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Review
. 2009;48(28):5094-115.
doi: 10.1002/anie.200806273.

Palladium(II)-catalyzed C-H activation/C-C cross-coupling reactions: versatility and practicality

Xiao Chen  1 , Keary M Engle, Dong-Hui Wang, Jin-Quan Yu
Affiliations
Review

Palladium(II)-catalyzed C-H activation/C-C cross-coupling reactions: versatility and practicality

Xiao Chen et al. Angew Chem Int Ed Engl. 2009.

Abstract

In the past decade, palladium-catalyzed C-H activation/C-C bond-forming reactions have emerged as promising new catalytic transformations; however, development in this field is still at an early stage compared to the state of the art in cross-coupling reactions using aryl and alkyl halides. This Review begins with a brief introduction of four extensively investigated modes of catalysis for forming C-C bonds from C-H bonds: Pd(II)/Pd(0), Pd(II)/Pd(IV), Pd(0)/Pd(II)/Pd(IV), and Pd(0)/Pd(II) catalysis. A more detailed discussion is then directed towards the recent development of palladium(II)-catalyzed coupling of C-H bonds with organometallic reagents through a Pd(II)/Pd(0) catalytic cycle. Despite the progress made to date, improving the versatility and practicality of this new reaction remains a tremendous challenge.

