A,p-unsaturated 2-acyl imidazoles

Bis(oxazolinyl)pyridine-Ce(IV) triflate complex 78 catalyzed the enantioselective 1,3-DC of acyclic nitrones with a,p-unsaturated 2-acyl imidazoles. For example, C-phenyl A -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>. 

Scheme 6.35 AFC reaction of indoles with a,p-unsaturated 2-acyl imidazole catalyzed by chiral-at-metal octahedral Ir complex A-91 reported by Meggers.

In 2009, Roelfes and co-workers reported the catalytic AFC alkylation reaction with olefins in water mediated by a DNA-based catalyst. The DNA-based catalyst is self-assembled by combining a Cu" complex with salmon testes DNA (st-DNA), which is inexpensive and readily available. With 4,4 -dimethyl-2,2 -bipyridine (dmbpy) as the ligand, 30 mol% (0.3 mM) of [Cu(dmbpy)(N02)2] (Cu-dmbpy) and 1.4 mg mL of st-DNA (2 mM in base pairs) were found to be the optimal reaction conditions for the AFC reaction of indoles with o,p-unsaturated 2-acyl imidazoles 98. The AFC products 99 were obtained in good yields and enantioselectivity (Table 6.11). Particularly noteworthy was that with 0.15 mol% catalyst, good yields and high ee values (up to 93 /o) were also obtained for various a,p-unsaturated 2-acyl imidazoles 98 and indoles. 

Later, this catalytic system was successfully applied to the Friedel-Crafts alkylation of various a,P-unsaturated 2-acyl imidazoles with indole derivatives [152]. The corresponding products were obtained in moderate to excellent yields with moderate to excellent enantioselectivities, the best selectivity being displayed with... 

Furthermore, enantioselective additions of pyrroles to a,P-unsaturated 2-acyl imidazoles catalyzed by the same catalyst system have been accomplished (69-99%, 77-96% ee) [153]. Using this methodology, a short enantioselective synthesis of an alkaloid ( + )-heliotridane has been attained. This process was then extended to a one-pot asymmetric synthesis of 2-substituted indoles from 4,7-dihydroindoles. 

Evans and coworkers reported Ce(IV)-PyBOX catalyzed highly enantioselective nitrone cycloaddition by employing a,P-unsaturated 2-acyl imidazoles. Five mole percent of Ce(OTf)4/Ph-PyBOX promoted the reaction under mild conditions (0°C, EtOAc), giving products in up to 99% yield, 97% ee, and endojcxo =... 

Scheme 13.25 Ce(IV)/PyBOX-catalyzed asymmetric 1,3-dipolar cycloaddition using a,p-unsaturated 2-acyl imidazole and transformation of isoxazoline adduct.

Evans and coworkers [44] expanded the scope of enanti-oselective Friedel-Crafts alkylation of indoles 122 through the utilization of a series of p-snbstituted a,p-unsaturated phosphonates 123 and a,p-nnsaturated 2-acyl imidazoles 124 (Scheme 10.25). The active catalyst was proposed to be the respective complex of these enones in a bidentate fashion with bis(oxazolinyl)pyridine-scandium(III) triflate 125. Generally, this asymmetric addition reaction was found to be... 

In parallel with the directed hydroarylation of olefins, a series of papers described the formation of ketones from heteroarenes, carbon monoxide, and an alkene. Moore first reported the reaction of CO and ethylene with pyridine at the position a to nitrogen to form a ketone (Equation 18.28). Related reactions at the less-hindered C-H bond in the 4-position of an A/-benzyl imidazole were also reported (Equation 18.29). - Reaction of CO and ethylene to form a ketone at the ortho C-H bond of a 2-arylpyridine or an N-Bu aromatic aldimine has also been reported (Equations 18.30 and 18.31). Reaction at an sp C-H bond of an N-2-pyridylpiperazine results in both alkylative carbonylation and dehydrogenation of the piperazine to form an a,p-unsaturated ketone (Equation 18.32). The proposed mechanism of the alkylative carbonylation reaction is shown in Scheme 18.6. This process is believed to occur by oxidative addition of the C-H bond, insertion of CO into the metal-heteroaryl linkage, insertion of olefin into the metal-acyl bond, and reductive elimination to form the new C-H bond in the product. 

Allylation of acyloyl-imidazoles and pyrazoles61 with allyl halide mediated by indium in aqueous media provides a facile regioselective synthesis of P, y-unsaturated ketones (Scheme 11.1), which has been applied to the synthesis of the monoterpene artemesia ketone. The same product can be obtained by indium-mediated allylation of acyl cyanide (Eq. 11.35).62 Samarium, gallium, and bismuth can be used as a mediator for the allylation of nitrones and hydrazones to give homoallylic hydroxylamine and hydrazides in aqueous media in the presence of Bu4NBr (Scheme 11.2).63 The reaction with gallium and bismuth can be increased dramatically under microwave activation. 

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