Homocoupling enolates

Intermolecular coupling of a vinyl ether with styrene at a carbon anode in methanol is successful, giving a mixture of the cross coupled product and the two homocoupled products [49], Intramolecular coupling between an enol ether and an alkene centre, as in 24 and 25, proceeds to give the cyclized product in good yield [50], Five and six membered rings can be constructed in this way. An easily oxidised vinyl ether group is necessary to initiate the reaction and the second alkene... 

Lei, A. Srivastava, M. Zhang, X. Transmetala-tion of Pd enolates and its application in the Pd-catalyzed homocoupling of alkynes a room-temperature, highly efficient route to diynes./. Org. Chem. 2002, 67,1969-1971. 

Lei, A. Zhang, X. A novel Pd-catalyzed homocoupling reaction initiated by transmetalation of Pd enolates. Tetrahedron Lett. 2002, 43, 2525-2528. 

A wide series of oxidants, spanning from TiCLj to iodine, has been used in the oxidative homocoupling of chiral 3-arylpropionic acid derivatives aimed at the preparation of lignans. The /f,/f-selectivity in the reactivity of 34 has been explained by a radical coupling mechanism (equation 20). The initially formed lithium (Z)-enolate may transform into the titanium enolate 35, which undergoes oxidation to the radical intermediate 36 via a single electron transfer process. The iyw-Z-type radicals 36 couple each other at the less hindered S-side si face) to give the R,/f-isomers 37 stereoselectively. 

The same research group has recently reported that the oxidative homocoupling of chiral aroylacetic acid derivatives proceeds stereoselectively when the sodium enolate derived from 38 is oxidized with bromine (equation 21). Good stereoselectivity was also observed in the oxidative homo- and heterocoupUng reactions of the lithium eno-lates of chiral 3-phenylpropionamides with iodine, copper(II) pentanoate and ferrocenium hexafluorophosphate. ... 

Symmetrical (equation 22a) and unsymmetrical 1,4-diketones (equations 22b and 22c) are obtained in good yield with the vanadium(V) alkoxo derivatives VO(OR)Cl2 (R = Et,, -Pr)65 xfjg same reagent induces cross coupling between allyl silanes and silyl enolates to y,5-unsaturated ketones. Noteworthy is the fact that only traces of the homocoupled 1,4-diketones and 1,5-hexadienes are produced. 

Combination of the reagents TiCU, BuaN, and TMSOTf, was reported to be effective for Claisen condensation, as exemplified in Eqs (42) and (43) [129]. When acyl-oxazolidinones were subjected to reaction with TiCU and a tertiary amine, homocoupling reaction at the a-position of the acyl group took place to give succinic acid derivatives [146], The lithium enolate of an ester or amide has been alkylated with an (N,C>)-acetal in the presence of Ti(0-/-Pr)4 (Eq. 44) [147,148]. 

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. 

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... 

Scheme 5.135 Homocoupling of titanium enolates of oxazolidinone 552, mediated by TADDOL 553.

This paragraph dealing with enantioselective hydroxylation, amination, halo-genation, and homocoupling of enolates again shows that, beginning with stoichiometric additives, promising approaches toward catalytic versions have been developed in recent years. 

When identical silyl enol ethers are used in the coupling reaction (Rj = R/, R = R ), homocoupling to symmetrical 1,4-diketones can be achieved (Scheme 11). For the synthesis of unsymmetrical 1,4-diketones, the two silyl enol ethers must differ significantly in terms of their oxidation potentials. This can be realized by selecting monosubstituted silyl enol ethers (R = H) and 1,2-disubstituted silyl enol ethers for the coupling reaction. Another possible way to reduce the oxidation potential is by the use of mesomeric stabilization vide supra).In the coupling reactions presented so far, the reactivity of silyl enol ethers is twofold. The component that is more easily oxidized forms the radical cation and consequently the a-carbonyl radical. In contrast, the second component acts as an electron-rich double bond in the radical addition reaction. 

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