Mn-, Fe-, and Co-Catalyzed Radical Hydrofunctionalizations of Olefins

Abstract

Cofactor-mimetic aerobic oxidation has conceptually merged with catalysis of syngas reactions to form a wide range of Markovnikov-selective olefin radical hydrofunctionalizations. We cover the development of the field and review contributions to reaction invention, mechanism, and application to complex molecule synthesis. We also provide a mechanistic framework for understanding this compendium of radical reactions.

Figure 1

Proton transfer versus HAT Markovnikov hydrofunctionalization of alkenes.

Figure 2

Relative rates of radical addition to different alkenes.

Figure 3

Co(dmg)₂(pyr)Cl and Mn(TTP)Cl were structural models for cobalamin (Vitamin B₁₂) and the heme cofactor of cytochrome P-450 respectively.

Figure 4

Unusual reactivity of Mn(TPP)Cl in the presence of NaBH₄.

Figure 5

Okamoto and Oka’s 1^st generation hydration reaction with full substrate scope.

Figure 6

Okamoto and Oka’s second generation styrene hydration reaction with full substrate scope.

Figure 7

Structures of the cobalt(II) tetraphenylporphyrine (CoTPP) and cobalt(II) bis[3-(salicylideneimino)propyl]methylamine (CoSalMDPT) complexes.

Figure 8

Co^II, Fe^III and Mn^III tetra-t-butylphthalocyanine. [The Fe^III and Mn^III complexes bear coordinated counterions, frequently halides].

Figure 9

Boger’s FePc-catalyzed and Fe₂ox₃-mediated aerobic hydration of alkenes.

Figure 10

Boger’s vinblastine redox hydration and representative examples from its predecessors the patent literature. ^aBoger’s conditions, ref . ^bMitsui chemists’ conditions, ref . ^cMitsui chemists’ conditions, ref . ^dAllelix, Inc. chemists’ conditions, ref . HPLC yields in parentheses.

Figure 11

Catharanthine and vindoline are the constitutive subunits of vinblastine.

Figure 12

Ishibashi’s cyclization of 1,6-dienes with FePc as catalyst.

Figure 13

Taniguchi’s method for 1,4-diol formation from alkenes. a. Selected substrates. b. Abridged mechanistic proposal.

Figure 14

Drago’s oxidation of linear alkenes with expanded scope.

Figure 15

Mukaiyama’s first reduction-hydration reaction with full substrate scope.

Figure 16

Mukaiyama’s second generation reaction with full substrate scope.

Figure 17

Use of Et₃SiH in Mukaiyama’s reduction-hydration reaction.

Figure 18

Mildest conditions known for Mukaiyama’s reduction hydration reaction with full substrate scope.

Figure 19

Mukaiyama’s method for formation of α-hydroxy esters from α,β-unsaturated esters with full substrate scope. The reaction is assumed to proceed via radical intermediates.

Figure 20

Magnus’ modification of Mukaiyama’s method for formation of α-hydroxy ketones from α,β-unsaturated ketones.

Figure 21

Magnus’ synthesis of α-cyanohydrins from α,β-unsaturated nitriles with selected substrate scope.

Figure 22

Yamada’s asymmetric α-hydroxylation.

Figure 23

Manganese(III)-catalyzed Mukaiyama hydration with Ph(i-PrO)SiH₂ in THF.

Figure 24

The Isayama/Mukaiyama hydroperoxidation with full substrate scope. Modp and dedp ligands are shown.

Figure 25

Isayama’s α-triethylsilylperoxidation of α,β-unsaturated esters.

Figure 26

Woerpel’s synthesis of 1,2-dioxolanes.

Figure 27

Matsushita and Sugamoto’s hydroperoxidation of conjugated alkenes.

Figure 28

Mukaiyama’s method for direct conversion of vinyl silanes to ketones with examples of substrate scope. ecbo = 2-ethoxycarbonyl-1,3-butanedionato.

Figure 29

Matsushita’s synthesis of γ-oxo-α,β-unsaturated esters, amides and nitriles. Co(tdcpp) = [5,10,15,20-tetra(2,6-dichlorophenyl)porphinato]cobalt(II)

Figure 30

Inoue’s method for the synthesis of ketones from silylperoxides.

