Lithium dialkylcuprates conjugate additions

The preparation and some synthetic applications of lithium dialkylcuprates were described earlier (Section 14 11) The most prominent feature of these reagents is then-capacity to undergo conjugate addition to a p unsaturated aldehydes and ketones... 

Conjugate Addition. To a solution of 1.5 mmol of lithium dialkylcuprate at — 25 CC is added 1 mmol of methyl ( )-3-[(25,45,55)-3-benzyloxycarbonyl-4-methyl-5-phenyl-2-oxazolidinyl]-propenoate dissolved in 1 mL of dry diethyl ether. After 30 ntin at — 25 C, the mixture is treated with an aq NH3/NH4C1 pH 8 buffer solution and then stirred at r.t. for 15 min. After diethyl ether extraction, the organic layers are dried over Na,S()4 and filtered and the solvent is evaporated under reduced pressure. The crude products are checked by H- and l3C-NMR analyses in order to determine the diastereomer ratios (g 95 5) and then purified by flash chromatography (hexane/ethyl acetate 80 20) yield 70-72%. 

Addition to enals. s Conjugate addition of lithium dialkylcuprates is favored over 1,2-addition by use of low temperatures and a nonpolar solvent (pentane). However, 1,2-addition becomes more important if the double bond is trisubstituted. 

Review Taylor has reviewed the conjugate addition-enolate trapping reactions of organocopper reagents, in particular of lithium dialkylcuprates (131 references). 

The mechanism of conjugate addition of lithium dialkylcuprates to enones has been explored by the determination of 13C kinetic isotope effects by an NMR method reductive elimination from Cu is implicated as the rate-determining step.109... 

A second solution to the synthesis of 4-methyl-2-octanone by conjugate addition of a lithium dialkylcuprate reagent to an a,[3-unsaturated ketone is revealed by the disconnection shown ... 

Mechanistic picture of the conjugate addition of lithium dialkylcuprates to enones is not clearly delineated, despite essential meaning of this reaction in organic synthesis. l3C KIE studies were used in order to determine the rate-limiting step for the reaction of Bu2CuLi with cyclohexanone (Equation (45)).80... 

Selenium-stabilized carbanions can be also generated by 1,4-addition of nucleophilic reagents to a-selanyl a,[3-unsaturated carbonyl compounds. The conjugate addition of trialkylsilyllithium compounds to 133, followed by reaction with allyl iodide, afforded the addition products 134 with good m-stereoselectivity (R = Me dr 86 14 R = Ph dr 94 6) (Scheme 34).214 The addition of lithium dialkylcuprates to 2-phenylselanylcycloalk-2-enones has also been used for the synthesis of natural products.215,216... 

A group at Miles Laboratories has been particularly active in this regard, having synthesized many 7- and 8-alkyl derivatives of 4,5-epoxymorphinans. They generated 229 a series of 8/3-alkyldihydrocodeinones (143) by the conjugate addition of lithium dialkylcuprates to codeinone (52) according to Scheme 2.19. Three products were isolated, the 8/3-alkyldihydrocodcinone, 143 (54%) ... 

Conjugate Addition Reactions.—The use of polymer-bound dialkylcuprates gives comparable or higher than normal yields in the conjugate addition to enones the major advantage lies in the ease of work-up. The mechanism of conjugate addition of cuprates and the mechanism and stereochemistry of the addition of lithium dimethylcuprate to jS-cyclopropyl-substituted enones have been reported. 

Silyl enol ethers can be prepared from ketones by trapping the kinetically formed lithium enolate with EtsSiCl (eqs 7 and 8), or by the conjugate addition of a dialkylcuprate to an a,p-unsaturated ketone with silylation of the enolate intermediate (eq Surprisingly, the addition of Lithium Di-n-... 

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