Copper alkoxides

Transfer of the hydride from the Cu to the electrophilic carbon and cleavage of the copper alkoxide by the silane regenerates 69. Recent reports point to the influence of the type of the counter ion X" of the homoleptic 66-67 on the activity, the BF being superior to the PF analogue this effect has been attributed to differences in the rate of active catalyst generation from the homoleptic [Cu(NHC)2] X and NaO Bu due to solubility differences of the inorganic salts formed during the displacement of the NHC by BuO" [54] (Scheme 2.10). 

Tanaka et al. (152) demonstrated that a chiral copper alkoxide could be used substoichiometrically to deliver MeLi to an enone in conjugate fashion. The precatalyst is formed from amino alcohol 221, MeLi and Cul, Eq. 123a. Under stoichiometric conditions, this catalyst mediates the conjugate addition of MeLi to the macrocyclic enone, affording muscone in 91% ee. Lower enantioselectivity is observed using a substoichiometric amount of 222 (0.5 equiv), affording a 79% yield of muscone in 76% ee, Eq. 123b. These selectivities are attained by portion-wise addition of the substrate and MeLi to the alkoxy-cuprate. This catalyst also exhibits a complex nonlinear effect (78, 153). 

The mechanism proposed for this transformation is outlined in Scheme 24 (235). The slow step of this reaction is silyl transfer from the copper alkoxide 353. This step may occur through the intermediacy of an external silicon source (intermolecular) or by internal transfer of the silyl group (intramolecular). To probe this issue, these workers conducted a double-crossover experiment involving two distinct nucleophiles with different silyl groups, 342a and 359, and examined the products prior to desilylation. The results show conclusively that silicon transfer has a significant intermolecular component, and is somewhat sensitive to the solvent, Eq. 199. 

Further evidence for the intermediacy of a chiral metal enolate in the aldol process was provided in a subsequent publication (255). The authors found that this reaction could be equally well catalyzed by a Cu(I) complex (generated from the phosphine) and TB AT. Further, Tol-BINAPCuOf-Bu is also a competent catalyst for this reaction, underscoring the ability of the copper alkoxide to mediate desily-lation of the dienolsilane. The authors suggest that the dienolsilane effects the reduction of Cu(II) to Cu(I), although in light of the work of Lectka and co-workers (249) in this area, it seems equally likely that the phosphine mediates this reduction prior to introduction of the dienolsilane. Nevertheless, the intermediacy of a metal bound enolate seems assured. 

Takaya and co-workers (256) disclosed that chiral copper alkoxide complexes catalyze the transesterification and kinetic resolution of chiral acetate esters. Selec-tivities are very poor (E values of 1.1-1.5) but it was noted that the Lewis acid BINAP CuOTf was not an effective catalyst. The observation thatp-chlorophcnyl-BINAP-CuOf-Bu complex gave faster rates than BINAP-CuOt-Bu suggests that both the Lewis acidic and Lewis basic properties of the copper alkoxide are required for optimal reactivity. 

Scheme 18 Allylic substitution reactions between copper alkoxides and allylic carbonates...

Disubstituted dihydrofurans and dihydropyrans were prepared via allylic etherification [68] in a similar manner to dihydropyrroles (cf Section 9.4.6). Thus, diaste-reoisomeric ethers were generated by the reaction of cinnamyl tert-butyl carbonate with the copper alkoxide prepared from (Rj-l-octen-3-ol, depending on which enantiomer of the phosphoramidite ligand was used (Scheme 9.39). Good yields and excellent selectivities were obtained. RCM in a standard manner gave cis- and trans-dihydrofuran derivatives in good yield, and the same method was used for the preparation of dihydropyrans. 

However, copper alkoxides with longer chains appear to be more soluble in their parent alcohol. S. Shibata et al. (20) have used the n-butoxides of Y, Ba and Cu dissolved in n-butanol and hydrolyzed with water. They obtain a precipitate of oxides that is composed of a very fine submicron powder that readily sinters starting above 250°C. However, the different reaction rates for the hydrolysis and the precipitation of the three different cations lead to cationic segregation. 

