Intermolecular Copper-Catalyzed Carbon−Hydrogen Bond Activation via Carbene Insertion

Díaz‐Requejo, M. Mar; Belderraín, Tomás R.; Nicasio, M. Carmen; Trofimenko, Swiatoslaw; Pérez, Pedro J.

doi:10.1021/ja016798j

Cited by 148 publications

(87 citation statements)

References 20 publications

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“…The metal carbenoids behave as very electrophilic species and the electron-withdrawing ester group reinforces the high reactivity, generating a system characterized by poor regioselectivity between different C-H bonds [27][28][29] . In recent years, extensive efforts have been made to attenuate the carbenoid reactivity by altering the nature of the catalysts, with some improvements having been made by using very bulky ligands with copper 30 and silver 31 complexes. The major breakthrough in this field, however, was the discovery that carbenoids functionalized with both donor and acceptor groups were much more chemoselective than the traditional carbenoids, as shown in Fig.…”

Section: C-h Functionalization By Metal Carbenoidsmentioning

confidence: 99%

Catalytic C–H functionalization by metal carbenoid and nitrenoid insertion

Davies

Manning

2008

Nature

2,174

812

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Novel reactions that can selectively functionalize carbon-hydrogen bonds are of intense interest to the chemical community because they offer new strategic approaches for synthesis. A very promising 'carbon-hydrogen functionalization' method involves the insertion of metal carbenes and nitrenes into C-H bonds. This area has experienced considerable growth in the past decade, particularly in the area of enantioselective intermolecular reactions. Here we discuss several facets of these kinds of C-H functionalization reactions and provide a perspective on how this methodology has affected the synthesis of complex natural products and potential pharmaceutical agents.I n 2006, 31 new chemical entities were introduced to the world pharmaceutical market and 2,075 molecules were in phase I or II of clinical development 1 . The majority of these were smallmolecule (relative molecular mass ,1,000) organic compounds 2 . As knowledge about the specific interactions of drugs in vivo increases, often so does the structural complexity of new drug targets. A major obstacle to the development of such drugs is the difficulty associated with synthesizing large quantities in an economical fashion, because complex multi-step syntheses are usually required. In the general media, it is often overlooked that the accessibility of the components required for these new treatments will often govern their eventual success or failure. Likewise, a design element of any pharmaceutical agent is the expectation that the target compounds can be made economically. Therefore, new strategies for synthesis can become enabling technologies, making available new targets and materials that would have been previously out of range. For example, new methodologies such as metal-catalysed crosscoupling 3 and olefin metathesis 4-6 have rapidly become central transformations in the synthesis of new pharmaceutical agents. Selective C-H functionalization is a class of reactions that could lead to a paradigm shift in organic synthesis, relying on selective modification of ubiquitous C-H bonds of organic compounds instead of the standard approach of conducting transformations on pre-existing functional groups. The reactive sites in each type of transformation are very different, as illustrated in Fig. 1.The many opportunities associated with C-H functionalization has made this field an active area of research. Organometallic chemists have focused much attention on developing 'C-H activation' strategies, whereby a highly reactive metal complex inserts into a C-H bond, activating the system for subsequent transformations 7-9 . One of the major challenges associated with this chemistry has been to render it catalytic in the metal complex 10 . A partial solution to this problem has been to use neighbouring functionality to direct less reactive metal complexes to the site for functionalization. Numerous reviews have been written about this method for C-H functionalization [11][12][13][14][15][16][17] . Here, however, we highlight another approach, in which a divalent c...

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Section: C-h Functionalization By Metal Carbenoidsmentioning

confidence: 99%

Catalytic C–H functionalization by metal carbenoid and nitrenoid insertion

Davies

Manning

2008

Nature

2,174

812

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“…[3a, b] The major difficulty was the high reactivity of the traditional carbenoid intermediates derived from diazoacetate derivatives. Some progress has been made in taming this reactivity by the use of very bulky catalysts [4] but the major breakthrough in this area came about with the development of donor/acceptor substituted carbenoids. [3c, d] These carbenoids display much greater selectivity than the traditional carbenoids and enable the intermolecular C À H insertion to be a very general C À H activation process.…”

Section: Introductionmentioning

confidence: 99%

Influence of a β‐Alkoxy Substituent on the CH Activation Chemistry of Alkyl Ethers

Davies

Yang

2003

Adv Synth Catal

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“…112 The substrate scope could be even extended according to a related publication in 2003. 95 They applied a homoscorpionate-copper(I) catalyst (164) to the successful functionalization of (mostly cyclic) aliphatic ethers and also of acetals by ethyl diazo glycine (91) ( Table 6).…”

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confidence: 99%