Borane carbonyl reduction

Figure 11.2 Catalysts and ligands for carbonyl reduction by borane.

Deoxygenation of carbonyl compounds (6, 98 7, 54 8, 79-80). This easily prepared borane is as effective as catechol borane for reduction of tosylhydrazones of carbonyl compounds to the corresponding methylene compounds. 

You may have noticed that only one of the three alkyl groups of a trialkyl-borane is converted to an aldehyde by the carbonylation-reduction-oxidation sequence. To ensure that carbonylation takes the desired course without wasting the starting alkene, hydroboration is achieved conveniently with a hindered borane, such as 9-BBN, 12. With 12, only the least-hindered alkyl group rearranges in the carbonylation step ... 

Organocatalytic asymmetric carbonyl reductions have been achieved with boranes in the presence of oxazaborolidine and phosphorus-based catalysts (Section 11.1), with borohydride reagents in the presence of phase-transfer catalysts (Section 11.2), and with hydrosilanes in the presence of chiral nucleophilic activators (Section 11.3). 

Reduction of aldehydes and ketones is possible with borane. Stereoselective reduction of ketones is possible when a heteroatom is located a- or p- to the carbonyl group. Treatment of a (3-hydroxy-ketone with catecholborane results in the selective formation of the syn 1,3-diol product (7.94). The borane reacts preferentially with the alcohol to release hydrogen gas and to form the boronic ester 107. A second equivalent of the borane then effects the reduction to give the syn diastereomer. For the preparation of the anti diastereomer, triacetoxyborohydride can be used (see Scheme 7.86). 

Lithiated 71 (Ar = o-An, u-Tol and 1-Naphth) reacted with carbon dioxide affording the phosphinocarboxylic acid boranes 74 in 55-60% yields. Their deprotection using TFA, with retention of conflguration, and coupling with (S)-(—)-2-(diphenylphosphino)methylpyrrolidine furnished amidodiphosphines 81 (48-51% yield). Finally, carbonyl reduction with borane (and concomitant N-and P-protection) followed by a deboronation step gave access to P,N ligands 82. 

Scheme 4 outlines the synthesis of key intermediate 7 in its correct absolute stereochemical form from readily available (S)-(-)-malic acid (15). Simultaneous protection of the contiguous carboxyl and secondary hydroxyl groups in the form of an acetonide proceeds smoothly with 2,2 -dimethoxypropane and para-toluene-sulfonic acid and provides intermediate 26 as a crystalline solid in 75-85 % yield. Chemoselective reduction of the terminal carboxyl group in 26 with borane-tetrahydrofuran complex (B H3 THF) affords a primary hydroxyl group that attacks the proximal carbonyl group, upon acidification, to give a hydroxybutyrolactone. Treat-... 

The Leuckart-Wallach reaction is the oldest method of reductive amination of carbonyl compounds. It makes use of formamide, formic acid or ammonium formate at high temperature. The final product is a formamide derivative, which can be converted to an amine by reduction or hydrolysis. The method has been applied to the preparation of 1,2-diamines with a norbornane framework, which are interesting rigid analogues of 1,2-diaminocyclohexanes. As a matter of fact, starting from N-acetyl-2-oxo-l-norbornylamine 222, the diamide 223 was obtained with excellent diastereoselectivity and then converted to the M-methyl-N -ethyl derivative 224 by reduction with borane [ 104] (Scheme 34). On the other hand, when the reac-... 

Besides direct reduction, a one-pot reductive amination of aldehydes and ketones with a-picoline-borane in methanol, in water, and in neat conditions gives the corresponding amine products (Scheme 8.2).40 The synthesis of primary amines can be performed via the reductive amination of the corresponding carbonyl compounds with aqueous ammonia with soluble Rh-catalyst (Eq. 8.17).41 Up to an 86% yield and a 97% selectivity for benzylamines were obtained for the reaction of various benzaldehydes. The use of a bimetallic catalyst based on Rh/Ir is preferable for aliphatic aldehydes. 

It is well known that in the cyclization of a y-hydroxy aldehyde to form the corresponding six-membered ring hemiacetal through intramolecular cyclization the hemiacetal form always predominates (48). This might account for the fact that no noticeable carbonyl absorption has been observed in the IR and NMR spectra of 54. However, the equilibrium between the hemiacetal and the aldehyde forms might shift in favor of the aldehyde form as the borane reduction proceeds until 54 is completely transformed to 55. 

Kragl and Wandrey made a comparison for the asymmetric reduction of acetophenone between oxazaborolidine and alcohol dehydrogenase.[59] The oxazaborolidine catalyst was bound to a soluble polystyrene [58] and used borane as the hydrogen donor. The carbonyl reductase was combined with formate dehydrogenase to recycle the cofactor NADH which acts as the hydrogen donor. Both systems were run for a number of residence times in a continuously operated membrane reactor and were directly comparable. With the chemical system, a space-time yield of 1400 g L"1 d"1 and an ee of 94% were reached whereas for the enzymatic system the space-time yield was 88 g L 1 d"1 with an ee of >99%. The catalyst half-life times were... 

The organic analogues of the reactions to be discussed here are the borane reductions of aldehydes and ketones and the addition of metal alkyls across ketonic carbonyls, equation 15. In contrast to the ease of these organic reactions, qualitative data which has accumulated in our laboratory over the last decade demonstrates that the carbonyl group in organometallies is fairly resistant to addition across CO. For example, many stable adducts of organometallie carbonyls with aluminum alkyls are known, eq. lc, but under similar conditions a ketone will quickly react by addition of the aluminum alkyl across the CO bond. A similar reactivity pattern is seen with boron halides. 

Boranes have opened the door to asymmetric reduction of carbonyl compounds. The first attempt at modifying borane with a chiral ligand was reported by Fiaud and Kagan,75 who used amphetamine borane and desoxyephedrine borane to reduce acetophenone. The ee of the 1-phenyl ethanol obtained was quite low (<5%). A more successful borane-derived reagent, oxazaborolidine, was introduced by Hirao et al.76 in 1981 and was further improved by Itsuno and Corey.77 Today, this system can provide high stereoselectivity in the asymmetric reduction of carbonyl compounds, including alkyl ketones. 

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