Triphenylphosphine catalysts

The avermectins also possess a number of aUyflc positions that are susceptible to oxidative modification. In particular the 8a-methylene group, which is both aUyflc and alpha to an ether oxygen, is susceptible to radical oxidation. The primary product is the 8a-hydroperoxide, which has been isolated occasionally as an impurity of an avermectin B reaction (such as the catalytic hydrogenation of avermectin B with Wilkinson s rhodium chloride-triphenylphosphine catalyst to obtain ivermectin). An 8a-hydroxy derivative can also be detected occasionally as a metaboUte (42) or as an impurity arising presumably by air oxidation. An 8a-oxo-derivative can be obtained by oxidizing 5-0-protected avermectins with pyridinium dichromate (43). This also can arise by treating the 8a-hydroperoxide with base. 

G-19 Dicarboxylic Acids. The C-19 dicarboxyhc acids are generally mixtures of isomers formed by the reaction of carbon monoxide on oleic acid. Since the reaction produces a mixture of isomers, no single chemical name can be used to describe them. Names that have been used include 2-nonyldecanedioic acid, 2-octylundecanedioic acid, l,8-(9)-heptadecanedicarboxyhc acid, and 9-(10)-carboxystearic acid. The name 9-(10)-carboxystearic acid can be used correctiy if the product is made with no double bond isomerization (rhodium triphenylphosphine catalyst system). 

Batch Experiments with Thermomorphic Systems. As a reference, we tested the hydroformylation of 1-octene in a completely homogeneous system using the same rhodium triphenylphosphine catalyst that is used for hydroformylation of lower aldehydes. This is sample R39 in Table 28.1, and gives us a baseline to compare the performance of our systems in terms of conversion and selectivity. To maintain consistency, we performed all the reactions at 100°C using the same amounts of reactants, catalysts and solvents. Under these conditions we only detected aldehyde products no alcohol or alkene isomers were formed. 

Most recently new applications for substrate-controlled branched-selective hydroformylation of alkenes substituted with inductively electron-with drawing substituents have emerged. A recent example is the hydroformylation of acrylamide with a standard rhodium/triphenylphosphine catalyst, which yields the branched aldehyde exclusively (Scheme 4) [40]. Reduction of the aldehyde function furnishes 3-hydroxy-2-methylpropionamide, which is an intermediate en route to methyl methacrylate. 

LPO process. Propene hydroformylation can be done with a rhodium triphenylphosphine catalyst giving a linearity ranging from 60 to 96 % depending on the phosphine concentration. At very high phosphine concentration the rate is low, but the linearity achieves its maximum value. The commercial process (Union Carbide Corporation, now Dow Chemicals) operates presumably around 30 bar, at 120 °C, at high triphenylphosphine concentrations, and linearities around 92%. The estimated turnover frequency is in the order of only 300 mol(product).mol 1 (Rh).h Low ligand... 

This complex easily looses CO, which enables co-ordination of a molecule of alkene. As a result the complexes with bulky phosphite ligands are very reactive towards otherwise unreactive substrates such as internal or 2,2-dialkyl 1-alkenes. The rate of reaction reaches the same values as those found with the triphenylphosphine catalysts for monosubstituted 1-alkenes, i.e. up to 15,000 mol of product per mol of rhodium complex per hour at 90 °C and 10-30 bar. When 1-alkenes are subjected to hydroformylation with these monodentate bulky phosphite catalysts an extremely rapid hydroformylation takes place with turnover frequencies up to 170,000 mole of product per mol of rhodium per hour [65], A moderate linearity of 65% can be achieved. Due to the very fast consumption of CO the mass transport of CO can become rate determining and thus hydroformylation slows down or stops. The low CO concentration also results in highly unsaturated rhodium complexes giving a rapid isomerisation of terminal to internal alkenes. In the extreme situation this means that it makes no difference whether we start from terminal or internal alkenes. 

The same methodology was extended to the synthesis of other condensed pyrrole derivatives too. N-Boc 2-amino-3-iodothiophene was alkylated with ethyl 4-bromocrotylate to give the A-crotyl derivative, which on treatment with a palladium-triphenylphosphine catalyst cyclized efficiently to the appropriate pyrrolo[2,3-6]thiophene (3.12.),16... 

Allenyl ketones and aryl halides undergo coupling and cyclization in the presence of a palladium-triphenylphosphine catalyst and silver carbonate. The reaction leads to the formation of furane derivatives, the aryl group being introduced into the 3-position (3.72.) 90... 

The reaction of /V-pentenyl-2-iodoindole in the presence of a palladium-triphenylphosphine catalyst led to the formation of a mixture of isomeric products in good yield (4.8.), Addition of thallium(I) acetate favoured the formation of an exocyclic double bond, while in its absence the product containing the endocyclic olefin moiety is formed preferentially. The shortening of the A-alkenyl chain by one carbon leads to the selective formation of a five membered ring.9 Starting from indole-carboxamide derivatives both /3-. and carbolinones are available in intramolecular Heck coupling. 

The susceptibility of the indole ring towards electrophilic attack has also been exploited by Merour in the annulation of a coumarin unit to the indole ring. The heating of the o-bromophenyl ester of indole-2-carboxylic acid in the presence of a palladium-triphenylphosphine catalyst led to the formation of the tetracyclic product in 66% yield (4.32.)40... 

The analogous open chain carboxylic acid, Z-non-2-en-4-ynoic acid, when treated with 4-iodoanisole in the presence of a palladium-triphenylphosphine catalyst and potassium carbonate gave a mixture of three products, two of which were isolated (4.41.) z) the pyrone derivative arising from the attack of the anisylpalladium complex at the 4-position, followed by ring closure //) the furane derivative (major product) arising from the... 