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Figures

Scheme 1
Scheme 1
Pd(0)-catalyzed reactions of aryl(alkyl) halides
Scheme 2
Scheme 2
Pd(II)-catalyzed functionalization of C–H bonds
Scheme 3
Scheme 3
C–H activation through cyclopalladation or the CIPE
Scheme 4
Scheme 4
Pd(II)-catalyzed olefination of arenes: Pd(II)/Pd(0) catalysis
Scheme 5
Scheme 5
Directed ortho-olefination of benzoic acid
Scheme 6
Scheme 6
ortho-Selective olefination of arenes
Scheme 7
Scheme 7
Synthesis of ibogamine
Scheme 8
Scheme 8
Synthesis of (+)-austamide
Scheme 9
Scheme 9
Catalytic olefination of indoles via electrophilic palladation
Scheme 10
Scheme 10
Intramolecular olefination of indoles using O2 as the oxidant
Scheme 11
Scheme 11
Oxidant-free olefination of indoles
Scheme 12
Scheme 12
Regioselective olefination of pyrroles
Scheme 13
Scheme 13
Heterocycle synthesis via olefination of arenes
Scheme 14
Scheme 14
Olefination of pyridine N-oxides
Scheme 15
Scheme 15
meta-Selective olefination of electronic-deficient arenes
Scheme 16
Scheme 16
ortho-Methylation of anilides
Scheme 17
Scheme 17
Proposed Pd(II)/Pd(IV) catalytic cycle
Scheme 18
Scheme 18
X-ray structures of Pd(IV) complexes
Scheme 19
Scheme 19
Pd-catalyzed arylation of aldehydic C–H bonds
Scheme 20
Scheme 20
Arylation of C–H bonds via Pd(II)/Pd(IV) catalysis
Scheme 20
Scheme 20
Arylation of C–H bonds via Pd(II)/Pd(IV) catalysis
Scheme 21
Scheme 21
Arylation of C–H bonds using ArI
Scheme 22
Scheme 22
ortho-Alkylation of C–H bonds via Pd(0)/Pd(II)/Pd(IV) catalysis
Scheme 22
Scheme 22
ortho-Alkylation of C–H bonds via Pd(0)/Pd(II)/Pd(IV) catalysis
Scheme 23
Scheme 23
ortho-Alkylation and cyanation of arenes
Scheme 24
Scheme 24
Synthesis of tetrasubstituted helical alkenes
Scheme 25
Scheme 25
Early arylation of C–H bonds involving Pd(IV) intermediates
Scheme 26
Scheme 26
Arylation of electron-rich heterocycles via Pd(0)/Pd(II) catalysis
Scheme 27
Scheme 27
Regioselective arylation of heterocycles
Scheme 28
Scheme 28
Alkylation of arenes by alkyl halides
Scheme 29
Scheme 29
Development of intermolecular arylation reactions with arenes
Scheme 30
Scheme 30
ortho-Arylation of benzanilides, benzadehydes and benzoic acids
Scheme 31
Scheme 31
Arylation of benzene with aryl bromides
Scheme 32
Scheme 32
Intramolecular Arylation of sp3 C–H bonds
Scheme 33
Scheme 33
Carbocyclization through arylation of C–H bonds
Scheme 34
Scheme 34
Arylation of sp3 C–H bonds with external ArB(OH)2
Scheme 35
Scheme 35
Reaction involving the migration of aryl Pd to allylic Pd
Scheme 36
Scheme 36
Synthesis of dihydrobenzofurans
Scheme 37
Scheme 37
Rh(I) and Ru(II)-catalyzed ortho-C–H coupling
Scheme 38
Scheme 38
Comparison of conventional cross-coupling with C–H activation/C–C coupling
Scheme 39
Scheme 39
Problematic homocoupling of organometallic reagents in the presence of Pd(II)
Scheme 40
Scheme 40
C–H coupling with organotin reagents
Scheme 41
Scheme 41
C–H coupling with organoboron reagents
Scheme 42
Scheme 42
C–H coupling with organosilane reagents
Scheme 43
Scheme 43
Coordination modes of Pd(II) with carboxylic acids
Scheme 44
Scheme 44
A working model for table salt-promoted C–H insertion
Scheme 45
Scheme 45
Comparison of iridium carboxylates and palladium carboxylates
Scheme 46
Scheme 46
Coupling of C–H bonds with substrates without a nitrogen-containing directing group
Scheme 47
Scheme 47
ortho-Lithiation
Scheme 48
Scheme 48
An alternative catalytic cycle
Scheme 49
Scheme 49
Coupling of electron-rich arenes with organometallic reagents
Scheme 50
Scheme 50
meta- and para-Selective coupling of mono-substituted arenes with organometallic reagents: a lingering challenge
Scheme 51
Scheme 51
An early example of arene–arene coupling
Scheme 52
Scheme 52
Coupling of heterocycles with benzene
Scheme 53
Scheme 53
Heterocoupling using directing groups
Scheme 54
Scheme 54
An early example of sp3–sp3 C–H activation/C–C coupling
Scheme 55
Scheme 55
sp3 C–H activation/C–C coupling
Scheme 56
Scheme 56
Derivatives of a biologically active natural product
Scheme 57
Scheme 57
Desymmetrization of germinal aryl and methyl groups
Scheme 58
Scheme 58
Desymmetrization of methylene C–H bonds
Scheme 59
Scheme 59
Proof of concept
Scheme 60
Scheme 60
A simplified stereomodel for asymmetric C–H insertion
Scheme 61
Scheme 61
Enantioselective coupling of sp3 C–H bonds
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References

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    1. For reviews on C–H activation chemistry, see: Crabtree RH. Chem Rev. 1985;85:245.Shilov AE, Shul’pin GB. Chem Rev. 1997;97:2879.Stahl SS, Labinger JA, Bercaw JE. Angew Chem Int Ed. 1998;37:2181.Bergman RG. Nature. 2007;446:391.Brookhart M, Green MLH, Parkin G. Proc Natl Acad Sci. 2007;104:6908.

    1. For comprehensive reviews on cyclopalladation reactions, see: Ryabov AD. Synthesis. 1985:233.Canty AJ. In: Comprehensive organometallic chemistry II: a review of the literature 1982–1994. Abel EW, Stone FGA, Wilkinson G, editors. Pergamon; 1995. pp. 225–255.

    1. a) For an early example of cyclopalladation of sp2 C-H bonds directed by azo groups, see: Cope AC, Siekman RW. J Am Chem Soc. 1965;87:3272.b) For an early example of cyclopalladation of sp3 C–H bonds directed by oximes see: Constable AG, McDonald WS, Sawkins LC, Shaw BL. J Chem Soc Chem Commun. 1978:1061.

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