Organometallic reagents reactions with carbonyl compounds

Nitriles are similar in some respects to carboxylic acids and are prepared either by SN2 reaction of an alkyl halide with cyanide ion or by dehydration of an amide. Nitriles undergo nucleophilic addition to the polar C=N bond in the same way that carbonyl compounds do. The most important reactions of nitriles are their hydrolysis to carboxylic acids, reduction to primary amines, and reaction with organometallic reagents to yield ketones. 

Isomerization of allylic alcoholsAllylic alcohols can be isomerized to carbonyl compounds by several organometallic reagents at elevated temperatures. The reaction can be conducted at 25-30° overnight with [Rh(CO)2Cll2 under phase-transfer conditions. Cleaner reactions obtain if benzyltriethylammonium chloride is used as catalyst. 

To show how these general principles of nucleophilic substitution and addition apply to carbonyl compounds, we are going to discuss oxidation and reduction reactions, and reactions with organometallic reagents—compounds that contain carbon-metal bonds. We begin with reduction to build on what you learned previously in Chapter 12. 

Carbonyl compounds that also contain N - H or O - H bonds undergo an acid-base reaction with organometallic reagents, not nucleophilic addition. 

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). 

The use of chiral chelating agents in reactions of organometallic reagents with carbonyl compounds has been intensively investigated (134-138). However, the influence of such chiral addends in the aldol process has not met with much success. In the presence of the... 

The formation of chiral alcohols from carbonyl compounds has been fairly widely studied by reactions of aldehydes or ketones with organometallic reagents in the presence of chiral ligands. Mukaiyama et al. 1081 obtained excellent results (up to 94% e.e.) in at least stoichiometric addition of the chiral auxiliary to the carbonyl substrate and the organometallic reagent. 

We will now discuss the reactions of carbonyl compounds with organometallic reagents, another class of nucleophiles. 

B Reaction of a,p-Unsaturated Carbonyl Compounds with Organometallic Reagents... 

Modern aspects of electrophilic aromatic substitution chemistry address the development of enantioselective variants of these direct (hetero)arene functionalization reactions. For example, enantiomerically enriched metal catalysts, as well as organocatalysts, allowed for the asymmetric addition reactions of (hetero)arenes onto (a,P-unsaturated) carbonyl compounds. Additionally, highly enantioselective arylations of carbonyl compounds were accomplished with organometallic reagents... 

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