Silver catalysis aldol reactions

Chlorodifluoromethylketones underwent aldol reactions (Eq. 124) via zinc enolates, to afford good yields of a,a-difluoro-/ -hydroxy ketones, in a study by the Kyoto group [327]. Copper(I) or silver salt catalysis was essential and boron-trifluoride additive appeared to exert a key role in the conversion to the enolate. Earlier [328], chlorodifluoromethyl ketones had been converted to the di-fluoroenoxy silanes by the action of zinc in the presence of chlorotrimethyl silane. A difluoroenoxy silane was used by McCarthy and co-workers [329] to synthesise a kynureninase inhibitor (Eq. 125) Lewis acid-mediated reaction with a chloroglycinate installed the key carbon-carbon bond. 

The chemical reactions possible with silver catalysis are multiple and cover cycloadditions, cycloisomerizations, allylations, aldol reactions, and even C-H bond activation. Also, asymmetric versions are known, even though they still need to be improved.3-10... 

Silver salts or reagents have received much attention in preparative organic chemistry because they are useful catalysts for various transformations involving C-G and C-heteroatom bond formation.309 Especially, the silver(i)/ BINAP (2,2 -bis(diphenylphosphino)-l,T-binaphthalene) system is a very effective catalyst for a variety of enantio-selective reactions, including aldol, nitroso aldol, allylation, Mannich, and ene reactions. Moreover, silver salts are known to efficiently catalyze cycloisomerization and cycloaddition reactions of various unsaturated substrates. Recently, new directions in silver catalysis were opened by the development of unique silver complexes that catalyze aza-Diels-Alder reactions, as well as carbene insertions into C-H bonds. 

Scheme 7.11 Domino aldol-tyclisation reaction catalysed by chiral cinchona alkaloid catalysis and silver catalysis.

The reaction of silyl and tin enolates with nitrosobenzene, the so-called nitroso aldol reaction, was studied by Yamamoto and coworkers aiming at an overall enantioselective hydroxylation [254, 255]. This approach faces, however, the problem that in a noncatalyzed reaction, the nucleophilic silyl and stannyl enol ethers 514 attack the nitrogen atom of the ambident electrophile nitrosobenzene 515 so that the formation of hydroxyamino ketones 516 results [254a]. Fortunately, the authors developed suitable procedures wherein, under catalysis by chiral silver-bisphosphane complexes, aminooxy ketones 517 result in high ambidoselectivity. Alternatively, a controlled attack at nitrogen under formation of hydroxyamino ketones also became feasible by tuning of the catalytic system [254b,c] (Scheme 5.127). 

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