Methylene 3,5-dihydroimidazol

In a related fashion, asymmetric amination of ( )-cinnamic acid yields L-phenylalanine using L-phenylalanine ammonia lyase [EC 4,3,1,5] at a capacity of 10,000 t/year [1274, 1601], A fascinating variant of this biotransformation consists in the use of phenylalanine aminomutase from Taxus chinensis (yew tree), which interconverts ot- to p-phenylalanine in the biochemical route leading to the side chain of taxol [1602], In contrast to the majority of the cofactor-independent C-0 and C-N lyases discussed above, its activity depends on the protein-derived internal cofactor 5-methylene-3,5-dihydroimidazol-4-one (MIO) [1603], Since the reversible a,p-isomerization proceeds via ( )-cinnamic acid as achiral intermediate, the latter can be used as substrate for the amination reaction. Most remarkably, the ratio of a- vs, 3-amino acid produced (which is 1 1 for the natural substrate, R = H) strongly depends on the type and the position of substituents on the aryl moiety While o-substituents favor the formation of a-phenylalanine derivatives, / -substituted substrates predominantly lead to p-amino analogs, A gradual switch between both pathways occurred with m-substituted compounds. With few exceptions, the stereoselectivity remained exceUent (Scheme 2,215) [1604, 1605],... 

Synthesis oe Heterocyclic Compounds. In some cases, dehydroamino acids obtained from unsaturated 5(477)-oxazolones have been used as intermediates to prepare other heterocyclic compounds. For example, reaction of 2-benzoylamino-3-substituted-2-alkenoic acids 485 with alkyl or arylisothiocyanates affords 4-aryl-methylene-l,2-disubstituted-5-oxo-4,5-dihydroimidazoles 486 (Scheme 7.155). ... 

NMR and mass spectroscopy indicate that it is 5-hydroxy-4-methylene-4,5-dihydroimidazole (265). 

Heating 2- and 4-dialkylamino-3-azidopyridines 104 in nitrobenzene at 170°C results in a loss of nitrogen from the azide group to give a nitrene that attacks the K-methylene group of the o-dialkylamino substituent with further formation of dihydroimidazoles 105, which are then oxidized by nitrobenzene to IPs 106. Here IcP yields are 40-70%, and the yields of IbPs do not exceed 1(U15% (63JCS1666). 

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