Carbonylation of C-H Bonds

Murai found that C-H bonds in imidazoles also undergo carbonylation (Eq. 9.23). The coupling occurred regioselectively at the 4-position (a to the sp nitrogen), with no 5 -isomer being detected [3 5]. A variety of functional groups, such as ketone, ester, cyano, acetal, N, 0-acetal, ketal, and silyl groups, were tolerated under the reaction conditions. 

The carbonylation reaction is also applicable to other five-membered N-hetero-cycles, such as thiazoles, oxazoles, and pyrazoles [36], The reactivity of the substrates increases with increasing pfCa values of the conjugate acids of the N-heterocycles according to the series imidazole (pfCj 7.85) thiazole (pfCa 3.37) oxazole (pKa 2.91) pyrazole (pKa 2.09). This indicates that the coordination of the substrates by the sp nitrogen to the ruthenium center is the key step in the carbonylation of C-H bonds in N-heterocycles. 

Murai reported that Ru3(CO)i2 catalyzes carbonylation at a C-H bond to the sp ring nitrogen (Eq. 9.24). The Ru3(CO)i2-catalyzed the reaction of 1,2-dimethylben-zimidazole with an alkene, and CO provided the corresponding y3-acylated product in high yield with complete site selectivity [37]. 

In contrast to the carbonylation of a parent pyridine, in which carbonylation takes place at C-H bonds a to the pyridine nitrogen, 2-phenylpyridine did not undergo a-carbonylation, but, instead, orfho-carbonylation took place. When the reaction of 2-o-tolylpyridine with CO (20 atm) and ethylene was conducted at 160 °C, the ortho-C-H bond y to the sp nitrogen) in the benzene ring underwent carbonylation (Eq. 9.25) [38]. Carbonylation took place selectively at a C-H bond y to the sp nitrogen ortho-C-H bond). C-H bonds in the pyridine ring and meta- and para-C-H bonds in the benzene ring are completely unreactive. 

In the reaction of m-substituted substrates, carbonylation takes place exclusively at the less-congested position (i.e., the 6-position), irrespective of the electronic nature of the substituents, indicating that the regioselectivity is determined by steric factors. In the case of 2-naphthylpyridine, carbonylation takes place selectively at the 3-position, presumably because of steric hindrance by the peri-hydrogen on the naphthalene ring. In sharp contrast to the a and /3 carbonylations described above, this reaction is restricted to ethylene as the olefin partner. The use of 1-hexene resulted in no reaction. 

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This chapter mainly treats transition metal-catalyzed direct functionalization of carbon-hydrogen bonds in organic compounds. This methodology is emphasized by focusing on important functionalizations for synthetic use. The contents reviewed here are as follows (i) alkylation of C-H bonds, (ii) alkenylation of C-H bonds, (iii) arylation of C-H bonds, (iv) carbonylation of C-H bonds, (v) hydroxylation and the related reactions, and (vi) other reactions and applications. 

Since the direct carbonylation of C-H bonds with CO leading to aldehydes is endothermic, the reaction is conducted under photochemical conditions.109,109a 109e On the other hand, the direct coupling of a C-H bond, CO, and an olefin leading to a ketone is exothermic and can proceed under thermal reaction conditions. 

Abstract Ruthenium-catalyzed carbonylation reactions are described. The purpose of this chapter is to show how ruthenium complexes as catalysts are important in the recent development of carbonylation reactions. This review does not present a complete, historical coverage of ruthenium-catalyzed carbonylation reactions,but presents the most significant developments of the last 10 years. The emphasis is on novel and synthetic transformations of genuine value to organic chemists. Especially, this review will focus on carbonylative cycloadditions and carbonylation of C-H bonds. The review is generally organized according to the nature of the reaction. 

The C-N multiple bond of an isocyanide is weaker than the C-O multiple bond in CO. Thus, the insertion of an isocyanide into a C-H bond in a reaction that is analogous to the carbonylation of C-H bonds should be more favorable thermodynamically. An example of this reaction catalyzed by [RhCl(CO)(PMe3)j] under photochemical conditions is shown in Equation 18.34. A more efficient, albeit more complex, reaction of an isocyanide involves intramolecular insertion into the o-methyl group in 2,6-dimefhylphenylisocyanide, whidr leads to an indole product in high yield (Equation 18.35). ... 

The use of A, A/ -bidentate directing group in the carbonylation of C-H bonds has been achieved by the use of carbon monoxide (CO) as the carbonyl source in conjunction with Ru3(CO)i2 [40] or Co(acac)2 as the catalysts [41]. Ge recently reported on the Ni(ll)/Cu(ll)-catalyzed carbonylation of benzamides containing an 8-aminoquinoline as the directing group with DMF as the carbonyl source (Scheme 15) [42]. The presence of both a Ni and a Cu catalyst was required for the reaction to proceed. The product yield was improved by the addition of a... 

On the other hand, Pd-catalysed phosphaannulation of phosphonic acids (610) by carbonylation of C-H bonds afforded oxaphosphorinanone oxides (611) in moderate to good yield (Scheme 178). ... 

In 2014, Lee and coworkers also reported an efficient phosphaannulation by Pd-catalyzed carbonylation of C-H bonds of phosphonic and phosphinic acids for the synthesis of oxaphosphorinanone oxides (Scheme 4.29) [43]. In the reaction, AgOAc and PhI(OAc)2 gave the best result. In the transformation, ethyl hydrogen benzylphosphonate and methyl-substituted phosphonate were totally ineffective. It indicated that introduction of two substituents at the a-position was essential for successful carbonylation. Both electron-donating and electron-withdrawing groups on the aryl ring were tolerated. 

Scheme 4.29 Palladium-catalyzed carbonylation of C-H bonds of phosphonic and phosphinic adds.

Until now, most of the palladium-catalyzed carbonylation of C-H bonds preferentially proceeds under the acidic conditions which may favor the generation of the cationic Pd(II) species and inhibition of the possible reduction of Pd(II) to Pd(0) by CO. But this procedure runs under basic conditions (in DMF with basic DABCO and KI as the additive. Table 15.27). Many kinds of substituents on the aromatic ring of enamides were tolerated and especially the bromo and... 

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