Importantly, H2 gas can be turned into a strong acid on binding to electrophilic cationic complexes. Free H2 is an extremely weak acid with a TpKa near 35 in THF (23), and heterolytic splitting of r 2-H2 in relatively electron-rich neutral complexes is usually achieved only by strong bases. For example, we have shown Eq. (4) that copper alkoxides deprotonate W(CO)3(PR3)2(H2) and FeH2(H2)(PR3)2 to give heterobi-metallic species with bridging hydrides (24). 

It is important to note that this new protocol operates under completely neutral conditions. Indeed, addition of BuOK to the copper chloride - Phen/alcohol mixture generates the corresponding copper alkoxide. Prom that point onward, the oxidation proceeds under neutral conditions since all the base has been consumed. It is noteworthy that sensitive substrates do not undergo epimerization or racemization. 

Several methods have been recommended for the preparation of pure methylcopper, each having advantages over previously reported methods. Costa et al. consider the [Pb(CH3)4 + Cu(N03)2] method superior to the Grignard route, as reproducible analyses are obtained 82). However, Thiele and Kohler recommend the reaction of zinc dialkyls with cop-per(II) chloride in ether at — 78°C for the preparation of pure yellow methylcopper, red-brown ethylcopper, and orange propylcopper, uncontaminated by copper alkoxides (277). The mechanism was considered to be a reduction of copper(II) to copper(I) chloride, followed by the reaction of the latter with the zinc dialkyl. The results from the recent... 

Copper alkoxide complexes are typically yellow in color and are made from Cu starting materials, for example, in the metathesis reaction shown in equation (10). Cu OR complexes are generally soluble in etheral solvents and some... 

Hydrosilylations by complexed CuH have been applied to several substrate types (Scheme 1-17). As illustrated by the following examples, the stereochemical outcomes from both 1,2-additions (to aryl ketones and aryl imines ) and 1,4-conjugate additions (cyclic ketones, P-aryl and/or P-silyl enoates, and unsaturated lactones) can be controlled by these ligand-accelerated reactions. One of the key tricks to this chemistry is to take advantage of the tolerance of CuH complexes to alcohols and water.In fact, several methods rely on the presence of a bulky alcohol (e.g., t-BuOH) to significantly enhance reaction rates. It takes relatively little added alcohol (volume-wise) to accelerate the hydrosilylation, usually on the order of 1-3 equivalents. The role of this additive is usually ascribed to the more rapid quenching of an intermediate copper alkoxide or enolate, which necessarily generates a copper alkoxide, an ideal precursor to rapid reformation of CuH in the presence of excess silane. Thus, the rate increase is presumably due to... 

Network of various proposed mechanisms for the reaction of copper alkoxides, amides, and amides with aryl halides. 

Whitehorne and Schaper reported an active copper alkoxide catalyst, 23, for LA ROP [24]. Their catalyst worked properly in dichloromethane at room temperature and produced atactic polymer in a first-order kinetic respect to LA and catalyst concentration. 

Copper(I) alkoxides were mandatory to achieve rhodium-catalyzed allylie etherifications with aliphatic alkoxide derivatives (eq 29). A one-pot procedure that involves the treatment of the corresponding alcohol with LHMDS to generate the lithium enolate, followed by the addition of a copper salt, allowed the preparation of the requisite copper alkoxide. 

A plausible catalytic cycle for the direct asymmetric aldol reaction is shown in Fig. 7. Key to the success of the reaction is chemoselective enolate formation of ynones 8 in the presence of enolizable aldehydes, which is mediated by soft-soft interaction 10 between the ynone moiety and the copper catalyst. This interaction selectively acidifies the a-protons of ynones. The aldol addition of chiral Cu (I) enolate 12 to an aldehyde affords copper aldolate 13. The soft-soft interaction between the Cu(I) atom and the n electrons of the alkyne moiety in 13 would help suppress the imdesired retro-aldol reaction due to the existence of additional coordination. Nevertheless, facile protonation of imstable 13 and formation of aldol product 14 is crucial, rationahzing the inquiry of (sub)stoichiometric amounts of trifluoroethanol. Protonation of 13 regenerates the copper alkoxide catalyst. 

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