Recent Advances in Catalysis Involving Bidentate N-Heterocyclic Carbene Ligands

Abstract

Since the discovery of persistent carbenes by the isolation of 1,3-di-l-adamantylimidazol-2-ylidene by Arduengo and coworkers, we witnessed a fast growth in the design and applications of this class of ligands and their metal complexes. Modular synthesis and ease of electronic and steric adjustability made this class of sigma donors highly popular among chemists. While the nature of the metal-carbon bond in transition metal complexes bearing N-heterocyclic carbenes (NHCs) is predominantly considered to be neutral sigma or dative bonds, the strength of the bond is highly dependent on the energy match between the highest occupied molecular orbital (HOMO) of the NHC ligand and that of the metal ion. Because of their versatility, the coordination chemistry of NHC ligands with was explored with almost all transition metal ions. Other than the transition metals, NHCs are also capable of establishing a chemical bond with the main group elements. The advances in the catalytic applications of the NHC ligands linked with a second tether are discussed. For clarity, more frequently targeted catalytic reactions are considered first. Carbon-carbon coupling reactions, transfer hydrogenation of alkenes and carbonyl compounds, ketone hydrosilylation, and chiral catalysis are among highly popular reactions. Areas where the efficacy of the NHC based catalytic systems were explored to a lesser extent include CO₂ reduction, C-H borylation, alkyl amination, and hydroamination reactions. Furthermore, the synthesis and applications of transition metal complexes are covered.

Keywords: N-heterocyclic carbenes; catalysis; chiral; coupling reactions; polymerization; transfer hydrogenation.

Figure 1

Selected examples of tethering bidentate NHCs ligands bearing neutral or anionic moieties.

Scheme 1

“Direct method” of metalation of a bidentate NHC ligands with tethered triazolyl to support palladium (II) ions [113].

Scheme 2

“Modular Approach” to synthesis palladium complexes of a bidentate NHC ligands with tethered triazolyl group [113]. DIPEA = N,N-diisopropylethylamine.

Scheme 3

Transfer hydrogenation of alkynes catalyzed by Pd(NHC)allyl complexes [113].

Scheme 4

In situ generation of piano-stool iron(II) complexes featuring bidentate NHC-C_p donors [116].

Scheme 5

Catalytic transfer hydrogenation catalyzed by complexes 14 and 16 [116].

Scheme 6

Synthesis of proligand 18. [117]. Reagents and conditions: (i) Cu₂O (5 mol%), 8-hydroxyquinoline (20 mol%), Cs₂CO₃, MeCN, 100 °C (ii) iPrl, MeCN, 90 °C.

Scheme 7

Synthesis of ruthenium NHC-amine complex 19 [117].

Scheme 8

Azolium salts containing a chiral moiety. Reagents and conditions: (i) SOCl₂, EtOH, 3 h, RT; (ii) NaBH₄, EtOH, 48 h, RT; (iii) TsCl, Et₃N, CH₂Cl₂, DMAP, 20 h, RT; (iv) thiazole, MW, 130 °C, 2 h; (v) 1-methyl-1,2,4-triazole, MW, 130 °C, 2 h; (vi) 1-substituted-imidazole, MW, 130 °C, 1.5 h. [118].

Scheme 9

Synthesis of precatalyst 29 [119]. Cp* = Me₅-Cp.

Figure 2

Proposed structure of iridium complex with NHC-amidate ligand [119].

Figure 3

Ru(II) carbonyl complexes investigated in transfer hydrogenation reaction [120].

Scheme 10

Chelation of bidentate NHC-PR₂ ligand [122].

Scheme 11

Amide functionalized NHC ligand and its metal complexation [29]. Cp* = Me₅-Cp.

Scheme 12

Different coordination motifs of NHC-carboxylate [123]. Reagents and conditions: (i) Ag₂O, CH₂Cl₂, RT, 18 h; (ii) [(η⁶-p-cymene)RuCl₂]₂, CH₂Cl₂, RT, 24 h.

