Reductive amination with NaBH

These derivatives are prepared from the readily prepared hydroperoxide by the standard acid catalyzed ketal formation. Cleavage is achieved under basic conditions by treatment with Triton B in THF at rt, 62-87% yield. This group is stable to Grignard reagents, the Wadsworth-Emmons reaction, and reductive amination with NaBH(OAc)3. ... 

Sodium cyanoborohydride is remarkably chemoselective. Reduction of aldehydes and ketones are, unlike those with NaBH pH-dependent, and practical reduction rates are achieved at pH 3 to 4. At pH 5—7, imines (>C=N—) are reduced more rapidly than carbonyls. This reactivity permits reductive amination of aldehydes and ketones under very mild conditions (42). 

Yet a third method for the synthesis of a-amino acids is by reductive amination of an a-keto acid with ammonia and a reducing agent. Alanine, for instance, is prepared by treatment of pyruvic acid with ammonia in the presence of NaBH As described in Section 24.6, the reaction proceeds through formation of an intermediate imine that is then reduced. 

The N-substituted aminoacids required could be prepared by microwave-assisted reductive amination of aminoacid methyl esters with aldehydes, and although in the Westman report soluble NaBH(OAc)3 was used to perform this step, other reports have shown how this transformation can be performed in using polymer-supported borohydrides (such as polymer-supported cyanoborohydride) under microwave irradiation [90]. An additional point of diversity could be inserted by use of a palladium-catalyzed reaction if suitably substituted aldehydes had been used. Again, these transformations might eventually be accomplished using supported palladium catalysts under microwave irradiation, as reported by several groups [91-93]. 

Reduction of C=N bonds. A simple method for the synthesis of a-stannyl-amines containing a secondary amino group involves borohydride reduction of the corresponding imidoylstannanes. 3-Unsubstituted 4-isoxazolines are available by a reductive elimination of 3-thioisoxazolium salts with NaBH. ... 

The synthetic utility of this method is increased by intercepting the oxazolinium salts with various nucleophiles to prepare lactams that bear an (o-fiinctionalized carbon chain. It is also possible to form azacycles containing a 2-dicyanomethylene group. Direct reduction of the oxazolinium salts with NaBH gives amines. ... 

Recent studies have demonstrated (ref. 10) the potential synthetic utility of C-N bond formation via heteromercuration of carbamate derivatives of unsaturated amines. This prompted us to utilize the dehydration products 19a and 20a in the tropane synthesis via intramolecular heteromercuration. Thus the 1 1 mixture of 19a and 20a was treated with mercuric acetate followed by reduction with NaBH to furnish N-carbobenzoxynortropane (26) in 45% yield (based on reacted starting material). The product 26 must result from reductive demercuration of both organomer-curials 24 and 25 initially formed from the asymmetrical and symmetrical olefins 19a and 20a, respectively, via cationic intermediates 22 and 23 as depicted in Fig. 3. Thus separation of the olefin mixture is not necessary since both the olefins can equally be utilized as the reaction substrates in this cycliza-tion. 

Another interesting application involved the formation of allylic amines 33a-e in enantiomerically pure form as published by the Jprgensen group (Scheme 5.18) [25]. This Mannich reaction was conducted between the benzothiazolesulfonyl-derived aldehydes 31a-e and the Boc-protected aldimine 23a. After the initial Mannich reaction, a subsequent reduction with NaBH was carried out to give rise to the allylic amines 33a-e in moderate yields, but high E/Z-ratios and enantioselectivity. 

Yao et al. reported a chemo- and stereoselective asymmetric total synthesis of (-)-lannotinidine B 179 through two reductive amination in a domino fashion. Thus, the tricarbonyl compound 175 was treated with benzylamine in the presence of NaBH(OAc)3 to give 178 via 176 and 177 (Scheme 9.30) [90]. Similar reductive amination strategies have been apphed for several other natural products [22a]. 

The AMEBA linker " was installed upon NaH-mediated alkylation of Merrifield resin with 4-hydroxy-2-methoxy-benzaldehyde in DMF at 120°C for 5 min under microwave irradiation (Scheme 8.20). The authors then chose to attach 4-methyl-3-nitroaniline to the linker through a previously established two-step reductive amination protocol, involving the imine formation mediated by Ti(0 Pr)4 followed by reduction of the imine using NaBH (OAc)3 (Scheme 8.20). The free amino group was then acylated with 4-(chloromethyl) benzoyl chloride using DIPEA in DMF to form the corresponding amide. 

Microgram amounts of neutral sugars could be detected by reductive amination [NaBH CN-(NH )3 to produce 1-amino-l-deoxy-aldltols, followed by derlvatlzation with the fluorescent labelling reagent NBD-F ( 7-f luoro-i -nitrobenz-2-oxa-l, 3-dlazole ), and reversed phase h.p.l.c. analysis. These derivatives were also suitable for t.l.c. analysis on boric acid Impregnated silica... 

The reduction of a series of the imine macrobicycles of this type with NaBH, has been performed in [14] by Scheme 2.2 to give the corresponding amine capsules. 

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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