Carbonyl group organometallic addition

Scheme 6.43. Two examples of nucleophilic addition reactions to alkenes bearing electron-withdrawing carbonyl groups. These addition reactions both result in the formation of new carbon-carbon bonds. The second addition reaction involves use of an organometallic reagent (a dialkyl lithium cuprate, sometimes called a Gilman Reagent (Chapter 7).

The addition of carbon nucleophile, including organometallic compounds, enolates, or enols, and ylides to carbonyl gro is an important method of formation of carbon-carbon bonds. Such reactions are- ctremely important in synthesis and will be discussed extensively in Part B. Here, we will examine some of the fundamental mechanistic aspects of addition of carbon nucleophiles to carbonyl groups. 

Besides 1,3-oxathianes, the 1,3-dithiane 1-oxide moiety can be used for directing the nucleophilic addition of an organometallic reagent to a carbonyl group in a diastereoselective manner. The addition of methylmagnesium iodide to the 2-acyl-l,3-dithiane 1-oxide 23A leads exclusively to the diastereomer which is formed by Re-side attack. On the other hand, addition... 

Formation of C —C Bonds by Addition of Benzyl-Type Organometallic Compounds to Carbonyl Groups... 

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. 

Bicyclic ketones react with organometallic reagents to give the products of addition from the less hindered face of the carbonyl group. 

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. 

Organometallic reagents are better known for their involvement in the alkylations at ring nitrogen atoms in many heterocycles. However, under proper circumstances, they can promote addition to carbonyl groups. Such is the case when 68 is allowed to react with an excess of Me2BuMgLi at 0°C. The secondary alcohol 69 is obtained in fair yield (Equation 28) <20040L1991>. 

Reactions at the Carbonyl Group 1,2-Additions of Organometallic Compounds ... 

Most main group organometallic compounds undergo nucleophilic reactions with carbonyl groups, whereas 1,4-conjugate addition to enones... 

The low temperature reaction of pentanedial with a range of alkyl Grignard reagents leads to 6-substituted tetrahydropyran-2-ols (72HCA249). The major side reaction involves addition of the organometallic compound to both carbonyl groups. 

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