Reductive amination, and

Anton DL, R Kutny (1987) Escherichia coli 5-adenosylmethionine decarboxylase. Subunit structure, reductive amination, and NHj-terminal sequences. J Biol Chem 262 2817-2822. 

A combination of a reductive amination and a Michael addition has been used to synthesize the anticancer alkaloid camptothecin (2-955) via 2-954, starting from the quinoline carbaldehyde 2-953 and benzylamine (Scheme 2.214) [487]. 

In the chemistry described in Scheme 6.151, Coats and a group of researchers from Johnson and Johnson utilized successive reductive aminations and Suzuki cross-coupling reactions to prepare a 192-member library of tropanylidene benz-amides [295], This series of tropanylidene opioid agonists proved to be extremely tolerant with regard to structural variation while maintaining excellent opioid activity. 

This chapter aims to provide an overview of the current state of the art in homogeneous catalytic hydrogenation of C=0 and C=N bonds. Diastereoselec-tive or enantioselective processes are discussed elsewhere. The chapter is divided into sections detailing the hydrogenation of aldehydes, the hydrogenation of ketones, domino-hydroformylation-reduction, reductive amination, domino hydroformylation-reductive amination, and ester, acid and anhydride hydrogenation. 

Catalytic reduction (Raney-Ni, H2) of the nitroso acetal-mesylate 243 resulted in reductive cleavage of both N-O bonds followed by intramolecular reductive amination and finally intramolecular iV-alkylation providing the masked 7-epiaustraline alkaloid 244 (Scheme 65) <1998JA7357>. 

Table 5.8 Transfer hydrogenation, reductive amination and dehalogenation of water-soluble compounds with 24, 27 28, and hydrogen donors."...

The two main resin linkers developed so far are shown in Scheme 18, i.e. tris(alk-oxy)benzylamide- 412 and 4-alkoxybenzylamide-type linkers)341 the former being TFA labile and thus fully compatible with Fmoc/tBu and the latter strongly acid labile and correspondingly compatible with Boc/Bzl chemistry. As shown in the case of the tris(alk-oxy)benzaldehyde handle such handles may be introduced into the C-terminal amino acid ester by reductive amination, and after suitable N -protection coupled to amino-functionalized resins (see Scheme 18). Alternatively, the tris(alkoxy)benzaldehyde-functionalized resin, BAL resin, (see Scheme 14) is used to link the C-terminal amino acid ester by reductive amination. To overcome the difficult acylation of the V -arylamino acid ester derivative on resin (best results with 10 equivalent symmetrical anhydrides), synthesis in solution of the C-terminal dipeptide building block containing the amide handle followed by its attachment to the resin has been proposed)341 ... 

Compare this synthesis with Solved Problem 19-5(b) to see how reductive amination and acylation-reduction can accomplish the same result. 

The second alternative is to convert to an imine, which can be disconnected to amine plus carbonyl compound, This approach is known as reductive amination, and we discussed it in detail in Chapter 14. 

In Schemes 8.204 and 8,205 above we showed that tritylamines can be generated by reductive amination and N-alkylation of trityiamine. However, N-alkyla-tion of amines by triphenylmethyl chloride (mp 110-112 °C) or triphenylmethyl bromide (mp 152-154 °C) in an aprotic solvent such as chloroform or chloro-form-DMF mixtures together with a base such as triethylamine is the most common method for introduting the trityl group [Scheme 8,212]434 4,4 -Dimethoxy-trityl tetrafluoroborate and 4i4, 4"-trimethoxytrityl tetrafluoroborate are also... 

The synthetic scheme used to prepare the library is shown in Fig. 8.10. The reaction steps, amide coupling, ozonization, reductive amination, and catalytic reduction, are trivial for carbohydrate substrates, and the authors decided that assessment of the chemistry for the library synthesis would not have been necessary. The availability of 8.19 in multigram quantities reduced the significance of potentially low-yielding steps. The rehearsal of the monomers was also avoided because of the small size of the two monomer sets Mi (four Fmoc-protected a-amino acids, Fig. 8.10) and M2 (six amines. Fig. 8.10), which were inspired by a model for the interaction between paromomycin and RNA (55). Finally, such a small array could be considered as a model library for a much larger solution-phase library of potential RNA binding molecules. 

Although the use of NaBH CN alone for reductive amination has thus far dominated ai lications in synthesis, modified cyanoborohydride derivatives and other reagents, which offer viable alternatives and potential improvements, have recently been introduced. Thus, Zn(BH3CN)2 (methanol solvent) is apparently equally effective for reductive aminations and amine methylations and, in most cases, requires... 

You might Imagine that pyridoxamine is a product of reductive amination of pyridoxal with ammonia. In practice It doesn t work like that. Nature uses an amine transfer rather than a simple reductive amination, and the family of enzymes that catalyse the process Is the family of aminotransferases. 

DSM, working initially with DuPont and then later with Shell, have developed a process using butadiene and carbon monoxide feedstocks to make caprolactam without ammonium sulfate production in the mid-1990s. Called Altam, the process employs four steps - carbonylation, hydroformylation, reductive amination and cyclization. DSM claims cost reductions of 25-30%, simplified plant operations and lower energy consumption, but the process never reached commercial scale. 

In another approach, the two applications were combined and an ion-exchange resin was used both as a reagent and as the purification agent in a synthesis of tetramic acids [42] (Scheme 13). Starting from amino add esters 38, reductive amination and subsequent couphng with acids led, after extractive work-up, to... 

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