Figure 31

Shigehisa and coworkers’ hydroalkoxylation method.

Figure 32

Matsushita’s synthesis of (−)-pyrenophorin (26).

Figure 33

Wakamatsu’s synthesis of (+)-schizandrin, (+)-gomisin A (29), (+)-isoschizandrin and metabolites thereof.

Figure 34

Tietze’s synthesis of 7-desmethyl-2-methoxy-calamenene (32).

Figure 35

Xu and Dong’s synthesis of yingzhaosu C (35).

Figure 36

Enders’ synthesis of stigmolone (37).

Figure 37

Magnus’ synthesis of (±)-lahadinine B (40).

Figure 38

Walker and Bruce’ one-pot conversion of codeine (41) into oxycodone (44).

Figure 39

Paquette’s synthetic work towards pectenotoxin-2.

Figure 40

Shibasaki and coworkers synthesis of (±)-garsubellin A (49).

Figure 41

Baran’s synthesis of (+)-cortistatin A (52).

Figure 42

Carreira’s synthesis of the core (55) of banyaside, suomilide and spumigin HKVV.

Figure 43

Harwood’s hydroperoxidation studies towards mycaperoxide B (58).

Figure 44

Boger’s synthesis of vinblastine (2).

Figure 45

Modification of avermectin B₁ with manganese(III) hydration technology.

Figure 46

Gang and Romo’s synthesis of (+)-omphadiol (63).

Figure 47

Peng and Danishefsky’s approach towards maoecrystal V (66).

Figure 48

Herzon et al.’s synthesis of (+)-periglaucine B (68).

Figure 49

Endoma-Arias and Hudlicky’s synthesis of kibdelone fragment 71.

Figure 50

Mulzer’s synthesis of the core (74) of bielschowskysin (75).

Figure 51

Carreira’s synthesis of (±)-indoxamycin B (78).

Figure 52

Vatele’s synthesis of (−)-ent-plakortolide I (81).

Figure 53

Wu’s synthesis of the chamigrane endoperoxide secondary metabolites.

Figure 54

Rizzacasa’s formal synthesis of spirangien A (89).

Figure 55

Metz’s synthesis of (−)-oxyphyllol (92).

Figure 56

Baran’s synthesis of ouabagenin (95).

Figure 57

Hiroya’s synthesis of trichodermatide A (97).

Figure 58

Tietze et al.’s synthesis of blennolide C (100) and gonytolide C.

Figure 59

Inoue’s synthesis of ryanodol (104).

Figure 60

Baran’s synthesis of ent-atisine diterpenes and related alkaloids.

Figure 61

Baran’s modification of steroids by C-H oxidation.

Figure 62

Maimone’s synthesis of (+)-cardamom peroxide (118).

Figure 63

Cramer’s synthesis of (−)-palustrol (120) via Mukaiyama hydration of (+)-ledene (119).

Figure 64

Xie’s synthesis of (−)-conolutine (124).

Figure 65

Zhu and coworkers’ synthesis of (−)-scholarisine G (126) from (+)-melodinine E (125).

Figure 66

Baran’s synthesis of fumitremogin A (130) and verruculogen (131).

Figure 67

Baran’s synthesis of polyoxypregnanes.

Figure 68

Zhu and Yu’s synthesis of linckosides A (139) and B (140).

Figure 69

Song et al.’s used of [Co] and [Mn] radical chemistry in the syntheses of a) rac-crotobarin (143), b) rac-crotogroudin (146), and c) the scopadulane-type diterpenoid skeleton.

Figure 70

Metz’s synthesis of brosimacutin L (152).

Figure 71

Baran’s synthesis of (+)-phorbol (156).

Figure 72

Li and coworker’s synthesis of rubriflordilactone B (159).

Figure 73

Nitrosation of styrenyl alkenes from Okamoto et al.

Figure 74

2^nd generation conditions for hydronitrosation from Okamoto et al.

Figure 75

Kato and Mukaiyama’s hydronitrosation of α,β-unsaturated carboxamides with substrate scope.

