Palladium catalysts and ligands

FIGURE 2. Representative palladium catalysts and ligands In the Heck reaction. Numbers below the respective structures refer to the corresponding citations. 

Regioselective C-H activation is often used for intramolecular biaryl preparations in Pd-mediated transformations. Thus concise syntheses of a large collection of alkaloids have been reported using variations of this approach (239-241), which differ mainly in terms of the functionalization of the precursor, palladium catalysts, and ligands. An efficient synthesis of racemic y-lycorane was recently disclosed whereby the key step is the intramolecular a-arylation of a cyclohexanone derivative (242). Some heterocycKc synthetic precursors (e.g. substituted indoles, quinolines, quinolones, phenanthridines, and phenanthridinones) have also been prepared en route to the alkaloids [hippadine, trisphaeridine (70), and crin-asiadine] via Pd- and Cu-mediated reactions (243,244). 

Weber and coworkers reported catalyst screening of the Stille coupling reaction using a capillary microreactor (75 pm i.d., 6.7 m length) [17]. Optimum palladium catalysts and ligands were screened effectively by the flow regime, where the reaction products were analyzed by on-line gas chromatography. 

Preparation of 4-isopropylanisole An oven-dried, screw-cap test tube, which was equipped with a magnetic stir bar and fitted with a Teflon septum, was charged with Pd(OAc)2 (2.25 mg, 0.0100 mmol) and biarylphosphine ligand CPhos (8.73 mg, 0.0200 mmol). The vessel was evacuated and backfilled with argon (this process was repeated three times) and then 4-bromoanisole (125 pL, 1.00 mmol) and THF (2 mL) were added via syringe (aryl chlorides or amines that were solids at room temperature were added with the palladium catalyst and ligand). The solution was cooled to 0 °C in an ice bath and a THF solution of isopropylzinc bromide solution (1,94 mL, 1.20 mmol, 0.617 M in THF),... 

Table 5-1. Selection of palladium-catalysts and ligands for cross-coupling reactions.

Palladium-catalyzed carbon-carbon cross-coupling reactions are among the best studied reactions in recent decades since their discovery [102, 127-130], These processes involve molecular Pd complexes, and also palladium salts and ligand-free approaches, where palladium(O) species act as catalytically active species [131-135]. For example, the Heck reaction with aryl iodides or bromides is promoted by a plethora of Pd(II) and Pd(0) sources [128, 130], At least in the case of ligand-free palladium sources, the involvement of soluble Pd NPs as a reservoir for catalytically active species seems very plausible [136-138], Noteworthy, it is generally accepted that the true catalyst in the reactions catalyzed by Pd(0) NPs is probably molecular zerovalent species detached from the NP surface that enter the main catalytic cycle and subsequently agglomerate as N Ps or even as bulk metal. 

Following the pioneering work by Alterman, several microwave-assisted palladium-catalyzed aminations have been reported for a number of different substrates, using different types of palladium sources and ligands. The examples shown in Scheme 6.59 include bromoquinolines [124], aryl triflates [125], and intramolecular aminations in the synthesis of benzimidazoles [126]. In all cases, the use of micro-wave irradiation dramatically reduced the required reaction times and in many cases also improved the yields. Several authors have also found that the microwave-driven reaction required significantly less catalyst than its conventionally heated counterpart [126]. 

Fluorous ligands introduce an ease of purification in that the tagged phosphine ligand, the palladium catalyst complexed ligand, and the oxidized ligand can be completely removed by direct fluorous solid-phase separation (F-SPE) prior to product isolation. Similarly, an example of a fluorous palladium-catalyzed microwave-induced synthesis of aryl sulfides has been reported, whereby the product purification was aided by fluorous solid-phase extraction [91]. 

Cyclic alkynyl carbonates undergo carbonylation in the presence of a palladium catalyst and carbon monoxide (5 MPa) in MeOH to give allenic carboxylates (Eq. 9.118) [92], Bu3P proved superior to Ph3P as the catalyst ligand. An enynyl cyclic carbonate underwent double vicinal carbonylation at 80 °C to produce a five-membered lactone product in 52% yield (Eq. 9.119). When the reaction was performed at 50 °C, the bicyclic enone lactone was produced in 75% yield along with 10% of the y-lactone. 

