Grignard reagent-derived cuprates

The catalytic amount of Li2CuCl4 forms a cuprate with the Grignard reagent derived from 5. 

Sodium cuprate yielded less reduction product and less thiophilic addition product than lithium cuprate at both —50 and 0 °C. In the case of silyl thiones chiral at silicon, the reactions with organolithium derivatives and Grignard reagents produce a-silylsulfides with medium to good levels of asymmetric induction and, interestingly, the asymmetry induced at the a-carbon is retained in the subsequent desilylation431 (equation 118), the process being stereoselective. 

Chloro-l-lithio- -pentene, CH2=C(Li)CH2CH2CH2Cl (I)." Both the Grignard and the cuprate reagents derived from 2 undergo conjugate addition to enones in moderate yield. In some cases use of BF, etherate as catalyst improves yields significantly. The products are cyclized by base to annelated methylenecyclohexanes. Overall yields vary from 40 to 70%. 

It was later found that the amount of ligand 2 could be decreased to 0.32 equiv if the cuprate derived from a Grignard reagent and Cul was used (eq 3). 4 ... 

It should be noted that direct substitution of sulfonate or iodide derivatives at C6 is sensitive to steric hindrance. Kishi reported a failure in the substitution of a primary tosylate by vinyl cuprate in the synthesis of mycalamides where C4 had two geminal methyl substituents. An alternate five step route was developed to introduce the vinyl substituent [119]. Direct substitution of a primary triflate by an aryl Grignard reagent is a key step in the formal synthesis of (+)-apicularen A from D-glucal [194]. Displacement of a triflate with an alkynyllithium has also been used in the total synthesis of (+)-panaxacol [195]. 

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