Gilman cuprates 1,2-additions

Since the preformed aggregate Bu3Cu2Li showed a diastereoselectivity of 83 17 in the presence of boron trifluoride16, the low diastereoselectivity noted above was presumably due to a faster addition reaction of butyllithium, which is formed by the treatment of the Gilman cuprate with the boron trifluoride-diethyl ether complex16,, s. 

A drawback of the Z enoates is usually lower reactivity, reflected in prolonged reaction times and higher reaction temperatures. This may be overcome by switching to more reactive enone systems. Thus, addition of the functionalized cyano-Gilman cuprate system 67 to Z enone 66 proceeded smoothly at low temperatures, with excellent acyclic stereocontrol at the /i-stereocenter [26, 27]. Stereocontrol upon... 

An interesting chromium system example is represented by complex 145. Addition of cyano-Gilman cuprates occurred with complete diastereoselectivity to give conjugate adducts 146 (Scheme 6.28). Interestingly, the opposite diastereomer was accessible by treatment of enone 145 with a titanium tetrachloride/Grignard reagent combination [71c]. 

Scheme 10. Working hypothesis for the o-DPPB group to act as an organometallic reagent directing group for the conjugate addition of Gilman cuprates to acyclic enoates.

The enoates 17 were obtained in good yield and diastereoselectivity by subjecting the crude hydroformylation products 6 to Horner-Wadsworth-Emmons olefination conditions (HWE). Reaction of enoates 17 with dialkyl Gilman cuprates gave the anti 1,4-addition... 

Pyridylmethyllithium species generally react as hard anions giving rise to 1,2-addition products when coupled with a,/3-unsaturated carbonyl derivatives. It has been found that the corresponding cyano-Gilman cuprates such as 42 also undergo 1,2-addition to a,/3-unsaturated ketones but do add in a conjugate fashion to cr,/3-unsaturated esters and lactones such as 43 in good yield and stereoselectivity <200314(60) 1843> (Scheme 7). 

In addition, Figures 10.27,10.32 and 10.46 present the current view on (1) the mechanisms of the addition of Grignard reagents to carbonyl compounds, (2) the mechanism of the additions of organolithium compounds to ,/i-unsaturated ketones and (3) the mechanism of the 1,4-addition of Gilman cuprates to ce,/J-unsaturated ketones, respectively. 

Many copper-containing organometallic compounds add to a,/3-unsaturated ketones in smooth 1,4-additions (for the term 1,4-addition see Figure 10.31). The most important ones are Gilman cuprates (Figure 10.43, left). For sterically hindered substrates, their rate of addition can be increased by adding Me3SiCI to the reactants. 

So far only little is known about the mechanisms of such 1,4-additions. To start with, it is uncertain whether they only depend on the metal used or on both metal and substrate. At the beginning of the new millennium, however, the prototype of this reaction, i.e., the 1,4-addition of Gilman cuprates to a,fi-unsaturated ketones, could finally be assigned a mechanism after many years of studies and with a proper finish of crystallographic, NMR-spectroscopic, kinetic and quantum-chemical studies (Figure 10.46, see farther below). 

Figure 10.45 also shows that lithium dialkyl cuprates in solutions containing lithium iodide or lithium cyanide—in addition to the dimeric or monomeric Gilman cuprates presented in Figure 10.44—may contain the following species the contact ion pairs A and C in diethyl... 

Figure 10.46 shows the current views on the mechanism of the 1,4-addition of Gilman cuprates to cyclohexenone. The numerous details, which have been elucidated or made plausible over the past years, force us to break down the general view of this mechanism into two halves. 

Fig. 10.46. Mechanistic possibilities for the 1,4-addition of a Gilman cuprate to an a,/f-unsaturated ketone. Part 1 shows the reaction up to the rate-determining step (F -> G). For the sake of greater clarity the solvation of the lithium atoms is left unconsidered here.

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