Copper catalysis aldehydes

The conjugate addition of organometallic reagents R M to an electron-deficient alkene under, for instance, copper catalysis conditions results in a stabilized car-banion that, upon protonation, affords the chiral yS-substituted product (Scheme 7.1, path a). Quenching of the anionic intermediate with an electrophile creates a disubstituted product with two new stereocenters (Scheme 1, path b). With a pro-chiral electrophile, such as an aldehyde, three new stereocenters can be formed in a tandem 1,4-addition-aldol process (Scheme 1, path c). 

Tlie latter reagent undergoes 1,2-addition to a,p-unsaturated aldehydes 1,4-addition, with copper catalysis, is observed with cyclohexenone alone. A more satisfactory reagent for the conjugate introduction of the hydroxymethyl group is the allyldimethylsilylmethyl Grignt reagent... 

Treatment of aldehydes with two equivalents of a-bromoketones and Bu Sb produces a,//-unsaturated ketones and debrominated ketones [109], whereas the b.-cal-aly/ed reaction with equimolar amounts of the ketones and It jSb gives -hydroxy-ketones (Scheme 14.45) [110]. The olefination of carbonyl compounds with diazo esters is mediated by BujSb under copper catalysis (Scheme 14.46) [111]. 

Zinc homoenolates (9) react with allyl halides and diene monoepoxides under copper catalysis. Treatment of a zinc homoenolate (9) with a catalytic amount of copper(I) in a polar solvent (e.g. DMA) generates a copper species which undergoes Sn2 allylation (Scheme 23). Polar solvents accelerate the reaction and greatly improve the Sn2 selectivity. Copper-catalyzed reaction with the acetal of an unsaturated aldehyde proceeds without allylic isomerization (Scheme 23). ... 

Cooperative catalysis using chiral imidazolidinones and metal catalysts is not restricted to carbon electrophiles. In 2012, the MacMillan group [50] disclosed a general approach to undertake enantioselective -oxidation of aldehydes with TEMPO by combining organocatalysis with copper catalysis (Scheme 26.5b). 

In the same year, Chi et al. developed an enantioselective oxidative coupling of tertiary amines with ahphatic aldehydes by combination of copper catalysis and aminocatalysis (Scheme 2.6) [31]. Both A -Aryl tetrohydroisoquinolines and simple A-Aryl tertiary amines can undergo this enantioselective alkylation reaction. Soon afterwards, organocatalytic enantioselective CDC reaction of ethers with aliphatic aldehydes [32] and Cu-catalyzed asymmetric CDC reaction of iV-carbamoyl tetrahydroisoquinohnes with terminal alkynes [33] were reported. 

Several research groups have detailed syntheses of benzofurans via similar routes [110,111], including use of on-water chemistry [112] and the use of aldehyde substrates with copper catalysis to yield 2-unsubstituted benzofurans [113]. 

Nonactivated terminal acetylenes have been added to enamines derived from aldehydes. A long reaction time or catalysis by copper(I) chloride is necessary. Thus the enamine (16) formed the adduct (72) on heating with phenylacetylene (64). 

For the Cu(OTf)2-promoted reaction between ethyl diazoacetate and cinnam-aldehyde dimethyl acetal, products 143-145 account for only 35% the total yield. C/C and C/H insertion products 151 and 152 are obtained additionally in 49 and 14% yield, respectively154). It was assumed that the copper compound acts through Lewis-acid catalysis here, just as it is believed to do when orthoesters are used as substrates 160). According to this, catalyst-induced formation of a methoxy-... 

The utilization of copper complexes (47) based on bisisoxazolines allows various silyl enol ethers to be added to aldehydes and ketones which possess an adjacent heteroatom e.g. pyruvate esters. An example is shown is Scheme 43[126]. C2-Symmetric Cu(II) complexes have also been used as chiral Lewis acids for the catalysis of enantioselective Michael additions of silylketene acetals to alkylidene malonates[127]. 

The addition of an enolsilane to an aldehyde, commonly referred to as the Mukaiyama aldol reaction, is readily promoted by Lewis acids and has been the subject of intense interest in the field of chiral Lewis acid catalysis. Copper-based Lewis acids have been applied to this process in an attempt to generate polyacetate and polypropionate synthons for natural product synthesis. Although the considerable Lewis acidity of many of these complexes is more than sufficient to activate a broad range of aldehydes, high selectivities have been observed predominantly with substrates capable of two-point coordination to the metal. Of these, benzy-loxyacetaldehyde and pyruvate esters have been most successful. 

