Phosphine ligands Pd

Since more reactive alkenes, such as vinyl arenes or sterically strained polycycles, react more readily in the hydroamination reaction, several asymmetric hydroami nation reactions utilizing these substrates have been disclosed. Weakly basic anilines can react with vinyl arenes to give the Markovnikov addition products 6 and 7 with good yields and enantioselectivities in the presence ofa chiral phosphine ligand Pd complex as demonstrated by Hartwig (Eq. 11.3) [13] and later by Hii (Eq. 11.4) [14]. 

The first example of C-0 bond oxidative addition has been observed by use of a coordinatively unsaturated palladium(O) complex having basic bulky phosphine ligands, Pd(PCy3)2 at room temperature to give Pd(j7 -allyl)(PCy3)(OAc) accompanied by formation of aphosphonium salt, Cy3P(CH=CHMe)+(OAc) (Eq. 3.7)... 

Reductive Elimination from Pd" Complexes with Nitrogen and Phosphine Ligands [Pd(CH=CH2)2X2l (X=NHj, PHj)... 

Catalyst Pd(PPh3)4 Pd(PPh3)4 or Pd(II) catalyst/Phosphine ligand Pd(PPh3)4... 

Attention should be paid to the fact that the ratio of Pd and phosphine ligand in active catalysts is crucial for determining the reaction paths. It is believed that dba is displaced completely with phosphines when Pd2(dba)3 is mixed with phosphines in solution. However the displacement is not eom-plcte[16]. Also, it should be considered that dba itself is a monodentate alkene ligand, and it may inhibit the coordination of a sterically hindered olefinic bond in substrates. In such a case, no reaction takes place, and it is recommended to prepare Pd(0) catalysts by the reaction of Pd(OAc)2 with a definite amount of phosphinesflO]. In this way a coordinatively unsaturated Pd(0) catalyst can be generated. Preparation of Pd3(tbaa)3 tbaa == tribenzylidene-acetylacetone) was reported[17], but the complex actually obtained was Pd(dba)2[l8],... 

Fundamental reactions of Pd are briefly explained in order to understand how reactions either promoted or catalyzed by Pd proceed. In schemes written for the explanation, phosphine ligands are omitted for. simplicity. First, a brief explanation of chemical terms specific to organopalladium chemistry is given. 

The diazonium salts 145 are another source of arylpalladium com-plexes[114]. They are the most reactive source of arylpalladium species and the reaction can be carried out at room temperature. In addition, they can be used for alkene insertion in the absence of a phosphine ligand using Pd2(dba)3 as a catalyst. This reaction consists of the indirect substitution reaction of an aromatic nitro group with an alkene. The use of diazonium salts is more convenient and synthetically useful than the use of aryl halides, because many aryl halides are prepared from diazonium salts. Diazotization of the aniline derivative 146 in aqueous solution and subsequent insertion of acrylate catalyzed by Pd(OAc)2 by the addition of MeOH are carried out as a one-pot reaction, affording the cinnamate 147 in good yield[115]. The A-nitroso-jV-arylacetamide 148 is prepared from acetanilides and used as another precursor of arylpalladium intermediate. It is more reactive than aryl iodides and bromides and reacts with alkenes at 40 °C without addition of a phosphine ligandfl 16]. 

The benzoic acid derivative 457 is formed by the carbonylation of iodoben-zene in aqueous DMF (1 1) without using a phosphine ligand at room temperature and 1 atm[311]. As optimum conditions for the technical synthesis of the anthranilic acid derivative 458, it has been found that A-acetyl protection, which has a chelating effect, is important[312]. Phase-transfer catalysis is combined with the Pd-catalyzed carbonylation of halides[3l3]. Carbonylation of 1,1-dibromoalkenes in the presence of a phase-transfer catalyst gives the gem-inal dicarboxylic acid 459. Use of a polar solvent is important[314]. Interestingly, addition of trimethylsilyl chloride (2 equiv.) increased yield of the lactone 460 remarkabiy[3l5]. Formate esters as a CO source and NaOR are used for the carbonylation of aryl iodides under a nitrogen atmosphere without using CO[316]. Chlorobenzene coordinated by Cr(CO)j is carbonylated with ethyl formate[3l7]. 

The coupling of the enol triflate 703 with the vinylstannane 704[397] has been applied to the synthesis of glycinoeclepin[576]. The introduction of a (Z)-propenyl group in the / -lactam derivative 705 proceeds by use of tri-2-furylphosphine[577]. However, later a smooth reaction to give the propenyl-iactam in 82% yield was achieved simply by treating with Pd(OAc)2 in NMP or CH2CI2 for 3-5 min without addition of LiCI and the phosphine ligand[578]. 

Asymmetric allylation of carbon nucleophiles has been carried out extensively using Pd catalysts coordinated by various chiral phosphine ligands and even with nitrogen ligands, and ee > 90% has been achieved in several cases. However, in most cases, a high ee has been achieved only with the l,3-diaryl-substitiitcd allylic compounds 217, and the synthetic usefulness of the reaction is limited. Therefore, only references are cited[24,133]. 

