Ketones cross coupling

Sugino 448 obtained the crossed coupling product 147 in 70% yield and current efficiency on coelectrolysis of acrylonitrile and acetone in aqueous sulfuric acid at a mercury cathode. At lead and cadmium mixed couplingwas suppressed and hydrocarbon formation increased. With methyl ethyl ketone and diethyl ketone crossed coupling was achieved in 60% and 30% yield, respectively. With acetone and maleic acid 10% terebic acid (148) was obtained. Tomilov 449- coupled acetone and acrylic acid in 95% yield (70% current efficiency) to... 

P. Lehwald, R. Michael, R. Caroline, L. Hung-Wen, M. Michael, Enantioselective intermolecular aldehyde-ketone cross-coupling through an enzymatic carboligation reaction, Angew. Chem. Int. 49 (2010) 2389-2392. 

Moderate yields of acids and ketones can be obtained by paHadium-cataly2ed carbonylation of boronic acids and by carbonylation cross-coupling reactions (272,320,321). In an alternative procedure for the carbonylation reaction, potassium trialkylborohydride ia the presence of a catalytic amount of the free borane is utilized (322). FiaaHy, various tertiary alcohols including hindered and polycycHc stmctures become readily available by oxidation of the organoborane iatermediate produced after migration of three alkyl groups (312,313,323). 

Formation o( oleltns by coupling or cross coupling of ketones, mediated by low valent titanium Also coupling ol enol ethers of 1,3-dicarbonyl compounds. 

The McMurry reagent reductively couples trifluoroacetophenones to the eorresponding stilbenes [67] (equation 55), and cross-coupling of ketones is also reported [68] (equation 56). 

In a cross-coupling benzoin condensation of two different aldehydes, usually a mixture of products is obtained, with the ratio being determined by the relative stabilities of the four possible coupling products under thermodynamic control. If, however, an acyl silane, e.g. 5, is used as the donor component, the a-silyloxy-ketone 6 is obtained as a single product " ... 

The Suzuki reaction was also used to prepare the polyketone since this particular reaction tolerates the subsequent step (Scheme 6.19).135 Palladium-catalyzed cross-coupling of aromatic diacid chlorides and bis(trimethylstannane) monomers was utilized to prepare poly(arylene ether ketone)s.136... 

The hydrosi(ly)lations of alkenes and alkynes are very important catalytic processes for the synthesis of alkyl- and alkenyl-silanes, respectively, which can be further transformed into aldehydes, ketones or alcohols by estabhshed stoichiometric organic transformations, or used as nucleophiles in cross-coupling reactions. Hydrosilylation is also used for the derivatisation of Si containing polymers. The drawbacks of the most widespread hydrosilylation catalysts [the Speier s system, H PtCl/PrOH, and Karstedt s complex [Pt2(divinyl-disiloxane)3] include the formation of side-products, in addition to the desired anh-Markovnikov Si-H addition product. In the hydrosilylation of alkynes, formation of di-silanes (by competing further reaction of the product alkenyl-silane) and of geometrical isomers (a-isomer from the Markovnikov addition and Z-p and -P from the anh-Markovnikov addition. Scheme 2.6) are also possible. 

Palladium-Catalyzed Arylation of Enolates. Very substantial progress has been made in the use of Pd-catalyzed cross coupling for arylation of enolates and enolate equivalents. This reaction provides an important method for arylation of enolates, which is normally a difficult transformation to accomplish.171 A number of phosphine ligands have been found to promote these reactions. Bulky trialkyl phosphines such as /n. v-(/-butyl)phosphinc with a catalytic amount of Pd(OAc)2 results in phenylation of the enolates of aromatic ketones and diethyl malonate.172... 

The medicinal chemists subsequently discovered an improved route to racemic acid 9 that started with 2-bromo-2-cyclopente-l-one 11 (Scheme 7.2) [5]. Suzuki-Miyaura cross-coupling of 11 with 4-fluorophenyl boronic acid 12 provided 13 in 67% yield. Conjugate addition of cyanide furnished ketone 14 in 71% yield. Reduction of 14 with NaB H4 gave a 2.8 1 mixture of desired 15 and undesired 16 which were separated by silica gel chromatography. The observed diastereoselec-tivity with the cyano group was similar to ester 6. Hydrolysis of 15 with 5 M NaOH in MeOH gave racemic acid 9 in 91% yield, which was resolved as outlined in Scheme 7.1. 

