Enolates intermolecular heterocoupling

Intermolecular heterocoupling of two different lithium enolates through singleelectron oxidation can generate 1,4-dicarbonyl products, but statistically yields should be poor. Nonetheless, useful yields can be obtained and kinetic and Li-NMR studies suggest that selective formation of the heterocoupled products is due to preferential heteroaggregation of the lithium enolates, especially when one substrate is sterically encumbered." ... 

The intermolecular heterocoupling of equimolar amounts of two different enolates through single-electron oxidation has shown that synthetically useful yields beyond those predicted by statistics can be obtained. The collection of data obtained from kinetic, Li NMR, and synthetic experiments shows that the selective formation of heterocoupled products is a consequence of heteroaggregation of lithium enolates. 

Baran and coworkers developed the intermolecular heterocoupling of lithium enolates and elaborated oxidation systems that did not only avoid the (usually undesired) homocoupling but also do not require a large excess of one component [242]. For asymmetric versions, Evans lithium enolates were used and coupled with the lithium enolates of achiral ketones and esters. Two oxidants were studied in detail, Cu(II) and Fe(III), and the choice of the oxidant was found to have a distinct impact on the stereochemical outcome. This is illustrated for cfs-lithium enolate 507 derived from AT-phenacyl oxazolidinone and cfs-enolate 504 of propiophenone. In the Fe(acac)g oxidation system, the formation of 0 tf-coupling product 509 occurs predominantly, whereas syn-513 prevails if Cu(2-ethylhexanoate)2 was used. In both cases, however, diastereomeric mixtures were obtained with typical anti-syn and syn-anti ratios of about 2 1. The proposed mechanism is outlined in a simplified manner in Scheme 4.107 the lithium enolate 504 of the ketone is transmetallated to the iron(III) enolate 505 that might be considered an oxallyl radical 506, wherein the polarity is altered the species 506 features an electrophilic a-carbonyl atom that becomes susceptible to an attack of the nucleophilic AT-acyl oxazolidinone enolate 507. As a result, the radical 508 forms that is finally oxidized to the product 509. The authors... 

In a related study, intramolecular oxidative coupling of enolate derivatives has been investigated by Schmittel and co-workers [167]. The intermolecular version of this reaction provides a useful route to 1,4-dicarbonyl compounds but typically suffers from low levels of stereoselectivity. Furthermore, in mixed systems, the desired heterocoupling products are often accompanied by appreciable amounts of homocoupling products. It was hoped that the use of a single metal for both enolate precursors with concomitant intramolecularization of the bond-forming event might overcome some of these problems. 

Demartino MP, Chen K, Baran PS (2008) Intermolecular enolate heterocoupling scope, mechanism, and application. J Am Chem Soc 130 11546-11560... 

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