Conjugate copper-catalyzed

Copper-catalyzed Enantioselective Conjugate Addition Reactions of Organozinc Reagents... 

A remarkable number of new BINOL- and TADDOL-based diiral ligands for tlie copper-catalyzed conjugate addition of R Zn reagents have recently been introduced, witli botli monodentate and bidentate ligands having proven capable of inducing bigli enanboselectivities [6, 11, 12, 46]. 

The copper-catalyzed additions of sulfonyl chlorides to conjugated dienes and trienes73 as well as to aryl-substituted cyclic olefins74 and substituted styrenes have been described75 for example, arenesulfonyl chlorides add to vinylarenes providing good to excellent yields75 of /J-chlorosulfones ... 

CHROMIUM TRIOXIDE-PYRIDINE COMPLEX, preparation in situ, 55, 84 Chrysene, 58,15, 16 fzans-Cinnamaldehyde, 57, 85 Cinnamaldehyde dimethylacetal, 57, 84 Cinnamyl alcohol, 56,105 58, 9 2-Cinnamylthio-2-thiazoline, 56, 82 Citric acid, 58,43 Citronellal, 58, 107, 112 Cleavage of methyl ethers with iodotri-methylsilane, 59, 35 Cobalt(II) acetylacetonate, 57, 13 Conjugate addition of aryl aldehydes, 59, 53 Copper (I) bromide, 58, 52, 54, 56 59,123 COPPER CATALYZED ARYLATION OF /3-DlCARBONYL COMPOUNDS, 58, 52 Copper (I) chloride, 57, 34 Copper (II) chloride, 56, 10 Copper(I) iodide, 55, 105, 123, 124 Copper(I) oxide, 59, 206 Copper(ll) oxide, 56, 10 Copper salts of carboxylic acids, 59, 127 Copper(l) thiophenoxide, 55, 123 59, 210 Copper(l) trifluoromethanesulfonate, 59, 202... 

Chiral diaminocarbene complexes of copper were used in asymmetric conjugate addition of diethylzinc to Michael acceptors. Achiral copper carbene complexes derived from imidazolium salts were synthesized and characterized for the first time by Arduengo in 1993 [43]. In 2001, Woodward reported the use of such Arduengo-type carbene in copper-catalyzed conjugate addition and showed their strong accelerating effect [44]. The same year, Alex-... 

It is important to remember that the yield and reproducibility of hydrozircona-tions and the subsequent transformations depend on the presence of ionic impurities in 1 which often hamper the desired transformations. For example, in situ preparations of 1 with liEtjBH and BuMgCl were not appropriate for hydrozircona-tion/copper-catalyzed conjugate addition sequences otherwise preformed 1 is well adapted for these protocols. 

Meerwein Arylation Reactions. Aryl diazonium ions can also be used to form certain types of carbon-carbon bonds. The copper-catalyzed reaction of diazonium ions with conjugated alkenes results in arylation of the alkene, known as the Meerwein arylation reaction.114 The reaction sequence is initiated by reduction of the diazonium ion by Cu(I). The aryl radical adds to the alkene to give a new (3-aryl radical. The final step is a ligand transfer that takes place in the copper coordination sphere. An alternative course is oxidation-deprotonation, which gives a styrene derivative. 

The synthesis in Scheme 13.5 also makes use of an aromatic starting material and follows a retrosynthetic plan similar to that in Scheme 13.3. The starting material was 4-methoxybenzaldehyde. This synthesis was somewhat more convergent in that the entire side chain except for C(14) was introduced as a single unit by a mixed aldol condensation in step A. The C(14) methyl was introduced by a copper-catalyzed conjugate addition in Step B. 

Copper-catalyzed cyclopropanation of benzene and its derivatives by a diazoacetic ester yields a norcaradiene 230 which undergoes spontaneous ring opening to cyclo-heptariene 231. At the temperatures needed for successful cyclopropanation, sigma-tropic H-shifts leading to conjugated isomers of cycloheptatriene carboxylates cannot be avoided. The situation is complicated by the formation of regioisomers upon cyclopropanation of substituted benzenes, and separation of the cycloheptatriene isomers may became tedious if not impossible. 

