Decarboxylative direct arylation

Acylation of Indoles. A decarboxylative direct arylation of indoles containing a pyrimidyl directing group was reported (eq 158). 2... 

In 2009, Larrosa and co-workers developed the first decarboxylative direct C-H arylation methodology that allowed the intermolecular coupling of a variety of electron-poor benzoic acids with N-pivaloylindoles (090L5506). Remarkably, this process occurs with high chemo- and regioselectivity in both coupling partners and led to the formation of C3-arylated products exclusively, with good yields (Scheme 45). The authors proposed... 

Scheme 3.12 Intermolecular decarboxylative direct C-3 arylation of indoles with benzoic acids, as reported by Larrosa and coworkers [24].

The direct arylation of less electron-rich azoles via cleavage of the relatively acidic C-H bond of their C2-position with ortho-substituted benzoic acids was achieved (Scheme 4.14) [18]. Similarly, the decarboxylative arylation procedure on C-H bond was successfully applied to electron-deficient polyfluoroarenes... 

In a process developed by Myers et al., aromatic carboxylic acids were directly employed as substrates for Heck olefinations, albeit in the presence of a large excess of silver carbonate [38]. This base both facilitates the decarboxylation step and acts as an oxidant, generating arylpalladium(II) intermediates. In related processes, arylphosphonic [39] and arylboronic acids [40] were used as aryl sources in the presence of an oxidant. 

Decarboxylation of excited singlets of aromatic esters (Eq. 13.6) is a concerted process, and it can account for a significant fraction of the reaction by appropriately substituted aryl esters, especially in bulk polymers and other media that are capable of imposing conformational constraints on guest molecules.Because photoinduced decarboxylation occurs before lysis of the aryl esters, it does not influence the rates at which the A B singlet pair react. For that reason, the relative yields of decarboxylation products need not be considered in analyses of the radical pairs unless their formation precludes sufficient radical pair production for their easy direct or indirect detection. 

As a preparative method the direct decarboxylation of olefinic acids is almost limited to the formation of styrenes and stilbenes from substituted cinnamic acids. Thermal decomposition of cinnamic acid gives styrene (41%). The yield is nearly quantitative if the reaction is carried out in quinoline at 220° in the presence of a copper catalyst. The yields of substituted styrenes where the aryl radical contains halo, methoxyl, aldehyde, cyano, and nitro groups are in the range of 30-76%. cis-Stilbene and cis-p-nitrostilbene are prepared in this way from the corresponding a-phenylcinnamic acids (65%). One aliphatic compound worthy of mention is 2-ethoxypropene, prepared by heating -ethoxycro-tonic acid at 165° (91% yield). The mechanism of acid-catalyzed decarboxylations of this type has been studied. Isomerization of the double bond from the a,/5- to the /5, y-position before decarboxylation very likely occurs in many instances. ... 

For purposes of classification the 4-aminopyrazoles are considered to be 4-imino-2-pyrazolines and analogs of 2-pyrazolin-4-ones. These compounds are listed in Table XL. Such compounds can be prepared by direct cyclization using ethyl diazoacetate and ethyl cyanoacetate.92 This is the same as eq. 243, except that the malonic ester is replaced by ethyl cyanoacetate. Purines can be hydrolyzed to 4-imino-2-pyrazolines by using strong acid.1210 1846 By far the most frequently used preparation is reduction of appropriately substituted pyrazoles, such as 4-nitro,368,812,819,1015,1019,1049 4-nitroso1165 or 4-aryl-azo.671 974,995 The hydrolysis of the carbethoxy 4-imino-2-pyrazolines derived from ethyl cyanoacetate and ethyl diazoacetate forms 4-imino-2-pyrazolin-3-carboxylic acid which is readily decarboxylated to the parent compound.92... 

O/t/20-arylation of benzoic acids is often preferable to ortho-arylation of benzamides if conversion of the amide moiety to other functional groups is desired. However, only a few reports have dealt with the orf/io-functionalization of free benzoic acids due to challenges that involve such transformations. The reactions can be complicated by decarboxylation of the product and the starting material. Despite those difficulties, several methods for direct o/t/io-arylation of benzoic acids have been developed. Yu has shown that arylboronates are effective in arylation of benzoic acids under palladium catalysis [59], The reactions require the presence of palladium acetate catalyst, silver carbonate oxidant, and benzoquinone. Even more interestingly, the procedure is applicable to the arylation of unactivated sp3 C-H bonds in tertiary carboxylic acids such as pivalic acid (Scheme 13) if aryl iodide coupling partner is used. Aryl trifluoroborates can also be used [60],... 

Heck carbonylation involving the oxidative addition of aryl halides is not applicable to aliphatic halides, since alkyl halides react directly with nucleophiles. Tsuji developed a process of carbonylating allyl carbonates to form carboxylic esters by palladium-catalyzed carbonylation that is applicable to aliphatic substrates [60]. The process probably involves (a) the oxidative addition of allyl carbonates to Pd(0) species to form r/ -allyl palladium species, (b) CO insertion into the allyl-Pd bond to give acylpalladium species, (c) decarboxylation of the carbonate ligand to give alkoxide, and (d) liberation of butenoate esters by combination with the alkoxides as shown in Scheme 1.21. 

A complex consisting of Cu 1.10-phenanthroline [which mediates decarboxylation of arylcarboxylic acids with formation of aryl Cu species] and Pd(acac)2 [for coupling] was made and used to catalyse the decarboxylative cross-coupling of the Cu species with aryl halides. This bimetallic system allows direct coupling of a variety of aryl, heteroaryl or vinyl carboxylic acids with aryl or heteroaryl bromides, chlorides or iodides at 160° in N methylpyrrolidine in the presence of K2CO3. [Goossen et al. JAm Chem Soc 129 4824 2007]. 

Following the previous successful application of the asymmetric decarboxylative protonation reaction in the catalytic asymmetric synthesis of isoflavanones we hoped to expand the scope of this work to the catalytic asymmetric synthesis of tertiary a-aryl cyclohexanones and, in particular, cyclopentanones given the dearth of reported methods for their direct asymmetric synthesis to date (see Sect. 4.6). 

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