Methylamine chiral derivative

Chiral polymer-supported thiiranes 401 were prepared by free radical copolymerization of TMA ((3)-thiiranylmethyl-methacrylate) and ethylene glycol dimethacrylate (EDMA) (Equation 60) <2006TA1944>. These chiral thiiranes were transformed into polymer-supported aminothiols by the facile ring opening of the thiirane group with benzylamine and methylamine. These derivatives, complexed with [RuCl2(p-cymene)]2, were used in assymmetric reduction of acetophenone to gave (A)-l-phenylethanol (39% ee from methylamine and 50% ee from benzylamine derivatives). 

In this thiamine pyrophosphate-mediated process, ben2aldehyde (29), added to fermenting yeast, reacts with acetaldehyde (qv) (30), generated from glucose by the biocatalyst, to yield (R)-l-phen5l-l-hydroxy-2-propanone (31). The en2ymatically induced chiral center of (31) helps in the asymmetric reductive (chemical) condensation with methylamine to yield (lR,23)-ephedrine [299-42-3] (32). Substituted ben2aldehyde derivatives react in the same manner (80). 

The double dynamic system comprised 24 chiral aminonitrile intermediates, carrying different substituents on the aromatic moiety and the /V-position, and was subsequently challenged by the lipase-mediated amidation resolution process. Not only H-XMR spectroscopy was used to follow the reactions HPLC, through the integration of preparative Zorbax and chiral OD-H columns, was used to confirm the product formations and to analyze the enantioselectivities. According to both analyses, the results indicated that only /V-methyl aminonitriles, produced from methylamine A, were transformed by the lipase resolution process. The major product was found to be amide 33A, derived from its corresponding intermediate 32A. The other products were amides 36A and 30A. 

Racemic 2-aminobutan-l-ol (1) is a cheap chemical which can be easily resolved into both its enantiomers on an industrial scale. The asymmetric synthesis of chiral amines from hydrazines derived from (7 )-(—)-2-aminobutan-l-ol [(R)-(—)-l], using the general strategy disclosed in early works, is summarized here. The title hydrazine (4) is prepared as follows (eq 1). Treatment of the amino alcohol [(7 )-(—)-l] with excess ethyl formate followed by LAH reduction of the intermediate formamide gives the N-methylamine [(7 )-(—)-2]. IV-Nitrosation of the latter afforded (R)-(+)-3 which is next reduced to the hydrazine [( )-(—)-4] by means of LAH. Being unstable, the hydrazine (4) must be used immediately without purification. 

The work on methylamine — clearly the simplest aliphatic amine — also demonstrates, however, that not only the amine, but also the deamination method must be simple. We discussed the stereochemistry of the deamination in the rearrangement of a derivative of chiral methylamine (7.30) in Section 7.3, but first, we have doubts whether Gautier s result (1980, inversion) of the pyrolysis of that N-methyl-N-nitroso-toluenesulfonamide in an aprotic solvent at 95 °C is comparable with the direct nitrosation of an amine in water, and second, the result of Gautier is contrary to that of the stereochemical investigation of a somewhat more complex amide deamination, namely that of N-(l-methylpropyl)-N-nitroso-4-toluenesulfon-amide (White et al., 1981 see Sect. 7.3). ... 

In 2011, WulfTdescribed the first three-component catalytic asymmetric aziridi-nation reaction of an aldehyde 92, bis(dimethylanisyl)methylamine (163), and ethyl diazoacetate (164) to provide the corresponding chiral aziridine-2-carboxylic esters (165) [55]. When promoted by a chiral boroxinate catalyst in situ generated from B(OPh)3 and chiral Hgand (S)-VAPOL (2,2 -diphenyl-(4-biphenanthrol)), the reaction afforded products 165 with good yields and excellent diastereoselectivities and enantioselectivities (Scheme 11.36). This novel methodology furnished an effective solution to the problem of unstable imines derived from aliphatic aldehydes that cannot be purified. 

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