Snieckus and co-workers reported the directed lithiation of 3-furanecarboxylic acid diethylamide (6.21.), which proceeded selectively in the 2-position, and the subsequent zinc-lithium exchange. The so formed fiiranylzinc reagent underwent Negishi-coupling with 2-bromotoluene in the presence of a palladium-triphenylphosphine catalyst to give 2-(o-tolyl)furane in good yield.26... 

The Heck reactions of thiophenes, particularly in the 2-position are well documented. In a recent example 2-bromothiophene was converted into a thienyl-vinylboronic acid derivative using a conventional palladium-triphenylphosphine catalyst and tributylamine as base (6.59.),... 

V-Methylinudazole, when heated in DMF with bromobenzene in the presence of a palladium-triphenylphosphine catalyst and potassium carbonate furnished two products (6.87.) the 5-phenyl and the 2,5-diphenyl derivative. The product distribution suggests that the preferential site of the arylation is the more electron-rich 5-position.118 Prolonged heating in a polar, high boiling solvent in the presence of base is characteristic of such transformations. 

Another alternate to the Sonogashira coupling was reported by Blum and Molander, where sodium tetraalkynylaluminatcs were coupled with bromoazines and bromoazoles in the presence of a palladium-triphenylphosphine catalyst system. 5-Bromopyrimidine coupled with the TMS-acetylide, for example, to give the cthynylpyrimidinc in excellent yield (7.41.),59 The transmetalating reagents were prepared in situ by the reaction of the appropriate acetylene derivative with sodium aluminiumhydride. 

The TV-protected 3-amino-2-chloropyridine derivative in 7.45. for example was found to react with styrene in the presence of a palladium acetate-triphenylphosphine catalyst system at elevated temperatures to give a near quantitative yield of a single coupling product.64 In the process sodium acetate was used as base. The formation of a single regioisomer might be attributed to the steric bulk of pyridine s substituents in position 3. 

Aryl chlorides Aryl chlorides will substitute alkenes only under very special conditions, and then catalyst turnover numbers are generally not very high. Palladium on charcoal in the presence of triethylphos-phine catalyzes the reaction of chlorobenzene with styrene,58 but the catalyst becomes inactive after one use.59 Examples employing an activated aryl chloride and highly reactive alkenes, such as acrylonitrile, with a palladium acetate-triphenylphosphine catalyst in DMF solution at ISO C with sodium acetate as base react to the extent of only 51% or less.60 Similar results have been reported for the combination of chlorobenzene with styrene in DMF-water at 130 C, using sodium acetate as the base and palladium acetate-diphos as a catalyst.61 Most recently, a method for reacting chlorobenzene with activated alkenes has been claimed where, in addition to the usual palladium dibenzilideneacetone-tri-o-tolylphosphine catalyst, nickel bromide and sodium iodide are added. It is proposed that an equilibrium concentration of iodobenzene is formed from the chlorobenzene-sodium iodide-nickel bromide catalyst and the iodoben-zene then reacts in the palladium-catalyzed alkene substitution. Moderate to good yields were reported from reactions carried out in DMF solution at 140 C 62... 

Essentially the same substituents as listed above may be present in the alkene being substituted, with the possible exception of chloro, alkoxy and acetoxy groups on vinyl or allyl carbons. These groups, especially chloro, may be lost or partially lost with palladium when the final elimination step occurs. For example, vinyl acetate, iodobenzene and triethylamine with a palladium acetate-triphenylphosphine catalyst at 100 C form mainly (E)-stilbene, presumably via phenylation of styrene formed in the first arylation step (equation 21 ).6 ... 

In the case of rhodium as a catalyst metal for the hydroformylation of methyl oleate, lower pressure and lower temperature have to be compared to cobalt catalysis [20, 21], The use of rhodium is also advantageous because of the lower isomerization. Frankel showed that with a rhodium triphenylphosphine catalyst, hydroformylation occurs only on the ninth and tenth carbon atoms of the methyl oleate [22]. 

A convenient catalyst precursor is RhH(CO)(PPh3)3. Under ambient conditions this will slowly convert 1-alkenes into the expected aldehydes, while internal alkenes hardly react. At higher temperatures pressures of 10 bar or more are required. Unless a large excess of ligand is present the catalyst will also have some isomerization activity for 1-alkenes. The internal alkenes thus formed, however, will not be hydroformylated. Accordingly, the 2-alkene concentration will increase while the 1-alkene concentration will decrease this will slow down the rate of hydroformylation. This makes the rhodium triphenylphosphine catalyst... 

In 1965 Wilkinson invented the rhodium-tris(triphenylphosphine) catalyst as a hydrogenation catalyst [60]. It still forms the basis for many of the chiral hydrogenations performed today. The most effective homogeneous hydrogenation catalysts are complexes consisting of a central metal ion, one or more (chiral) ligands and anions which are able to activate molecular hydrogen and to add the two H atoms to an acceptor substrate. Experience has shown that low-valent Ru,... 

Rhodium triphenylphosphine catalysts are sensitive to steric influences of the alkene substrate the rates of hydrogenation decrease with increasing alkene substi-... 

A useful reaction for small scale carbonylations is the in situ generation of CO from chloroform in aqueous alkaline solution, a reaction used for example in the carbonylation of aromatic and benzylic halides in the presence of Ru, Rh, or Pd triphenylphosphine catalysts.82... 

Homogeneous hydrogenation and 4 hydroformylation of olefins by (10) rhodium-triphenylphosphine catalysts... 

---