Addition of organometallic reagents to aldehydes and ketones

Aprotlc solvents contain no acidic protons, unlike, say, water or alcohols. 

Because they are so reactive, organolithiums are usually reacted at low temperature, often -78 °C (the sublimation temperature of solid CO2), in aprotic solvents such as Ht20 or THF. Organo-lithiums also react with oxygen, so they have to be handled under a dry, inert atmosphere of nitrogen or argon. 

Other common, and commercially available, organolithium reagents include n-butyllithium and phenyllithium, and they react with both aldehydes and ketones. Note that addition to an aldehyde gives a secondary alcohol while addition to a ketone gives a tertiary alcohol. 

Victor Grignard (1871-1935) of the University of Lyon was awarded the Nobel Prize for chemistry in 1912 for his discovery of these reagents. 

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Denmark, S. E. Fu, J. Catalytic enantioselec-tive addition of allylic organometallic reagents to aldehydes and ketones. Chem. Rev. 2003,... 

Enantioselective addition of allylic organometallic reagents to aldehydes and ketones using heterocycles as ligands 03CRV2763. 

Catalytic Enantioselective Addition of Allylic Organometallic Reagents to Aldehydes and Ketones Denmark. S EFu, J. Chem. Rev.2003,103,2763. 

As for C-C bond formation via an addition of organometallic reagent to aldehyde, ketone or imine or allylation, supported-complexes of prolinol, ephedrine and oxazoline derivated constitute the best catalytic systems. 

To be accurate, the definition should be restricted to asymmetric reactions catalyzed by a combination of l,r-binaphthalene-2,2 -diol (BINOL, 4) and Ti(0 -Pr)4. Nonetheless, this chapter will give some background on non-chiral Lewis acid promoters, and include other asymmetric catalytic systems. We will not discuss the allylations that are promoted by Lewis bases, which are reviewed elsewhere, nor cover the reactions with other electrophiles. Excellent reviews already exist on "Selective Reactions Using Allylic MetaM and Catalytic Enantioselective Addition of Allylic Organometallic Reagents to Aldehydes and Ketones , as well as in the comprehensive monograph "Modern Carbonyl Chemistry. The use of BINOL-based catalysts in other fields of organic synthesis has also been reviewed. ... 

This book chapter is limited to Lewis acid-mediated reactions, and does not discuss the important field of Lewis base-mediated allylations, nor does it describe the reactions of allylsilanes with other electrophiles such as epoxides, imines, and allyl-X (X = -Cl, -OR, -OAc). The SaJcurai reaction has been covered under different forms in reviews focusing on The Stereochemistry of the Sakurai reaction , Intramolecular Addition Reactions of Allylic and Propargylic Silanes ," Selective Reactions Using Allylic Metals , Catalytic Enantioselective Addition of Allylic Organometallic Reagents to Aldehydes and Ketones , and Modem Carbonyl Chemistry . ... 

An extension of the approach to additional chemical reactions has been reported by other groups. Flynn and co-workers [21] have developed some protocols for the Moffatt oxidation of secondary alcohol to ketones (Figure 8) and the addition of organometallic reagents to aldehydes. The same group has also developed the use of tetrafluorophthalic anhydride to assist in the purification of reaction mixtures [22]. 

Peptidyl fluoromethyl ketones can readily be synthesized by addition of organometallic reagents to peptide aldehydes and other carbonyl compounds 28 one variation of this reaction is suitable for the stereoselective synthesis of trifluoromethyl ketones. 23,31 ... 

The addition of organometallic reagents to 5-aiyl sulfenimines (193) yields, upon aqueous work-up, substituted primary amines (195). The scope of these additions has not been extensively explored, largely because of the difficulties encountered in sulfenimine preparation. Recently, the generation of sulfenimines from N.N-bis(trimethylsilyl)sulfenamides and aldehydes or ketones has provided a more convenient access to these molecules. ... 

One of the most effective ways of preparing enantiomerically pure secondary amines is the addition of organometallic reagents to chiral sul fmimines, which are prepared by the condensation of an aldehyde (or ketone) with a sulfinamide. The preparation of /-butyl sulfinamide had been problematic, but the synthesis (and supplies) now seems to be more reliable. 

How are a-hydroxy ketones made Because they contain alcohol groups, you might consider methods first introduced in Chapter 8 for the synthesis of alcohols addition reactions of organometallic (carbanionic) reagents to aldehydes and ketones. However, if you tried to apply this approach, you would encounter a... 

Stereoselectivity in addition of organometallic reagents to some chiral aldehydes and ketones... 

Table 8.2. Stereoselectivity in Addition of Organometallic Reagents to Some Chiral Aldehydes and Ketones"... 

The addition of various alk-2-enyl organometallic species to aldehydes and ketones continues to be of interest, not least for its stereochemical outcome (c/. 6, 166 5,162). Such additions of allyl-boron species have been discussed in the published lecture mentioned earlier in another recent survey of additions of but-2-enyl organometallic reagents to aldehydes, the erythro threo syn anti) selectivity [equation (5)] and the Cram anti-Cram selectivity with a-chiral... 

The carbonyl group of acid derivatives reacts with the nucleophilic carbanion available from organo-metallic reagents. However, the reactions of the individual classes of compounds are not as straightforward as the addition reactions of organometallic compounds with aldehydes and ketones. Addition of a carbanion to the acyl carbon atom generates a tetrahedral intermediate that can decompose to give a ketone that will react further with another equivalent of the carbanion. 

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