We are very grateful to Umicore AG and Co. KG for the supply of the rhodium and palladium catalysts and to BASF AG for the donation of carbon monoxide and syngas. We also thank Celanese AG and European Oxo GmbH for the supply of TPPTS solution. We would like to thank the Bundesministerium fiir BUdung und Forschung (ConNeCat-project Smart Solvents—Smart Ligands ) and the Fonds der Chemischen Industrie for financial support. 

Organometallic catalysts give better yields, and (2i, (53 )-2,6-dimethylmorpholine 196 has been reacted with aromatic bromides 197 <2002TL9291> and 198 and triflate 199 <2004JME2887> using a palladium catalyst with ligand 200, under three different sets of conditions to give the morpholino derivatives 201-203 (Scheme 18). 

An efficient aqueous phase Suzuki-Miyaura reaction of activated aryl chlorides with aryl boronic acids has been reported. The method uses a new D-glucosamine-based dicyclohexylarylphosphine ligand for the palladium catalyst and works well with nitro-and cyano-activated chlorides.32 The aryl fluoride bond has been considered inert to palladium-catalysed substitution reactions. However, a computational study, backed up by experiment, shows that the presence of a carboxylate group ortho to fluorine will allow reaction both with phenylboronic acids in a Suzuki-type reaction and with organotin reagents in a Stille-type reaction the presence of the adjacent oxyanion stabilizes the transition state.33... 

Pennequin I, Mortreux A, Petit F, Mentech J, Thiriet B (1994) Telomerisation of conjugated diene with sugar (derivs.) - by a reaction in aq. soln. and in the presence of a palladium catalyst and a ligand. FR 2693188... 

Aryl iodides 590 react with nona-1,2-diene in the presence of a palladium catalyst and a chiral bisoxazoline ligand to afford isochromans 591 in good yield with moderate enantioselectivity (Equation 244) <1999JOC7312>. 

Another type of substitution reaction is increasing in popularity—the use of an allylic substrate, such as an allyl acetate where the nucleophile is introduced with stereochemical control in the presence of a palladium catalyst and a chiral ligand. Reactions where a chiral anion, be it derived from a chiral heteroatom group, such as a sulfoxide, or an auxiliary, such as Evans s oxazolidinones, are not included in this chapter because the alkyl halide is usually relatively simple and the stereochemical selectivity is derived from the system itself. 

Scheme 2 shows the mechanism generally accepted for the catalytic arylation of olefins with aryl iodides in the presence of a tertiary phosphine-coordinated palladium catalyst and a base (4). Oxidative addition of aryl iodide (Arl) to a Pd(0) species (A), which is most commonly generated from palladium diacetate and a tertiary phosphine ligand, forms an arylpalladium iodide complex (B). Coordination of olefin on B followed by insertion of the coordinated olefin into the Pd-Ar bond forms a a-alkylpalladium species (C), which undergoes p-hydrogen elimination reaction to give the arylation... 

The addition of 2-methyl-2-vinyloxirane to / -keto esters in the ptesence of a palladium catalyst and a chiral phosphine ligand proceeds regio- and stereoselectively to give 2-hydroxytetrahydrofuran-3-carboxylates (Equation 93) <2001JA12907>. 

Hydrosilylation of monosubstituted alkenes with palladium catalysts and trichlorosilane follows a course which favors branched products. By using a chiral phosphine ligand, asymmetric reaction is feasible. Initially, menthyldiphenylphosphine (MDPP, 93) and neomenthyldiphenylphosphine (NMDPP, 94) were employed with little success. Later, (/ )-/VA -dimethyl-l-[(S)-2-diphenylphosphinoferroce-nyl]ethylamine [(R)-(S)-PPFA] (95) and its enantiomer were prepared, and these have proved to be the... 

Ecteinascidin 743 is a potent antitumor agent that was isolated from a marine tunicate. T. Fukuyama et al. applied the intramolecular Heck reaction as the key step in the assembly of the central bicyclo[3.3.1] ring system.Toward this end, the cyclic enamide precursor was exposed to 5 mol% of palladium catalyst and 20 mol% of a phosphine ligand in refluxing acetonitrile to afford the desired tricyclic intermediate in 83% isolated yield. 

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