Palladium reductive carbonylation

Hydroboration and oxidation of 160 yields an alcohol that is subsequently oxidized with PDC to give ketone compound 161. Enolization and triflation converts this compound to enol triflate 162, which can be further converted to x,/i-unsaturated ester 163 upon palladium-mediated carbonylation methox-ylation. The desired alcohol 164 can then be readily prepared from 163 via DIBAL reduction. Scheme 7 50 shows these conversions. 

It is worth mentioning that some precursors easily catalyze the reductive carbonylation of alkynes from the C0/H20 couple. Here, the main role of water is to furnish hydrogen through the water-gas-shift reaction, as evidenced by the co-production of CO2. In the presence of Pd /KI terminal alkynes have been selectively converted into furan-2-(5H)-ones or anhydrides when a high concentration in CO2 is maintained. Two CO building blocks are incorporated and the cascade reactions that occur on palladium result in a cyclization together with the formation of an oxygen-carbon bond [37,38]. Two examples are shown in Scheme 4. 

The single step conversion of methyl acetate to ethylidene diacetate is catalyzed by either a palladium or rhodium compound, a source of iodide, and a promoter. The mechanism is described as involving the concurrent generation of acetaldehyde and acetic anhydride which subsequently react to form ethylidene diacetate. An alternative to this scheme involves independent generation of acetaldehyde by reductive carbonylation of methanol or methyl acetate, or by acetic anhydride reduction. The acetaldehyde is then reacted with anhydride in a separate step. 

Scheme II. Possible General Mechanism for Palladium Catalyzed Reductive Carbonylation...

Concurrent with acetic anhydride formation is the reduction of the metal-acyl species selectively to acetaldehyde. Unlike many other soluble metal catalysts (e.g. Co, Ru), no further reduction of the aldehyde to ethanol occurs. The mechanism of acetaldehyde formation in this process is likely identical to the conversion of alkyl halides to aldehydes with one additional carbon catalyzed by palladium (equation 14) (18). This reaction occurs with CO/H2 utilizing Pd(PPh )2Cl2 as a catalyst precursor. The suggested catalytic species is (PPh3)2 Pd(CO) (18). This reaction is likely occurring in the reductive carbonylation of methyl acetate, with methyl iodide (i.e. RX) being continuously generated. 

In addition to the successful reductive carbonylation systems utilizing the rhodium or palladium catalysts described above, a nonnoble metal system has been developed (27). When methyl acetate or dimethyl ether was treated with carbon monoxide and hydrogen in the presence of an iodide compound, a trivalent phosphorous or nitrogen promoter, and a nickel-molybdenum or nickel-tungsten catalyst, EDA was formed. The catalytst is generated in the reaction mixture by addition of appropriate metallic complexes, such as 5 1 combination of bis(triphenylphosphine)-nickel dicarbonyl to molybdenum carbonyl. These same catalyst systems have proven effective as a rhodium replacement in methyl acetate carbonylations (28). Though the rates of EDA formation are slower than with the noble metals, the major advantage is the relative inexpense of catalytic materials. Chemistry virtually identical to noble-metal catalysis probably occurs since reaction profiles are very similar by products include acetic anhydride, acetaldehyde, and methane, with ethanol in trace quantities. 

Trifluoroalanine has also been prepared by reducing trifluoropyruvate imines (ethyl trifluoropyruvate is available commercially it is prepared either from per-fluoropropene oxide or by trifluoromethylation of ethyl or f-butyl oxalate). These imines are obtained by dehydration of the corresponding aminals or by Staudinger reaction. They can also be obtained by palladium-catalyzed carbonylation of trifluoroacetamidoyl iodide, an easily accessible compound (cf. Chapter 3) (Figure 5.4). Reduction of the imines affords protected trifluoroalanines. When the imine is derived from a-phenyl ethyl amine, an intramolecular hydride transfer affords the regioisomer imine, which can further be hydrolyzed into trifluoroalanine. ... 