Scheme 13

Bis-NHC and its palladium complexes [124]. tBu-DAB: 1,4-di(tert-butyl)-1,4-diaza-1,3-butadiene. a: R = 2,4,6-Me₃C₆H₂, n = 1; b: R =2,4,6-Me₃C₆H₂, n = 2; c: R = Me, n = 1; d: R = Bn, n = 1; e: R = tBu, n = 1.

Scheme 14

Bis-NHC and its ruthenium complexes [125].

Figure 4

NHC-pyridine type chelating ligands and their iridium complexes [127].

Scheme 15

Multistep synthesis of bidentate NHC-pyridine type ligands and their Ir complexes [127]. (i) MsCl, Et₃N, DMAP (cat.), NaN₃, THF, 0 °C, 20 min, then DMSO, RT, 2.5 h (quant.). (ii) Pd/C, H₂, RT, 4 h, EtOH (quant.). (iii) nBuLi, RNH₂, THF (95%). (iv) HCO₂H, Ac₂O, THF (87%). (v) Ac₂O, HClO₄ (aq.) (75–80%). (vi) Toluene; Et₂O, HClO₄ (aq.) (41–65%). (vii) LiOtBu, THF, [{Ir-(cod)Cl}₂], RT, 2 h, then NaBArF, CH₂Cl₂, 30 min (44–72%). DMAP = 4-(N,N-dimethylamino)pyridine, DMSO = dimethylsulfoxide, Ms = methanesulfonyl.

Scheme 16

Synthesis of Ir(I) and Rh(I) complexes using bidentate NHC-N donors [129]. Reagents and conditions: (i) MeOTf, DCM, −78 °C → RT, (ii) Me₃O·BF₄, DCM, (iii) 1. NaH, [M(cod)Cl]₂, MeOH; 2. L, 50 °C, (iv) 1. KOtBu, [M(cod)Cl]₂ in THF; 2. AgOTf, DCM.

Scheme 17

Pd nanoparticles supported with NHC-sulfur ligands [131].

Scheme 18

Hydrogenation of styrene with Pd nanoparticles [131].

Scheme 19

Bidentate NHC ligands and their ruthenium complexes [132]. Reagents and conditions: (i) Ag₂O, solvent; (ii) 0.5[RuCl₂(p-cymene)]₂; (iii) KPF₆, solvent.

Scheme 20

Conversion of levulinic acid to lactone [132].

Figure 5

Metal complexes of NHC-NH₂ chelates [134,135,136,137,138,139].

Figure 6

Chiral NHC-NH₂ ligand 81 and its ruthenium complexes 82 and 83 [31,140].

Scheme 21

Synthesis of chiral NHC-NH₂ ligands 84 and 85 [30]. Reagents and conditions to the left: (i) toluene, reflux 1 h; (ii) HCl(aq); (iii) Na₂CO₃, KPF₆; to the right: (i) CH₃CN, reflux 1 h; (ii) HCl(aq); (iii) Na₂CO₃, KPF₆.

Scheme 22

Rhodium and iridium complexes of bidentate NHC-NH₂ ligand [30].

Scheme 23

Mn(I)-NHC-based hydrogenation catalyst [145]. Reagents and conditions: (i) KPF₆ in basic H₂O/DCM; (ii) KN(SiMe₃)₂ in THF; (iii) Mn(CO)₅Br.Using Mn(I)-NHC complex 92 a high TON of at least 17,000 was achieved in the TH reaction of acetophenone with 94% yield. Besides, a low catalyst loading in this case was close to catalysts based on Ru and Ir metals [145].

Scheme 24

NHC-olefin ligands and their Ru(II) complexes [146]. P1–3 are defined in the text.

Scheme 25

Ru(II) complexes with NHC-C ligands [147].

Scheme 26

Novel Co complexes with NHC-N donor ligands [149].

Figure 7

An Ir(I) complex with NHC-P donor [150].

Scheme 27

Chiral NHC ligands in allylic alcohol synthesis [101].

Scheme 28

Addition of arylboronate to isatin [85].

Figure 8

Chiral mono- and bidentate NHC-hydroxy ligands [85].

Figure 9

Chiral bidentate NHC-hydroxy ligands [154].

Figure 10

Structure of a magnesium NHC-phenoxy chelate [154].

Figure 11

Chiral mono- and bidentate NHC ligands [156].

