With cuprates

The titaniated (25)-2,5-dihydro-2-isopropyl-3,6-dimethoxypyrazines derived from cyclo(L-Val, Gly) or cyclo(L-Val, Ala) (1, R1 = H, CH3) react with a,/I-unsaturatcd aldehydes exclusively by 1.2-addition (cf. nearly exclusive 1,4-addition of ,//-unsaturated ketones with cuprate complexes of 2,5-dialkoxy-3,6-dihydropyrazines, see Section D. 1.5.2.3.1.4.) in a highly diastereoselective mode to give virtually only the (l S,2R)-diastereoniers 2 ". In reactions with the corresponding lithiated pyrazines both regioselectivity and diastereofacial differentiation at C-2 are also remarkably high (dc 95 %), but the diastereomeric excess at C-l is substantially smaller (30 50%) ... 

Formation of the very unstable dehydroalanine derivatives A p-dimethylaminophe-nyl- and Af-p-nitrophenyhnethylenedehydroalanine methyl ester could only be verified by -NMR. Because of Michael-type reactions with cuprates, the iV-arylmethylenedehy-droalanine methyl esters have been applied as building blocks in the synthesis of amino acids.[18]... 

Ring-opening reactions of tartrate acetal 211 with cuprates and dialkyl boron bromides were conducted (Scheme 96). 9 The reaction proceeds stereoselectively in favor of the formation of 212. Ester groups are tolerant to these reaction conditions. 

Scheme 2.2 Allene synthesis via SN2 substitution of propargylic acetates 7 with cuprates.

Conjugated acetylenic esters react readily with cuprate reagents, with syn addition being kinetically preferred.63 64 65 66 67... 

Vinyl triphenylphosphonium ion has been found to react with cuprate reagents by nucleophilic addition, generating an ylide structure. This intermediate can then be... 

Gawlcy and co-workers2 report that KDA is superior to LDA and to n-BuLi for deprotonation of dimethylhydrazones (7, 126-130) or of oxime ethers. The reaction is generally complete in THF at —78° in 15 minutes or less. The potassium counterion does not interfere with cuprate formation or conjugate addition. 

The Lewis acid catalyzed conjugate addition of allylsilanes (140) to (142) and allylstannanes (154) and (155) to ot,0-enones, described by Sakurai,68a,68b is highly efficient and experimentally simple in contrast to the allylcuprate additions. Various substituents can be incorporated into the allylsilanes (allylstannanes), e.g. alkoxy, alkoxycarbonyl and halogen, some of which are incompatible with cuprate reagents 69 In addition, Heathcock and Yamamoto report that diastereoselectivity is correlated to the alkene geometry of both the allylmetals and the acceptor units for example, allylation of ( )-enones (143) and (146) affords predominantly the syn adducts (144) and (147), while (Z)-enone (149) gives predominantly the anti adduct (150 Scheme 25).680 On the other hand, with cyclohexen-2-one the (Z)-silane (141) affords predominantly the threo adduct (152), while (142) affords erythro adduct (ISS).686 The more reactive allylstannanes (154) and (155) also afford similar diastereoselectivity.68e,f... 

Two highly unusual reactions were noted in this study which merit attention. First, the treatment of (59) with cuprate (60) gave rise to 1,2-addition of the alkyne as the only product (67% equation 57). Second, when trifluoromethyl ketone (59) was treated with either the higher or lower order methylcu-prates, the cyanohydrin (61) was isolated in addition to the normal 1,4-addition product (equation 58). 

Diastereoselective 1,4-addition of cuprates to enones. 5-Trimethylcyclohex-enone (1) has been resolved by kinetic resolution via the adduct with p-toluenethiol by cinchonidine. It undergoes highly diastereoselective addition with cuprates in the presence of ClSi(CH3)3 and HMPT to furnish only the trans-1,4-adducts in 88-95% yield. ... 

Recently, a more detailed study on the coupling reaction of vinylic tellurides with cuprates was published, showing that the stereochemistry of the coupled product depends on the reaction conditions. When the reaction was performed at room temperature, the pure ( )-olefin or a mixture of (Z/E)-isomers was formed. At lower temperature, the (Z)-isomer was the main product (Scheme 117). 

Cheng, K.F., Nagakura, I., and Piers, E. 1982. Reaction of P-halo aP-unsaturated ketones with cuprate reagents. Efficient syntheses of PP-dialkyl ketones and P-alkyl P-unsaturated ketones. A synthesis of (Z)-jasmone. The Canadian Journal of Chemistry, 60(10) 125 6-63. 

Compounds with acidic hydrogen atoms react rapidly with cuprates. Phenylacetylene has been mentioned as one example (223). Another is diethyl phenylmalonate (144), which on addition to lithium dimethylcuprate gave a rapid evolution of methane and the formation of a methyl-copper-like precipitate which did not redissolve. Subsequent to the addition of benzoyl chloride and the customary work-up, only acetophenone and the phenylmalonate were isolated. The reaction may be summarized by Eq. (23). The failure to isolate the acylated product may be ascribed to the formation of the enolate, (II). 

Asymmetric -methylation of a, -enones. Chiral bidendate ligands derived from L-prolinol can be used for asymmetric Michael additions to a, 3-enones with cuprates of the type CH,L CuMgBr (10, 266). The highest optical yield in conjugate addition to chalcone is observed when L is (S)-N-methylprolinol (88% ee). The tridentate chiral ligand 1 is equally effective for asymmetric 3-methylation of chalcone with CH,L CuLi and CuBr the chemical yield is 95%. Reduction of the amide carbonyl group of 1 results in practically total loss of chiral induction. 

Vinylic substitution reactions with cuprates, e.g. 20, in Ar,Ar-diniethylacetamide also give good... 

Two interesting reactions of these products have been reported. One is conversion to sulfenylated enones (equation I). The other is coupling with cuprates with complete regioselectivity and inversion (equation II). 

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