Ketone copper, chemoselectivity

In 2003, Velusamy and Punniyamurthy reported on a copper(II)-catalyzed C—H oxidation of alkylbenzenes and cyclohexane to the corresponding ketones with 30% hydrogen peroxide (Scheme 131). The reaction was catalyzed by the copper complex 192a depicted in Scheme 131 and yields were high in the case of alkylbenzenes (82-89%) whereas cyclohexanone was obtained with a low yield of 18%. Chemoselectivity was very high in every case neither aromatic oxidation nor oxidation at another position of the alkyl chain was observed. 

A simple example that also shows some chemoselectivity is the preparation of the ketones 12 R = Et or Pr by reaction of the bromoacid chloride 11 with the appropriate dialkyl copper lithium. The bromoacid 10 is available and can be converted into a range of bromoketones by this method.3... 

A number of methods to increase the thermal stability of Kdbrich reagents have centered around replacement of the lithium counterion normally present with a variety of transition metals, chiefly titanium, hafnium and copper." For example, the reagent derived from transmetalladon of lithium dichlorometh-ane with titanium isopropoxide could be reacted with various ketones and aldehydes to afford halohydrin adducts in good yields at temperatures as high as 0 °C. Competition experiments established the chemoselectivity of this reagent (Scheme 14). The direct activation of severid allylic halides has been accomplished with tin and chromium ° reagents (equation 26). Transmetallation of an alkyllead precursor has also been noted. 

Acylation of copper derivatives with acid chlorides works well, but they do not react with free carboxylic acids, unlike the more basic alkyl-lithiums. A dramatic illustration of chemoselectivity comes in the interaction of Bu2CuLi with the free acid 59 and its acid chloride 61. Reaction occurs24 at the alkyl iodide with the one to give 60 and at the acid chloride with the other to give the ketone 62. Acylation can also be achieved by many other metal complexes, from A1 to Zr, but to make those we need hydrometallation, the subject of the next section. 

We recently reported on the different reactivity of copper catalysts when supported on pure silica or on mixed oxides. Thus, the use of very pure, pyrogenic silica, allowed to obtain a catalyst showing excellent chemoselectivity in the hydrogenation of a,P-unsaturated ketones containing also an isolated olefmic bond [Ij. 

Chemoselective Hydrogenation of Unsaturated Ketones in the Presence of Copper Catalysts... 

During our studies on the use of supported copper catalysts in selective hydrogenation reactions, we found that these systems can be effectively applied to the chemoselective hydrogenation of a,P-unsaturated ketones giving quantitative yields in the corresponding saturated ketone also when another olefinic bond is present in the molecule [3]. 

Cho reported the addition of alkyl radicals from alkyl iodide to a,P-unsaturated ketones, esters, and nitriles mediated by indium in aqueous media. Recently, enantiomeiically pure natural and unnatural a-amino acids have been synthesized from a chiral methyleneoxazolidinone by such a highly diastereoselective 1,4-conjugate addition of alkyl iodides in aqueous media (Eq. 10.31). The zinc-copper conjugate addition reaction exhibits high chemoselectivity with the possibility of using functionalized iodides to afford a single diastereomer in short reaction times with good yields. 

Iminium-based organocatalysis is somewhat less explored than enamine-based organocatalysis and has been mostly used in the activation of a,/S-conjugated aldehydes and ketones. Therefore, this type of catalysis has unsurprisingly been the subject of a limited number of studies under the umbrella of the metal-organic cooperative catalysis concept. In 2011, the Cdrdova group [55] reported the first enantioselective and chemoselective /3-silyl addition to a./S-unsaturated aldehydes using copper salts and chiral pyrrolidine derivatives as catalysts. As proposed, the chiral secondary amine forms an iminium salt with... 

The mechanism of chemoselective copper(II)-mediated NazarovAVagner-Meerwein rearrangement sequence of divinyl ketones has been reported to involve an initial 4 r electrocyclization and proceed via two different sequential [l,2]-shifts, with selectivity that depends on either migratory ability or the steric bulkiness of the substituents at C( 1) and C(5) (Scheme 168). ... 

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