Highly substituted ketone

C = C triple bonds are hydrated to yield carbonyl groups in the presence of mercury (II) ions (see pp. 52, 57) or by successive treatment with boranes and H2O2. The first procedure gives preferentially the most highly substituted ketone, the latter the complementary compound with high selectivity (T.W. Gibson, 1969). 

If cyclic ketones are monosubstituted in the a-position, their rates of reaction decrease as compared to the rate for the parent ketone (9,41). More highly substituted ketones (e.g., diisobutyl ketone, diisopropyl ketone) can be caused to react using newer preparative techniques (39,43,44, see Section VII). Monosubstituted acetones often can give selfcondensation products, but the recent literature (13,39,43) contains reports of the successful formation of the enamines of methyl ketones. 

The requirement that an enolate have at least one bulky substituent restricts the types of compounds that give highly stereoselective aldol additions via the lithium enolate method. Furthermore, only the enolate formed by kinetic deprotonation is directly available. Whereas ketones with one tertiary alkyl substituent give mainly the Z-enolate, less highly substituted ketones usually give mixtures of E- and Z-enolates.7 (Review the data in Scheme 1.1.) Therefore efforts aimed at increasing the stereoselectivity of aldol additions have been directed at two facets of the problem (1) better control of enolate stereochemistry, and (2) enhancement of the degree of stereoselectivity in the addition step, which is discussed in Section 2.1.2.2. 

The addition of sulfur nucleophiles to aldehydes and ketones may be exemplified by the formation of hydrogensulfite (bisulfite) adducts (3.12). These are sulfonates that are water soluble. However, their stcric bulk means that whereas they are formed from aldehydes and methyl ketones, more highly substituted ketones are reluctant to form these derivatives. 

The Julia coupling has also been successfully utilized for the synthesis of more complex alkenes. There are limitations to the application of the method to tri- and tetra-substituted alkenes, since the addition of the sulfone anion to a highly substituted ketone forms a -alkoxy sulfone that is difficult to trap and isolate. There is a tendency for highly substituted p-alkoxy sulfones to revert back to the ketone sulfone. There have been several recent examples of the synthesis of trisubstituted ( )-alkenes worthy of note. 

The preparation of disubstituted epoxides is similarly accomplished by the addition of nucleophiles to more highly substituted ketones. Selective reduction of keto sulfides with either L-Selectride or zinc... 

One versatile strategy for the synthetic approach to a,a -disubstituted asymmetric ketones has been elaborated (Scheme 7.122). For example, metallation of diethyl alkylphosphonates and acylation of the copper reagents with acyl halides followed by two consecutive alkylations, at the a-carbon and then at the y-carbon, dephosphonylation, and hydrolysis produces highly substituted ketones in 43-73% yields. ... 

A noteworthy route to highly substituted ketones involves the acylation of or-anions of carboxylic acid salts with acyl chlorides. Symmetrical and unsym-metrical, alicyclic, aliphatic, and aromatic ketones may be prepared in this manner (Scheme 6). ... 

However, less highly substituted ketones usually give mixtures of E- and Z-enolates. Therefore, efforts aimed at expanding the scope of stereoselective aldol condensations have been directed at two facets of the problem (1) control of enolate stereochemistry and (2) enhancement of the degree of stereoselectivity in the addition step. 

The first term of equation (1) formulates the effect of a-alkyl substituents on

alkyl substituents attached to the a-carbon atom of the R group. The second term increases the calculated < i values for the case of ketones with sec-H-atoms in the y-position n is the number of these atoms. Depending on the interpretation of the reactive state involved, the second term (0.038 ) may either be related to the additional alkene product from singlet excited state participation in the type-II process or to an enhanced triplet reactivity. Presumably a third term would be required to account for tertiary H-atoms in the y-position. The exponential term in equation (1) introduces a temperature dependence to the ipn values for the highly substituted ketones p = 1 when there are two or more alkyl substituents on the a-carbon atom and p = 0 for all other cases. Equation (2) is presumably related to... 

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