Why use a weaker reducing agent?
Robinson, John.; Snyder,.
Theres no need to isolate the intermediate imine (which tend to be somewhat unstable anyway the reduction can be performed in situ (i.e.Its possible to use the familiar reducing agent sodium borohydride (NaBH4) for this process.N (1c) 1H NMR (300 MHz, CDCl3).198.16 (m,.967.92 (m,.85 (d,.0 Hz,.607.33 (m,.31 (s,.99 (s,.87 (bs, 1H 13C NMR (75.4 MHz, CDCl3) 140.5, 136.1, 134.1, 132.1, 128.9, 128.6, 128.5, 128.0, 127.2.Sequential Reductive Aminations, another useful feature of reductive amination reactions is that two (or three if one starts with ammonia) reductive aminations can be employed in sequence.Once the imine is formed, the CN bond can be reduced, giving us a new alkyl group attached to nitrogen.In short, reductive amination is a very powerful and useful protocol for the formation of amines.It is considered the most important way to make amines, and a majority of amines made in the pharmaceutical industry are made this way.Buchwald-Hartwig cross coupling is one of them.The nice part is that the groups just go on once.In the schemes below, well use NaBH3CN, but NaBH4 and NaBH(OAc)3 can be considered to work just as well.Alkynes reductive amination wont work.10 The sequence from keto-acid to amino acid can be summarized as follows: HO2CC(O)R HO2CC(NCH2X)R HO2CCH(nchx)R HO2CCH(NH2)R.
In Overman, Larry.
Click to see image, after the imine is formed, it must be reduced to the amine. .
Reductive Amination, enter reductive amination!Once the imine forms at pH 4-5, some of it will be converted into its conjugate acid, an iminium salt.N (1i) 1H NMR (300 MHz, CD3OD).15 (d,.3 Hz,.87 (t,.8 Hz,.72 (d,.6 Hz,.206.03 (m,.13 (s, 2H 13C NMR (75.4 MHz, CD3OD) 159.0, 157.3, 151.6, 132.1, 130.6, 129.7, 116.1, 106.5, 105.2.The process is catalyzed by pyridoxamine phosphate, which is converted into pyridoxal phosphate after the reaction.For example, look at the synthesis of the tertiary amine below.Reductive amination is extremely versatile and can be used to install a large variety of different alkyl groups on an amine.717 Kalbasi, Roozbeh Javad; Mazaheri, reduction carte imagine r adidas Omid (2015).Typical reagents that meet these criteria include sodium cyanoborohydride (NaBH3CN) and sodium triacetoxyborohydride (NaBH(ococh3)3).See also edit References edit Warren, Stuart Wyatt, Paul (2008).Say you have a primary amine such as benzylamine and would like to make.Biochemistry edit A step in the biosynthesis of many - amino acids is the reductive amination of an -ketoacid, usually by a transaminase enzyme.