Ammonia borane, reduction with

The double bond in indole and its homologs and derivatives is reduced easily and selectively by catalytic hydrogenation over platinum oxide in ethanol and fluoroboric acid [456], by sodium borohydride [457], by sodium cyanoborohydride [457], by borane [458,459], by sodium in ammonia [460], by lithium [461] and by zinc [462]. Reduction with sodium borohydride in acetic acid can result in alkylation on nitrogen giving JV-ethylindoline [457]. 

The other alkylborohydrides, 9-BBN and Sia2BH, also transform tertiary amides to alcohols [BK5, PSl]. Alcohols are obtained via the action of LiBH4 in MeOH-hot diglyme on some tertiary amides [S03] or by the controlled reduction with Li pyrrolidinoborohydride in THF [FFl] (Figure 3.69). This latter method, however, has some limitations. The reduction of 3.183 by Li pyrrolidinoborohydride or better by LiNH2BH3 obtained from borane ammonia and n-BuLi does not promote any racemization [MY2, MY4] (Figure 3.69). 

There are many advantages to the use of NH3 as hydrogen source for vehicular fuel cell vehicle applications. However, a major drawback is ammonia s extreme toxicity and adverse health effects. By complexing NH3 with diborane, a stable, non-toxic and non-cryogenic material (H3BNH3) can be prepared. This ammonia-borane complex is stable in water and ambient air and when heated liberates H2 in a sequence of reactions between 137°C and 400°C that reaches about 20% of the initial mass of H3BNH3. Successfiil implementation of ammonia-borane as a potential future transportation fuel, however, requires new chemical techniques and/or processes for its s mthesis that promise substantial reduction in its production costs. 

Various 2-furanone chiral building blocks are readily accessible from 0-acetyllactate derivative 222 according to the series of reactions outlined in Scheme 37. Deprotonation of 222 with 2-4 equivalents of LiHMDS gives (/S)-7-methyltetronic acid (257) in nearly quantitative yield [88]. Reduction of 257 with ammonia—borane affords a 25 75 mixture of 258 and 259, whereas catalytic hydrogenation over rhodium/carbon produces an 85 15 mixture of 258 and 259 [89]. Dehydration of the mixture with phosphorus oxychloride furnishes the 55 -butenolide 260 [(+ )-angelica lactone]. Dihydrofiiranone 262 is made by benzoylation of the tetrabutylammonium salt of 257 followed by catalytic hydrogenation. 

Ammonia borane acts as a metal-free reductant for ketones and aldehydes in methanol solution, via the MeOH BHj complex.In THF, borate esters are the only organic products, with dissociation of ammonia from ammonia borane being rate determining. H-, B-, and C-NMR studies, deuterium labelling, and kinetic isotope effects are... 

Scheme 9.111. The reduction of fra s-P-(2-carbomethoxycyclohexane)propanoic acid. The upper part of the scheme shows reduction with sodium (Na) in ethanol (CH3CH2OH) and liquid ammonia (NH3 (y), where the ester is reduced in preference to the carboxylic acid. The lower part of the scheme shows reduction with borane in THF (oxacyclopentane) where the opposite result obtains. For the preparation and reduction of trms- -(2-carbomethoxycyclohexane)propanoic acid, see Paquette, L. A. Nelson, N. A. /. Org. Chem., 1962,27, 2272.

High-level CCSD(T) calculations for the mechanism of double-hydrogen transfer (DHT) in the reduction of ketones to alcohols or of borate esters and imines to amines with ammonia borane suggest a concerted process which starts with the DHT forming alcohol and NH2BH2, followed by alcoholysis of NH2BH2 to form the first B-0 bond. 

In an altanate process, the enzymatic dynamic resolution of racemic amino add 82 was also demonstrated by combining amino add oxidase with chemical reduction. (J )-selective oxidation with Celite-immobilized (J )-amino add oxidase from T. variabilis expressed in E. coli in combination with chemical imine reduction with borane-ammonia gave a 75% in process yield and 100% ee of (S)-amino add 82a [147]. 

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. 

Reduction of pseudoephedrine amides with metal amide-borane complexes, and lithium amidotrihydroborate (LAB) in particular, furnishes the corresponding primary alcohols in high yield. In the initial report, LAB was prepared by deprotonation of the commercial, solid reagent borane-ammonia complex, using slightly less than 1 equiv of butyllithium as base (eq 11). In... 

Reductive amination of ketones is accomplished in two steps. The borane complex is used to reduce RR C=N1 C1 which are formed by condensation of the ketones with ammonia in the presence of TiCl,-Ti(OPr )4. 

The synthesis of the fluoroketone that combines the retroamide type bond (76) is shown in Scheme 5. The 2,2-difluoro-3-hydroxyester 11 from a Reformatsky reaction was converted to the primary amide 12 by treatment with ammonia in diethyl ether. Reduction of the amide with borane dimethyl sulfide and protection of the resulting amine gave the protected intermediate 13. For the preparation of peptides XIV and XV, the hydroxy function was oxidized to the corresponding ketone using pyridinium dichromate. 

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