Carbonyls Grignard addition

As examples of their addition to carbonyl compounds, Grignard reagents react with formaldehyde, H2C = 0, to give primary alcohols, with aldehydes to give secondary alcohols, and with ketones to give tertiary alcohols. 

The reduction of carbonyl compounds by reaction with hydride reagents (H -) and the Grignard addition by reaction with organomagnesium halides (R - +MgBr) are examples of nucleophilic carbonyl addition reactions. What analogous product do you think might result from reaction of cyanide ion with a ketone ... 

Johnson s classic synthesis of progesterone (1) commences with the reaction of 2-methacrolein (22) with the Grignard reagent derived from l-bromo-3-pentyne to give ally lie alcohol 20 (see Scheme 3a). It is inconsequential that 20 is produced in racemic form because treatment of 20 with triethyl orthoacetate and a catalytic amount of propionic acid at 138 °C furnishes 18 in an overall yield of 55 % through a process that sacrifices the stereogenic center created in the carbonyl addition reaction. In the presence of propionic acid, allylic alcohol 20 and triethyl orthoacetate combine to give... 

These differences in the course of the reaction of Grignard and sodium compounds are not limited to carbonations but are also observed in carbonyl addition reactions. Whereas cinnamylmagnesium bromide always reacts at the secondary carbon atom next to the benzene ring, the sodium compound may react at either the secondary or the primary position, depending on the electrophilic reagent.403... 

FIGURE 18b. Carbonyl addition process for the alkoxy Grignard model corresponding to that of Scheme 17b-l... 

Unlike previous alkyne-aldehyde additions [23], the generation of an alkynyl carbanion is unlikely owing to the large pK, difference between the terminal acetylene and the solvent water [24]. A mechanism was proposed involving the simultaneous activation of the C-H bond of alkyne by the ruthenium catalyst and the aldehyde carbonyl by the indium ion. The ruthenium intermediate then underwent Grignard-type addition followed by an in situ hydrolysis in water to give the desired carbonyl addition product and regenerated the ruthenium and indium catalysts to catalyze further reactions (Fig. 3). 

CARBONYL ADDITIONS, CERIUM(III) CHLORIDE-PROMOTED, 76, 237 Carbonyl compounds, reactions with organolithiums or Grignard reagents, 76, 228 Carboxylic acid amides, 77, 27 Cells, storage of, 76, 80 Centrifugation, 76, 78... 

To use the Grignard addition in synthesis, you must be able to determine what carbonyl and Grignard components are needed to prepare a given compound—that is, you must work backwards, in the retrosynthetic direction. This involves a two-step process ... 

The emphasis of this chapter will be on the mechanistic aspects of the ( normal ) addition reaction of Grignard reagents to the carbon-oxygen double bond, as is found for ketones. However, it will become clear that for reactions with other substrates, the general mechanistic aspects of these carbonyl addition reactions are also applicable. 

Another side reaction, caused by changes in the solvent composition, was studied in 1980 (in the former USSR) and, unfortunately, was also published in rather inaccessible journals [37]. The reactions of phenylmagnesium bromide with the aliphatic ketones, 2-butanone and 3,3-dimethyl-2-butanone (methyl-fcrt-butyl ketone), were studied. Besides the carbonyl addition reaction, leading to a tertiary alcohol, enolization also takes place with this type of ketones. The enolate, on hydrolysis, yields the starting ketone however, before hydrolysis, in the reaction mixture of the Grignard reagent and the ketone, the enolate can react further with the ketone to form a condensation product (Scheme 16). 

Activated alkyl halides such as a-bromocarboxylates were arylated with aryl Grignard reagent [Eq. (105) 229]. The expected side reaction is carbonyl addition of the Grignard reagent, and it was minimized by the use of t-butyl ester. 

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