Scheme 29

Copper catalyzed 1,4 addition of organoboronates to alkenes [156].

Scheme 30

Cu-NHC catalyzed hydroboration of 1,1-disubstitued aryl olefines [106].

Figure 12

Bulky enantioselective chiral ligands in olefin hydroboration [106].

Figure 13

Dimeric silver complexes with NHC-sulfonate donors [90].

Scheme 31

Allenylboronic acid pinacol ester addition to alkenes [102].

Figure 14

Different reactivity of organometallic reagents [102].

Scheme 32

Sodium alkoxide mediated ally transfer reaction from allylboronate [102].

Figure 15

Azolium salts containing a chiral moiety [97].

Scheme 33

Chiral azolium salts containing a sulfonate moiety [97]. Reagent and conditions: (i) BH₃·SMe₂, THF, 60–90 °C, 3 d; (ii) MeOH, 90 °C, 2 h;(iii) (EtO)₃CH, EtOH, 100 °C, 17 h.

Scheme 34

Allylic alkylation of vinyl bromide substrates [163].

Figure 16

Proligands introduced for allylic alkylation of allylphosphates [164].

Scheme 35

Multicomponent synthesis of chiral bidentate imidazolium salts [168].

Scheme 36

Enantioselective allylic alkylation of alkynyl nucleophiles [98].

Figure 17

Bidentate NHC-OH ligand for enantioselective allylic alkylation [98].

Figure 18

Mono- and bidentate chiral NHC ligands developed by Sawamura [81].

Scheme 37

Reaction of boron pro-nucleophiles with alkynes [81].

Figure 19

Phosphine donor and NHC donor ligands for addition of dimethyl zinc to acylimiazole [172].

Figure 20

Sawamura’s enantioselective allylic alkylation ligands [174].

Scheme 38

Enantioselective allylic alkylation [174].

Scheme 39

Synthesis of a Pd complex bearing a bidentate NHC-amidato ligand [176].

Scheme 40

Synthesis of dimeric palladium complex with NHC-S donors [177].

Scheme 41

Iron(II) complex with a bis-NHC ligand for crosscoupling reactions [179].

Scheme 42

Palladium complexes with bulky bis-NHC ligands [180].

Scheme 43

Imidazolium based NHC with pyridine side chain for Suzuki–Miyaura crosscoupling [181].

Scheme 44

Bis-NHC ligands with flexible alkyl linkers [183].

Scheme 45

Synthesis of selenium containing NHC ligand [184].

Scheme 46

Novel bidentate methylene-bridged NHC ligands [188].

Figure 21

A palladium complex with bis-NHC ligand stabilized on polystyrene [188].

Scheme 47

Formation of Pd Complexes with free carbenes [190]. X = Cl for 192a–c, OAc for 192a′–c′.

Figure 22

Side chain influence in an NHC ligand on catalytic activity of palladium complex. [191].

Figure 23

A bis-NHC palladium complex supported on nanomagnetic particles [192].

Scheme 48

Chelation of bidentate NHC-PR₂ ligands onto Pd(0) [193].

Scheme 49

Novel iron(II)-NHC for Kumada-type coupling reactions [194].

Figure 24

Nickel-based NHC ligand for Suzuki coupling [195].

Scheme 50

Chiral NHC ligands for catalytic asymmetric aryl–aryl coupling reactions [196]. dba: dibenzylideneacetone.

Figure 25

Pd complexes bearing chiral bicyclic imidazoles [197].

Scheme 51

Synthetic route to oxazolines 202a–c [197].

Figure 26

Synthetic route to bicyclic imidazoles [197].

Scheme 52

Bis-NHC ligands and their coordination to palladium [198].

Figure 27

Structures of dendrons used for the synthesis of bulky bis(imidazolium) salts [198].

Figure 28

Bidentate C^NHC-C-based ligands introduced by Verpoort et al. [199].

Scheme 53

Ti and Zr complexes with ortho-aryloxide-NHC ligand for olefin polymerization reactions [63].

Scheme 54

Palladium complexes with NHC-N donor ligands for styrene polymerization [204]. Reagents and conditions: (i) Ag₂CO₃, CH₂Cl₂, reflux; (ii) [PdBr₂(cod)], CH₂Cl₂; (iii) AgPF₆, MeCN; (iv) [PdMeBr(cod)], CH₂Cl₂ or MeCN.

