Organocuprate

The most frequently used organocuprates are those m which the alkyl group is pri mary Steric hindrance makes secondary and tertiary dialkylcuprates less reactive and they tend to decompose before they react with the alkyl halide The reaction of cuprate reagents with alkyl halides follows the usual 8 2 order CH3 > primary > secondary > tertiary and I > Br > Cl > F p Toluenesulfonates are somewhat more reactive than halides Because the alkyl halide and dialkylcuprate reagent should both be primary m order to produce satisfactory yields of coupled products the reaction is limited to the formation of RCH2—CH2R and RCH2—CH3 bonds m alkanes... 

Outline two ways in which 4 methyl 2 octanone can be pre pared by conjugate addition of an organocuprate to an a p unsaturated ketone... 

Like other carbon-carbon bond forming reactions organocuprate addition to enones is a powerful tool m organic synthesis... 

Fig. 8. Synthesis of PGE using an organocuprate reagent where DiBAL-H is diisobutylalurninurnhydride and R = (CH2 )g COOCH2 CH3.

A number of conjugate additions delivering excelent enantioselectivities tlirougli tlie use of organocuprates in tlie presence of stoichiomenic amounts of cliital fnon-transferable) ligands ate known today [7-9],... 

Organocuprates react rapidly witli adylic balides for acetates), propargyl balides for acetates), and vinyloxiranes, frequently witli u2 regioselectivity. Tbe reaction ordinarily takes place witli oiui fwitli respect to tlie leaving group) steteoclieniistry. 

Viprostol (81) also incorporates a hydroxy group moved to C-16 and protects this from facile metabolic oxidation by vinylation. It is a potent hypotensive and vasodilatory agent both orally and transdermally. The methyl ester moiety is rapidly hydrolyzed in skin and in the liver so it is essentially a prodrug. It is synthesized from protected E-iodo olefin 78 (compare with 75) by conversion to the mixed organocuprate and this added in a 1,4-sense to olefin 79 to produce protected intermediate 80. The synthesis of viprostol concludes by deblocking with acetic acid and then reesterification with diazomethane to give 81 [19]. 

Scheme 2.27 Ibuka s ring-opening reaction of (5-aziridinyl-a,(S-enoates with organocuprates.

Scheme 2.28 Wipfs ring-opening reaction of (3-aziridinyl-a, 3-enoates with organocuprates.

Treatment of cyclic vinylaziridine 105 with organocuprates of the R2CuLi type proceeds in a highly syn-selective manner (Scheme 2.29) [46], The syn stereochemistry of the reaction reflects the effect of the acetonide group, which directs the nucleophilic attack to the less hindered a-face. The formation of SN2 products 109 from the cyclic (chlorovinyl)aziridine 107 can be explained by assuming a syn-SN2 ... 

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