Carbonyl Arylation

The acidity of protons in a position of carbonyl compounds can be exploited in Pd-catalysed ketone arylation. This transformation is atom-economical, and is usually performed under mild conditions although strong bases are often employed. 

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Several new methods for the synthesis of the oxazole nucleus were published. A new consecutive three-component oxazole synthesis by an amidation-coupling-cycloisomerisation sequence was developed. The synthesis started from propargylamine 92 and acyl chlorides. To extend this process, a four component sequence involving a carbonylative arylation by substitution of one acyl chloride with an aryl iodide and a CO atmosphere was also performed <06CC4817>. 

A similar substituted furan synthesis was realized via a Pd-catalyzed tandem carbonylation-arylation using an a,p-acetylenic ketone, carbon monoxide, and bromothiophene [104],... 

These transformations are efficient under biological conditions only if another activating group is present (carbonyl, aryl, etc.) [77]. Such an activating group is important to render the elimination product (resulting from the loss of a fluoride ion) a better Michael acceptor. Moreover, if one or several fluorine atoms are present on the double bond, the latter is also more reactive (Fig. 22). Thus, the elimination, promoted by the enzyme, of a fluoride ion from a jS-fluoro amino acid leads to a very reactive Michael acceptor. The latter can undergo an irreversible addition of a nucleophile residue of the active site of the enzyme, which is thus inhibited (Fig. 23) [78,79]. 

In a further variant of this type of carbonylation, aryl, vinyl and heterocyclic bromides and iodides underwent a double carbonylation to give a-ketoamides (equation 119). 

Formylation reactions providing aldehydes succeeded under similar conditions in 51-86% yield. The process does not occur according to a p-hydride elimination/hydroformylation sequence. The authors favored, however, a two-electron mechanism for these reactions. A similar carbonylation/arylation method was also reported [243]. 

The arylation of enol esters has also been improved (95). Previously a wide range of products were produced including j8-aryl carbonyls, arylated enol esters, styrene, and stilbene derivatives (96). It has also been found that arylated enol esters can be obtained as major products if the reactions are carried out with stoichiometric amounts of aryl mercuric acetate and palladium acetate in anhydrous acetonitrile or in excess enol ester solution. The products are those arising from addition of the phenyl group to the carbons not containing the ester. Thus, with vinyl acetate and phenyl mercuric acetate, the product is the enol acetate of phenyl acetaldehyde ... 

Fig. 1-26. Carbonylative aryl-acetylide coupling catalyzed by [Pd(dppl)].

It is noted that a novel Pd-catalyzed Grignard-type nucleophilic carbonyl arylation occurs competitively in some cases [60,61] the product ratio depends on the structure of the substrates (Eq. 17) [61]. 

RXN21 Tandem Carbonylation-Arylation with Alkynes 120... 

In 2006, the group of Artok showed that 5-aryl-2(5H)-furanones could be prepared in moderate to good yields by a rhodium-catalyzed carbonylative arylation of internal alkynes with aryl boronic acids (Scheme 1.9a) [22]. a,P-Unsaturated ketones (chal-cone derivatives) were formed as the major product when some TFA (trifluoroacetic acid) was added under the same reaction conditions [23a]. By varying the catalytic system, indanones could be produced as the main product [23b]. The chemical behavior of terminal alkynes is different, and either a,P-unsaturated ketones or furans starting from propargylic alcohols can be achieved (Scheme 1.9b) [24, 25]. In the case of vinyl ketones, 1,4-diketones were obtained by rhodium-catalyzed coupling of arylboronic acids in the presence of 20-40 bar of CO [26]. In 2007, Chatani demonstrated that indenones could be accessed by a carbonylative rhodium-catalyzed cyclization of alkynes with 2-bromophenylboronic adds (Scheme 1.9c) [27]. Here, the key intermediate is a vinylrhodium(I) spedes that is formed by transmetaUation of RhCl with 2-bromophenylboronic acid followed by insertion of... 

Additionally, the reactions with alkynes and iron catalyst were also applied to the carbonylative homocoupling of aryl iodides to give benzophenones [49]. As catalyst system, Fe(CO)5-Co2(CO)g was used under phase-transfer conditions to give carbonylate aryl iodides in moderate yields. 

In palladium-catalyzed carbonylations, aryl triflates are used regularly as substrates [145-151], while arene diazonium salts [152-156] and diaryl iodonium salts [157-162] are less commonly applied. 

For instance, Choi and Chung described for the first time the rhodium-catalyzed carbonylative arylation of allenols using 53 (Scheme 10.2) [127]. 

In another approach, poly(aryl ether sulfones) were synthesized by the electrophilic Friedel-Crafts reactions of sulfonyl halides with aromatic hydrocarbons. The critical step in these polymerizations is the formation of the carbon-sulfur bond. High polymers were obtained, though they were not always completely linear. Carbonyl aryl carbon-carbon bonds are created in Friedel Craft reactions leading to poly(aryl ketones). 

Figure 4.19 Direct C-H Pd/Mg-La mixed oxide oxidative carbonyl arylation described by Kishore et al. [42].

Scheme 8.4 Buchwald and Hartwig palladium-catalyzed carbonyl arylation reactions via ketone enolates...

FeClj catalyses the carbonylation-arylation of A -arylacrylamides with aldehydes using TBHP oxidant in CsHsCl to afford oxindoles in 90% yield. Similar catalytic activity is shown by FeCl2 and Fe(OAc)2. Oxindoles can be further transformed to give diverse indole alkaloids. The FeCl2-catalysed oxidative amidation of tertiary amines with aldehydes using TBHP gives amides in moderate to excellent yields. Aromatic aldehydes are more reactive than aliphatic aldehydes. The mechanistic studies indicate that a peroxide and an iminium ion are the reactive intermediates. " ... 

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