Dehydroboration-reduction

This produces an olefin and a borate ester which may be hydrolyzed to the alcohol. Alternatively, the reaction may proceed by a two-step sequence involving a dehydroboration-reduction pathway. 

The use of elevated pressures (2,000-6,000 atm.) accelerates asym. reduction of prochiral ketones with B-3-pinanyl-9-borabicyclo[3.3.1]nonane while suppressing competing dehydroboration-reduction which erodes enantioselectivity at atm. pressure. E Neat Alpine-Borane at 0° treated with 3-acetylpyridine via a syringe under Nj, stirred for 20 min at room temp., the mixture [in a capped syringe] placed in a high-pressure cell, pressurized to 6,000 atm. for 1.5 days, and worked up by the standard oxidative procedure - (S)-methyl(3-pyridyl)carbinol. Y 67% (100% e.e. ... 

Similar to the reduction of aldehydes, reduction of ketones with Alpine-Borane also involves two competing reaction pathways, a bimolecular -hydride elimination process (cyclic mechanism) affording optically active product [6], and a dehydroboration-reduction sequence yielding racemic product [2] (Scheme 26.1). 

Methyl alkynic ketones are reduced with slightly lower efficiency and f-butyl alkynic ketones are reduced very slowly. In the latter case, dehydroboration of Alpine-Borane to give 9-BBN competes with the rate of reduction and the liberated 9-BBN reduces the ketone to give products of lower enantiomeric purity. This problem may be overcome by using high pressure or by using 6-10-cij -myrtanyl-9-BBN (eqs 5 and 6). ... 

Other Ketones. Ketones such as acetophenone are reduced rather slowly by THF solutions of Alpine-Borane (eq 9). A competing dehydroboration process leads to reduction via 9-BBN (eq 10). 

At 65 °C, Alpine-Borane undergoes 50% dehydroboration in 500 min. At rt there is approximately 1-2% dehydroboration per day. Running the reaction neat increases the rate of the favorable bimolecular reduction. Alternatively, high pressure may be used to increase the rate of the bimolecular process and retard the rate of the dehydroboration reaction (eq 11 ). ... 

Scheme 7.4. Limiting mechanisms for carbonyl reduction of carbonyls by a trialkylborane (a) pericyclic mechanism, (b) Two step mechanism involving dehydroboration of a trialkylborane followed by carbonyl reduction by the resultant dialkylborane.

To circumvent the problem of competitive dehydroboration with ketones, the Alpine-borane reductions can be conducted in neat (excess) reagent [57] or at high pressure (6000 atm, [58]). Experiments done in neat reagent take several days to go to completion, and afford enantioselectivities of 70-98% [57. At pressures of 6000 atmospheres, the reactions are faster and dehydroboration is completely suppressed. Ketones are reduced with slightly higher enantioselectivities (75-100% es) under these conditions [58]. 

However, with slower-reacting and sterically hindered carbonyl compounds, the organoborane reduction may take an alternate pathway involving a prior dehydroboration process (Eqs. 4.18, 4.19) [11]. 

The cause for this poor selectivity in the reduction of simple and unreactive ketones with Alpine-Borane is presumed to be the dehydroboration of the reagent in these slow reductions followed by an achiral and very fast reduction of the carbonyl group by 9-BBN produced in the dehydroboration stage. This problem can be overcome by minimizing the unimolecular dissociation of Alpine-Borane by conducting... 

The rationale for this difference is that, due to the lower reactivity of ketones, a competing dehydroboration of the reagent takes plaees and the resulting 9-BBN by-product performs an achiral reduction thus eroding the enantioselectivity (Figure 14.10). 

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