Borane, reduction nitriles

Scheme 17 Reduction of nitriles using borane dimethyl sulfide and microwave irradiation...

Primary amino methylene substituents were introduced by a sequence of cya-nodehalogenation and subsequent reduction of the resulting nitrile with borane dimethyl sulfide. To incorporate tertiary aminomethylene substituents into the 2-pyri-done framework, a microwave-assisted Mannich reaction using preformed iminium salts proved to be effective. 

Similarly, lipase-catalyzed kinetic resolution has also been applied to intermediate nitrile alcohol 46 (Scheme 14.14). Best results were obtained by using immobilized Pseudomonas cepacia (PS-D) in diisopropyl ether, leading to excellent yield and enantiomeric excess of the desired (5)-alcohol 46a, along with (/J)-nitrile ester 47. Reduction of 46a with borane-dimethylsulhde complex, followed by conversion to the corresponding carbamate and subsequent lithium aluminum hydride reduction gave rise to the desired (S)-aminoalcohol intermediate 36, a known precursor of duloxetine (3). 

Enantioselective reduction of jS-keto nitriles to optically active 1,3-amino alcohols has been carried out in one step using an excess of borane-dimethyl sulfide complex as a reductant and a polymer-supported chiral sulfonamide as a catalyst with moderate to high enantioselectivity (Figure 3.11). The facile and enantioselective method to prepare optically active 1,3-amino alcohols has been used to prepare 3-aryloxy-3-arylpropylamine type antidepressant drugs, for example (l )-fluoxetine. 

The following reactions proceed with the participation of the allylic boron system (i) allylboration and protolytic cleavage of organic compounds with multiple bonds, (ii) allylboron-alkyne condensation,598 599 (iii) reductive mono-and trans-a,a -diallylation of nitrogen aromatic compounds, (iv) disproportionation processes between tribut-2-enylborane and BX3 (X = C1, Br, OR, SR). Allylboration of carbonyl compounds, thioketones, imines, or nitriles leads to the homoallylic alcohols, thiols, or amines (Equations (136) and (137). It is most important that 1,2-addition to aldehydes and imines proceeds with high diastereoselectivity so that ( )-allylic boranes and boronates give the anti-products, while -products are formed preferentially from (Z)-isomers. 

Borane is typically used as a THF (BHs-THF) or dimethylsulfide complex (BH3 SMe2). Although the reactivity of the two complexes is similar, the boron dimethylsulfide species is more stable over longer periods of time. Borane will chemoselectively reduce a carboxylic acid in the presence of an ester or nitrile. Reviews (a) Seyden-Penne, J. Reductions by the Alumino- and Borohydrides in Organic Synthesis, Wiley-VCH New York, 1997, 2" edition, (b) Brown, H. C. ... 

The reduction of indoles by pyridine-borane in CF3COOH [K3] or BH3 THF in CF3COOH [MMl] is compatible with amide, nitrile, or ester groups. It is interesting to emphasize that LAH in ether media reduces these groups without affecting the... 

Reduction. This borohydride reduces nitriles to afford stable aldimine-borane complexes, which can be used to prepare homoallylic amines on further reaction with R2BCH2CH=CH2. 

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