Conjugate addition of lithium

The conjugate addition of lithium cuprates to cinnamates 1 bearing a chiral oxazolidine or imidazolidine ring at the ortho position produced 2 in good to excellent yield upon hydrolysis14. 

The conjugate addition of lithium dimethylcuprate to spiroketone 5 gave predominantly (S j-6 [(S)/(R) 92 8] in which methyl group attacked from the side syn to the oxygen atom, whereas the addition of lithium dimethylcuprate-chlorotrimethylsilane afforded exclusively the anti-adduct (S)-621,... 

The conjugate addition of lithium dimethylcuprate to chalcone in the presence of (2S)-1-(2,2-dimethyl-l-oxopropyl)-2-diphenylphosphinomethylpyrrolidine gave the corresponding S-adduct with 84% ec in 79% yield79. 

The stereoselective conjugate addition of lithium (Z)-dialkenylcuprates to vinyl sulfones gives (Z)-olefms in the range of 70-80% overall yield and no ( )-isomer is detected (equation 66)56. The degree of stereoselectivity is higher than 90%. 

Asymmetric conjugate addition of lithium amides to alkenoates has been one of the most powerful methods for the synthesis of chiral 3-aminoalkanoates. High stereochemical controls have been achieved by using either chiral acceptors as A-enoyl derivatives of oxazolidinones (Scheme 4) 7 7a-8 chiral lithium amides (Schemes 5 and 6),9-12 or chiral catalysts.13,14... 

The first naturally occurring tricyclo[6.3.0.0 ]undecane to be synthesized was isocomene (757), a colorless oily sesquiterpene hydrocarbon isolated from several plant sources. In 1979, Paquette and Han reported an efficient, stereospecific approach starting with a preformed bicyclic enone, to which the third five-membered ring was appended with proper attention to stereochemistry and position of unsaturation (Scheme LXXX) The pivotal steps are seen to be the stannic chloride-induced cyclization of aldehyde 732 and the conjugate addition of lithium dimethylcuprate to 733 which sets the stereochemistry of the last methyl group. 

Cuprate conjugate additions. One step in a recent synthesis of (-t-)-modhephene (3). a natural sesquiterpene with a (3.3.3)propellane skeleton, involved conjugate addition of lithium dimethylcuprate to 1. The desired reaction proved difficult... 

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. 

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... 

The conjugate addition of lithium bis(phenyldimethylsilyl)cuprates to tt./t-unsaUi rated esters forms enolates, which readily react with aldehydes to give 2-substituted 3-silyl esters (equation 129)509. The products are useful as intermediates in the synthesis of allylsilanes and natural products. Yields of this reaction may be significantly increased by... 

Stereocontrolled conjugate addition of lithium dimethylcuprate to the electron deficient 2,3-double bond of allenes 851 leads to 5,6-dihydropyranM-oncs 852 in moderate yield (Equation 343) <2000J(P1)3188>. Similarly, the Ag(l)-catalyzed intramolecular cyclization of the allenic acid 853 is accelerated upon addition of diisopropylethyl-amine to afford the 3,6-dihydropyran-2-one 854, an intermediate during the total synthesis of (—)-malyngolide (Equation 344) <2000JA10470>. 

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... 

For the sake of brevity, such important transformations as the conjugate addition of lithium enolates on activated olefins or the halogenation, amination, oxidation. .. of enolates have not been considered here. Each of these reactions has been the object of considerable developments lately, in particular for their asymmetric versions, and giving even short accounts about the state of the art would have been extremely space-consuming. 

The conjugate addition of lithium peroxides on enones is a non-classical route to epoxidation. The original lithium enolate rearranges immediately in situU3. Note that a catalytic asymmetric version of this reaction was also developed (Scheme 41)184. 

The treatment of vinylcopper derivatives, resulting from the conjugate addition of lithium cuprates on propargylic esters, by methyllithium is a way to prepare lithium cumulenolates (Scheme 43)188. Those can be trapped as the corresponding vinyl iodides. Note that the authors propose a naked vinylcopper intermediate while a VinylCuMe or a (Vinyl)2Cu is more likely to be involved. 

Mori started with the early introduction of the chiral centre [298] in using (3-oxidation of pentanoic acid A by the yeast, Candida rugosa, IFO 0750 [299]. The obtained (R)-3-hydroxypentanoic acid B was transformed into C in a few conventional steps. The second building block was prepared from methyl 2-pentynoate D conjugate addition of lithium dimethyl cuprate yielded E, which was further converted into the frans-configured vinyl bromide F. Hydro-boration of C yielded G which upon Suzuki s palladium catalysed cross-coupling with F furnished 157 after treatment of the reaction product with hydrochloric acid followed by chromatographic purification. The synthesis of ent-157 used (S)-3-hydroxypentanoic acid. 

Chelation control has also been implicated in conjugate addition reactions. For example, during a synthesis of the macrolide antibiotic 6-ep/-erythromycin, Mul-zer and co-workers86 found that the stereochemistry at the anomeric centre (l position) of the tetrahydropyranyl protecting group had a profound effect on the stereochemistry of conjugate addition of lithium dimethylcuprate to the ynone 49.1 [Scheme 1.49]. 

Marshall and Ruden (196) have reported a conjugate addition of lithium dimethylcuprate to a cyclopropyl enone. The major products are the 1,4-adduct and one from a previously unreported 1,6-addition to the cyclopropyl ring [Eq. (96)]. 1,6-Conjugate additions are known for dienoates (206) and 2,2-di(carboxyethyl)vinylcyclopropane 94, cf. 59). 

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 addUion-cyclization. 3-Substituied 2-carbomethoxycyclopentanones are prepared conveniently in one step from dimethyl (2E)-hexenedioate by conjugate addition of lithium dialkyl cuprates or higher-order cyan[Pg.348]

Conjugate addition of lithium enolates to a,/3-unsaturated thioamides is also promoted by the addition of 1-2 equiv. of HMPT. ... 

The conjugate addition of lithium pentamethyldisilane (73) to cyclic enones is a general reaction (e.g., 74 and 76) and required no conversion to the corresponding copper species. The yields of the adducts 75 and 77 range from 50% to 60% [68]. 

Scheme 22. Conjugate addition of lithium pentamethyldisilane (73) to cyclic enones [68]...

In addition, conjugate addition of lithium alkynides and thermally unstable lithium carbenoids, which is very difficult to achieve in organocopper chemistry, is realized with this amphiphilic conjugate alkylation system (Sch. 98). 

Yunker, M B, Plaumann, D E, Fraser-Reid, B, The stereochemistry of conjugate addition of lithium dialkyl cuprate reagents to some carbohydrate a-enones. Can. J. Chem., 55, 4002-4009, 1977. Baer, H H, Ong, K S, Raeactions of nitro sugars. IX. The synthesis of branched-chain dinitro sugars by Michael addition. Can. J. Chem., 46, 2511-2517, 1968. 

Conjugate additions. Enals undergo selective allylation with diallylcerium chloride in the presence of ATPH. Regioselective Robinson annulations can be initiated by the conjugated addition of lithium enolates to enones. - Remarkably, silyllithium reagents add to the p-position of aromatic carbonyl compounds in the presence of ATPH. ... 

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