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Nitrogen Centered Radical Ligands

2015. 7. 4.
Nagashima Nozomu

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1. Introduction

3Aminyl radical1)
2)

D. E. Wiliams, JACS, 1966, 88, 5665
Y. Teki et al. JOC, 2000, 65, 7889

 Sterically protected aminyl radicals were reported and play an important rolein chemical processes.
 Resonance effect by electron donating group stabilizes N radical.

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Preparation and Reactivity of N radical Reactive aminyl radicals are also formed thermally or photolytically byhomolytic bond cleavage or by N oxidation.
 These N radicals are high reactive and short-lived intermediate
L. Stella et al. ACIE, 1983, 22, 337

Metal coordinated N radicals should show New Reactivity

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Metal Coordinated N radical
 Advantage
1. Sometimes becomes Catalysis.
2. Bioinspired Reactivity.
3. N-Radical is more reactive than O-radical.

Arch. Biochem. Biophys. 2005, 433, 227

 N radical is really formed?

 Electron is sometimes localized at the metal.
→ Metal Radicalcan not react as N radical.
 Metal should stabilize N radical by electron transfer.

Some analyses (EPR, DFT, X-ray analysis etc..) are needed.

6Electron Paramagnetic Resonance (EPR)
 Method for studying materials with unpaired electrons.
 EPR is like NMR for electron spin.

 g valueFree Radical: g = 2.0023
Organic Radical: g ≒ 2Organometallic Radical 0<g<6

 g value is parameter for evaluating where radical is localized.

7Electron Paramagnetic Resonance (EPR)
 Method for studying materials with unpaired electrons.
 EPR is like NMR for electron spin.

 g valueFree Radical: g = 2.0023
Organic Radical: g ≒ 2Organometallic Radical 0<g<6

 g value is parameter for evaluating where radical is localized.
http://www.msl.titech.ac.jp/~hosono//facilities/ESR.htm

8Examples of EPR Spectra It is difficult to evaluate EPR spectrum because each peak overlaps.
 Method: Compare calculated spectra and experimental data.
JACS, 133, 12264
Supporting information

92. Aminyl Radical Observation

10First Example of Synthesis of Stable Aminyl Radical Aminyl radical compound was synthesized through deprotonation and oxidation.
 d8-Rh(I) is suitable for stabilizing N radical.
 Trop moiety contributes as Shield of N radical.

 Aminyl radical is really formed??

H. Grutzmacher et al. Science, 2005, 307, 235.

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Aminyl radical or Amido? (1) Almost trigonal planar around N1 suggests the oxidation mainlyoccurs at N1 atom.
 Shortening of Rh-N1 implies aminyl radical complex.
H. Grutzmacher et al. Science, 2005, 307, 235.

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Aminyl radical or Amido? (1) Almost trigonal planar around N1 suggests the oxidation mainly
occurs at N1 atom.
 Shortening of Rh-N1 implies aminyl radical complex.
H. Grutzmacher et al. Science, 2005, 307, 235.

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Aminyl radical or Amido? (2) EPR spectrum

JACS, 2001, 123, 5818.

 g value is near to 2.00 → Radical is also delocalized on N?
 DFT calculations

 More than half of radicals are on N1
H. Grutzmacher et al. Science, 2005, 307, 235.

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Reactivity of Aminyl Radical Aminyl radical reacts with Sn-H bond and S-H bond.
 This aminyl radical is nucleophilic radical because thiyl radical is known
as electrophilic radical.
H. Grutzmacher et al. Science, 2005, 307, 235.

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Observation of 16 electron Rh --- N radical This Rh catalyst also includes Trop substituents which stabilize aminyl radical.

Radical is delocalized on N.
H. Grutzmacher et al. JACS, 2006, 128, 6578.

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Oxidation Reaction by Ir Complex

1. No reaction with only BQ, SQ, andHQ22. No reaction without KOtBu
3. Violet SQ radical was detected in all
the reactions.