In 1993, Alexakis et al. reported the first copper-catalyzed asymmetric conjugate addition of diethylzinc to 2-cyclohexenone using phosphorous ligand 28 (32% ee).36 An important breakthrough was achieved by Feringa et al. with chiral phosphoramidite (S,R,R)-29 (Figure 1), which showed excellent selectivity (over 98% ee) for the addition of 2-cyclohexenone.37 Since then, efficient protocols for the conversion of both cyclic and acyclic enones, as well as lactones and nitroalkenes, have been developed featuring excellent stereocontrol. 

A remarkable number of chiral phosphorus ligands (phosphoramidites, phosphites, and phosphines with modular structures) have been introduced into the copper-catalyzed conjugate addition of R2Zn reagents, and high enantio-selectivities (>90%) are now possible for all three different classes of substrates 2-cyclohexenones and larger ring enones, 2-cyclopentenones, and acyclic enones. 

Feringa, B. L. Naasz, R. Imbos, R. Arnold, L. A. Copper-catalyzed Enantioselective Conjugate Addition Reactions of Organozinc Reagents. In Modem Organocopper Chemistry Krause, N. Ed. Wiley-VCH GmbH Weinheim, 2002 Chapter 7, pp 224—258. 

Figure 18. Stereochemical model for conjugate additions catalyzed by arenethiolato—copper complexes. [Adapted from (145, 146).]...

In 1996, Feringa and co-workers (164) reported the use of binaphthol-derived phosphoramidite 232a as a ligand for the copper-catalyzed conjugate addition. Addition of 2 equiv of 232a to Cu(OTf)2 forms an effective catalyst for the selective... 

Figure 21. Selectivity of copper-catalyzed conjugate addition of Et2Zn to cyclohexenone in the presence of several ligands.

Organoaluminum reagents have been used in the copper-catalyzed conjugate addition to enones with some success. Iwata and co-workers (182) demonstrated that dimethoxyphenyl oxazoline (247) provides modest selectivities in the copper-catalyzed conjugate addition of trimethylaluminum to 3,4,4-trimethylcyclohexadi-enone to provide the adduct in 68% ee, Eq. 145. The use of TBSOTf is crucial to attain high conversion and selectivity in this process. Woodward and co-workers (183) subsequently reported that a Cu(I) complex of thiocarbamate 248 provides modest facial discrimination in the addition of trimethylaluminum to a linear enone to afford 245b in 51% ee, Eq. 146. The authors note that this catalyst system decomposes under the reaction conditions at ambient temperature. 

Copper-Catalyzed Conjugate Addition of Functionalized Organozinc Reagents to a,p-Unsaturated Ketones Preparation of Ethyl 5-(3-Oxocyclohexyljpentanoate. 

Copper-catalyzed monoaddition of hydrogen cyanide to conjugated alkenes proceeded very conveniently with 1,3-butadiene, but not with its methyl-substituted derivatives. The most efficient catalytic system consisted of cupric bromide associated to trichloroacetic acid, in acetonitrile at 79 °C. Under these conditions, 1,3-butadiene was converted mainly to (Z )-l-cyano-2-butene, in 68% yield. A few percents of (Z)-l-cyano-2-butene and 3-cyano-1-butene (3% and 4%, respectively) were also observed. Polymerization of the olefinic products was almost absent. The very high regioselectivity in favor of 1,4-addition of hydrogen cyanide contrasted markedly with the very low regioselectivity of acetic acid addition (vide supra). Methyl substituents on 1,3-butadiene decreased significantly the efficiency of the reaction. With isoprene and piperylene, the mononitrile yields were reduced... 

Manganese-copper-catalyzed conjugate addition of organomagnesium reagents to a,p-enones is a general synthetic method. Table I shows that the reaction can be successfully performed even with enones of low reactivity. 30% Manganese chloride is necessary to obtain good yields. In most cases, however, 0.1% cuprous chloride is sufficient.3... 

This manganese-copper-catalyzed conjugate addition reaction compares favorably with the classical copper-catalyzed reaction. The two reactions are easily and similarly carried out under mild conditions, but the first one gives higher yields. This difference, already observed in the case of p-monosubstituted o,p-ethylenic ketones, is especially noticeable with p,p-disubstituted or [Pg.70]

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