Coupling, organometallic reaction

Coupling reactions have been achieved with a variety of aromatic and heteroaromahc rings using a thiomethyl group and an organozinc reagent. A variety of funchonality is tolerated in the reachon (Eq. 7.26) [44]. SPhos, 2-(2, 6 -dimethoxybiphenyl)dicyclohexylphosphine, is a catalyst for the reaction [45]. 

Many other kinds of organometallic compounds can be prepared in a manner similar to that of Grignard reagents. For example, alkyllithium reagents, RLi, can be prepared by the reaction of an alkyl halide with lithium metal. Alkyllithiums are both nucleophiles and bases, and their chemistry is similar in many respects to that of the alkylmagnesium halides. 

One of the most valuable reactions of alkyllithiums is their use in making lithium diorganocopper compounds, R2CuLi, called Gilman reagents. These reagents are easily prepared by reaction of an alkyllithium with cop-per(I) iodide, Cul, in ether solvent. 

Henry Gilman (1893-1986) was bom in Boston, Massachusetts, and received his Ph.D. in 1918 at Harvard. He then became professor of chemistry at Iowa State University (1919-1962), where he remained active until his death at age 93. An extremely prolific researcher, Gilman published over 1000 scientific papers during his career. Remarkably, he lost much of his eyesight at age 53 but still went on to accomplish some of his finest work in later years. 

This organometallic coupling reaction is extremely versatile and ver useful in organic synthesis because it makes possible the preparation larger molecules from smaller pieces. As the following examples indkats the coupling reaction can be carried out on aryl and vinylic halides as we as on alkyl halides  

The mechanism of the reaction appears to involve initial formation a triorganocopper intermediate, followed by coupling and loss of RCu. Rm coupling is not a typical polar nucleophilic substitution reaction of the so( considered in the next chapter. 

One particularly valuable reaction of alkyllithiums is in making lithium diorganocop per compounds, UR2CU, by reaction with copper(l) iodide in 

How strong a base would you expect a Grignard reagent to be Look at Table 9.1 on page 326, and predict whether the following reactions will occur as written. (The p/Cg of NH3 is 35.) 

How might you replace a halogen substituent by a deuterium atom if you wanted to prepare a deuterated compound  

An organocopper coupling reaction is carried out commercially to synthesize muscalure, (9Z)-tricosene, the sex attractant secreted by the common housefly. Minute amounts of muscalure greatly increase the lure of insecticide-treated fly bait and provide an effective and species-specific means of insect control. 

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In a useful extension to this chemistry, the coupling of the starting iodoaniline with trimethylsilylalkynes was found to give the silylated species 5, which can bp a useful precursor to either 2-unsubstituted indoles or 2-halogenated derivatives as shown in Scheme 8. These could then be taken on further with standard organometallic coupling reactions. 

Organometallic coupling reactions are useful for forming large molecules from small pieces. 

In summary, the development in the field of total syntheses of the antitumor agent camptothecin nicely illustrates the progress of modern synthesis over the last decade. Radical reactions and organometallic coupling reactions, for example, have reached such a level of maturity that they now belong to the standard repertoire of key steps in the construction of complex molecules. 

Another, mechanistically closely related reaction is the cross-coupling reaction of aryl, benzyl, vinyl, or allyl halides with organometallic coupling reactions, such as Grignard reagents or, preferably, less reducing organometallics such as tin compounds or boronic acids RB(OH)2 the latter allow the reaction to be conducted even in aqueous media.83 The principal reaction steps are ... 

Scheme 1 Typical organometallic coupling reactions for the synthesis of conjugated polymers.

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