Grignard reactions abnormal

Reduction by Grignard reagents is a very common reaction, was a statement by Kharasch and Weinhouse in their paper [18]. However, Whitmore and George, a few years later, in 1942 [21], in their classic paper on this subject used the following title Abnormal Grignard Reactions. Among others, they reported ... 

The vicinal methylbenzyl alcohols have been prepared in general by the abnormal reaction of the appropriately substituted Grignard reagent with formaldehyde. The present method is preferred because it yields purer products than the Grignard approach. 

Rearrangement of several substituted chlorohydrins of fixed conformation has recently been reported by Curtin and Harder,3M and attention is directed to this interesting paper, since it is related to the abnormal reaction of a-haloketonos with Grignard reagents and hence pertinent to epoxide chemistry,... 

A related isomerization, that of phenylacetylcobalt carbonyl to o-toluyl-cobalt carbonyl, has recently been studied (143). It also appears to proceed via a tricarbonyl but could not proceed via Eqs. (9) and (10). This rearrangement has much in common with the so-called abnormal reactions of benzyl Grignard and benzyllithium reagents to produce ortho-substituted products (13, 13f). It is possible that a cyclic intermediate similar to that postulated in the Grignard rearrangements may be involved, Eq. (87). 

Cornforth46 has severely criticized this scheme and stated that all claims in this paper should be accepted as fact after, but not before, verification by independent experiment. Amongst other points, he noted that the conversion of (151) into (152) requires (a) an abnormal reaction of a /S-keto-ester with a Grignard reagent, and (b) a so-called dehydration involving the wholly unexplained disappearance of a C-methyl group. 

Among the best known abnormal reactions of Grignard reagents is the one in which reduction of the substrate occurs. 

The addition of Grignard reagents to C—ir-bonds is undoubtedly one of the most fimdamental and versatile reactions in synthetic organic chemistry. Nevertheless, it is also well recognized that these reactions are often accmnpanied by undesirable side reactions such as enoUzation, reduction, condensation, conjugate addition and pinacol coupling. In some cases, such abnormal reactions prevail over the normal addition reaction , resulting in poor yields of the desired products. 

This subject has been reviewed <9icos(3)223,9iCOS(3)342>. The reactions of Grignard reagents with oxiranes can yield normal and/or abnormal alcohols <84CHEC-I(7)l 12). Schleyer and co-workers... 

The product of addition to cinnamic ester is an obvious abnormal product formed by llte reaction of a Grignard rcagenl. Such products are formed by the reaction ol Iree radicals, which since they tire uncharged kx>k for radical stabilization rather titan lor charge stabilization. The following types of abnormal products are considered as being formed by radical recombination even if the direct proof of the radical mechanism has not been given for all eases. 

USE OF CERIUM(III) CHLORIDE IN THE REACTIONS OF CARBONYL COMPOUNDS WITH ORGANOLITHIUMS OR GRIGNARD REAGENTS FOR THE SUPPRESSION OF ABNORMAL REACTIONS ... 

Discoimecting one bond farther from the carbonyl, the a,p abnormal case is provided indirectly by the reaction of Grignard reagents with epoxides. This is followed by oxidation if the carbonyl group is the desired functionality. The p,y disconnection with abnormal polarity is readily arranged if the a carbon is 5/7 -hybridized and insulates the carbonyl group from the nucleophilic p carbon. 

---