Scheme 55

Synthesis and derivatization reactions of molybdenum alkylidene complex 228 [205].

Figure 29

Design strategy for NHC-oxygen ligand [208].

Scheme 56

Synthetic strategy for bidentate NHC-PR₂(O) ligands [208].

Scheme 57

Palladium complexes bearing NHC-PR₂(O) ligands [208].

Scheme 58

Synthesis of titanium(IV) complexes [210].

Scheme 59

Synthesis of mixed ligand Ti(IV) complex [210]. 242, 245: R = 2,6-iPr₂C₆H₃; 243, 246: R = 2,4,6-Me₃C₆H₂.

Scheme 60

Synthesis of sulfonamide pre-ligands [212].

Scheme 61

Synthesis of palladium complex with bidentate NHC ligand [212].

Scheme 62

Synthesis of a nickel complex bearing bidentate NHC-Cp ligand [225] DME = dimethoxyethane.

Scheme 63

Synthesis of proligand 250 [113]. Reagents and conditions: (i) nBuLi; (ii) tetramethylfulvene; (iii) MeOH; (iv) MeI.

Scheme 64

Synthesis of Co(II) complexes bearing silyl-functionalized NHC [214]. Reagent and conditions: (i) CoCl₂, THF; (ii) Na/Hg.

Scheme 65

Iron and cobalt coordination of a free NHC-N-picolyl ligand leading to tetracoordinated complexes [215].

Scheme 66

Iron and cobalt coordination of free N-picolyl NHC ligands leading to tricoordinated complexes [215].

Scheme 67

Reactivity of NHC-N-picolyl ligands with iron and cobalt salts [215].

Figure 30

Ruthenium complex of redox-active ferrocenyl phosphine-NHC ligand [217].

Scheme 68

Synthesis of chiral salts and corresponding rhodium(I) complexes [218]. CMEE: chloromethyl ethyl ether.

Scheme 69

Chelation of sulfonated bis-NHC ligand [253]. Reagent and conditions: (i) 1 eq Ag₂O; (ii) 1 eq NaCl(aq), 50 °C; (iii) 0.5 eq [(p-cymene)MCl₂]₂ (M = Ru, Os), 50 °C.

Scheme 70

Chelation of sulfonated NHC-pyridine ligand [253]. Reagent and conditions: (i) 1 eq Ag₂O; (ii) 1 eq NaCl(aq), 50 °C; (iii) 0.5 eq [(p-cymene)RuCl₂]₂, 50 °C.

Scheme 71

Synthesis of bis(NHC) type ligand [244].

Scheme 72

Coordination of bis(NHC) ligand to ruthenium [244]. Reagents and conditions: (i) [Ru(trpy)Cl₃], trpy = terpyridine; (ii) Et₃N/LiCl; (iii) NH₄PF₆, ROH, 80 °C, 16 h (iv) AgBF₄; (v) NH₄PF₆, acetone/H₂O, 90 °C, 4 h; (vi) [Ru(tpm)Cl₃], tpm = tris(pyrazol-1-yl)methane; (vii) [Ru(bpea)Cl₃], bpea = N,N-bis(pyridin-2-ylmethyl)ethanamine.

Scheme 73

Synthesis of iridium complex supported with bidentate NHC-pyridine ligand [240]. Reagents and conditions: (i) Ag₂O (0.50 eq), 4 h; (ii) [Cp*IrCl₂]₂ (0.5 eq), 4 h, CH₂Cl₂, r.t, Cp* = pentamethylcyclopentadiene.

Figure 31

Design of bifunctional Cp*Ir complexes [245]. Cp* = Me₅-Cp.

Scheme 74

Synthesis of Ir complexes [245]. Cp* = Me₅-Cp.

Scheme 75

Synthesis of ruthenium complexes bearing NHC-aryloxide ligand [234].

Scheme 76

Postulated norbornene polymerization by complex 301c [234].

Scheme 77

Synthesis of molybdenum alkylidyne complexes with bidentate NHCs [246].