Phosphines enolate arylation

Enolate arylation has also been extended to aryl tosylates. The preferred catalyst includes a very bulky biphenyl phosphine D.179... 

Enolate Arylation Reactions. The direct coupling of aryl halides with enolates (or enolate equivalents) of ketones, esters, and amides is now well established. Malonic esters, cyanoacetates, and malononitrile can be arylated upon treatment with aryl halides in the presence of Pd(dba)2 and electron-rich phosphines or N-heterocyclic carbenes. Carbene ligands have also proven effective in promoting the a-arylation of protected amino acids. As a caveat to the use of Pd(dba)2, the arylation of azlactones in the presence of this palladium source and phosphines was less efficient than that with Pd(OAc)2. The dba ligands were found to react with azlactone substrates to form catalytically inactive palladium complexes. Diastereoselective enolate arylation has been achieved through the use of chiral auxiliaries appended to preformed enol silyl ethers (eq 23). The role of the zinc additive is not clear, however, it appears that discrete zinc enolates are not involved. 

As far as the influence of the phosphine ligand in the catalyzed reactions is concerned, P(tBu)j is effective in most cases. The rate of the reductive elimination of enolate complexes containing this and other bulky phosphines is faster, and the scope of many couplings catalyzed by complexes with these ligands is broader. Recently, it has been found that a catalytic quantity of phenol causes a remarkable increase in the efficiency of ketone enolate arylation [382]. 

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... 

In Section 8.2.3.2, we discussed arylation of enolates and enolate equivalents using palladium catalysts. Related palladium-phosphine combinations are very effective catalysts for aromatic nucleophilic substitution reactions. For example, conversion of aryl iodides to nitriles can be done under mild conditions with Pd(PPh3)4 as a catalyst. 

Rhodium(i) complexes are excellent catalysts for the 1,4-addition of aryl- or 1-alkenylboron, -silicon, and -tin compounds to a,/3-unsaturated carbonyl compounds. In contrast, there are few reports on the palladium(n) complex-catalyzed 1,4-addition to enones126,126a for the easy formation of C-bound enolate, which will result in /3-hydride elimination product of Heck reaction. Previously, Cacchi et al. described the palladium(n)-catalyzed Michael addition of ArHgCl or SnAr4 to enones in acidic water.127 Recently, Miyaura and co-workers reported the 1,4-addition of arylboronic acids and boroxines to a,/3-unsaturated carbonyl compounds. A cationic palladium(n) complex [Pd(dppe)(PhCN)2](SbF6)2 was found to be an excellent catalyst for this reaction (dppe = l,2-bis(diphenyl-phosphine)ethane Scheme 42).128... 

A new type of triaryl phosphine-functionalized imidazolium salt containing cations such as (6) has been prepared. Palladium complexes of (6) generated in situ have been used successfully in Heck-type reactions of aryl halides with acrylates and of 4-bromotoluene with styrene derivatives.34 The first Heck-type reaction of aryl halides with allenes has been reported. 1,3-Double arylations were observed with 3-substituted-l,2-allenyl sulfones, while 1-monoarylation was favoured with 3,3-disubstituted-l,2-allenyl sulfones.35 It has been shown that the a-arylation of methane-sulfonamides (7) may be achieved using palladium catalysis reaction proceeds through the sulfonamide enolates.36 It is also reported that palladium cross-coupling of alkynes with /V - (3 - i odophe n y I an i I i ncs) may lead to the formation of substituted carbazoles.37... 

A nonclassical substrate for the Heck reaction is 2,3-epoxycyclohexanone. The reactivity of this molecule under Heck coupling conditions is most likely attributed to its in situ isomerization to 1,2-cyclohexanedione. The 1,2-diketone subsequently reacts with aryl bromides as an olefin via the enol tautomer. Thus, within 5 to 30 min of directed microwave heating of the aqueous PEG mixture, up to 13 different C3-arylations were conducted using less than 0.05 mol % palladium acetate and no phosphine ligand (Scheme 12) [51]. 

The peptidic phosphine ligands that had been introduced by Hoveyda and co-workers271 for enantioselective copper-catalyzed Michael additions (see Section 9.12.2.2.1) were also employed successfully in silver-catalyzed asymmetric Mannich reactions.3 Thus, the aryl-substituted imines 372 reacted with various silyl enol ethers in the presence of stoichiometric amounts of isopropanol, as well as catalytic amounts of silver acetate and ligand 373 to... 

Acylation of aryl and alkenyl halides. The zinc salts of enol ethers and allenic ethers couple with aryl and alkenyl halides in the presence of several Pd(0) catalysts Pd[P(QH,),l4 or bis(dibenzylideneacetone)palladium with added phosphine ligands. 

Recently, CuUcin and Hartwig reported examples of arylpalladium enolates that are sufficiently stable to be isolated in pure form, but reactive to undergo reductive elimination of a-aryl carbonyl compounds in high yields (equations 51a and 51b). Of special interest is that the isolation of a large number of paUadium(II) enolates has allowed one to account for the dependence of the enolate coordination to palladium on the ancillary ligands. For example, it happens that the C-bound isomer is favoured if the enolate is located trans to a phosphine (equation 51a), but the O-bound form if favoured if located trans to an aryl group (equation 51b). 

Kim, D.Y, Mang, J.Y, and Oh, D.Y, Reaction of silyl enol ethers with phosphite using hypervalent iodine compound. A new synthesis of 2-aryl-2-oxoalkylphosphonates, Synth. Commun., 24, 629, 1994. Hohnquist, C.R., and Roskamp, E.J., Tin(II) chloride catalyzed addition of diazo sulfones, diazo phosphine oxides, and diazo phosphonates to aldehydes. Tetrahedron Lett., 33, 1131, 1992. 

Pd(0) catalyses the coupling of a variety of stabilised enolates, for example the reaction of bromopyri-dines with the sodium salts of sulfonyl and phosphonyl acetonitriles. Simple enolates can be arylated using Pd-carbene catalysts or using highly hindered phosphine ligands. ... 

ArykUion. Oxindole and ester enolates are arylated by ArX, with (dba)2Pd and a bulky phosphine ligand present,although in the case dealing with the esters [t-BusP PdBr]2 is equally effective. ... 

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