Aryl/heteroaryl, diaryl ketones

The hydrogenation of diaryl ketones or aryl heteroaryl ketones can even be conducted enantioselectively, if the ketones contain different steric or electronic properties. One impressive example of such a hydrogenation is shown in Equation 15.74. In this process, the aryl thazolyl ketone is reduced with the optimized Noyori catalyst with exceptionally high enantioselectivity. This product is then carried forward for the synthesis of an FDE-IV inhibitor. 

Further optimization of the catalytic system for the asymmetric reduction of diaryl- and aryl heteroaryl ketones was disclosed by Chan and Wu [26]. In modification of the blueprint of the successful catalyst introduced by Lipshutz [25] (vide supra), SEGPHOS L3 was replaced with ligand L8, whereas CuH was prepared from hydrated Cu(OAc)2 (5 mol%), f-BuONa (5 mol%), f-BuOH (4 equiv.) and PMHS (4 equiv.) (Scheme 12). With this catalytic system, the time required for... 

Direct Carbonylative Coupling. Unsymmetrical diaryl ketones were synthesized via the direct carbonylative coupling of aryl iodides and heteroarenes in the presence of catalytic [PdCl(cinnamyl)]2, l,3-bis(diphenylphosphino)propane (dppp) as the ligand, and stoichiometric Cul. Thus, heterocycles such as oxazoles, benzoxazoles, thiazoles, benzothiazoles, and imidazoles reacted, with 4-iodoanisole in 56-75% yields (eq 1). Aryl iodides containing a variety of electron-donating or electron-withdrawing substitutents were tolerated in the reaction (eq 2) however, aryl bromides provided only traces of products. The role of the stoichiometric copper salt was to form a heteroaryl-Cu species, which could easily transmetallate to Pd. No reaction was observed in the absence of the Cul additive. 

Iron(III)-catalyzed arylation of aroyl and heteroaroyl cyanides with aryl and heteroaryl magnesium reagents provides an easy and mild approach to polyfunctionalized diaryl ketones in high yields (Scheme 4-245). ... 

Nucleophilic displacement of chlorine, in a stepwise manner, from cyanuric chloride leads to triazines with heteroatom substituents (see Section 6.12.5.2.4) in symmetrical or unsymmetrical substitution patterns. New reactions for introduction of carbon nucleophiles are useful for the preparation of unsymmetrical 2,4,6-trisubstituted 1,3,5-triazines. The reaction of silyl enol ethers with cyanuric chloride replaces only one of the chlorine atoms and the remaining chlorines can be subjected to further nucleophilic substitution, but the ketone produced from the silyl enol ether reaction may need protection or transformation first. Palladium-catalyzed cross-coupling of 2-substituted 4,6-dichloro-l,3,5-triazine with phenylboronic acid gives 2,4-diaryl-6-substituted 1,3,5-triazines <93S33>. Cyanuric fluoride can be used in a similar manner to cyanuric chloride but has the added advantage of the reactions with aromatic amines, which react as carbon nucleophiles. New 2,4,6-trisubstituted 1,3,5-triazines are therefore available with aryl or heteroaryl and fluoro substituents (see Section 6.12.5.2.4). 

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