Addition to 9-Unsaturated Ketones

A number of alternative multi-step procedures for the synthesis of a-tert-alkyl ketones are known, none of which possess wide generality. A previous synthesis of 2-tert-penty1cyclopentanone involved reaction of N-1-cyclopentenylpyrrol 1 dine with 3-chloro-3-methy1-l-butyne and reduction of the resulting acetylene (overall yield 46 ). However, all other enamines tested afford much lower yields. Cuprate addition to unsaturated ketones may be useful in certain cases. Other indirect methods have been briefly reviewed. ... 

CO 1 0 c 1 X r Nucleophilic substitution and conjugate addition to unsaturated ketones ketones from acyl chlorides b,c... 

In basic aqueous solutions with a [Rh(COD)2]BF4 catalyst, phenyltin trichloride was found to react with aromatic aldehydes or unsaturated ketones. In the presence of a strong aqueous alkali (KOH) PhSnCU is readily hydrolysed and the products of this reaction, such as e.g. PhSn(OH)3 add to the carbonyl function of aldehydes or undergo conjugate addition to unsaturated ketones (Scheme 6.35). In the absence of KOH no reaction takes place at all. Yields are generally high [73]. 

Most of the focus has been on asymmetric conjugate additions to unsaturated ketones. A combination of copper... 

Scheme 2 shows a related study of the regio- and stereochemistry of magnesium enolate addition to unsaturated ketones [22]. Enolates were generated by reaction of either mesityl or isopropyl Grignard reagent, or diisopropyl magnesium with ketones. 1,4-Addition was observed with the dienolate of t-butylacetone. Increased reaction temperature also lead to 1,4-addition. 

Nafion resins have been used not only for the opening of epoxides but also for their isomerization to aldehydes or ketones [137]. Various other rearrangements and isomerizations are catalyzed by this solid acid, in some cases with selectivities higher than those obtained with other solid catalysts [138-140]. Other reactions that have been studied include the Peterson methylenation of carbonyl compounds [141], hetero-Michael additions to unsaturated ketones [142], the Koch-type carbon-ylation of alcohols to form carboxylic acids [143], dimerization of a-methylstyrene [144], addition of carboxylic acids to olefins [145] and Diels-Alder reactions [146]. Notably, in most cases, reutilization of the catalyst is considered but only after an appropriate washing protocol to regenerate its acidity/activity. 

Thus, treatment of enamines with BuLi yields the lithiated species, which was selectively C-methylated to give the corresponding a-methyl-substituted enamines in good yields. The reaction of the enamines with a, 8-unsaturated ketones is also explored (eq 73). Furthermore, the lithio-enamines undergo 1,2-addition to unsaturated ketones to give intermediates, which, upon cycliza-tion and prototropic rearrangement, provide a regioselective de novo synthesis of fluorinated pyridines. 

Nucleophilic substitution and conjugate addition to unsaturated ketones. 

Acyl azoliums generated from enals have been converted to cyclopropyl carboxylic esters with ee < 99% by reaction with sulfur ylides. Some FLPs have been found to i react by conjugate P/B addition to unsaturated ketones and esters, whereas 1,2-addition to corresponding aldehydes is usual. ... 

Early experiments in the area of enantioselective conjugate additions of stabilized anions employed chiral amines as catalysts [105]. A milestone result was Wynberg s utilization of cinchona alkaloids including quinine (109) as promoter for the addition of indanone 108 to methyl vinyl ketone (Equation 20) [106]. In the experiment, adduct 110 was obtained in 76% ee and 99% yield. Moreover, Wynberg also found thiophenols to be suitable nucleophiles for the quinine-catalyzed enantioselective addition to unsaturated ketones [107]. 

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