Electrophiles also react at C-5 of 1,3-dioxin-4-ones. Two ways of activation have been reported (1) magnesiation of 5-iodo-l,3-dioxin-4-ones afforded the Grignard reagents which can be cross-coupled with allyl halides in the presence of copper cyanide <2001TL6847> or with iodoalkenes under Pd(0) catalysis <2002T4787> and (2) Sc(OTf)3-catalyzed reaction of a side-chain-hydroxylated l,3-dioxin-4-one with aldehydes provided the bicyclic dioxinone in 60-85% yield (Scheme 27) <20050L1113>. 

Experimental observations indicate that the oxidation of cobalt (II) to cobalt (III) and the formation of ethylenediamine from N-hydroxyethylethylene-diamine occur simultaneously. This is quite the opposite to what is usually assumed in other instances of transition metal catalysis of organic reactions—for example, the catalytic effect of manganese in the oxidation of oxalic acid (7, 8), of iron in the oxidation of cysteine to cystine (22) and of thioglycolic acid to dithioglycolic acid (5, 23), of copper in the oxidation of pyrocatechol to quinone and in the oxidation of ascorbic acid (29, 30), and of cobalt in the oxidation of aldehydes and unsaturated hydrocarbons (4). In all these reactions the oxidation of the organic molecule occurs by the abstraction of an electron by the oxidized form of the metal ion. 

Infrared spectra of propene and isobutene on different catalysts were measured by Gorokhovatskii [143]. Copper oxide, which converts olefins to butadiene and aldehydes, shows adsorption complexes different from structures on a V2Os—P2Os catalyst which produces maleic acid anhydride. Differences also exist between selective oxidation catalysts and total oxidation catalysts. The latter show carbonate and formate bands, in contrast to selective oxides for which 7r-allylic species are indicated. A difficulty in this type of work is that only a few data are available under catalytic conditions most of them refer to a pre-catalysis situation. Therefore it is not certain that complexes observed are relevant for the catalytic action. 

The Boyer reaction - a relative of the Schmidt process - involves 2-oxazoline formation from a 2-azidoethanol and an aldehyde (RCHO).282 Using a 2-aryl-2-azidoethanol, a 2-oxazoline product and its 3-isomer are obtained using BF3 catalysis. However, on using copper(II) triflate, an acetal, RCH[OCH2CH(Ph)N3]2, resulted. 

Other unsaturated substrates arylated by various diaryl iodonium salts included butenone, acrylic acid, methyl acrylate and acrylonitrile [46]. Allyl alcohols with diaryliodonium bromides and palladium catalysis were arylated with concomitant oxidation for example, from oc-methylallyl alcohol, aldehydes of the general formula ArCH2CH(Me)CHO were formed [47]. Copper acetylide [48] and phenyl-acetylene [49] were also arylated, with palladium catalysis. 

Zeitler K (2006) Stereoselective synthesis of (E)-afi—unsaturated esters via carbene-catalyzed redox esterification. Qrg Lett 8 637-640 Zeitler K, Mager I (2007) An efficient and versatile approach for the immobilization of carbene precursors via copper-catalyzed [3+2]-cycloaddition and their catalytic apphcation. Adv Synth Cat 349 1851-1857 Zhao GL, Cordova A (2007) A one-pot combination of amine and heterocyclic carbene catalysis direct asymmetric synthesis of fi-hydroxy and fS-malonale esters from a,fS-unsaturated aldehydes. Tetrahedron Lett 48 5976-5980 Zhou ZZ, Ji FQ, Cao M, Yang GF (2006) An efficient intramolecular Stetter reaction in room temperature ionic liquids promoted by microwave irradiation. Adv Synth Cat 348 1826-1830... 

In a related context, 2-(/Koiuenesulfonyl)ethy]amine was used as an ammonia equivalent in an aza-ene reaction by which aldehyde 92.1 was converted to the bicycle 912 [Scheme 8.92].223 After N-acetylation and Pd(0)-catalysed hydro-stannylation, the alkenylstannane 914 dintensed under copper(II) nitrate catalysis. The 2-(p-toiuenesulfonyl)ethyl group was then discharged by p-elimination with potassium rm-butoxide. 

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