Grignard chemistry, rearrangements

Pathway 2 of Scheme 9 corresponds to one of the most interesting developments in the Beckmann rearrangement chemistry. By trapping of the electrophilic intermediate with a nucleophile (Nu ) other than water, an imine derivative 227 is produced that may be used for further transformations. Carbon or heteroatom nucleophiles have been used to trap the nitrilium intermediate. Reducing agents promote the amine formation. More than one nucleophile may be added (for example, two different Grignard reagents can be introduced at the electrophilic carbon atom). Some of the most used transformations are condensed in Scheme 11. 

The Pirrung synthesis is notable for its brevity and clever amalgamation of [2 + 2] photocycloaddition and Wagner-Meerwein rearrangement chemistry Enol ether 757 was reacted with the Grignard rea nt from 5-bromo-2-methyl-l-pentene, subjected to acid hydrolysis, and irradiated to generate the tricycle 738. Wittig olefination of this ketone and treatment with p-toluenesulfonic acid provided racemic isocomene. 

As shown by their reaction chemistry, cyclobutyl Grignards likewise do not rearrange to either their 3-butenyl or cyclopropyhnethyl isomers reaction of cyclobutyhnagnesium chloride with benzoic acid results in almost quantitative yield of cyclobutane accompanied by only 1% 1-butene. In contrast, the cyclopropyhnethyhnagnesium chloride is ca... 

The reactions of the isocyanurates have been reviewed previously (59HC(13)1, p.389). The following discussion will concentrate on three facets of isocyanurate chemistry ring cleavage, reactions with Grignard reagents and rearrangements. 

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,... 

Rearrangements are common in transition metal chemistry, and it is not within the scope of this discussion to cover this topic. However, many of these rearrangements occur to increase the electron density on the metal center. An example of this concept is addition of allylic Grignard reagents to a metal-centered electrophile. Typically an // -complex is formed from the expected a-bond that is formed, followed by coordination of the olefin as a 7c-bond, which is better represented as an // -complex [Eqs. (57-59) 160-162]. 

A critical discussion of Grignard rearrangements has been published recently (29). For this reason, the present review will concentrate on some selected aspects of organomagnesium rearrangement chemistry, rather than attempting to be comprehensive. The most recent literature will be summarized in some detail, but older results will be used more selectively. 

The role of the coenzyme Bj2 with a reducible cobalt(III)-alkyl bond which can function as nature s Grignard reagent (CRJ source), Meerwein s reagent (CRj source) or as radical source (C R3) - the latter in the important 1,2-rearrangements e.g. of glutamic acid - is one of the most well studied fields in bioinorganic chemistry (Scheme 1.15). This area therefore will not be covered in this book. 

This rearrangement, of which the mechanism has been theoretically deciphered recently [116], can be followed by an intramolecular Diels-Alder cyclization, affording complex polycyclic lactams [117]. In relation to this pyridinium chemistry, the transformation undergone by pyridine AT-oxides under the action of Grignard reagents is worth mentioning. It leads to substituted (Z)-dienal oximes in good yields [118]. 

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