Organomagnesium compounds, reaction mechanisms

The cleavage of the isoxazole ring by organomagnesium compounds may proceed by either one or both of two alternative mechanisms. Magnesium subhalides produced during the associated reaction may act as reducing agents as proved in specific cases.Another possibility is that the reduction involves a six-membered cyclic complex (171). 

Organomagnesium compounds react with imines, prepared from 3-methoxy-2-naphth-aldehydes by a 1.4-addition mechanism. This reaction can be performed with high diastere-oselectivity. The method was applied for the synthesis of optically pure S-tetralones . Vinyhnagnesium bromide reacts as an acceptor with a ketone dimethyl hydrazone zincate 207, yielding a 1,1-bimetallic species, which can be reacted sequentially with two different electrophiles (equations 131 and 132) . The reaction proceeds via a metalla-aza-Claisen rearrangement, where the dimethylhydrazone anion behaves as an aza-allylic system . 

Many reactions of organolithium or organomagnesium compounds depend upon the migration of the alkyl or aryl group from the metal on to the adjacent ligand. Such reactions are not clearly within the scope of this chapter as the reactions are organometallic in nature and the mechanisms... 

Imines derived from 3-methoxy-2-naphthaldehydes react with organomagnesium compounds by a 1,4-addition mechanism. This reaction can be performed with high diastereoselectivity by using an apropriate chiral auxiliary. The method was applied for the synthesis of optically pure /3-tetralones.243... 

The complexities of their constitution in solution make studies of the mechanism of reactions of organomagnesium compounds extraordinarily difficult. Few reactions have stimulated such a wealth of elegantly planned and meticulously executed experiments as those of Grignard reagents with carbonyl compounds (see Section 6.1). Fortunately an admittedly grossly oversimplified rationale for the reactivity of organomagnesium compounds, and in particular for the influence of solvation, is adequate for most applications in organic synthesis. In a monomeric, unsolvated species (2),... 

The mechanism of the reaction between organic halides and magnesium, leading to organomagnesium compounds, has been the subject of much speculation and study, and no little controversy. For the chemist wishing to prepare and use the organomagnesium compounds, information on the mechanism is especially relevant to two matters the nature and amount of by-products, and the stereochemistry of the organomagnesium product. 

Reduction of nitriles by organomagnesium compounds has not often been reported, though it may well occur, by mechanisms analogous to those for reduction of carbonyl compounds see p. 112. A few cases are also known in which the cyano group is displaced see Section 8.3.2). These initial reactions may then be followed by others, involving an excess of either the organomagnesium compound or of the nitrile [E], These further reactions are of limited usefulness in synthesis, but the more important ones are summarized in Scheme 5.3. 

Reactions of organomagnesium compounds with dialkyl sulfates or alkyl sulfonates often give satisfactory yields of the products of displacement of sulfate or sulfonate. Side-reactions have been observed, but they can often be avoided for example, an excess of the sulfate or sulfonate should be used with Grignard reagents, as some is consumed by nucleophilic attack by halide ion [A]. The dialkyl sulfates are reactive, but hazardous. Toluenesulfonates (tosylates) are less reactive, but their reactions are catalysed by copper complexes the reactions of trifluoromethanesulfonates (triflates) are catalysed by nickel complexes. Reactions of Grignard reagents with secondary tosylates appear to follow an Sn2 mechanism, with inversion of configuration [43],... 

Structural investigations can be of benefit for the synthetic use of organomagnesium compounds, since reaction mechanisms will be better understood. Crystal structures will aid in visualizing the reaction pathway and in understanding regio- or stereoselectivities. Models for the transition states will be based on a more realistic foundation. 

It has been made clear, in Chapter 11, that the nature of the Grignard reagent has a great influence on the mechanism of its reactions. The extremes in the reactivity spectrum of organomagnesium compounds in their interaction with ketones, for example, are (I) reactions in which a single electron transfer occurs as the first step, or (2) reactions in which a concerted bond-breaking-bond-making takes place within a cyclic transition state. 

This chapter will deal with the predictability of the results of reactions of organomagnesium compounds, in general, and of Grignard reagents, in particular, with substrates of different kinds. It is evident that such a predictability requires a clear understanding of the mechanisms of the reactions involved. For the single-electron transfer reactions (see Chapter 11 for the discussion of the mechanism of such reactions), encouraging results have recently been obtained. 

The application of the concept of reactivity in such structure reactivity relationships has not yet been firmly established in Grignard chemistry. Only rather recently have successful and reliable kinetic measurements been published, and their application in attempts to elucidate mechanisms of reactions of organomagnesium compounds has just begun (see Chapter 11). Detailed mechanistic studies, such as structures of transition states, entropies of reactions, and so on, are still scarce furthermore, such information is rather haphazard. 

Epstein, O. L., Savchenko, A. I., Kulinkovich, O. G. On the mechanism of titanium-catalyzed cyclopropanation of esters with aliphatic organomagnesium compounds. Deuterium distribution in the reaction products of (CD3)2CHMgBr with ethyl 3-chloropropionate in the presence of titanium tetraisopropoxide. Russ. Chem. Bull. 2000, 49, 378-380. 

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