Dimerization is the main path. However, trimerization to form 1.3,6,10-dodecatetraene (15) takes place with certain Pd complexes in the absence of a phosphine ligand. The reaction in benzene at 50 C using 7r-allylpalladium acetate as a catalyst yielded 1,3,6,10-dodecatetraene (15) with a selectivity of 79% at a conversion of 30% based on butadiene in 22 h[ 19,20]. 1,3,7-Octatriene (7) is dimerized to 1,5,7,10.15-hexadecapentaene (16) with 70% selectivity by using bis-rr-allylpalladium. On the other hand. 9-allyl-l,4,6.12-tridecatetraene (17) is formed as the main product when PI13P is added in a 1 1. ratio[21]. 

Cationic phosphine ligands containing guanidiniumphenyl moieties were originally developed in order to make use of their pronounced solubility in water [72, 73]. They were shown to form active catalytic systems in Pd-mediated C-C coupling reactions between aryl iodides and alkynes (Castro-Stephens-Sonogashira reaction) [72, 74] and Rh-catalyzed hydroformylation of olefins in aqueous two-phase systems [75]. 

An interesting parallel was found while the microwave-enhanced Heck reaction was explored on the C-3 position of the pyrazinone system [29]. The additional problem here was caused by the capability of the alkene to undergo Diels-Alder reaction with the 2-azadiene system of the pyrazinone. An interesting competition between the Heck reaction and the Diels-Alder reaction has been noticed, while the outcome solely depended on the substrates and the catalyst system. Microwave irradiation of a mixture of pyrazinone (Re = H), ethyl acrylate (Y = COOEt) and Pd(dppf)Cl2 resulted in the formation of a mixture of the starting material together with the cycloaddition product in a 3 1 ratio (Scheme 15). On the contrary, when Pd(OAc)2 was used in combination with the bulky phosphine ligand 2-(di-t-butylphosphino)biphenyl [41-44], the Heck reaction product was obtained as the sole product. When a mixture of the pyrazinone (Re = Ar) with ethyl acrylate or styrene and Pd(dppf)Cl2 was irradiated at 150 °C for 15 min, both catalytic systems favored the Heck reaction product with no trace of Diels-Alder adduct. 

Scheme 13.10 Decomposition of Pd-NHC complexes bearing chelating phosphine ligands...

The phosphine ligands suffer from P-C-bond cleavage, which result in the corporation of the phosphine aryl groups into an unwanted side product. This is due to the facile exchange of Ph and Ph Y between the Pd" centres and co-ordinated phosphines on an intermediates of type tranj-Pd(PPh,i)2(aryl)X ... 

Recently, Y. Yamamoto reported a palladium-catalyzed hydroalkoxylation of methylene cyclopropanes (Scheme 6-25) [105]. Curiously, the catalysis proceeds under very specific conditions, i.e. only a 1 2 mixture of [Pd(PPh3)4] and P(o-tolyl)3 leads to an active system. Other combinations using Pd(0 or II) precursors with P(o-tolyl)3 or l,3-bis(diphenylphosphino)propane, the use of [Pd(PPh3)4] without P(o-tolyl)3 or with other phosphine ligands were all inefficient for the hydroalkoxylation. The authors assumed a mechanism in which oxidative addition of the alcohol to a Pd(0) center yields a hydrido(alkoxo) complex which is subsequently involved in hydropal-ladation of methylenecyclopropane. 

Kurosawa et al. have reported that the relative stability of the ti-allyl palladium thi-olate 39 and the allyl sulfide/Pd(0) was highly ligand dependent. In the presence of PPhs or P(OMe)3 the stability was in favor of reductive elimination (Eq. 7.28), while in the presence of olefin or in the absence of any additional ligand the stability was in favor of oxidative addition (Eq. 7.29) [38]. This can explain the reactivity of the n-allyl palladium thiolate 33 and 38 proposed in Eq. (7.24) and path (c) of Scheme 7-10. The complex 33 should react with PhSH, but C-S bond-forming reductive elimination has to be suppressed in order to obtain the desired product 32. On the other hand, the complex 38 requires the phosphine ligand to promote the C-S bond-forming reductive elimination. 

Scheme 10.53 Pd-catalysed hydrosilylations of alkenes with (P-Af-sulfonylami-noalkyl)phosphine ligands.

Many procedures use Pb(OAc)2 or other Pd(II) salts as catalysts with the catalytic-ally active Pd(0) being generated in situ. The reactions are usually carried out in the presence of a phosphine ligand, with Lris-o-tolylphosphine being preferred in many cases. 7ra-(2-furyl)phosphine (tfp) is also used frequently. Several chelating diphosphines, shown below with their common abbreviations, are also effective. Phosphites are also good ligands.130... 

Heck reactions can be carried out in the absence of phosphine ligands.141 These conditions usually involve Pd(OAc)2 as a catalyst, along with a base and a phase transfer salt such as tetra-n-butylammonium bromide. These conditions were originally applied to stereospecific coupling of vinyl iodides with ethyl acrylate and methyl vinyl ketone. 

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... 

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