Intramolecular, addition Grignard reactions

In addition to these reactions in which the carbanions are supplied from carbonyl compounds, we will discuss in this chapter Grignard reactions, the benzilic acid rearrangement, the benzoin condensation, and the Kolbe synthesis of hydroxy aromatic acids. These reactions illustrate the addition of other kinds of carbanions to carbonyl groups. The benzilic acid rearrangement is an example of the intramolecular addition of a group with its pair of electrons to a carbonyl carbon atom. 

A full report on the short stereocontrolled synthesis of racemic patchouli alcohol has been presented,362 the key steps of which are the Grignard addition of the magnesium derivative of the bromide (796) to the dienone (797) followed by an intramolecular Diels-Alder reaction. The preparation of the two enantiomers of... 

Conjugate additions. Y"Chloro-a,P-unsaturated sulfoxides give cyclopropane derivatives on Grignard reactions. Apparently, intramolecular displacement of the Y Chloro substituent in the a-sulfmyl anion intermediates is highly favorable. 

Diynes containing a cyclopropane group undergo intramolecular and stereoselective cascade addition/cyclization reaction to give the corresponding 1-methyleneindene derivatives mediated by Grignard reagent/CuI with LiCl. ... 

It is well-established, that the addition of the Grignard reagents to nitriles results in a formation of the imine salts which, upon hydrolysis, yield ketones. However, if a good leaving group, for example a halide or a mesyl ester, is present in the molecule, the reaction can proceed via a different route. Namely, an intramolecular Sf,2 reaction takes place providing a cyclic imine. Despite the simplicity and the synthetic potential... 

Formally analogous to the foregoing Grignard additions are the intramolecular condensations of amides with aromatic systems, found in the Bischler-Napieralski reaction 101), which is of particular interest in isoquinoline and indole alkaloid syntheses (102). Condensations of amidines with reactive methylene compounds also led to enamines (103-106). 

This reaction is extended to the intramolecular ring closure of the intermediate radical 224 with olefinic or trimethylsilylacetylenic side chains [121]. Cu(BF4)2 is also effective as an oxidant (Scheme 89) [122]. Conjugate addition of Grignard reagents to 2-eyclopenten-l-one followed by cyclopropanation of the resulting silyl enol ethers gives the substituted cyclopropyl silyl ethers, which are oxidized to 4-substituted-2-cyclohexen-l-ones according to the above-mentioned method [123]. (Scheme 88 and 89)... 

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