Aldehydes with alpine-borane

Table 1. Optically Active. Labeled Primary Alcohols by Reduction of Aldehydes with Alpine-Borane...

Therefore, this avoids the necessity of prior preparation [6] of 1-deuterated aldehydes. The absolute configuration of the major products are consistently K)- when deuterated Alpine-Borane (from (+)-a-pinene) is used for the reduction. The product of (S)-configuration is readily obtained by using deuterated B-3-pinanyl-9-BBN prepared from (-)-a-pinene and 9-BBN-9-D. On the other hand, reduction of deuterated aldehyde with Alpine-Borane from (-h)-a-pinene affords (S)-alcohols and (f )-alcohols are obtained when (-)-a-pinene is used (Chart 26.3). 

The results of reduction of aldehydes with Alpine-Borane are summarized in Table 26.2 [8]. 

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). 

Enantioselective reduction is not possible for aldehydes, since the products are primary alcohols in which the reduced carbon is not chiral, but deuterated aldehydes RCDO give a chiral product, and these have been reduced enantioselectively with B-(3-pinanyl)-9-borabicyclo[3.3.1]nonane (Alpine-Borane) with almost complete optical purity. ... 

In the second step, achiral 9-borabicyclo[3.3.1]nonane (9-BBN) adds to the less hindered diastereotopic face of a-pinene to yield the chiral reducing agent Alpine-Borane. Aldehydes are rapidly reduced to alcohols. The reaction with deuterio-Alpine-Borane, which yields (R)-a-d-henzy alcohol in 98% enantiomeric excess ( ) reveals a very high degree of selectivity of the enantiotopic faces of the aldehyde group in a crowded transition state ... 

Pinanyl-9-BBN (Alpine borane 4) is a chiral borane that is readily oxidized by aldehydes. Aliphatic deuterioaldehydes undergo chiral reduction to give alcohols with 84-98% e.e. The chiral alkene is regenerated in the process, only the hydrogen at the 2-position having been utilized, and can be reused. Equation (52) serves as an illustration of the stereochemistry of the process. 

The reduction is bimolecular and thus the rate is dependent on concentration. Running the reaction neat provides the fastest rates. Usually an excess of Alpine-Borane is used to insure that the reaction does not become excessively slow at the end of the reduction. The excess organoborane may be destroyed by addition of an aldehyde such as Acetaldehyde. The resulting alkoxy-9-BBN may be treated with Ethanolamine to liberate the alcohol and precipitate the majority of the 9-BBN. Any remaining borane impurities may be removed by oxidation with basic Hydrogen Peroxide. 

Alpine-Borane,prepared by hydroborationofa-pinenewith9-borabicyclo[3.3. Ijnonane (9-BBN), reduces aldehydes, a-keto esters and acetylenic ketones with excellent enantioselectivity. The reduction proceeds via a cyclic process similar to the MPV reaction. 

Bland, L., Panigot, M. J. Reaction of Alpine-Borane with aldehydes reactivity rate assessment by observation of the disappearance of the carbonyl n - P peak by UV-visible spectroscopy. Journal of the Arkansas Academy of Science 2000, 54, 24-32. 

Reduction of aldehydes labeled with deuterium or tritium leads to primary alcohols which are chiral by virtue of the label. Alternatively, the label can be introduced by the use of deuterated Alpine-Borane, which can be prepared by hydroboration with 9-borabicyclo[3.3.1]nonane-... 

Alpine-Borane (Midland) Alpine-Borane is a trademark of Aldrich Chemical Company for B-3-pinanyl-9-borabicyclo[3.3.1]nonane. It is prepared by hydroboration of a-pinene with 9-borabicyclo[3.3.1]nonane (9-BBN). Synthesis of (1 )-Alpine-Borane is prepared from (17 )-(+)-a-pinene, and since (+)- and (-)-a-pinenes are commercially available, both enantiomers of the reagent can easily be prepared. The reagent is only suitable for very reactive substrates, such as labeled aldehydes and acetylenic ketones (Scheme 2.136) [64],... 

Both catalytic versions compare favorably with the stoichiometric methodology using (+)- or (—)-B-3a-pinanyl-9-BBN ((+)- or ( )-Alpine Borane, 59) in giving an equivalent stereochemical outcome of 80-100% e.e. . Employment of 1 -deutero or 1 -tritio aldehydes as substrates is also highly recommended, in order to avoid the inconvenient preparation of labeled reducing agent. The synthesis of (5)-[2- H, H]acetic acid (60) and (/ )-[l- H]-hexadecyloxypropane-1,2-diol (61) may serve as illustrative examples. 

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