Basicity of Grignard reagents

Another example illustrating the basicity of Grignard reagents is... 

The second major application for magnesium bases is elimination. The strong basicity of Grignard reagents allows a greater degree of elimination than do weaker bases,... 

Sometimes the strongly basic properties of Grignard reagents can be turned to synthetic advantage. A chemist needed samples of butane specifically labeled with deuterium, the mass 2 isotope of hydrogen, as shown ... 

The availability of oxepins that bear a side chain containing a Lewis basic oxygen atom (entry 2, Table 6.4) has further important implications in enantioselective synthesis. The derived alcohol, benzyl ether, or methoxyethoxymethyl (MEM) ethers, in which resident Lewis basic heteroatoms are less sterically hindered, readily undergo diastereoselective uncatalyzed alkylation reactions when treated with a variety of Grignard reagents [17]. The examples shown below (Scheme 6.7) demonstrate the excellent synthetic potential of these stereoselective alkylations. 

The weight of evidence, accumulated over many years of detailed studies using a combination of physicochemical techniques, including NMR, reveals that the solution composition of Grignard reagents is best represented by extended Schlenk equilibria (Scheme 1) . However, because of the complexity of the solution behaviour, the vast majority of their NMR spectra are analysed on the basis of the basic equilibrium first proposed by Schlenk and Schlenk (Scheme 2). 

Whereas THF and DME were suitable solvents, Lewis basic additives such as HMPA, DMSO or TMEDA hampered the reaction.82 These results point towards an intramolecular assistance of the zinc coordinated by the nitrogen atom. A related effect was evidenced in the additions of Grignard reagents to allylic alcohols83-87. Two mechanisms were proposed for the allylzincation of homoallylic amines involving formation of a complex with the... 

The most conspicuous property of aliphatic amines, apart from their fishy smell, is their high basicity, which usually precludes N-alkylations under acidic reaction conditions (last reaction, Scheme 6.3). Hence, alkylation of amines with tertiary alkyl groups is not usually possible without the use of highly stabilized carbocations which can be formed under basic reaction conditions. Rare exceptions are N-alkyla-tions of amines via radicals (Scheme 4.2), copper-catalyzed propargylations (Scheme 6.3), and the addition of amines to some Michael acceptors and allyl palladium or iridium complexes. Better strategies for the preparation of tert-alkylamines include the addition of Grignard reagents to ketone-derived imines [13] or the reduction of tert-alkyl nitro compounds. 

The reaction of Grignard reagents and organolithium compounds with aldehydes and ketones is perhaps the most useful method for the preparation of alcohols. The reaction is conducted under basic conditions and proceeds according to the following general mechanism ... 

Thiophenethiols are prepared by reduction of the sulfonyl chlorides or, more conveniently, by the reaction of Grignard reagents or thienyllithium compounds with sulfur. They have also been obtained by cleavage or thienyl alkyl sulfides with sodium in liquid ammonia. 3-Thiophenethiol is a by-product in the commercial thiophene synthesis. Thiophenethiols have recently also been prepared by a synthesis involving Friedel-Crafts reaction of 2,4-dinitrobenzenesulfenyl chloride with thiophenes, followed by basic cleavage of the resulting sulfide. ... 

Because of the quantum mechanical time scale of the NMR instrument, one can study certain time-dependent phenomena that are not generally accessible to the other branches of spectroscopy. Both molecular motion and chemical exchange may affect the appearance of NMR spectra. This unique characteristic has important implications in the study of Grignard reagents. This chapter is designed to provide information to the chemist who uses NMR as an investigative tool. It is assumed that the reader has a basic understanding of the theory and practice of NMR spectroscopy. Those who do not may find it helpful to consult one of several excellent texts on NMR spectroscopy [1-13]. 

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