroxide in the second step. This process replaces the B-C bonds with HO-C bonds. The boron reagent is converted to boric acid. The reaction was originally described by H.C. Brown in 1957 for the conversion of 1-hexene into 1-hexanol.[3]

Hexanol synthesis from 1-hexene Brown 1957

Knowing that the group containing the boron will be replaced by a hydroxyl group, it can be seen that the initial hydroboration step determines the regioselectivity. Hydroboration proceeds in an antimarkovnikov manner. Hydroborations are also stereoselective, with the new constituents adding in syn (on the same face of the alkene). Thus 1-methylcyclopentene reacts with diborane predominantly to the trans-alkane.[4]

Until all hydrogens attached to boron have been transferred away, the boron group BH2 will continue adding to more alkenes. This means that one equivalent of hydroborane will conduct the reaction with three equivalents of alkene. Furthermore, it is not necessary for the hydroborane to have more than one hydrogen. For example, reagents of the type R2BH are commonly used, where R can represents the remainder of the molecule. Such modified hydroboration reagents include 9-BBN, catecholborane, and disiamylborane.

Oxidation step

In the second hydroboration–oxidation step, the nucleophilic hydroperoxide anion attacks the boron atom. Alkyl migration to oxygen gives the alkyl borane with retention of stereochemistry (in reality, the reaction occurs via the trialkyl borate B(OR)3, rather than the monoalkyl borinic ester BH2OR).

Hydroboration-oxidation mechanism

Alkyne hydroboration

A hydroboration reaction also takes place on alkynes. Again the mode of action is syn and secondary reaction products are aldehydes from terminal alkynes and ketones from internal alkynes. In order to prevent hydroboration across both the pi-bonds, a bulky borane like disiamyl (di-sec-iso-amyl) borane is used.[5]

Hydroboration–oxidation of teminal alkyne

Related reactions

Oxymercuration

Oxymercuration–reduction is another reaction that converts an alkene into an alcohol. Unlike hydroboration–oxidation, oxymercuration-reduction is not stereospecific. Further, oxymercuration–reduction is a Markovnikov reaction. Therefore, oxymercuration–reduction and hydroboration–oxidation are complementary because they add with opposite regiochemistry.

Other boron-mediated C-X bond forming reactions

Amines can be obtained from the intermediate organoborane by action of chloramine.[6] Reaction with iodine or bromine afford the corresponding alkyl halides.[7][8] A carboxylic acid simply replaces the borane group by a proton.

References

  1. ^ Loudon, Marc G. (2002). "Addition Reactions of Alkenes.". Organic Chemistry (Fourth Edition ed.). New York: Oxford University Press. pp. 168–172. ISBN 0-19-511999-1. 
  2. ^ Brown, H. C.; Zweifel, G. (1959). "A STEREOSPECIFIC CIS HYDRATION OF THE DOUBLE BOND IN CYCLIC DERIVATIVES". Journal of the American Chemical Society 81: 247. doi:10.1021/ja01510a059.  edit
  3. ^ Brown, H.; Rao, B. C. (1957). "Communications - Selective Conversion of Olefins into Organoboranes Through Competitive Hydroboration, Isomerization and Displacement Reactions". Journal of Organic Chemistry 22 (9): 1137. doi:10.1021/jo01360a626.  edit
  4. ^ Hawthorne, M. F. (1961). "Amine Boranes. VIII. The Hydroboration of Terminal Olefins, Dienes and Terminal Acetylenes with Trimethylamine t-Butylborane". Journal of the American Chemical Society 83 (11): 2541–2544. doi:10.1021/ja01472a027.  edit
  5. ^ Brown, H. C.; Gupta, S. K. (1972). "Catecholborane (1,3,2-benzodioxaorole) as a new, general monohydroboration reagent for alkynes. Convenient synthesis of alkeneboronic esters and acids from alkynes via hydroboration". Journal of the American Chemical Society 94 (12): 4370. doi:10.1021/ja00767a072.  edit
  6. ^ Brown, H. C.; Heydkamp, W. R.; Breuer, E.; Murphy, W. S. (1964). "The Reaction of Organoboranes with Chloramine and with Hydroxylamine-O-sulfonic Acid. A Convenient Synthesis of Amines from Olefins via Hydroboration". Journal of the American Chemical Society 86 (17): 3565. doi:10.1021/ja01071a036.  edit
  7. ^ Brown, H. C.; Rathke, M. W.; Rogic, M. M. (1968). "A fast reaction of organoboranes with iodine under the influence of base. A convenient procedure for the conversion of terminal olefins into primary iodides via hydroboration-iodination". Journal of the American Chemical Society 90 (18): 5038. doi:10.1021/ja01020a056.  edit
  8. ^ Brown, H. C.; Lane, C. F. (1970). "Base-induced reaction of organoboranes with bromine. Convenient procedure for the anti-Markovnikov hydrobromination of terminal olefins via hydroboration-bromination". Journal of the American Chemical Society 92 (22): 6660. doi:10.1021/ja00725a057.  edit

9 "Catalytic Asymmetric Hydroboration: Recent Advances and Applications in Carbon-Carbon Bond-Forming Reactions" Eur. J. Org. Chem. Issue: 24, pp. 4695-4712. Published: DEC 15 2003

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