Carbonylation and Carbonylative Coupling

Numerous aryl bromides, iodides [203], borates [204] and triflates [205, 206] have been successfully carbonylated. Triflates could serve as a route for the synthesis of arenecarboxylic acid derivatives from phenols. This carbonylation using dppf in a catalytic mixture generally shows higher efficiency than PPhj or P(o-Tol)3 [207]. Poor performance is also noted for PPhj in a Pd-catalyzed vinyl substitution of aryl bromides [208]. Side-reactions involving the formation of [PPhjAr]Br and ArH are responsible. A system which is catalyzed effectively by PdCljfdppf) under 10 atm CO is the desulfonylation of 1-naphthalenesulfonyl chloride 58 in the presence of Ti(OiPr)4. Formation of isopropyl 1-naphthoate 59 can be explained in a sequence of oxidative addition, SOj extrusion, carbonylation and reductive elimination (Fig. 1-27) [209]. A notable side-product is di-l-naphthyl disulfide. 

A useful synthesis of ( )-j -ethoxycarbonylvinylsilanes by palladium-catalyzed regio- and stereospecific hydroesterification (EtOH -I- CO) (or carboethoxylation) of trimethylsilylacetylenes has been reported recently [210]. Alkoxycarbonyl or carbonyl functionalization of vinylsilanes are useful synthetic intermediates [211, 212]. The use of PdCl2(dppf) as a catalyst (with SnCl2 2 H2O as cocatalyst) is found to be superior and gives excellent yields. A key step in the reaction is thought to involve hydropalladation to give 60 or 61. The preference for 60 to 61 is understood 

Carbocarbonylation [216] of alkyl halide with a perfluoro substituent leads directly to the analogous carboxylic acids and esters, provided the ) -hydride elimination is slower than CO insertion. The use of PdCl2(dppf) in the esterification of 68 gives 

4-quinolones are known to be pharmacologically active [201,202]. The catalytic activity of PdCljCdppf) is also the highest among the Pd complexes tested. 

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All carbon signals and resolved couplings can be assigned C-6 is more deshielded (8c = 150.0) than C-7 (8c = 146.5) due to electron withdrawal of the carboxy carbonyl group in para position. 

Xia and co-workers synthesised a number of Pd-NHC complexes (33, 34, 36) for carbonylative Suzuki reactions (Fig. 9.6) [41], Various aryl iodides were carbonylatively coupled (P = 1 atm) with either phenylboronic acid or sodium tetraphenylborate. All the complexes were highly active, but 33 provided the best results with >76% selectivity for ketone in all the reactions. Xia followed this work with the double carbonylation of various aryl iodides with several secondary amines using the catalysts [CuX(Mes)] (37-X) and [Cu(IPr)X] (38-X) (X = I, Br, Cl) (3 MPa, 100°C, 10 h) (Scheme 9.7) [42],... 

Mn. Manganese is also effective for mediating aqueous carbonyl ally-lations and pinacol-coupling reactions. Manganese offers a higher reactivity and complete chemoselectivity toward allylation of aromatic aldehydes.178... 

Scheme 10 Plausible catalytic mechanism for alkyne-carbonyl coupling as supported by the effect of chiral Bronsted acid catalyst and deuterium-labeling...

The fluorines of a CF2 = group of an a,P-unsaturated carbonyl system are considerably deshielded, and the geminal and vicinal coupling con-... 

To complete the synthesis of nakiterpiosin (1), we first deprotected 52 and then coupled it to 51 under the previously described carbonylative conditions (Scheme 2.6). Photolysis of 64 readily provided the desired annulation product. 

A somewhat related process, the cobalt-mediated synthesis of symmetrical benzo-phenones from aryl iodides and dicobalt octacarbonyl, is shown in Scheme 6.49 [100]. Here, dicobalt octacarbonyl is used as a combined Ar-I bond activator and carbon monoxide source. Employing acetonitrile as solvent, a variety of aryl iodides with different steric and electronic properties underwent the carbonylative coupling in excellent yields. Remarkably, in several cases, microwave irradiation for just 6 s was sufficient to achieve full conversion An inert atmosphere, a base or other additives were all unnecessary. No conversion occurred in the absence of heating, regardless of the reaction time. However, equally high yields could be achieved by heating the reaction mixture in an oil bath for 2 min. 

