Copper hydride elimination

Carbenoid transformations involving competition between intramolecular cyclopropa-nation and /8-hydride elimination have been investigated149. The chemoselectivity of these catalytic transformations can be effectively controlled by the choice of catalyst. Rhodium(II) trifluoroacetate catalysed decomposition of diazoketone 111 proceeds cleanly to give only enone 112. However, rhodium(II) acetate or bis-(iV-t-butylsalicyladiminato) copper(II) cu(TBs)2 provides exclusively cyclopropanation product 113 (equation 102)149. 

The reaction of norbomene yields the cis exo diester (equation 66).93 This exo isomer is not obtained directly by Diels-Alder chemistry. Other cyclic alkenes such as cyclopentene yield cis diesters, but isomers are obtained as a result of (3-hydride elimination-readdition from intermediates such as (23) prior to CO insertion (equation 67). Thus the palladium walks around the ring to some extent, but always stays on the same face. The extent of rearrangement can be minimized by higher CO pressures since CO insertion becomes more competitive with (3-elimination. This rearrangement becomes a critical problem in the dicarboxylation of 1-alkenes, since a variety of diesters are formed and the reaction is not particularly useful. These reactions were carried out with catalytic amounts of palladium and stoichiometric amounts of copper chloride. 

Dihydro-2//-pyrans are obtained in good yield by cyclization of 5-alkenols, with palladium(II) acetate and copper(II) chloride in acetonitrile, via /(-hydride elimination and successive migration of the double bond81. 

The less highly substituted bond of a siloxycyclopropane is quantitatively opened by mercury(II) acetate to afford -mercurio ketones. In the same pot these are transformed to a-methylene ketones in virtually quantitative yield on treatment with one equivalent of palladium(II) chloride in the presence of lithium chloride and lithium carbonate (2 equiv each). Catalytic amounts of palladium(II) chloride (0.1 equiv) are sufficient in the second step, if two equivalents of copper(II) chloride is added as an oxidant. Mechanistically, the second step involves trans-metalation to a j -palladio ketone followed by /i-hydride elimination. In bicyclic systems it is sometimes necessary to add triethylamine to avoid HPdCl induced double-bond shifts in the reaction product. Examples are the rearrangements of 18, 20 and 22. ... 

This approach has been used to efficiently assemble 3-vinyl indoles 13 with alkenes (Scheme 6.20) [28]. It was observed in this case that the nature of the nitrogen substituent influences the ability to trap the 3-palladated indole, with carbamates providing the highest yields. The elimination of HX from the palladium after P-hydride elimination creates a Pd(0) complex that is unable to mediate subsequent cyclizations. As such, co-oxidants, such as stoichiometric copper(II) salts, are used in this reaction to regenerate the palladium(II) catalyst. However, by modifying reaction conditions, Lu has found that the addition of excess LiBr can inhibit P-hydride elimination, and instead allow the formation of the reduced product (Scheme 6.21) [29]. This not only allows access to 3-alkyl substituted indoles, but also eliminates the need for stoichiometric oxidants. 

Operates appears to depend on the concentration of the different ligands available to palladium the latter is likely to operate under the conditions employed in the industrial process. P-Hydride elimination then gives an if-enol complex 6.4. Reinsertion generates an isomeric -complex 6.5, which undergoes a second p-hydride elimination to give acetaldehyde. The reductive elimination of HCl has, at this point, reduced the palladium to zero, so the process is not catalytic. Copper salts are included copper(II) oxidizes Pd(0) to Pd(II), but is reduced to copper(I). The reaction is mn in the presence of air. Oxygen from air re-oxidizes the copper(I) to copper(II) in the second catalytic cycle. 

A similar, but shorter sequence was employed in a synthesis of dihydroxanthatin, with the addition of a copper(II) salt to make the process catalytic in palladium (Scheme 6.33). ° The (3-hydride elimination terminates a sequence that includes a nucleophilic attack and an intramolecular insertion. The alkene insertion from the first t -complex 6.98 to the second t -complex 6.99 proceeds with very high diastereoselectivity. Further aspects of this synthesis, employing metathesis chemistry, can be found in Scheme 8.113. 

The synthesis of indoles and benzofiirans by the palladium-catalysed cyclization of o-alkynyl anilines and phenols can also form part of tandem processes through interception of the -intermediate (Scheme 6.41). Inclusion of an alkene results in a Heck process, giving 3-vinylated indoles 6.129." As the 3-hydride elimination step causes reduction of the palladium(II) to palladium(O), an oxidizing agent, such as copper(n) must be included to maintain catalysis. The intermediate may also be intercepted by alkoxycarbonylation, giving an ester 6.130." Again an oxidant is needed. 

It has also been shown that reduction of the ethylenic bond in enones may occur via copper hydride derivatives formed by thermal decomposition of the lithium organocuprate. This can pose a problem since such decomposition occurs above 243 K in the temperature region where many cuprates are only beginning to react at appreciable rates with the substrate. However, addition of excess n-butyl-lithium appears to eliminate this complication. 

Similar to rhodium, copper mediates retro-allylation when it is complexed with an N-heterocyclic carbene ligand [31]. The allyl transfer takes place not only to aromatic aldehydes but also to aromatic imines (Scheme 5.43). Notably, secondary homoallylic alcohols transfer their allyl groups, retro-allylation dominating over P-hydride elimination from the copper alkoxide intermediates. 

Copper and Silver.—Although the decomposition of [Cu(Bu )(Bu P)] takes place by a predominantly non-radical pathway to give alkene and a copper(i) hydride intermediate, the thermal decomposition of neophyl(tri-n-butyl-phosphine)copper(i) (15) in ether solution between 30 and 125 °C occurs mainly by a free-radical mechanism, presumably because a /5-hydride elimination mechanism is not possible here. The resulting neophyl radicals take part... 

Alkenes can also be precursor to TC-allyl palladium complexes when treated with palladium(II) carboxylates that in turn react under 3-hydride elimination to yield an overall oxidation reaction.This reaction, being discovered over 50 years ago, is mostly performed with copper as reoxidant. This sp C-H activation is also the basis of other palladium-catalyzed reactions (see 10.3). 

In 1992 Murahashi, Hosokawa, and co-workers described the anti-Markovnikov oxidative addition of amides and carbamates to electron-deficient olefins by applying a palladium and copper cooperative catalysis under oxygen atmosphere [41]. The proposed mechanism involved a ff-bonded palladium(II) intermediate resulting from the addition of the nucleophile to the olefin, and subsequent ) -palladium hydride elimination to yield the functionalized alkene. Interestingly, both lactams and cyclic carbamates gave predominantly the corresponding E-enamide derivatives. Acyclic amides, conversely, afforded ElZ mixtures of products. The addition of a catalytic amount (5 mol%) of hexamethylphosphoric triamide (HMPA) was found notably beneficial for the reaction of 5-membered lactams and reduced the reaction time of such particular oxidative amidations (Scheme 2). 

---