2- Substituted 1,3-dihydroimidazole

Increasing steric bulk at one of the NHC side groups will cause interference with the active site of the complex and generate an amplifying effect on alternation control. A methyl substituted one-carbon spacer like in l-mesityl-3-((rR)-l-phenylethyl)-4,5-dihydroimidazol-2-yhdene is enough to dramatically improve the alternation rate [129]. In Fig. 3.31 the steric impact on monomer coordination for different situations is rationahsed. 

In 1991 Arduengo and co-workers42 reported the isolation and characterization of the first stable carbene, l,3-di(l-adamantyl)-2,3-dihydroimidazol-2-ylidene. Since that time many substituted nucleophilic carbenes have been prepared.43 From ab initio studies it can be shown that cyclic electron delocalization is partly responsible for the extraordinary stability of 2,3-dihydroimidazol-2-ylidenes.44... 

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). ... 

Halo-4,5-dihydroimidazoles are commonly generated in situ for the preparation of heteroatom substitutions at the 2-position, for example, (Scheme 113) by interaction with POCI3, as in the formation of 511 <2005BML4691>. 

In contrast to 83 and 85, 1,2-dimethyl-4,5-dihydroimidazole (89, n = 2) and 1,2-dimethyl- 1,4,5,6-tetrahydropyrimidine (89, n = 3) underwent direct acylation with two equivalents of aroyl chloride to give diacylenediamines 90 rather than enol benzoates. Their acid hydrolysis with sulfuric acid at water bath temperatures results in cleavage of one of the aroyl groups and benzoyl-substituted 1,1-enediamines 91 are formed in moderate yields (equation 31)103. 

Alkylidene imidazoles are best described as either ketene acetals or enamines, depending on the positions of substitution. 2-(2-Propylidene)imidazoles such as 787 (Scheme 195) react with azides to form spiroheterocycles 788. The reaction rates vary widely depending on the hybridization of C(4)-C(5) bond of the dipolarophiles dihydroimidazoles react in days while imidazoles take only hours <2005HCA1589>. 

While 2-substituted-4,4,6-trimethyl-5,6-dihydro-1,3-oxazines 2-substituted-4,4-dimethyl-2-oxazo-lines and l-benzyl-2-alkyl-4,S-dihydroimidazoles are inert to organometallic addition, their corresponding methiodide salts ST)- S9) are reactive and have been utilized for the synthesis of ketones (60 ... 

The unusual condensation of 2-bromoalkylidene malonitrile (66) with 4,5-dihydroimidazole-2-thione (67) gave a substituted 2,3-dihydro-l/7-pyrrolo[l,2-a]imidazole (68) in moderate yield <84TL390l>. A general synthesis of these systems is shown by the intramolecular cyclization reaction of l,3,4,5-tetrasubstituted-2-aminopyrrole (69) to give the corresponding pyrrolo[l,2-a] imidazole derivative (70) in good yield <86JHC393>. Both of these reactions are shown in Scheme 10. 

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],... 

Electron-rich and ortho-substituted aryl chlorides were converted to the respective anilines in excellent yields within 1 h on a 1 mmol scale, emphasizing the exceptional activation in combination with the electron-rich phosphine. Another class of strong a-donors are N-heterocychc carbenes. Their Pd(0) complexes can undergo facile oxidative addition of aryl halides. Nolan et al. [44] used the SIPr ligand (SIPr = (l,3-bis(2,6-diisopropyl)phenyl-4,5-dihydroimidazol-2-ylidene), 19) for the Pd-catalyzed arylation of stericaUy encumbered anilines with stericaUy demanding aryl chlorides at room temperature (Scheme 13.66). 

Much research has been geared to improve catalytic activity and stability by increasing the o donation via A-alkyl-substituted NHCs. However, many symmetrically A-alkyl-substituted complexes were either not formed or were unstable and displayed reduced activity compared to the parent complexes [55-57]. For example, complex 30 bearing l,3-di(l-adamantyl)-4,5-dihydroimidazol-2-ylidene could not be formed [55] and complex 31 reported by Louie and Grubbs failed to perform even the benchmark RCM of 17 [57]. The reduced stability of these complexes was attributed to the weak NHC-metal bond resulting from the sterically demanding alkyl substituents [56]. In contrast, the phosphine-free... 

By using mesityl-substituted NHCs, Grubbs and Nolan disclosed, practically simultaneously, the synthesis of the Ru-alkylidene complexes 19 (NHC = l,3-dimesitylimidazol-2-ylidene) soon thereafter, the Grubbs group firther introduced complexes 20 (Cy = cyclohexyl) and 21 (Cp = cyclopentyl) containing a saturated NHC (l,3-dimesityl-4,5-dihydroimidazol-2-ylidene). 

We have shown that the l,3-bis-(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene substituted Ru-based complex (4) are active catalyst precursor in the ROMP of COD. This air and water tolerant complex was shown to exhibit... 

Substituted imidazoles 55 are prepared by dehydrogenation of 2-substituted 4,5-dihydroimidazoles 54, which are obtained (a) from nitriles and ethylenediamine in the presence of catalytic amounts of sulfur under ultrasonic irradiation [400] and (b) from aldehydes and ethylenediamine in the system I2/KI/K2CO3/H2O, which effects C-N-oxidation of the primarily formed imidazolidines 56 to the imidazolines 54 [401] ... 

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