Bromophenyl)ethanol undergoes a palladium-catalyzed carbonylation which results in the formation of isochroman-l-one (79H(12)92l). It is considered that the reaction involves formation of an aryl-palladium complex (624) through insertion of the zerovalent palladium complex (623) into the aryl halide. Insertion of carbon monoxide followed by reductive elimination of the metal as a complex species leads to the isochromanone (Scheme 242). 

The nitrogen-sulfur bond in 161 (X = S, R = NPhth X = S02, R = OMe) is easily broken under certain conditions. For instance, attempts to obtain a palladium-catalyzed carbonylation reaction with the iodide gave only the ring-opened disulfide 162 and the sulfonic acid 163, presumably by reductive cleavage of the N-S bond by the triphenylphosphine in the reaction mixture <2000T5571>. 

Palladium-catalyzed ketone synthesis B. The reaction mixture is saturated with carbon monoxide, which intervenes in step 2 by forming a palladium(II) carbonyl complex. Before the transmetalation (above referred to as step 3) takes place a rearrangement is interposed. The ligand Rmisa rji cd undergoes a [l,2]-shift from Pd(II) to the carbon atom of carbon monoxide, leading to the formation of an acylpalladium(II) complex with the structure P lllsa llra cd-(C=0)-Pd(-X) L j. With regard to the above-mentioned steps 3-4 it behaves like the acyl-Pd(II) complex of the ketone synthesis A and, after reductive elimination, i.e. in step 5, yields... 

Chloromercurio-benzo[ ]furans 107 were key intermediates for the syntheses of natural product XH14 and its analogs. The synthesis proceeded by the palladium-catalyzed carbonylation reaction as a pivotal step. The 3-chloromercurio-benzo[ ]furan 107 was also reduced to form its hydride derivative by NaBH4 reduction, as illustrated in Scheme 54 <2002JOC6772>. 

A regioselective synthesis of 3-substituted A -butenolides by palladium-catalyzed reductive carbonylation can be carried out with a simple terminal alkyne as starting material (Equation 68) <1999TL989>. 

The insertion of CO into palladium carbon bonds is a common step in many palladium-catalyzed carbonylation reactions and polymerizations. This reaction takes place under moderate CO pressure (1-3 atm). From the range of compounds that can be carbonylated, it can be inferred that CO will insert into alkyl, aryl, and alkynic bonds (equation 13). One of the few types of Pd-C bonds inert to CO insertion is the Pd-acyl bond, thus only single carbonylations are normally observed. However, a few examples of double carbonylation have been reported. In the case of palladium-catalyzed formation of PhCOCONEt2 from Phi, CO, and NHEt2, reductive elimination from a bisacyl complex has been established as the mechanism, rather than CO insertion into a Pd-acyl bond. 

The reductive carbonylation of nitroarenes with transition metal catalysts is a very important process in industry, as the development of a phosgene-free method for preparing isocyanate is required. Ruthenium, rhodium, and palladium complex catalysts have all been well studied, and ruthenium catalysts have been shown to be both highly active and attractive. The reduction of nitroarene with CO in the presence of alcohol and amine gives urethanes and ureas [95], respectively, both of which can be easily converted into isocyanates [3,96]. 

A base reaction is also made responsible for the palladium(II)-catalyzed reductive carbonylation of nitroaromatics to isocyanates. Carhon monoxide affects the reduction step Pd ---> Pd° in protic media [14] according to eq. (9). The consecutive... 

Palladium-catalyzed carbonylative addition of terminal acetylenes and reduction of the thus formed selenoesters by means of "BusSnH can be achieved successively without isolation of the selenoesters. This one-pot transformation from acetylenes to -seleno-a,/7-unsaturated aldehydes is synthetically the equivalent to regio- and stereoselective selenoformylation of acetylenes (Scheme 15.89) [169]. 

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