Ketone naphthol reagents

The indium-induced Reformatsky reaction with stoichiometric amounts of chiral amino alcohols such as cinnco-nine and cinchonidine gives optically active /3-hydroxy esters with 40%-70% ee (Table 19). In contrast to the smooth reaction with uncomplexed indium-based Reformatsky reagents, ketones do not react with the complexed indium Reformatsky reagents. Other chiral ligands, including (—)-spartein, (—)-norephedrine, (+)-(l-methylpyrrolidin-2-yl)diphenylmethanol, (+)-Dibutyl tartrate and (+)-l,l -bi-2-naphthol, are not effective for this reaction.324... 

In 1979, Noyori and co-workers invented a new type of chiral aluminum hydride reagent (1), which is prepared in situ from LiAlEE, (S)-l, E-bi-2-naphthol (BINOL), and ethanol. The reagent, called binaphthol-modified lithium aluminum hydride (BINAL-H), affects asymmetric reduction of a variety of phenyl alkyl ketones to produce the alcohols 2 with very high to perfect levels of enantioselectivity when the alkyl groups are methyl or primary1 (Scheme 4.3a). 

By derivatizing an a,p-unsaturated acid into the mono ester of chiral 1,1 -bi-8,8 -naphthol the reaction with lithium dialkylcuprates leads to saturated ketones containing chirality centers at the p-carbon atoms." Consecutive 1,4-addition and 1,2-addition account for this result. The alkyl transfer to enones from Grignard reagents under copper catalysis is subject to chiral modification, e.g., by the introduction of 56" or 57." ... 

Bismuth.— The bismuth reagent, Ph3BiC03, converts ketones into a,a-diaryl-ketones, and arylates naphthols, as does PhsBi. " Use of the diphenyl-bismuthyl moiety as a potential new auxiliary group in organic synthesis has been reported. ... 

The direct regioselective C-acylation of phenol and naphthol derivatives was carried out by using carboxylic acids as acylating reagents. The reactions proceeded smoothly in the presence of a catalytic amount of Hf(OTf)4 to afford the corresponding aromatic ketones in good yields (eq 23). ... 

The reagent itself may be chiral. Enantiopure forms of l,l -bi-2-naphthol are readily available [35] and can be complexed with lithium aluminum hydride (LAH) to form the selective reducing agent BINAL-H, which reduces a variety of ketones, including the precursor to Pirkle s alcohol, 3.13, a chiral solvating agent mentioned in Section 3.3 (Eq. 3.7) [36]. 

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