One-pot C-H activation

Making use of an earlier finding that Sn compounds containing Sn—CH2R bonds were suitable for Stille cross-coupling reactions,one-pot C—H activation and cross-coupling products were isolated in modest yields (21 % from MeOBu and 5 % from n-CsH 12 based on Sn amide) as shown in Equation (9.13) (R CH2OBU or n-CsHn). ... 

Type of reaction C-C bond formation Reaction conditions Dichloromethane, room temperature Synthetic strategy One-pot C-H activation Cataiyst Cobalt acetylacetonate [Co(acac)2]... 

With microwave-assisted technology, Porcheddu and colleagues [11] prepared benzimidazoles via one-pot C-H activation of tertiary amines/oxidative cycliza-tion with 1,2-phenylenediamine in the presence of Pd/C (Scheme 14.10). To ascertain the heterogeneous character of the catalytically active species in this process, further leaching studies were performed. Both Sheldons hot filtration test and atomic absorption spectroscopy analysis (ICP-MS) of the filtrate detected no significant quantities of leached Pd in solution, suggesting that the reaction was a heterogeneous process. 

A very elegant synthetic approach was reported a year later by Davies et al., leveraging asymmetric C-H activation chemistry to accomplish a one-pot synthesis of d-threo methyiphenidate (Scheme 17.10) (Davies et al., 1999). A-Boc piperidine (33) was selectively alkylated by the carbene formed by decomposition of diazoester 34 in a reaction mediated by 25 mol% of chiral Rh (II) catalyst 35, giving the A-Boc protected (2R,2 R) isomer in a single step. TFA was added to accomplish removal of the Boc group after the C-H insertion reaction was complete, affording (R,R)-methylphenidate (2) with an ee of 86% in 52% overall yield. 

A plausible mechanism for the one-pot synthesis ofcarbazoles is shown in Scheme 5. It consists of two interlinked catalytic cycles. In the first cycle a classical Buchwald-Hartwig amination reaction occurs to generate an intermediate 5 which then enters the second cycle by oxidative addition to Pd(0). The resulting Pd(II) complex then undergoes intramolecular C-H activation to give a six-membered palladacycle which subsequently yields the carbazole by reductive elimination. 

The most important photocatalytical reactions are oxidation reactions which include the oxygenation of unsaturated systems, but also oxidations of saturated carbons with or without incorporation of oxygen (C-H activation). The photooxygenation of olefins in the presence of Ti or Mo catalysts leads one-pot to epoxy alcohols (17) via singlet oxygen (eq. (9)) [82]. 

Rhodium catalyzed the combination of alkynes and quinoline N-oxides to form alkylated quinolines (Scheme 62).This is a rare combination of the direct C—H activation as well as an O-atom transfer in one pot both of which are... 

Palladium catalyzed C—H activation and its application to multi-bond forming reactions, including construction of heterocycles 13COC2001. InCl3-catalyzed one-pot organic synthesis 12T8683. 

The direct coupling of diarylamines and aUcenes (e.g., styrenes) with Pd(OAc)j was described by Maiti and colleagues (Scheme 4, equation 1) [39], and Wu and coworkers reported a one-pot sequential Beckmann rearrangement, cycUzation, and indole C-3 chlorination to afford A-acylindoles (equation 2) [40]. Gong, Wu, and colleagues synthesized 2-trifluoromethyl-3-vinylindoles via a domino carbopalladation C-H activation protocol... 

The same group extended this methodology to incorporate a Sonogashira reaction into the domino sequence [14]. As a result, oxindole 40 could be synthesized from propiolamide 38 and 2 equiv of aryl iodide 39 in the presence of catalytic Pd(PPh3)4/CuI via a domino Sonogashira reaction/carbopaUadation/C-H activation sequence (Scheme 3.10). Overall three C-C bonds were formed from distinct catalytic cycles using only one catalyst. UnsymmetricaUy substituted oxindoles were also synthesized by a one-pot/two-step protocol where the second aryl iodide was simply added to the same reaction vessel after the Sonogashira reaction of the first aryl iodide. 

Phenanthridinone derivatives have been reported to be found in a number of natural alkaloids and exhibit a wide range of biological activities. In the case of starting from bi-functionalized arenes with transition metal catalysts, the intramolecular cyclization of 2-bromo-iV-arylbenzamides via C-H activation is the most direct pathway, which has been applied in the synthesis of anti-hepatitis C virus agents and materials. Remarkably, Yao, Xu and their co-workers developed a one-pot procedure for the synthesis of a pyrrolophenanthridone skeleton via an intramolecular Heck reaction and oxidation of N-(2-bromobenzyl) substituted indoles. Moderate to good yields of the desired products were isolated in one step (Scheme 3.67). From the point view of academic interest, the... 

Ellman, Bergman, and coworker reported a rhodium-catalyzed procedure for the synthesis of pyridines from alkynes and a,/ -unsaturated N-benzyl aldimines and ketimines in 2008 [107]. The reaction proceeded via C-H alkenylation/electrocyclization/aromatization sequence through dihydropyridine intermediates. The C-H activated complex was isolated and determination by X-ray analysis. Good yields of highly substituted pyridines were produced in one-pot manner (Scheme 3.50). 

Keywords Aldehydes, indoles, C-H activated acids (4-hydroxycoumarin, 4-hydroxy-6-methyl-2//-pyran-2-one, dimedone, AAA -dimethylbarbituric acid, Meldrum s acid), L-proline, solvent-free, room temperature, grinding, one-pot three-component condensation, gewt-(P-dicarbonyl)arylmethanes... 

Keywords Aldehydes, malononitrile, C-H activated acids, urea, organocatalyst, ethanol-water (1 1), room temperature, tandem Knoevenagel-cyclocondensation, one-pot three-component reaction, chemoselectivity, functionalized 2-amino-3-cyano-4//-pyrans and pyran annulated heterocycles... 

Zhu et al. report a domino copper-catalyzed synthesis of benzimidazoles from boronic acids and amidines." This involved a Chan-Lam-Evans Al-arylation, C—H activation, and C—N bond formation (Scheme 7.18). These steps could be carried out in a one-pot reaction to give both primary and secondary benzimidazoles in good yields under mild reaction conditions (Schemes 7.19 and 7.20). 

C-H Functionalization. The last decade has seen the development of an increasing number of conditions to functionalize p5Tidine regioselectively via C-H activation. The various metal-catalyzed methodologies essentially provide access to C2 functionalized arylated, olefinated, or alkylated products, and the activation of pyridine via coordination to the nitrogen lone pair is commonly encountered. For instance, the one-pot amination/benzoylation procedure provides access to N-benzyoyliminopyridinium yUde in 96% yield (eq 29). ... 

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