Grignard reaction: alkylation with carbonyl compounds

The competition between insertion and hydrogen transfer is also crucial to the selectivity of the reaction of aluminium alkyls with carbonyl compounds. Aluminium alkyls, like organolithium compounds and Grignard reagents, can add to aldehydes and ketones to form secondary or tertiary alcohols, respectively. If the aluminium alkyl has a j -hydrogen, however, reduction of the carbonyl compound is a common side reaction, and can even become the main reaction [16]. Most authors seem to accept that reduction involves direct j5-hydrogen transfer to ketone. 

Application of the alcohol interchange reaction (method 6) is limited by certain phenols and also di and trisubstituted glyoxides (while the reaction of metals with glycols gives only monosubstituted derivatives) [745, 621, 575, 1584,1369]. As redox processes (method 7) can be considered the Grignard-type reactions — the interaction of metal alkyls with carbonyl compounds,... 

Bis(dialkylamino)cyclopropenylium magnesium halides, like their lithium counterparts, react as nucleophiles in various reactions, but their use is much less extensive. Like typical Grignard reagents they undergo hydrolysis, alkylation and reactions with carbonyl compounds at the carbenoid carbon (equation 292)357. 

Reaction XLIII. (c) Condensation of a-Halogen Fatty Acid Esters with Aldehydes and Ketones by means of Zinc or Magnesium (Reformatsky-Grignard). (C., (1901), I., 1196 II., 30 (1902), I., 856.)—This is an extension of the Grignard and zinc alkyl reactions which enables a-halogen esters to be condensed with carbonyl compounds as if they were simple alkyl halogen compounds. The zinc or magnesium alkyl derivative is neither prepared beforehand nor isolated in the reaction, but there is little doubt that some such compound is transitorily formed. Zinc is the metal... 

Zinc alkyls and aryls are reactive to air and water and their reactions are similar to, but less vigorous than, those of Grignard reagents, from which they differ in the important respect that they do not react with CO2 and are usually prepared in an atmosphere of this gas. Zinc may be used to generate, in effect, the nucleophile CH2C02R from a-halo esters that can then react with carbonyl compounds as in the well-known Reformatsky reaction ... 

Further work on the palladium-catalysed reaction of butadiene with carbonyl compounds, which gives tetrahydropyrans, has been reported. The d-hydroxyaldehydes (237), obtained by the action of alkyl Grignard reagents on glutaraldehyde, form cyclic hemiacetals (238) which may be... 

The vinylmagnesium derivatives (40), obtained by Cu -mediated anft-addition of Grignard reagents to primary a-acetylenic alcohols, can by hydrolysed to ( )-allylic alcohols (41) (Scheme 18) or, if = H, halogenated and then alkylated to yield (Z)-allylic alcohols (42)." Reaction of (40) with carbonyl compounds gives substituted but-2-ene-l,4-diols. ... 

Organomercury compounds undergo a similar reaction. Alkyl and aryl Grignard reagents can be converted to carboxylic esters with Fe(CO)5 instead of CO. Amides have been prepared by the treatment of trialkyl or triarylboranes with CO and an imine, in the presence of catalytic amounts of cobalt carbonyl ... 

One of the important new directions in the study of addition reactions of organozinc compounds to aldehydes is the use of ionic liquids. Usually, application of these compounds in reactions with common organometallic reagents has a serious problem ionic solvents are usually reactive toward them, particularly Grignard and organolithium derivatives. It has been recently reported that carbonyl compounds react with allylzinc bromide formed in situ from allyl bromide and zinc in the ionic liquid 3-butyl-l-methylimidazolium tetrafluoroborate, [bmim][BF4].285 Another important finding is that the more reactive ZnEt2 alkylates aldehydes in a number of ionic liquids at room temperature.286 The best yields (up to 96%) were obtained in A-butylpyridinium tetrafluoroborate, [bpy][BF4] (Scheme 107). 

---