Cleavage of imidazoles

Cleavage of imidazoles to enediamides, useful In synthesis of 2substrtuted imidazoles. 

Cleavage of imidazoles dehydroamino acids,3 2,4-Disubstituted imidazoles4 undergo a Diels-Alder-like reaction with singlet oxygen in the presence of DBU (1-2 equiv.) to provide imine diamides, which isomerize to dehydroamino acid derivatives in the presence of base. Hydrogenation in the presence of catalysts with chiral phosphine ligands results in optically active amino acid diamides. The overall process is illustrated for the synthesis of the N-benzylamide of N-acetylleucine (equation I). 

Grace ME, Loosemore MJ, Semmel ML, Pratt RF. Kinetics and mechanism of the Bamberger cleavage of imidazole and of histidine derivatives by diethyl pyrocarbonate in aqueous solution. J Am Chem Soc. 1980 102 6784-6789. 

Figure 4. Proposed Mechanism for the Oxidative Cleavage of Imidazole Ring in Histidine with Glucosone-Cu(II) System.

The pyrazole ring is resistant to oxidation and reduction. Only ozonolysis, electrolytic oxidations, or strong base can cause ring fission. On photolysis, pyrazoles undergo an unusual rearrangement to yield imidazoles via cleavage of the N —N2 bond, followed by cyclization of the radical iatermediate to azirine (27). 

Depurination - N7 alkylation may cause cleavage of the imidazole ring and excision of the guanine residue, leading to DNA strand breakage. 

The amino acid 58 was used in the solid-phase synthesis of sequence-specific DNA binding polyamides containing N-methylimidazole and N-methylpyrrole amino acids <96JACS6141> and it was also reported that the imidazole-acridine conjugate 59 could effectively catalyze the cleavage of t-RNA <96TL4417>. 

The enantioselective P-borylation of a,P-unsaturated esters with (Bpin) was studied in the presence of various [CuCl(NHC)] or [Cu(MeCN)(NHC)] (NHC = chiral imidazol-2-ylidene or imidazolidin-2-ylidene) complexes. The reaction proceeds by heterolytic cleavage of the B-B bond of the (Bpin), followed by formation of Cu-boryl complexes which insert across the C=C bond of the unsaturated ester. Best yields and ee were observed with complex 144, featuring a non-C2 symmetric NHC ligand (Scheme 2.31) [114]. 

A two-step mechanism must be assumed for this very valuable reaction of carboxylic acids with CDI.[9] Obviously the first step is a nucleophilic attack of the carboxylic acid or —depending on the acidity —the carboxylate ion on the carbonyl group of CDI, leading after elimination of imidazole to a mixed anhydride of imidazole-iV-carboxylic acid and the attacking carboxylic acid. This intermediate must have a very short life-time since it has not been detected down to — 50 °C. Rapid cleavage of CO2 from this mixed anhydride involves exclusively the carbonyl group linked to the imidazole unit If... 

Mass spectrometry indicated this metabolite has undergone oxidative cleavage of the imidazole ring. 

Bis(oxazolinyl)pyridine-Ce(IV) triflate complex 78 catalyzed the enantioselective 1,3-DC of acyclic nitrones with a, 3-unsaturated 2-acyl imidazoles. For example, C-phenyl 7V-benzyl nitrone reacted with 77 in the presence of 78 to give the adduct 79 with excellent diastereo-and enantioselectivity. Isoxazolidine 79 was then converted into P -hydroxy-P-amino acid derivatives by hydrogenation of the N-0 bond in the presence of Pd(OH)2/C and cleavage of the 2-acyl imidazole with MeOTf in MeCN <06OL3351>. 

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