Figure 76

Kato and Mukaiyama’s hydronitrosation of α,β-unsaturated esters.

Figure 77

Mukaiyama’s and Kato’s synthesis of nitroso alkanes from alkenes.

Figure 78

Oximation of p-styrenes from Sugamoto et al.

Figure 79

Oximation of α,β-unsaturated esters, ketones and aldehydes from Sugamoto et al.

Figure 80

Oximation of α,β,γ,δ-unsaturated carbonyls from Sugamoto et al.

Figure 81

Boger’s nitrosation of unactivated alkenes.

Figure 82

Beller’s oximation of aryl substituted alkenes.

Figure 83

Lahiri et al.’s method for oximation of styrenes.

Figure 84

(a) Carreira’s cobalt catalyzed hydrohydrazination procedure (b) with selected substrates (c) and the cobalt precatalyst (168).

Figure 85

(a) Carreira’s manganese catalyzed hydrohydrazination procedure (b) with selected substrates. The conditions for the [Co] reactions are those shown in Figure 84.

Figure 86

(a) Carreira’s cobalt catalyzed hydrohydrazination procedure for dienes and enynes (b) with selected diene substrates (c) with selected enyne substrates (d) the cobalt precatalyst (169) and TMDSO.

Figure 87

Yamada and coworkers’ asymmetric hydrohydrazination.

Figure 88

Bunker et al.’s synthesis of propellamine.

Figure 89

(a) Cui and coworkers’ radical addition into diazo compounds (b) with selected examples of olefin and diazo variation, and intramolecular cyclization.

Figure 90

(a) Carreira’s cobalt catalyzed hydrohydrazidation procedure for alkenes (b) with selected substrates (c) the cobalt ligand (175) and TMDSO.

Figure 91

Boger’s method for hydroazidation using Fe₂ox₃/NaBH₄ with selected substrate scope.

Figure 92

(a) Shigehisa et al.’s cobalt catalyzed intramolecular hydroamination (b) with cobalt (II) precatalyst, oxidant, (c) selected examples of scope and (d) examples of heteroatom-selectivity reversal.

Figure 93

(a) Baran’s Fe(acac)₃ catalyzed hydroamination of olefins (b) with selected substrate scope.

Figure 94

Alternative conditions for hydroamination. ^aSee ref . ^bSee ref .

Figure 95

Boger’s hydroazidation of anhydrovinblastine (1) to azidovinblastine (186) and azidoleurosidine (187).

Figure 96

Van der Donk’s reductive cyclization of dienes catalyzed by vitamin B₁₂.

Figure 97

Norton’s reductive cyclization of dienes using CpCr(CO)₃H.

Figure 98

Norton’s demonstration of a polyene cyclization to obtain a decalin 197 initiated by chromium and vanadium hydrides.

Figure 99

Norton’s comparison of three kinds of metal hydrides in the reductive cyclization of diene 194.

Figure 100

Selected scope of Norton’s vanadium catalyzed reductive cyclization of enol ethers with substituted alkenes.

Figure 101

Van der Donk’s procedure for styrene dimerization.

Figure 102

(a) Carreira’s method for hydrocyanation of alkenes (b) with selected examples and (c) cobalt precatalysts.

Figure 103

Boger’s method for hydrocyanation of alkenes.

Figure 104

Radical addition into a polarized unsaturated electrophile.

Figure 105

Baran’s first-generation conjugate addition.

Figure 106

Heteroatom-bearing olefins in Baran’s second-generation conjugate addition.

Figure 107

Comparison of PhSiH₃ and Ph(i-PrO)SiH₂ in Baran’s conjugate addition.

Figure 108

Phenol synthesis from Cui and coworkers.

Figure 109

Hydromethylation via radical addition / functional-group ablation.

Figure 110

Hydromethylation reaction conditions and representative examples.

Figure 111

Radical conjugate addition-elimination to give β-substituted styrenes.

Figure 112

Cui’s Fe(acac)₃ catalyzed hydrostyrenylation protocol.

Figure 113

Gui et al.’s synthesis of oxindoles via radical cyclization onto an aryl ring.

Figure 114

Synthesis of chiral 8-aryl menthols via a HAT initiated Smiles-Truce rearrangement.

