Complexes palladium enolate

Enantioselective fluorination reactions catalyzed by chiral palladium enolate complexes have been the subject of considerable research . For instance, the fluorination of acyclic /S-ketoester (88, equation 24) using Af-fluorobenzenesulfonimide (NFSI) gave product 89 in high yields and with excellent enantioselectivity (ee up to 94%) . This reaction can be carried out in environmentally benign alcoholic solvents and provides valuable synthetic building blocks that find applications in medicinal chemistry, chemical biology and material sciences. 

Currently, a significant body of work deals with the use of chiral cationic palladium complexes bearing ligands of the BINAP type or related bisphosphine ligands such as SEGPHOS (Fig. 3). These are based on the pioneering work from Sodeoka on the direct formation of chiral palladium enolate complexes from the palladium precursors and 1,3-dicarbonyl compounds [10, 23]. Within this context, the combination of cationic BINAP-Pd complexes and N-fluoro-bis(phenylsulfonyl)imine (NFSI) was introduced by Sodeoka for the realization of an extremely efficient a-fluorination of 3-keto esters (Scheme 5). 

The four most common methods for the synthesis of late transition metal enolates are oxidative addition to halocarbonyl compoxmds, ligand metathesis with main group enolates or silyl enol ethers, nucleophilic addition of anionic metal complexes to halocarbonyl electrophiles, and insertion of an a,3-imsaturated carbonyl compoimd into a metal hydride. Examples of these synthetic routes are shown in Equation 3.47-Equation 3.50. Equation 3.47 shows the synthesis of a palladium enolate complex by oxidative addition of ClCHjC(0)CHj to Pd(PPh3), Equation 3.48 shows the synthesis of a palladium enolate complex by the addition of a potassium enolate to an aryl Pd(II) halide complex, and Equation 3.49 shows the synthesis of the C-bound W(II) enolate complex in Figure 3.7 by the addition of Na[( n -C5R5)(CO)jW] to the a-halocarbonyl compound. Finally, Equation 3.50 shows the synthesis of a rhodium enolate complex by insertion of but-l-en-3-one into a rhodium hydride. This last route has also been used to prepare enolates as intermediates in reductive aldol processes. - ... 

Fujii, A., Hagiwara, E., Sodeoka, M. (1999) Mechanism of Palladium Complex-catalyzed Enantioselective Mannich-type Reaction Characterization of a Novel Bin-uclear Palladium Enolate Complex. J. Am. Chem. Soc. 121 5450-5458. 

Ricci and coworkers [64] studied oxazoline moiety fused with a cyclopenta[P]thio-phene as ligands on the copper-catalyzed enantioselective addition of Et2Zn to chalcone. The structure of the active Cu species was determined by ESI-MS. Evans and coworkers [65] studied C2-symmetric copper(II) complexes as chiral Lewis acids. The catalyst-substrate species were probed using electrospray ionization mass spectrometry. Comelles and coworkers studied Cu(II)-catalyzed Michael additions of P-dicarbonyl compounds to 2-butenone in neutral media [66]. ESI-MS studies suggested that copper enolates of the a-dicarbonyl formed in situ are the active nucleophilic species. Schwarz and coworkers investigated by ESI-MS iron enolates formed in solutions of iron(III) salts and [3-ketoesters [67]. Studying the mechanism of palladium complex-catalyzed enantioselective Mannich-type reactions, Fujii and coworkers characterized a novel binuclear palladium enolate complex as intermediate by ESI-MS [68]. 

In these cases, NFSI was preferred to Selectfluor and the reactions were performed either in alcohol or in ionic liquids in which the palladium complexes can be immobilized and reused with excellent reproducibility even after 10 consecutive cycles. For example, the enantioselective electrophilic fluorination of 2-methyl-3-oxo-3-phenylpro-pionic acid tert-butyl ester in [hmim] [BF4] gives the corresponding fluorinated product in 93% yield with 92% ee, and still in 67% yield with 91% ee after 10 cycles. The fluorination of various cyclic and acyclic (3-keto esters was carried out with NFSI in ethanol in the presence of 2.5 mol% of catalyst, leading to excellent ee-values up to 94%. The reaction is not sensitive to water, can be run on a 1-g scale, and proceeds via a palladium enolate complex as for the titanium-4,5-bis(diphenylhydroxymethyl)-2,2-dimethyl-dioxolane (TADDOL) catalyst. The reaction was extended to tert-butoxycarbonyl lactones and lactams. Reactions with lactones proceeded smoothly in an alcoholic solvent with 2.5 mol% of catalyst and NFSI, while the less acidic lactam substrates required concurrent use of the Pd complex and 2,6-lutidine as a co-catalyst. Under the reaction conditions, the fluorinated lactones and lactams were obtained in good yields with excellent enantioselectivities (up to 99%... 

