Organocopper reagent,

Organocopper Reagents.—Although there have been a large number of reports this year on the general use of organocuprates in synthesis, few significant advances have been made in this area. 

Organocopper )V)V-dimethylhydrazone (DMH) derivatives have been used for the synthesis of a variety of 1,5-dicarbonyl compounds. In contrast to the normal Robinson annelation of 2-methylcyclohexanone, which leads to attachment of methyl vinyl ketone analogues at C-(2) and eventual formation of (56), the organocopper DMH derivative of 2-methylcyclohexanone reacts with methyl vinyl ketone to give the 1,5-diketone (57), which undergoes base cyclization to the octalones (58). 

Miyaura, M. Itoh, and A. Suzuki, Tetrahedron Letters, 1976, 255. E. J. Corey and D. Enders, Tetrahedron Letters, 1976, 11. 

The conversion of cis- and /ra j -5-methyl-2-cyclohexenyl acetate (63) into 3,5-dimethylcyclohexene (64) with Me2CuLi is stereospecific, the substitution occurring on the side of the ring opposite from the replaced acetate group.  

Use of organocopper reagents offers a very efficient method for coupling of two different carbon moieties. Since copper is less electropositive than lithium and magnesium, the C-Cu bond is less polarized than the C-Li and C-Mg bonds. This difference produces three useful changes in reactivity  

Relative reactivity RCOCl RCHO tosylates, iodides epoxides bromides ketones esters nitriles. 

Since only one of the organic groups of homocuprates is usually utilized, a non-trans-ferable group bonded to copper, such as RC C, 2-thienyl, PhS, r-BuO, R2N, Ph2P, or Me3SiCH2, is employed for the preparation of heterocuprate reagents. These cuprates are usually thermally more stable (less prone toward P-elimination of Cu-H), and a smaller excess of the reagent may be used. 

Cyanocuprates exhibit the reactivity of homocuprates and the thermal stability of heterocuprates. They are readily available by the reaction of CuC=N with 2 equivalents of RLi. The cyanocuprates are especially useful for substitution reactions of secondary halides and epoxides. 

Copper-catalyzed reactions of RMgX reagents are attractive when compatible with the functionality present in the starting material. The use of Grignard reagents is often the method of choice since they are readily available and only catalytic amounts of Cu(I) halides are required.  

FIGURE 15.48 Preparation of organocopper compounds and their reaction with acyl halides. 

FIGURE 15.49 Mechanism of reaction of organocopper compounds with acyl halides. 

Suggest reagents for each of the following transformations some may require more than one step (a) OH 

Carboxylic acids, esters, acid chlorides, and acid anhydrides can all be reduced to primary alcohols by lithium aluminum hydride. 

Amides and nitriles are reduced to amines by lithium aiuminum hydride. 

Early observations that certain Grignard reactions could be catalyzed by copper salts eventually led to systematic studies of organocopper compounds as reagents for carbon-carbon bond formation. Of these, lithium diorganocuprates known as Gilman reagents proved to be the most effective. 

Gilman reagents are prepared by the reaction of a copper(l) halide with two equivalents of an alkyl- or aryllithium in diethyl ether or tetrahydrofuran. 

Adding an alkyl halide to the solution of the lithium dialkylcuprate leads to carbon-carbon bond formation between the alkyl group of the halide and that of the cuprate. 

The process is called cross-coupling when the groups that are joined from the two reactants are different. Methyl and primary alkyl halides, especially iodides, work best. 

Elimination becomes a problem with secondary and tertiary alkyl halides. Lithium diaryl-cuprates are prepared in the same way as lithium dialkylcuprates and undergo comparable reactions with primary alkyl halides. 

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The simplest case is the substitution of a halogen at a saturated carbon atom by an alkyl group. Organocopper reagents exhibit strong carbanionic capacity, and do attack ester groups only slowly (D.E. Bergbreiter, 1975). Ketones, however, should be protected. The relative re-... 

Substituted epoxides are attacked by organocopper reagents at the least hindered carbon atom and form alcohols (C.R. Johnson, 1973A). With a, 9-unsaturated epoxides tram-allylic alcohols are produced selectively by 1,4-addltion (W. Carruthers, 1973 G.H. Posner, 1972). 

CONJUGATE ADDITION OF ORGANOCOPPER REAGENTS TO a,p-UNSATURATED CARBONYL COMPOUNDS... 

G. H. Posner, An Introduction to Synthesis Using Organocopper Reagents (J. Wiley, New York, 1980). 

Direct transmetalation of organoboranes to organocopper reagents is not a general reaction. Because of dieir similar bond energies and electronegativities, diis trans-nietalation is linided to die preparation of alkenylcopper and unfiinctionalized... 

Over tlie last 30 years, organocopper reagents have been utilized witli great success in organic synthesis. Hie resuUs presented in this cliapter bigliliglit tlie excellent... 

ObvioL isly, tlie na ture of tlie - organocopper reagent is an import nt factor witli... 

Treatment of allylic substrates ISO, possessing suitable leaving groups X in tlieir allylic positions, witli organocopper reagents may result eitlier in an S 2-type process fa-attack) or alternatively in an S 2 one fy-attack), giving tlie substitution products 151 and 152, respectively fSclieme G.30) [Ij]. 

To explain tlie stereodieniistiy of tlie allylic substitution reaction, a simple stereoelectronic model based on frontier molecular orbital considerations bas been proposed fl55. Fig. G.2). Organocopper reagents, unlike C-nudeopbiles, possess filled d-orbitals fd - configuration), wbidi can interact botli witli tlie 7t -fC=C) orbital at tlie y-carbon and to a minor extent witli tlie cr -fC X) orbital, as depicted... 

Witli tlie reagent PbCu in tlie presence of tlie additives BF and PBu- , ees of up to 9 596 were obtained, wb de values of up to 8 596 were acliievable witli a vinyl copper reagent. Chiral dienic acetals have also been studied tliree regioisomeric products could be obtained in tliis case as tlie result of Su2, Su2, or Su2" attaclt of tlie organocopper reagent [25]. Mixtures were indeed obtained witli alKyl copper reagents, but PbCu-BF resulted in fotniation of only tlie S 2 and Su2" products, witli selectivity for tlie latter fSclieme 8.12). 

Hydrolysis of tlie ctioI etliers obtained from tlie substitution reaction witli tlie organocopper reagent yielded diiral -substituted aldehydes witli ees of 62 and 7396 for tlie Su2" and S 2 products, respectively. 

Scheme 2.30 Ring-opening reaction with organocopper reagents to form (E)-allyl 111 amines.

Scheme 2.31 Stereochemical course of ring-opening reactions with organocopper reagents.

Gilman-type organocopper reagents 50 gingkolide B 308 glabrescol 283... 

With respect to the nucleophilic addition of organocopper reagents, a sharp contrast between the rigid isopropylidene glyceraldehyde and its open-chained analog, 2,3-bis(benzyloxy)propanal. was observed (compare Tables 15 and 16). With the isopropylidene-protected aldehyde a high syn diastereoselectivity could only be obtained when tetrahydrofuran was used as reaction solvent, and the diastereoselectivity dropped considerably in diethyl ether. In contrast, the latter solvent allows excellent syn selectivities in additions to the dibenzyl-protected glyceraldehyde81. On the other hand, tetrahydrofuran yields better results than diethyl ether in the... 

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