Cyano-Gilman cuprates

Initial attempts to perform the 1,5-substitution enantioselectively with chiral enyne acetates proceeded disappointingly. For example, treatment of the enantio-merically pure substrate 51 with the cyano-Gilman cuprate tBu2CuLi LiCN at -90 °C provided vinylallene 52 as a 1 3 mixture of E and Z isomers with 20 and 74% ee, respectively (Scheme 2.19) [28], As previously described for the corresponding Sn2 substitution of propargylic electrophiles, this unsatisfactory stereoselection may be attributed to a racemization of the allene by the cuprate or other organome-... 

The solution structures of cyano-Gilman cuprates and lower-order cyanocuprates have been studied by cryoscopic measurements in THF [141]. The results of this study have in several cases shown ways to obtain useful single crystals of several higher- and lower-order cyanocuprates and consequently to determine their structures in the solid state. It appears that a number of these cyanocuprates retain their observed solid-state structure when dissolved in THF. 

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 6.41. Stereoselective construction of a quaternary stereocenter by allylic substitution of mesylate 195 with a boron trifluoride-modified cyano-Gilman cuprate reagent.

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). 

The oxidation of cyano-Gilman cuprates has enabled the synthesis of new cyclophanes. Moreover, while BuhCuLi-LiCN has been reported to effect vinylallene formation by the 1,5-substitution of enyne acetates, it has been revealed that the application of Bu"3P to the reaction system considerably enhances the enantioselectivity of the synthesis. " Recent kinetic isotope studies into the chlorotrimethylsilane-mediated addition of lithiocuprates to cyclo-hexenone have suggested that reaction proceeds via an intermediate rr-com-plex. ... 

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