Grignard reagents aldehydes

Reaction with aldehydes Grignard reagents react with aldehydes... 

Primary alcohols are formed from formaldehyde + Grignard reagent. Secondary alcohols are formed from an aldehyde + Grignard reagent. Tertiary alcohols are formed from a ketone (or an ester) + Grignard reagent. 

Glycols, see Dihydroxy compounds Glyoxals, see a-(Ceto aldehydes Grignard reagents, see Organomag-nesium compounds Guareschi reaction, 434 Guerbet reaction, 181... 

Michael addition occurs with nonenolate anion nucleophiles such as Grignard reagents (see Chapter 15, Sections 15.1-15.4), but there is a competition between 1,2 addition (attack at the acyl carbon) and 1,4 addition (attack at the P-carbon of the C=C unit). When the carbonyl is relatively unhindered, as with conjugate aldehydes, Grignard reagents react almost exclusively at the acyl carbon. 

Aldehyde + Grignard reagent RCHO R MgX, (CH CHJjO > R RCHOH" Secondary alcohol... 

The Reformatsky Reaction consists of the interaction of an ester of an a-halogeno-acid with an aldehyde, a ketone or another ester in the presence of zinc. For example, if a mixture of ethyl bromoacetate and benzaldehyde is heated with zinc, the latter undoubtedly first combines with the ethyl bromoacetate to form a Grignard-like reagent (reaction A), which then adds on to the benzaldehyde Just as a Grignard reagent would do (reaction B). The complex so formed, on acidification gives ethyl p-phenyl-p-hydroxy-propionate (reaction C). Note that reaction A could not satisfactorily be carried out using... 

Action of the Grignard reagent upon an aldehyde, for example (CH3)2CmigBr + CH3CHO —> (CH3)2CHCH(OMgBr)CH,... 

The anion B is just the enolate anion of a carbonyl compound, actually the same as A. So there is no need to use a Grignard reagent or any other synthetic equivalent in this reaction anion B itself can be the intermediate and we simply treat the aldehyde with mild base ... 

The mam synthetic application of Grignard reagents is their reaction with certain carbonyl containing compounds to produce alcohols Carbon-carbon bond formation is rapid and exothermic when a Grignard reagent reacts with an aldehyde or ketone... 

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... 

An ability to form carbon-carbon bonds is fundamental to organic synthesis The addition of Grignard reagents to aldehydes and ketones is one of the most frequently used reactions m synthetic organic chemistry Not only does it permit the extension of carbon chains but because the product is an alcohol a wide variety of subsequent func tional group transformations is possible... 

FIGURE 14 2 Aretrosyn thetic analysis of alcohol preparation by way of the addition of a Grignard reagent to an aldehyde or ketone... 

Secondary alcohols may be prepared by two different combinations of Grignard reagent and aldehyde... 

Therefore one route involves the addition of a methyl Grignard reagent to a five carbon aldehyde... 

Alcohol synthesis via the reaction of Grignard reagents with carbonyl com pounds (Section 14 6) This is one of the most useful reactions in synthetic organ ic chemistry Grignard reagents react with formaldehyde to yield primary alco hols with aldehydes to give secondary alcohols and with ketones to form terti ary alcohols... 

Synthesis of alcohols using organolithi um reagents (Section 14 7) Organolithi um reagents react with aldehydes and ketones in a manner similar to that of Grignard reagents to produce alcohols... 

Sodium acetylide and acetylenic Grignard reagents react with aldehydes and ketones to give alcohols of the type... 

Reaction of Grignard reagents with aldehydes and ketones (Section 14 6)... 

Sodium borohydride and lithium aluminum hydride react with carbonyl compounds in much the same way that Grignard reagents do except that they function as hydride donors rather than as carbanion sources Figure 15 2 outlines the general mechanism for the sodium borohydride reduction of an aldehyde or ketone (R2C=0) Two points are especially important about this process... 

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

We ve seen how Grignard reagents add to the carbonyl group of aldehydes ketones and esters Grignard reagents react m much the same way with carbon dioxide to yield mag nesium salts of carboxylic acids Acidification converts these magnesium salts to the desired carboxylic acids... 

You have already had considerable experience with carbanionic compounds and their applications in synthetic organic chemistry The first was acetyhde ion m Chapter 9 followed m Chapter 14 by organometallic compounds—Grignard reagents for example—that act as sources of negatively polarized carbon In Chapter 18 you learned that enolate ions—reactive intermediates generated from aldehydes and ketones—are nucleophilic and that this property can be used to advantage as a method for carbon-carbon bond formation... 

Additionally, Grignard reagent reacts with an alkyl orthoformate to form an acetal which is then hydrolyzed to the corresponding aldehyde usiag dilute acid. 

With care, the monosubstituted Grignard reagent can be formed and it reacts with aldehydes and ketones to produce carbinols (see Grignard reactions). 

Titanium alkyls, known as tamed Grignard reagents, do not add to esters, nitriles, epoxides, or nitroalkanes at low temperatures. Rather, they add exclusively ia a 1,2 fashion to unsaturated aldehydes (208—210). 

---