An electron-rich metal can deprotonate the dicarbonyl derivative, affording the hydridopalladium intermediate 23, which can undergo a Tr-allyl 24 formation through diene insertion (which can be assimilated to a hydridopalladation of olefin) (Scheme 7). The attack of the enolate to the -jr-allyl species occurs with good enantioselectivity in the presence of the chiral ligand. The final product 21 is released and the palladium(O) complex 22 is regenerated. 

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... 

Addition of ketene silyl acetals to aldehydes and ketones is also mediated by achiral palladium(ll) acetate-diphosphine complexes (Equation (109)).46S,46Sa Although the precise mechanism is still unclear, high catalytic activity may be ascribed to the intermediacy of palladium enolates. 

Aldol reactions of silyl enolates are promoted by a catalytic amount of transition metals through transmetallation generating transition metal enolates. In 1995, Shibasaki and Sodeoka reported an enantioselective aldol reaction of enol silyl ethers to aldehydes using a Pd-BINAP complex in wet DMF. Later, this finding was extended to a catalytic enantioselective Mannich-type reaction to a-imino esters by Sodeoka s group [Eq. (13.21)]. Detailed mechanistic studies revealed that the binuclear p-hydroxo complex 34 is the active catalyst, and the reaction proceeds through a palladium enolate. The transmetallation step would be facilitated by the hydroxo ligand transfer onto the silicon atom of enol silyl ethers ... 

The details of the organic chemistry of the reaction of ethylene with PdCl2 (equation (1) above) are also known and are shown in Fig. 9.2. The palladium ion complexes with ethylene and water molecules and the water adds across the bond while still complexed to palladium. The palladium then serves as a hydrogen acceptor while the double bond reforms. Keto-enol tautomerism takes place, followed by release of an acetaldehyde molecule from the palladium. 

Palladium(0)-catalyzed a-allylation of silyl ethers is a reaction which can be carried out with ketones as well as with aldehydes91. It is highly regiospecific when applied to ketones. a-Allylations can also be performed with enol acetates using allyl carbonates in the presence of catalytic amounts of palladium(O) complexes and (tributyl)methoxytin92,93. The steric course of the reaction has not been studied systematically but a high level of diastereoselectivity is expected and possibilities for asymmetric induction by the use of chiral auxiliaries are envisaged. 

Similarly, the addition of triethylborane to lithium enolates allowed ready reaction with allyl nitro compounds catalyzed by palladium(O) complexes.108109... 

Oxa- Tr-allylpalladium complexes (10), which can also be envisioned as palladium enolates (11), are susceptible to (3-hydride elimination, and as such have been principally used in methodologies for the preparation of (3,(3-unsaturated carbonyl compounds. 

The reaction of 3-ketoacids with allyl carboxylates is also believed to proceed via a palladium enolate intermediate.126 Less than complete stereospecificity is also observed in these reactions (equation 163). Interestingly, the bicyclic lactone substrate employed to ascertain the stereointegrity of this reaction, in addition to being incapable of any syn-anti isomerization, cannot epimerize the starting material by car-boxylate attack at the metal. The observed stereochemical leakage could be due to epimerization of the intermediate allyl complex (equation 164) or reductive elimination of an allylpalladium enolate (retention) (equation 165). 

The mechanism of the trimethylsilyl enol ether cyclization may involve formation of a palladium enol-ate which adds to the double bond. However, another mechanism is also possible involving attack of a palladium(II)-alkene complex upon the silyl enol ether double bond. 

In 1998, a new type of Pd(II) binuclear complex was reported which was effective for Mannich reactions of an imine derived from glyoxylate and anisidine with silicon enolates [38,39]. In these reactions, use of solvents including a small amount of water was essential. It was shown that water played an important role in this system water not only activated the Pd(II) complex to generate a cation complex, but also cleaved the N-Pd bond of the intermediate to regenerate the chiral catalyst. This reaction reportedly proceeded via an optically active palladium enolate on the basis of NMR and ESIMS analyses. A unique binuclear palladium-sandwiched enolate was obtained in the reaction of the p-hydroxo palladium complex with the silyl enol ether [(Eq. (9)]. 