Oxidative cross-coupling reactions of alkylated derivatives of activated CH compounds, such as malonic esters, acetylacetone, cyanoacetates, and certain ketones, with nitroalkanes promoted by silver nitrate or iodine lead to the formation of the nitroalkylated products.67 This is an alternative way of performing SRN1 reactions using a-halo-nitroalkanes. 

The cross-coupling reactions of benzylic halides and acyl halides produced the expected ketones in good to high yields(39,47). The present method can supplement the corresponding Grignard reaction, which does not work well since benzylmagnesium halides undergo dimerization readily. 

Trapping experiments with electron deficient olefins such as acrylonitrile and 3-buten-2-one gave the expected 1,4-adducts from the proposed acylnickel intermediates. This provides strong support for the proposed mechanism. It was also demonstrated that allylic, vinylic and pentafluorophenyl halides could be cross-coupled with acid chlorides to give the corresponding ketones in good yields. 

The iron slurries react readily with ethyl a-bromoacetate. The resulting organoiron species adds readily to aldehydes and ketones to produce 3 -hydroxyesters in excellent yields. Addition of a mixture of an aryl aldehyde and an allylic halide to the iron slurry produced good yields of the cross-coupled alcohol. 

Nickel-bpy and nickel-pyridine catalytic systems have been applied to numerous electroreductive reactions,202 such as synthesis of ketones by heterocoupling of acyl and benzyl halides,210,213 addition of aryl bromides to activated alkenes,212,214 synthesis of conjugated dienes, unsaturated esters, ketones, and nitriles by homo- and cross-coupling involving alkenyl halides,215 reductive polymerization of aromatic and heteroaromatic dibromides,216-221 or cleavage of the C-0 bond in allyl ethers.222... 

The palladium-catalyzed cross-coupling reaction featured in this procedure occurs under neutral conditions in the presence of many synthetically useful functional groups (e.g. alcohol, ester, nitro, acetal, ketone, and aldehyde). The reaction works best in N,N-dimethylformamide with bis(triphenylphosphine)palladium(ll) chloride, PdCI2(PPh3)2, as the catalyst. Lithium chloride is added to prevent decomposition of the catalyst.143 13 It is presumed that conversion of the intermediate aryl palladium triflate to an aryl palladium chloride is required for the transmetallation step to proceed.9... 

Reductive Cross-Coupling of Nitrones Recently, reductive coupling of nitrones with various cyclic and acyclic ketones has been carried out electrochem-ically with a tin electrode in 2-propanol (527-529). The reaction mechanism is supposed to include the initial formation of a ketyl radical anion (294), resulting from a single electron transfer (SET) process, with its successive addition to the C=N nitrone bond (Scheme 2.112) (Table 2.9). 

Cross-coupling reactions of nitrones with aldehydes and ketones make it possible to synthesize vicinal amino alcohols, which are common in natural products. These transformations have been performed by a new method of reduction... 

Iron-catalyzed cross-coupling reactions of various acyl chlorides or thioesters with Grignard reagents have been pioneered by Marchese et al. and other research groups.322 These transformations provide general and convenient access to a wide range of ketones and have been further extended to the use of a supported iron(lll) complex.323... 

In the Pd-catalyzed cross-coupling reactions of acylzirconocene chlorides with allylic halides and/or acetates (Section 5.4.4.4), the isolation of the expected p,y-unsaturated ketone is hampered by the formation of the a, P-un saturated ketone, which arises from isomerization of the p,y-double bond. This undesirable formation of the unsaturated ketone can be avoided by the use of a Cu(I) catalyst instead of a Pd catalyst [35], Most Cu(I) salts, with the exception of CuBr - SMe2, can be used as efficient catalysts Thus the reactions of acylzirconocene chlorides with allyl compounds (Table 5 8 and Scheme 5 30) or propargyl halides (Table 5.9) in the presence of a catalytic amount (10 mol%) of Cu(I) in DMF or THF are completed within 1 h at 0°C to give ffie acyl--allyl or acyl-allenyl coupled products, respectively, in good yields. ill... 

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