Ketones to tertiary alcohols

Addition of Grignard reagents and organolithium compounds (Sections 14 6-14 7) Aldehydes are converted to secondary alcohols and ketones to tertiary alcohols... 

Similarly, acetals were converted to ethers (113,114), ketones to tertiary alcohols (111), and acyl halides to ketones (113). The reaction of Me3SiPl with 1-hexanal has been used as a key step in the total synthesis of the sperimidine alkaloid anhydrocannabisativine (115). 

The use of other mixed reagents to promote acylation and subsequent enolization of the ketone during its formation have been reported by Fehr. The success of the method depends on the ease of ketone deprotonation and thus was limited to substituted allylic nucleophiles. The final product was obtained entirely in the form of the a. -unsaturated ketone. A combination of the nucleophilic Grignard reagent and the nonnucleophilic base lithium diisopropylamide converts sterically hinder ester (50) into a-damas-cone (52) via (51) (Scheme 16). The ratio of ketone to tertiary alcohol was 98 2 (many cases gave selectivity greater than 9 1) however, a few examples showed a substantial amount of tertiary alcohol formation. 

The type of alcohol produced depends on the carbonyl compound Substituents present on the carbonyl group of an aldehyde or ketone stay there—they become sub stituents on the carbon that bears the hydroxyl group m the product Thus as shown m Table 14 3 (following page) formaldehyde reacts with Grignard reagents to yield pri mary alcohols aldehydes yield secondary alcohols and ketones yield tertiary alcohols... 

Three combinations of Grignard reagent and ketone give rise to tertiary alcohols... 

Perhaps the most valuable reaction of alcohols is their oxidation to yield car-bony compounds—the opposite of the reduction of carbonyl compounds to yield alcohols. Primary alcohols yield aldehydes or carboxylic acids, secondary alcohols yield ketones, but tertiary alcohols don t normally react with most oxidizing agents. 

Thirdly, if it is not possible to apply the SRS technique, it can be established whether a primary, secondary or tertiary alcohol is present by oxidizing the alcohol on the chromatographic zone and then subjecting the oxidation product to a detection reaction. On oxidation primary alcohols form aldehydes, secondary alcohols ketones and tertiary alcohols are not oxidized. 

When the carbonyl carbon is substituted with a potential leaving group, the tetrahedral adduct can break down to regenerate a C=0 bond and a second addition step can occur. Esters, for example are usually converted to tertiary alcohols, rather than ketones, in reactions with Grignard reagents. 

Entries 3 to 5 show the use of alternative sources of the one carbon unit. In Entry 3, a tertiary alcohol is formed with one of the alkyl groups being derived from the dithioacetal reagent. Related procedures have been developed for ketones and tertiary alcohols using 2-lithio-2-alkyl-l,3-benzothiole as the source of the linking carbon.14 Problem 9.3 deals with the mechanisms of these reactions. 

Trifluoromethylation can be achieved with the use of imidazolylidene carbene 1 [159], Song and co-workers found this transformation is tolerant of both electron-rich and electron-poor aldehydes (Table 26). Even enolizable aldehydes undergo trifluoromethylation in 81% yield (entry 3). Selective reaction occurs with an aldehyde in the presence of a ketone in the substrate (entry 5). The use of activated ketones as acceptors leads to tertiary alcohols in good yields (entries 7 and 8). 

Addition of Grignard or organolithium reagents to a ketone gives tertiary alcohol. For example, acetone reacts with methyl magnesium bromide to yield t-butanol. 

Branched acyclic alkanes also exhibit a slightly different behavior toward ozone on silica gel.105 Although tertiary alcohols are usually the main products, C—C bond cleavage to yield ketones always occurs and may become the predominant reaction. Atomic oxygen generated by microwave discharge of a C02/He mixture is a more selective reagent in the transformation of these compounds to tertiary alcohols.106... 

Unlike the reactions discussed previously in this chapter, oxidation of alcohols involves the alkyl portion of the molecule, or more specifically, the C-H bonds of the hydroxyl-bearing carbon (the a carbon). Secondary alcohols, which have only one such C-H bond, are oxidized to ketones, whereas tertiary alcohols, which have no C-H bonds to the hydroxylic carbon, are oxidized only with accompanying degradation into smaller fragments by cleavage of carbon-carbon bonds. 

Nucleophilic attack by the vinyl Grignard reagent leads to tertiary alcohol 8 11 Grignuril reagents react with formaldehyde to give primary alcohols and with other aldehydes to give secondary alcohols, whereas ketones are transtormed into tertiary alcohols. 

Aldehydes and ketones, possessing tertiary alcohols,241 halides,209d epoxides,242, 243 and sulfonates244 at the (3-position, may suffer such elimination reactions. The use of more hindered or weaker bases than Et3N (see page 146), and a low-temperature quenching245 can help to avoid these eliminations. 

Grignard reagents add to carbonyl compounds. The products, after hydrolysis, are alcohols whose structures depend on that of the starting carbonyl compound. Formaldehyde gives primary alcohols, other aldehydes give secondary alcohols, and ketones give tertiary alcohols. 

The metal lias to a great extent replaced zinc, which was used in 1849 by Frankland in the preparation of paraffin hydrocarbons and the zinc alkyls, and subsequently by Wagner for preparing secondary alcohol from aldehydes, by Saytzeff in preparing tertiary alcohols from ketones, and by Butlerow iu the preparation of both ketones and tertiary alcohols from acid chlorides. 

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