The imines 12 (X = 4-CH3-QH4-SO2 (Ts), Ar, C02R, COR, etc.) preformed or generated in situ from N,0- or N,N-acetals or hemiacetals are another important class of Mannich reagents frequently used for diastereo- and/or enantioselective aminoalkylation reactions catalyzed by chiral Lewis acids (usually copper or palladium BINAP complexes such as 13). Among other things excellent results were obtained in the aminoalkylation of silyl enol ethers or ketene acetals [24], A typical example is the synthesis of Mannich bases 14 depicted in Scheme 5 [24b], Because of their comparatively high electrophilicity imines 12 could even be used successfully for the asymmetric aminoalkylation of unactivated alkenes 15 (ene reactions, see Scheme 5) [24h, 25], and the diastereo- and/or enantioselective aminoalkyla-... 

Lewis acid catalysts activate the aldehyde by coordination to the carbonyl oxygen. Shibasaki et al. [13] were able to demon,strate that the activation of the enol ether is possible too. The reaction of the aldehyde 37 with the silyl enol ether 38 in the presence of the catalyst 39 proceeds with good, but still not excellent enantioselectivity to yield the aldol adduct 40. Only 5 mol % of the chiral palladium(II) complex 39 was used (Scheme 6a). Activation of the Pd(lI)-BINAP complex 39 by AgOTf is necessary. Therefore, addition of a small amount of water is important. 

The neutral palladium(II) compound 43 is transformed by addition of AgOTf into the cationic complex 44. In the presence of water an exchange of the triflate anion to hydroxide occurs (44 — 45). Finally, the palladium enolate 46 is formed from the palladium complex and the silyl enol ether. 

Fig. 9. (A) A Pd-enolate complex observed by ESI(+)-MS during the palladium-catalyzed allylic substitution of l-acetoxy-l,3-diphenylpropene by acetylacetone 15. (B) A Pd-allyl complex observed by ESI(+)-MS during the palladium-catalyzed substitution of allylic acetates with sodium para-toluenesulfonate 20. ...

As far as late-transition elements are concerned, it is worthwhile to discuss some reactions occurring at C-bonded nickel and palladium enolates. Treatment of the nickel complex 73, derived from the afkynylenone 72 and Ni(cod)2, with dry dioxygen yielded the [3.1.0]bicyclohexane derivative 75 (equation 50), with the carbene species 74 as possible intermediate. ... 

Cationic Pd complexes can be applied to the asymmetric aldol reaction. Shibasaki and coworkers reported that (/ )-BINAP PdCP, generated from a 1 1 mixture of (i )-BINAP PdCl2 and AgOTf in wet DMF, is an effective chiral catalyst for asymmetric aldol addition of silyl enol ethers to aldehydes [63]. For instance, treatment of trimethylsi-lyl enol ether of acetophenone 49 with benzaldehyde under the influence of 5 mol % of this catalyst affords the trimethylsilyl ether of aldol adduct 113 (87 % yield, 71 % ee) and desilylated product 114 (9 % yield, 73 % ee) as shown in Sch. 31. They later prepared chiral palladium diaquo complexes 115 and 116 from (7 )-BINAP PdCl2 and (i )-p-Tol-BINAP PdCl2, respectively, by reaction with 2 equiv. AgBF4 in wet acetone [64]. These complexes are tolerant of air and moisture, and afford similar reactivity and enantioselec-tivity in the aldol condensation of 49 and benzaldehyde. Sodeoka and coworkers have recently developed enantioselective Mannich-type reactions of silyl enol ethers with imi-nes catalyzed by binuclear -hydroxo palladium(II) complexes 117 and 118 derived from the diaquo complexes 115 and 116 [65]. These reactions are believed to proceed via a chiral palladium(fl) enolate. 

Palladacycles have also been characterized by IR spectroscopy <20050M945>. Thus, to provide insight into the bonding mode of palladium enolates in complexes 28-30, IR spectroscopic analyses were performed by Lu et al. They revealed z/(C=0) bands at 1687, 1676, and 1676cm for compounds 28, 29, and 30, respectively. 

Here again, the reaction involved an intramolecular displacement of the iodide by an ester enolate (Scheme 10). Preparation of stable azapalladacycle ( )-93 commenced with treatment of sulfonamide 90, accessible via A -alkylation of A -trifluoromethanesulfonyl-2-iodoaniline with palladium(O) (Pd2(DBA)3 DBA = dibenzylideneacetone) and tetramethylethylenediamine (TMEDA) to afford palladium(ll) complex 91. An easy ring closure of complex 91 provided palladacycle ( )-92 in 92% yield via addition of /-BuOK (IM in solution in THE, 1.2equiv) at room temperature. Displacement of tetramethylethylenediamine with triphenyl-phosphine delivered palladacycle ( )-93 in quantitative yield. 

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