Figure 115

Cobalt-catalyzed reductive coupling with aldehydes.

Figure 116

Cobalt-catalyzed reductive carboxylation of acrylonitirles.

Figure 117

Syn-diastereoselective cobalt-catalyzed aldol cycloreduction.

Figure 118

Anti-diastereoselective cobalt-catalyzed Michael cycloreduction and formal [2+2].

Figure 119

Cobalt-catalyzed direct synthesis of oxime ethers from alkenes.

Figure 120

Carreira’s application of Baran’s conjugate addition reaction during Carreira’s work on hippolachnin A (245).

Figure 121

Pronin’s synthesis of emindole SB (251).

Figure 122

Radical hydrofluorination of olefins.

Figure 123

Boger’s iron-mediated radical hydrofluorination. (a) Typical reaction conditions employed. (b) selected examples of substrate scope.

Figure 124

Cobalt-catalyzed radical hydrofluorination. (a) Typical reaction conditions employed. (b) Selected examples of substrate scope. (c) Catalyst and hydride source.

Figure 125

(a) Carreira’s hydrochlorination reaction. (b) Selected substrates. (c) Cobalt(III) ligand (175) and cobalt salen complex (21).

Figure 126

Boger’s hydrochlorination method.

Figure 127

Ishibashi and coworkers’ halocyclization reaction.

Figure 128

Herzon’s method for hydrobromination and hydroiodination of alkenes.

Figure 129

Iron-catalyzed hydrothiolation of styrenes.

Figure 130

Cobalt-catalyzed hydrothiolation of alkenes.

Figure 131

An example of cobalt-mediated hydroselenation of alkenes.

Figure 132

Synthesis of analogs containing C-X bonds.

Figure 133

Hydrogenation versus isomerization pathways for a simple alkene.

Figure 134

α,β-unsaturated carbonyl compounds which undergo reduction rather than hydroformylation.

Figure 135

Wender’s mechanistic proposal for the radical reduction of an aldehyde.

Figure 136

Partial reduction of polyaromatic compounds under the action of (CO)₄Co-H.

Figure 137

A reduced side product was observed by Mukaiyama’s team during development of their hydration reaction.

Figure 138

Magnus’ conjugate reduction method with substrate scope.

Figure 139

Halpern’s examination of [Co]-H reduction of polyaromatics prompted him to posit transition metal HAT as a mechanistic pathway.

Figure 140

The Shenvi group developed a HAT hydrogenation method when they could not achieve chemo- and stereoselective reduction to the thermodynamic product 291 with any known method.

Figure 141

HAT bypasses high energy intermediates in dissolving metal pathway.

Figure 142

Selected examples of Shenvi’s HAT reduction method.

Figure 143

Example of divergent stereocontrol.

Figure 144

Herzon’s synthesis of (−)-acutumine (314).

Figure 145

Herzon showed that HAT bypasses dehalogenation pathways.

Figure 146

Herzon’s method for alkyl halide synthesis by reduction of vinyl halides.

Figure 147

Kano’s hydrogenation of styrene.

Figure 148

Thomas’ alkene reduction method.

Figure 149

Some structural motifs accessible through TM HAT isomerization.

Figure 150

Van der Donk and coworkers demonstrated the cycloisomerization of dienes with vitamin B₁₂.

Figure 151

Several competing pathways are available to a diene 320 reacting with a metal hydride via TM HAT.

Figure 152

Norton observed isomerization (330) in the reaction of diene 327 with CpCr(CO)₃H.

Figure 153

Thorpe-Ingold effect favors reductive cyclization of 194 under [Cr] catalysis.

Figure 154

Isomerization product 330 is favored by a putative [Co]-H.

Figure 155

A second example of distinct behavior of a chromium hydride versus a cobalt hydride.

Figure 156

Examples of isomerization and cycloisomerization from Norton and coworkers.

Figure 157

Selected examples of HAT isomerization and cycloisomerization from Norton and coworkers.

Figure 158

The Co(Salen^tBu,tBu)Cl precatalyst employed in Shenvi’s HAT isomerization reaction.

Figure 159

Selected substrate scope of Shenvi’s HAT isomerization reaction.