Palladium(0)-catalyzed coupling reactions - i. e. the Heck and Sonogashira reactions, the carbonylative coupling reactions, the Suzuki and Stille cross-coupling reactions, and allylic substitutions (Fig. 11.1) - have enabled the formation of many kinds of carbon-carbon attachments that were previously very difficult to make. These reactions are usually robust and occur in the presence of a wide variety of functional groups. The reactions are, furthermore, autocatalytic (i.e. the substrate regenerates the required oxidation state of the palladium) and a vast number of different ligands can be used to fine-tune the reactivity and selectivity of the reactions. 

The Fukuyama indole synthesis involving radical cyclization of 2-alkenylisocyanides was extended by the author to allow preparation of2,3-disubstituted derivatives <00S429>. In this process, radical cyclization of 2-isocyanocinnamate (119) yields the 2-stannylindole 120, which upon treatment with iodine is converted into the 2-iodoindole 121. These N-unprotected 2-iodoindoles can then undergo a variety of palladium-catalyzed coupling reactions such as reaction with terminal acetylenes, terminal olefins, carbonylation and Suzuki coupling with phenyl borate to furnish the corresponding 2,3-disubstituted indoles. 

Morimoto, Kakiuchi, and co-workers were the first to show that aldehydes are a useful source of CO in the catalytic PKR [68]. Based on 13C-labeling experiments, it was proposed that after decarbonylation of the aldehyde, an active metal catalyst is formed. This was proven by the absence of free carbon monoxide. As a consequence CO, which is directly generated by previous aldehyde decarbonylation, is incorporated in situ into the carbonylative coupling. The best results were obtained using C5F5CHO and cinnamaldehyde as CO source in combination with [RhCl(cod)]2/dppp as the catalyst system. In the presence of an excess of aldehyde the corresponding products were isolated in the range of 52-97%. 

Co complexes, Buchwald reported the Ti-catalyzed carbonylative coupling of enynes-the so-called Pauson-Khand-type reaction [28]-and realized the first such catalytic and enantioselective reaction using a chiral Ti complex [29]. Here, a variety of enynes were transformed into bicyclic cyclopentenones with good to high ee-values however, several steps were required to prepare the chiral Ti catalyst, while the low-valent complex proved to be so unstable that it had to be treated under oxygen-free conditions in a glove box. 

By contrast, in 2000 Shibata reported the Ir-catalyzed enantioselective Pauson-Khand-type reaction of enynes [30aj. The chiral Ir catalyst was readily prepared in situ from [lrCl(cod)]2 and tolBINAP (2,2 -bis(di-p-tolylphosphino)-l,T-binaphthyl), both of which are commercially available and air-stable, and the reaction proceeded under an atmospheric pressure of carbon monoxide. The Ir-catalyzed carbonylative coupling had a wide generality in enynes with various tethers (Z), substituents on the alkyne terminus (R ) and the olefinic moiety (R ). In the case of less-reactive enynes, a lower partial pressure of carbon monoxide achieved a higher yield and ee-value (Table 11.1) [30b]. 

Vaska s complex ([IrCl(CO)(PPh3)2]) also catalyzed the carbonylative coupling of diynes, which provided bicyclic cyclopentadienones (Scheme 11.23) [35]. Due to the instability of the products, the substrates are limited to symmetrical diynes with aromatic groups on their termini nonetheless, this reaction still serves as the catalytic and practical procedure for the synthesis of cyclopentadienones, which are anti-aromatic with a 47t system and serve as active synthetic intermediates. 

Titanium in a low valence state, as prepared by treatment of solutions of titanium trichloride with potassium [206] or magnesium [207] in tetrahydro-furan or with lithium in dimethoxyethane [206], deoxygenates ketones and effects coupling of two molecules at the carbonyl carbon to form alkenes, usually a mixture of both stereoisomers. If a mixture of acetone with other ketones is treated with titanium trichloride and lithium, the alkene formed by combination of acetone with the other ketone predominates over the symmetrical alkene produced from the other ketone [20(5] Procedure 39, p.215). 

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