Addition of Organometallic Reagents to Carbonyl Groups

For acyl chlorides, anhydrides, esters, carboxamides, and carboxylate anions, the tetrahedral adduct can undergo elimination. The elimination forms a ketone, permitting a second addition step to occur. 

The rate at which dissociation of the tetrahedral adduct occurs depends on the reactivity of the heteroatom substituent as a leaving group. The order of stability of the tetrahedral 

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For reviews of the addition of organometallic compounds to carbonyl groups, see Eicher, T. in Patai, Ref. 2, p. 621 Kharasch, M.S. Reinmuth, O. Grignard Reactions of Nonmetallic Substances, Prentice-Hall Englewood Cliffs, NJ, 1954, p. 138. For a review of reagents that extend carbon chains by three carbons, with some functionality at the new terminus, see Stowell, J.C. Chem. Rev., 1984, 84, 409. 

Although the addition of organometallic reagents to carbonyls is a very versatile reaction, it cannot be used with molecules that contain both a carbonyl group and N—H or O-H bonds. 

The addition of organometallic reagents to the carbonyl group of conveniently substituted aldonolactones constitutes a viable chain-extension method. The reaction leads to the formation of hemiacetals of glyculoses, 1-methylene sugars, and C-glycosyl compounds, which are precursors of, or occur as subunits of, a variety of natural products. 

The hemiacetals obtained by nucleophilic addition of organometallic reagents to the carbonyl group of aldonolactones may be reduced to the corresponding C-glycosyl compounds. For example, treatment of 2,3,4,6-tetra-... 

The stereoselectivity of reduction of carbonyl groups is effected by the same combination of steric and stereoelectronic factors which control the addition of other nucleophiles, such as enolates and organometallic reagents to carbonyl groups. A general discussion of these factors on addition of hydride is given in Section 3.10 of Part A. 

As well as the addition of achiral organometallic reagents to chiral aldehydes (see also Sections 1.3.2. and 1.3.3.), the addition of chiral organometallic reagents to carbonyl compounds is a well-known and intensively studied process which may lead to enantiomerically and/or diastereomerically enriched products. Chiral organometallic reagents can be classified into three groups ... 

Like reduction, addition of organometallic reagents converts an sp hybridized carbonyl carbon to a tetrahedral sp hybridized carbon. Addition of R - M always occurs from both sides of the trigonal planar carbonyl group. When a nevr stereogenic center is formed from an achiral starting material, an equal mixture of enantiomers results, as shown in Sample Problem 20.1. 

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