Reduction reactions Sodium triacetoxyborohydride

The synthetic importance of reaction (a) ° comes from the fact that it reduces to one step the pathway for conversion of an acid chloride into a nitrile (instead of the classical and rather inconvenient two-step route via an acid amide). Reaction is an example of a new transformation for aliphatic amines. Previously, there were no methods available for the direct transformation of an amino into a nitro group and the stepwise procedures were too cumbersome to be of practical use. Transformation of a nitro group into a carbonyl is a well-known reaction. Its modification, shown in reaction represents a welcome opportunity to obtain a protected carbonyl group as the immediate result of such a transformation. The viability of the sequential reactions (b) plus (c) enables the employment of a > CHNH2 moiety as a synthetic equivalent to a protected carbonyl group. A one-pot sequence of imine formation and its reduction with sodium triacetoxyborohydride represents a convenient... 

A reductive amination/cyclization step was performed on the aldehyde 392 upon reaction with a variety of amines in the presence of sodium triacetoxyborohydride in THF/AcOH at room temperature to give the tetrahydropyr-ido[2,3 pyrituidine 393 (Equation 34) <2005BML1829>. 

For ammonia and primary amines there are two possible pathways, but when secondary amines are involved, only the hydrogenolysis pathway is possible. Other reducing agents167 can be used instead of hydrogen and a catalyst, among them zinc and HCI, sodium cyano-borohydride NaBHjCN,168 sodium triacetoxyborohydride,169 sodium borohydride,170 iron pentacarbonyl and alcoholic KOH,171 BH -pyridine,172 and formic acid. When the last is used, the process is called the Wallach reaction. In the particular case where primary or secondary amines are reductively methylated with formaldehyde and formic acid, the method is called the Eschweiler-Clarke procedure. It is possible to use ammonium (or amine) salts of formic acid,173 or formamides, as a substitute for the Wallach conditions. This method is called the Leuckart reaction, and in this case the products obtained are often the N-formyl derivatives of the amines instead of the free amines. Primary and secondary amines can be N-ethylated (e.g., ArNHR —< ArNREt) by treatment with NaBH4 in acetic acid.175... 

The example previously described in Fig. 12 involves a reductive alkylation, a widely used derivatization reaction in combinatorial chemistry. The use of sodium triacetoxyborohydride has been thoroughly validated for the solid-phase reaction format. With this reagent the pH is maintained... 

A popular and effective method for converting aldehydes to amines is through a reductive amination protocol. Typically, the aldehyde and amine react to fonn an intermediate imine or iminiiim ion and tlien a reducing agent (i.e., sodium triacetoxyborohydride) is added to carry out the reduction of the intermediate species to afford the amine. The reaction is accelerated in the presence of acetic acid (0.1 -3 equivalents). Reviews (a) Baxter, E. W. Reitz, A. B. Org. React. 2002, 59, 1-714. (b) Hutchins, R. O. In Comprehensive Organic Synthesis Trost, B. M. Fleming, L, Eds. Pergamon Press Oxford, U. K., 1991 Vol. 8, Chapter 1.2 Reduction of C=N to CHNH by Metal Hydrides, pp. 25-54. 

Aldehydes are reduced faster than ketones (keeping this reaction cold will increase selectivity). Alternatively, sodium triacetoxyborohydride could be used for this reduction see problem 18-13. 

This method has been used for the preparation of a prototype combinatorial Hbrary of 1000 piperazinediones [118]. The key step of the experimental procedure is a reductive alkylation with sodium triacetoxyborohydride, which has been thoroughly validated for the solid-phase reaction format. 

Various methods have been applied for the reduction of alicyclic p-enamino esters, but these reactions in general gave diastereomeric mixtures [64-69]. For example, the sodium triacetoxyborohydride reduction of enamino ester 30 (R = Ph, CH2Ph) resulted in about 10% tram isomer 32 besides the main cis product 31 [69]. 

Benzyl ethers can be prepared from THP ethers by the Me3SiOTf-catalyzed reaction with PhCHO and EtiSiH." Analogously, amides, carbamates, and ureas are A -alkylated via condensation with aldehydes followed by in situ reduction with Et SiH. The aldehyde may be replaced by a thioester that is subject to reduction in situ. Thus, a mixture of sodium triacetoxyborohydride, triethylsilane, and Pd-C catalyst is employed. ... 

In 2005, Ramesh Chandra MoUiotra published a remarkable three-step-one-pot procedure, based on two consecutive reductive amination reactions with sodium triacetoxyborohydride. The overall-yield is 40%. [Ill]... 

In addition to the classical reactions, this book covers many techniques and reactions that have more recently gained wide use among practicing chemists. Molecular-orbital theory is introduced early and used to explain electronic effects in conjugated and aromatic systems, pericyclic reactions, and ultraviolet spectroscopy. Carbon-13 NMR spectroscopy is treated as the routine tool it has become in most research laboratories, and the DEPT technique is introduced in this edition. Many of the newer synthetic techniques are also included, such as asymmetric hydrogenation and epoxidation, use of sodium triacetoxyborohydride, Birch reduction, Swern oxidations, alkylation of 1,3-dithianes, and oxidations using pyridinium chlorochromate. 

Lhommet s team has reported a second synthesis of (—)-lupinine (926) based on a convenient multicomponent condensation of the 5-ketoester 1024, (S)-phenylglycinol (1025) and acrolein (Scheme 127). That the reaction yielded a 2 1 mixture of chiral tetrahydro[l,3]oxazolo[3,2-mixture—effectively a masked iminium ion—with sodium triacetoxyborohydride led to the piperidine (—)-1027 as a single isomer. Hydrogenolysis of 1027 followed by treatment with p-toluenesulfonic acid brought about cyclization to the bicycHc lactam (- -)-1028, which underwent reduction of both the ester and the lactam with lithium aluminum hydride to complete this short synthesis of (—)-926. 

Stereoselective syntheses of (Z, , )- and ( ,ZJ5)-trienylesters and nitriles have been developed based on the reaction of tricarbonyl(Ti -dienone)iron complexes with the anions of ethyl acetate and acetonitrile, respectively. Diastereoselective intramolecular double reductive aminations of tricarbonyl(ri -2,4-dienone)iron complexes with 1,4- or 1,5-keto-aldehyde side chains using primary amines in the presence of sodium triacetoxyborohydride provides piperidines (Scheme 4-144) " and pyrrolidines, respectively. ... 

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