Copper-catalyzed addition reaction

The initial focus of our work was to test the generality of the copper catalyzed addition reaction. We found that under mild conditions (50-60°C, no solvent) in the presence of 10-20 mol % copper powder, iododifluoroacetates added cleanly to... 

Terminal, internal and cyclic alkenes gave similar results. Vinyl silanes also worked well. The results of this copper catalyzed addition reaction are summarized in Table IV. 

Reaction 31 appears to be little affected by substituent electronic effects or by steric effects of either sulfonyl chloride or styrenes. Treatment of /5-chlorosulfones with triethylamine in benzene affords the corresponding a, /5-unsaturated sulfones in excellent yield. The copper-catalyzed addition of sulfonyl iodides to simple and cyclic alkenes has also been exploited76. 

In a context of industrial interest, the copper-catalyzed addition of acetic acid36 to 1 (hydroacetoxylation) in the absence of oxygen was shown to be non-regioselective, a 1 0.5 mixture of 1,2- and 1,4-addition products being obtained in a yield of 60% based on butadiene. The effect of various additives on the regiochemistry and the yield has been carefully studied. The butadiene conversion was mainly efficient with the CuBr-LiBr catalytic system (equation 12). The role of the catalyst in the reaction mechanism has been discussed but not fully understood. It has been shown that the dominant formation... 

Kinetic experiments have been performed on a copper-catalyzed substitution reaction of an alkyl halide, and the reaction rate was found to be first order in the copper salt, the halide, and the Grignard reagent [121]. This was not the case for a silver-catalyzed substitution reaction with a primary bromide, in which the reaction was found to be zero order in Grignard reagents [122]. A radical mechanism might be operative in the case of the silver-catalyzed reaction, whereas a nucleophilic substitution mechanism is suggested in the copper-catalyzed reaction [122]. The same behavior was also observed in the stoichiometric conjugate addition (Sect. 10.2.1) [30]. 

The copper-catalyzed addition of amines and amides Goldberg Reaction) are placed in this section ... 

The displacement of halogen with a copper(I) acetylide and subsequent or synchronous copper catalyzed addition of a neighboring nucleophilic substituent to the triple bond (equation 2) constitutes a versatile synthesis of heterocycles. This reaction has been utilized both for the synthesis of furo[3,2-c]pyridines (equation 3) and furo[3,2-6]pyridines (equation 4) (68JHC227, 72MI31700>. 

For example, the copper catalyzed addition of Grignard compounds to alkynyl substituted /(-lactones 55 delivers /S-allenic acids 56 in high yields [38], During these reactions, the central chirality of one of the stereogenic centers of the /Mactone is transferred to the axial chirality of the allene. 

The synthesis of novel azetidine derivatives remains the subject of intensive study. New procedures for the preparation of this class of compounds include, e.g., rearrangement of /3,7-aziridino-a-amino esters <2007OL4399>, copper-catalyzed multicomponent reactions of terminal alkynes, sulfonyl azides, and carbodiimides <20070L1585>, regioselective addition of 1,3-dicarbonyl dianions to iV-sulfonyl aldimines <2007T4779>, elaboration of a-amino acids <2007TL2471>, palladium-catalyzed iV-arylation of azetidines <2007S243> and... 

Finally, the best enantioselectivity with this system was obtained by using cop-per(II) acetate, with propionic acid as additive, and by conducting the reaction at lower temperatures (70 %, 57 % ee) [20]. Later, the use of an azanorbornane add, which was a bicyclic analog of proline, resulted in better activity and enantioselectivity (65 % ee) [21], In the same year, Pfaltz reported the use of chiral bisoxazoline 3 in the enantioselective copper-catalyzed acyloxylation reaction (Scheme 3) [22], Although long reaction times were required, the enantioselectivity achieved with... 

Terminal alkynes undergo copper-catalyzed additions to enamines such as A -benzyl-l, 2,3,4-tetrahydropyridine 203 to give 2-alkynyl-piperidines 204 in high yield (Equation 18). A wide variety of functionalities can be tolerated on the alkyne and the reaction can be performed enantioselectively to give products with moderate (54-90%) enantiomeric selectivity <2002AGE2535>. 

In contrast to tliis the introduction of longer alkyl drains with the aid of copper-promoted addition reactions to Asteroids normally proceeds with unsatisfactory oi p ratios [ISh 16]. In some cases improvement of the diastereoselectivity by fin e tiinin g of th e rea ction con diti on s h as h een p o ssihle. The rati o of th e epimeric products IS and 16 in the copper-catalyzed 1 6-addition of 4-pentenylmagnesiiim bromide to dienone 14 for example was improved from 58 42 to 82 18 by adjustments to the quantity of niideophile and the solvent composition (Eq. 4.6) [16f ]. 

Cyclocodimerization and cyclooligomerization reactions of cyclopropenes catalyzed by nickel complexes require alkenes with electron-withdrawing substituents as reaction partners. In this respect, these reactions are complementary to the copper-catalyzed additions discussed in the previous section which do not proceed with electron-poor alkenes due to the low nucleophilicity of the copper-carbene complex. 

Stereoisomeric ethyl 4,5-dimethylspiropentane-l-carboxylates 11 were prepared by copper-catalyzed addition of ethyl diazoacetate to cis- and tra .v-l,2-dimethyl-3-methylenecyclo-propane and by cyclopropanation of four isomeric ethyl 2-ethylidene-3-methylcyclopropane-l-carboxylates. The ethoxycarbonyl group was removed from the spiropentane system by saponification followed by treatment with lead tetraacetate, iodine and reaction with tributyltin hydride, both with irradiation. ... 

Conjugate addition to an a,3-unsaturated carbonyl compound is achieved routinely by using a lithium organocopper reagent or a copper-catalyzed Grignard reaction. " It should be noted that in many of these examples, and in particular in the case of lithium diorganocuprates, the resultant enolate has... 

Etiolates formed by organocopper conjugate addition may be acylated cleanly by acid chlorides to give 3-diketones. Although 0- and C-acylation are both possible, the latter is favored by the use of acid chlorides rather than anhydrides and by the use of diethyl ether as solvent, rather than DME. Good yields of 3-diketones have been obtained by acylation of the anions derived from both acyclic and cyclic unsaturated ketones with cuprates, or in copper-catalyzed Grignard reactions. Some synthetic applications are given in Scheme 54. 

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