Halides organocuprate reagents

Scheme 8.1 gives several examples of the use of coupling reactions of organocuprate reagents with halides and acetates. Entries 1 to 3 are examples of the... 

Fig. Reaction of an organocuprate reagent with an alkyl halide.

Organocuprate reagents also couple with aryl and vinyl halides to make substituted benzenes and elongated alkenes. Recent research has developed many additional coupling methods using other transition metals in the reagents and catalysts. 

Reaction of an oi anic halide with an organocuprate reagent (Section 26.1)... 

In addition to their reactions with acid chlorides, epoxides, and a,P-unsaturated carbonyl compounds (Sections 20.13-20.15), organocuprate reagents (R2CuLi) also react with organic halides R X to form coupling products R-R that contain a new C-C bond. Only one R group of the organocuprate is transferred to form the product, while the other becomes part of RCu, a reaction by-product. 

Since organocuprate reagents (RgCuLi) are prepared in two steps from alkyl halides (RX), this method ultimately converts two organic halides (RX and R X) into a hydrocarbon R-R with a new carbon-carbon bond. A hydrocarbon can often be made by two different routes, as shown in Sample Problem 26.1. 

Coupling of an organocuprate reagent (RgCuLi) with an organic halide (R X)... 

In the example in Scheme 1.170, the TJ-alkene is formed from the -alkenyl halide. Likewise, the Z-alkene is formed selectively from the Z-alkenyl halide. Alkenyl tri-llates are also good substrates for alkylation with organocuprate reagents. Treatment of the alkenyl triflate 170 with methyl magnesium bromide and copper(I) iodide as catalyst, gave the alkylated product 171, used in a synthesis of paeonilactone A (1.171). 27... 

The advent of versatile organocuprate reagents in organic synthesis has led to their increased use as effective reagents for the unsymmetrical coupling of alkyl halides It... 

Organocuprates can be prepared from organolithium reagents and cuprous halides. Organocuprates react with alkyl halides to form a new C-C bond in the product 24,25, 32, 33, 42. 

Reaction of organocuprate reagents with acyl halides is extremely facile and provides a new technique for ketone synthesis (Vig et al., 1968a Jukes et al., 1970a Posner et al., 1970, 1972, 1973 Jallabert et al., 1970 Normant and Bourgain, 1970 Luong-Thi et al., 1971). The reaction proceeds under conditions sufficiently mild that carbonyl, ester, or cyano functionalities are not affected. 

Before translating this retrosynthetic analysis into a synthesis in the forward direction, notice that the side chain, which we intend to use as a nucleophile for 1,4-addition, will have to be introduced as an organocuprate reagent, which in turn has to come from a halide via an organolithium species. However, it also contains a carbonyl function, which will need to be protected, so that the organolithium reagent can be prepared successfully (recall Section 17-8) ... 

Addition of organocuprate reagents to a,j8-enones is solvent dependent indeed the addition is retarded by the inclusion of HMPA in the reaction medium to the extent that halide-ion displacement occurs preferentially. " Copper-catalysed conjugate addition of the magnesio-acetal (25) to cyclic enones is the key step in a new cyclopentene annelation procedure [equation (36)]. ... 

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... 

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