Sodium triacetoxyborohydride reductive amination

Sodium triacetoxyborohydride is an alternative to NaBH3CN for reductive amination. This reagent can be used with a wide variety of aldehydes or ketones with primary and secondary amines, including aniline derivatives.93 This reagent has been used successfully to alkylate amino acid esters.94... 

Sodium cyanoborohydride [123], sodium triacetoxyborohydride [124] or NaBH4 coupled with sulfuric acid [125] are common agents used for the reductive amination of carbonyl compounds. These reagents either generate waste or involve the use of corrosive acids. The environmentally friendlier procedures developed by Varma and coworkers have been extended to a solvent-free reductive amination protocol for carbonyl compounds using moist montmorillonite K 10 day supported sodium borohydride that is facilitated by microwave irradiation (Scheme 6.39) [126]. 

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... 

Reductive Animation for Synthesis of PAL-Resin-Bound Amines (59) (Fig. 10)15. To a suspension of 4-formyl-3,5-dimethoxyphennoxymethyl functionalized polystyrene resin (PAL)25 (10.0 g, 11.3 mmol) in DMF (350 ml) a primary amine (56.5 mmol) is added followed by addition of sodium triacetoxyborohydride (7.18 g, 33.9 mmol) and acetic acid (6.52 ml, 113 mmol). The suspension is shaken gently at RT overnight. Resin 59 is washed with methanol (4 x 300 ml) and CH2C12 (4 x 300 ml) and dried under vacuum. Subsequent derivatization products can be cleaved from the resin by a 2 h treatment with CH2Cl2/TFA/Me2S/H20 45 45 5 5. 

A dynamic kinetic resolution has been employed to achieve a catalytic asymmetric reductive amination of aldehydes.332 Reductive amination of ketones and aldehydes by sodium triacetoxyborohydride has been reviewed, highlighting its advantage over other reagents.333... 

An alkylation by reductive amination using aldehyde 253 in the presence of sodium triacetoxyborohydride in 1,2-dichloroethane afforded the adamantyl compound 253, which after further deprotection produced an A, A -disu Instituted guanidine derivative 254 interesting for potential biological activity (Scheme 105 <2000JME2362>). 

Breitenbucher and Hui (104) have recently reported the SP synthesis of a medium-large discrete library L3 of 8448 benzopyrans using the reductive amination cocktail formed from titanium isopropoxide and sodium triacetoxyborohydride, known in solution but whose applications to SP were rare and limited to single experiments (105, 106). The benzopyran scaffold is present in a number of biologically active compounds (107-110), and this library was tested in several biological assays (111). 

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... 

Another route to the formation of piperidine heterocycles is cyclization via reductive amination utilizing various hydride sources. The scheme below depicts a bis reductive amination, using sodium triacetoxyborohydride as the hydride source, to generate exo- l% and endo- 19 azabicyclo[3.2.1]octane amino acids in moderate yields <06JOC8467>. 

Sodium triacetoxyborohydride Na[BH(OAc)3] ° and hydrogenation (H2, Pd/C) are used as alternatives to sodium cyanoborohydride for the reductive amination of carbonyl compounds. Also, Zn[BH4]2 is a particularly effective agent for the reductive amination of a,p-unsaturated aldehydes and ketones. ... 

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. 

Abdel-Magid, A.E. Carson, K.G. Harris, B.D., et al. Reductive amination of aldehydes and ketones with sodium triacetoxyborohydride. Studies on direct and indirect reductive amination procedures. J. Org. Chem. 1996, 61, 3849-3862. 

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]... 

Reductive amination of aldehydes and ketones gives primary, secondary, and tertiary amines. Sodium triacetoxyborohydride (STAB-H) [93] or platinum-catalyzed hydrogenations are used as shown in Equations 6.59 [94] and 6.60 [95]. 

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. ... 

The reductive amination of carbonyl compounds can be carried out using sodium cyanoborohydride, sodium triacetoxyborohydride or NaBH coupled with sulfuric acid. These reagents involve the use of corrosive acids and/or produce waste stream. The environmentally benign methods using wet montmorillonite KIO clay supported sodium borohydride facilitated by microwave irradiation has been developed by Varma and Dahiya (1998). Clay montmorillonite KIO not only behaves as a Lewis acid but it also provides water from its interlayers that enhance the reducing ability ofNaBH.. 

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