Alcohols enable carbonyl addition

The C-C reductive coupling of r-unsaturated compounds with carbonyl electrophiles by ruthenium-catalysed transfer hydrogenation leading to carbonyl allylation, vinylation, and propargylation has been reviewed. The ability of primary alcohols to function both as hydrogen donors and as aldehyde precursors, enabling carbonyl addition directly from the alcohol oxidation level, has been discussed. ... 

Nucleophilic addition to less reactive ketone carbonyls by Lewis acid activation is also possible. Evans and co-workers have reported enol silane addition to pyruvate esters mediated by chiral copper Lewis acids (Sch. 36) [72]. The aldol reactions proceed with high facial selectivity to provide the tertiary alcohol products 153. The chemical efficiency is, however, reduced when a bulky alkyl group is present at the ketone carbonyl. Addition of more functionalized enol silanes (155) to keto esters enables the establishment of two contiguous chiral centers, a substitution pattern present in a variety of natural products. The stereochemistry of the major product is syn, irrespective of the enol silane geometry. Once again, bidentate coordination of the substrate to the Lewis acid was essential for obtaining high selectivity. 

Pseudo-first-order rate constants for carbonylation of [MeIr(CO)2l3]" were obtained from the exponential decay of its high frequency y(CO) band. In PhCl, the reaction rate was found to be independent of CO pressure above a threshold of ca. 3.5 bar. Variable temperature kinetic data (80-122 °C) gave activation parameters AH 152 (+6) kj mol and AS 82 (+17) J mol K The acceleration on addition of methanol is dramatic (e. g. by an estimated factor of 10 at 33 °C for 1% MeOH) and the activation parameters (AH 33 ( 2) kJ mol" and AS -197 (+8) J mol" K at 25% MeOH) are very different. Added iodide salts cause substantial inhibition and the results are interpreted in terms of the mechanism shown in Scheme 3.6 where the alcohol aids dissociation of iodide from [MeIr(CO)2l3] . This enables coordination of CO to give the tricarbonyl, [MeIr(CO)3l2] which undergoes more facile methyl migration (see below). The behavior of the model reaction closely resembles the kinetics of the catalytic carbonylation system. Similar promotion by methanol has also been observed by HP IR for carbonylation of [MeIr(CO)2Cl3] [99]. In the same study it was reported that [MeIr(CO)2Cl3]" reductively eliminates MeCl ca. 30 times slower than elimination of Mel from [MeIr(CO)2l3] (at 93-132 °C in PhCl). 

Application of metal salts and well-defined metal complexes in ROP has enabled the exploitation of a three-step coordination-insertion mechanism, first formulated in 1971 by Dittrich and Schulz [17]. This proceeds through coordination of lactide by the carbonyl oxygen to the Lewis acidic metal center, leading to the initiation and subsequent propagation by a metal alkoxide species. This species can be either isolated or generated in situ by addition of an alcohol to a suitable metal precursor to result in the formation of a new chain-extended metal alkoxide, as shown in Scheme 3 [16]. 

The mechanism for an aldol condensation has two parts (Mechanism 22.6). The first part is just an aldol addition reaction, which has three mechanistic steps. The second part has two steps that accomplish the elimination of water. Normally, alcohols do not undergo dehydration in the presence of a strong base, but here, the presence of the carbonyl group enables the dehydration reaction to occur. The a position is first deprotonated to form an enolate ion, followed by expulsion of a hydroxide ion to produce a,p unsaturation. This two-step process, which is different from the elimination reactions we saw in Chapter 8, is called an Elcb mechanism. In an Elcb mechanism, the leaving group only leaves after deprotonation occurs. 

The addition of BF3 improves some of the usual organocop-per reactions, enables some unprecedented ones, e.g. the direct alkylation of allylic alcohols. It also favors 1,4- over 1,6-addition to methyl sorbate 1,6-addition predominates with Bu2CuLi-LiI, and also with BuMgBr/CuCl, but 1, 4-addition is observed for BuCu-BFs. One particularly interesting application of the BF3 procedure is the conjugate addition of Cu aldimines to a./S-unsaturated carbonyl compounds (eq 1), which after hydrolysis gives 1,4-diketones. ... 

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