Pyridines reductive amination

Reductive amination with pyridine bases 99UK61. 

Reductive amination of benzaldehyde with (R)-81 provided the corresponding benzyl amine, which was reductively alkylated with formaldehyde to give 82 (Scheme H) " Compound 82 was debenzylated by hydrogenation in the presence of Pearlman s catalyst to afford frovatriptan ((/J)-6). Alternatively, monomethylation of amine (/ )-81 was affected by treatment with carbon disulfide and dicyclohexylcarbodiimide in pyridine to provide isothiocyanate 83, which was reduced with sodium borohydride to give (l )-6. 

With the aim of developing new analogues of the cyclic AMP phosphodiesterase inhibitor lixazinone (554), the synthesis of agents 553 and 555-557 was undertaken (Scheme 167) (88JMC2136). Thus, all possible 1,2-related N-r-Boc aldehydes 551 were prepared by directed metalation on isomers 549, with the exception of that which required the use of a metal-halogen exchange reaction on the bromo precursor 550 (attempts to metalate 4-TMS-3-N-f-Boc pyridine proved inefficient). As exemplified for one particular isomer, conversion of 551 into 552 by reductive amination... 

A-Aminopyridiniums and A-imines yield pyridines and amines upon reduction, e.g. (979) — (980) + PhNH2 (H2/Pt or Zn/NaOH). 

Dyes containing the pyridinium group linked to the diazo component via a carboxylic ester function (e.g., 40) [32017-47-3] are obtained by condensation of 4-nitrobenzoyl chloride with chloroethanol, reaction of the ester with pyridine, reduction of the nitro to an amino group, diazotization, and coupling with aromatic amines [124],... 

Buchanan, Bachofen, and Arnon (29) showed that the conversion of pyruvate to the above amino acids required DPN and NHs- They found a ferredoxin-dependent reduction of DPN with hydrogen gas was catalyzed by Ckromalium extracts, and concluded that DPNH2, formed from reduced ferredoxin, and NH3 were used in reductive amination reactions leading to the synthesis of amino acids. A ferredoxin-dependent reduction of pyridine nucleotides was shown first for spinach chloroplasts (Tagawa and Arnon (99) it was shown later in other photosynthetic bacteria, when ferredoxin was reduced either with dithionite (Yamanaka and Kamen (115)) or with hydrogen gas and hydrogenase (Weaver, Tinker, and Valentine (112)). 

As in pyrrole, the lone pair on the indole N is part of the aromatic sextet. One N in histidine is like that in pyridine, with the lone pair in an sp2 hybrid orbital. 24.9. Reductive amination of (a) CH3COCOOH ... 

The NN bond in -aminopyridiniums and A -imines can be easily reductively cleaved to yield pyridines and amines, e.g., H2Pt or ZnNaOH. Thermolysis of pyridine Af-acylimides 1023 gives isocyanates RNGO and pyridine. 

Inspired by the recent observation that imines are reduced with Hantzsch esters in the presence of achiral Lewis or Brpnsted acid catalysts (Itoh et al. 2004), we envisioned a catalytic cycle for the reductive amination of ketones which is initiated by protonation of the in situ generated ketimine 10 from a chiral Brdnsted acid catalyst (Scheme 13). The resulting iminium ion pair, which may be stabilized by hydrogen bonding, is chiral and its reaction with the Hantzsch dihydropyridine 11 could give an enantiomerically enriched amine 12 and pyridine 13. 

Reductive amination of carbonyl compounds. Sodium cyanoborohydride has been the reductant of choice for this reaction, even though it is highly toxic (4, 448-449). Borane-pyridine is recommended as a nontoxic substitute. The reactions are conducted in acetic acid, in which this borane is fairly stable, and a co-solvent such as CH2CI2 or THE... 

Construction of the second part of the molecule starts with palladium-catalyzed coupling of the substituted pyridine (238) with phenylboronic acid to give 239. Hydrogenation reduces both the nitro group and the supporting pyridine ring to afford 240 as the cis isomer. The enantiomers of this are then separated by resolution. The desired isomer is then subjected to reductive amination with aldehyde 237 affording 241. " ... 

Sainsbury and co-workers (121) have synthesized several ellipticine dimers tethered through the C-5 methyl group (333) (Scheme 53) or the C-9 position (334). The 9-methoxy derivative of 333 was also prepared. The nitrile 329 was available from the Sainsbury ellipticine synthesis (122) and was transformed into the alkaloid 17-oxoellipticine (148). A clever maneuver was to add nitric acid to protonate the pyridine nitrogen of 330. This precluded A-oxide formation during dithiane hydrolysis. Reductive amination in two steps afforded the amine 332. Coupling with adipic acid gave the target bisellipticine 333. 

Treatment of 462 with iodine and pyridine leads to a-iodination [208]. Successive reduction under Luche conditions, alcohol silylation, carbonylation of the iodoalkene, reduction of the obtained enal and alcohol silylation leads to 463. Ozonolysis of 463 gives the corresponding keto-aldehyde, which is then transformed into 464 via reductive amination with high diastereoselectivity syn anti> Deprotection delivers (-f)-465 (Scheme 13.107). 

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