Figure 160

Carreira’s synthesis of hippolachnin A (245)

Figure 161

Bosch et al. synthesis of serratezomine E (369).

Figure 162

Mukai et al. observed sulfonyl reduction under Co(acac)₂ reduction conditions.

Figure 163

Lu et al.’s synthesis of (+)-7,20-diisocanoadociane (374).

Figure 164

Reductive-oxidative cycle towards alkene hydrofunctionalization.

Figure 165

Acidities and bond strengths of metal hydrides.

Figure 166

Interaction between a metal hydride and an alkene.

Figure 167

Competition between cage escape and radical collapse towards hydrogenation/hydroformylation.

Figure 168

Evidence for the formation of a radical pair during the hydrogenation of alkenes.

Figure 169

Proposal for the reduction of polycyclic aromatic hydrocarbons.

Figure 170

Orchin’s explanation for the origin of the inverse kinetic isotope effect.

Figure 171

Reduction of a carbon-centered trityl radical.

Figure 172

Competition between reduction and rearrangement of substrate 396.

Figure 173

Reactivity of alkenes depending on their steric and electronic properties.

Figure 174

Competition between direct reduction, isomerization and radical cyclization.

Figure 175

Hydrogen atom transfer towards a trityl radical under catalytic conditions.

Figure 176

Tautomerization of metal complexes with redox active ligands.

Figure 177

Use of an alcohol as reductant in the hydration of alkenes.

Figure 178

Detection of a metal hydride during the hydration of styrenes.

Figure 179

Detection of pentavalent silane/alcohol species.

Figure 180

Early proposal for the hydration of alkenes in which H and C are counted as cations and electrons are assigned to Co as Co^I.

Figure 181

Peculiarities of cobalt complexes.

Figure 182

Mechanistic tests for the hydration of anhydrovinblastine.

Figure 183

Proposed catalytic cycle for the peroxidation of alkenes.

Figure 184

Regioselective peroxidation of α,β,γ,δ-unsaturated alkenes.

Figure 185

Mechanistic tests using a manganese catalyst.

Figure 186

Deuterium incorporation in the reduction of α,β-unsaturated ketones.

Figure 187

Catalytic hydrogenation of unactivated alkenes via HAT.

Figure 188

Diastereoselective radical addition to α,β-unsaturated substrates.

Figure 189

Mechanistic tests for the catalytic hydrogenation of alkenes.

Figure 190

Deuterium incorporation in the reduction of unactivated alkenes.

Figure 191

Deuterium incorporation in the reduction of haloalkenes.

Figure 192

Competition experiment between PhSiH₃ and PhSiD₃.

Figure 193

Initiation steps for the radical polymerization of alkenes.

Figure 194

Isomerization of alkenes via reverse HAT.

Figure 195

Proposed catalytic cycle for the reductive olefin coupling.

Figure 196

Radical trap experiments in the conjugate addition.

Figure 197

Proposed catalytic cycle for the radical addition to β-nitroalkenes.

Figure 198

Proposed catalytic cycle for the hydromethylation of alkenes.

Figure 199

Proposed catalytic cycle for the hydrohydrazination and hydroazidation of alkenes.

Figure 200

Mechanistic tests for the hydrohydrazination reaction.

Figure 201

Further mechanistic details for the hydrohydrazination and hydroazidation of alkenes.

Figure 202

Proposed catalytic cycle for the nitrosation of styrenes.

Figure 203

Proposed catalytic cycle for the hydroamination of alkenes.

Figure 204

Mechanistic tests for the hydrochlorination of alkenes.

Figure 205

Mechanistic tests for the hydrosulfurination of alkenes.

Figure 206

Hydrothiolation of iron complex 501.

Figure 207

Proposed catalytic cycle for the hydrofluorination of alkenes.

Figure 208

Mechanistic tests for the iron-mediated hydrofluorination of alkenes.

Figure 209

Proposed catalytic cycle for the reductive cycloaddition to an aldehyde.

Figure 210

Mechanistic tests for the reductive cycloaddition to an aldehyde.

Figure 211

Mechanistic tests for the hydroalkoxylation of alkenes.