Compounds which have affinity to metal can react with aminyl radical.
H. Grutzmacher et al. ACIE, 2007, 46, 3567.

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Substrate Scope Aliphatic alcohols are also dehydrogenated.
 Primary alcohols are converted into aldehydes
H. Grutzmacher et al. ACIE, 2007, 46, 3567.

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Other reactions by N radicalGrutzmacher’s method

Reaction is limited to only dehyrdrogenation.

Potentials of other reactions

Amination would also proceed by introducing N as SM.

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Other routes to get Ligand-Centered Radical
Aminyl Radical

See appendix 2.

Nitrene Radical

Radical density on N would be higher

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3. Nitrene Radical

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Benzylic C-H amination

 Reaction Mechanism

 Electron Transfer stabilizes nitrene
and promotes nitrene formation.
(3a to 4a) Only Troc-Azide and Ts-Azide
proceeded C-H amination reaction.
X. P. Zhang et al. Organometallics, 2010, 29, 389
B. de Bruin et al. JACS, 2011, 133, 12264.

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The Formation of Nitrene Radical
Singlet Nitrene 4a

Triplet Nitrene 4a

 Electron transfer from d orbital of Co to p orbital of N makes N radical.
(Singlet Nitrene) d orbital of Co and sp2 orbital of N makes covalent bond
(Triplet Nitrene)
B. de Bruin et al. Dalton Trans., 2011, 40, 5697.

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Radical is Really Generated on N?
 EPR spectrum shows N radical generation.

 Intermediate DFT calculation

 Unpaired electron mainly resides on thenitrene nitrogen.
B.de Bruin et al. JACS, 2011, 133, 12264.

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Reaction Profile by Substituents on Catalyst

DH for the reaction of methyl azidoformate with ethyl benzene.

 Mild electron-withdrawing substituent is best
Electron withdrawing group weakens the Na-Nb bond of the azide.
TS1 also involves oxidation of metal center by electron transfer.
B.de Bruin et al. JACS, 2011, 133, 12264.

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Important Step in Reaction

 Can this reaction proceed more efficiently by changing catalyst design?

B.de Bruin et al. JACS, 2011, 133, 12264.

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How promote the Co-N Bond Formation?

 The bond formation between N and Co is promoted through hydrogen bonding.
 Catalytic reactions with this catalyst are much faster than those with (TPP)Co.
.
B. de Bruin et al. JACS, 2011, 133, 12264.

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Intramolecular C-H Amination (1) Example to promote reaction by using Hydrogen Bonding Sulfamoyl azides are synthesizedfrom secondary amine.
 The reaction proceeded not onlywith benzylic position but alsowith aliphatic position.
X. P. Zhang et al. ACIE, 2010, 49, 10192

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Intramolecular C-H Amination (2) Hydrogen Bonding promotes the formation of Co-N Bond
X. P. Zhang et al. ACIE, 2010, 49, 10192

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Intramolecular C-H Amination ()1.3- diamination through C-H amination by using Nitrene Radical proceeds.

X. P. Zhang et al. ACIE, 2010, 49, 10192

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Bioinspired radical reaction
 P450 Cytochrome P450 makes reactive oxygen.
 Fe (IV) shows high-spin ground state.
 P450 also activates aliphatic C-H Bond.

J. H. Dawson et al. Chem. Rev. 1996, 96, 2841.

Nitrene radical which conjugates with Fe(IV)also shows high reactivity?

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Bioinspired Nitrene radical reaction (1) Catalyst Design

 Reaction

 Azide cyclization proceeds to make 5 membered ring.
T. A. Betley et al. Science, 2013, 340, 591.
JACS, 2011, 133, 4917.

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Bioinspired Nitrene radical reaction (2) Reaction

 Reaction proceeds to make 5 membered ring.
 If there is allyl C-H near N radical, it reacts with allyl C-H Bond.

T. A. Betley et al. Science, 2013, 340, 591.

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Bioinspired Nitrene radical reaction (3)123

1. Stereochemistry is retained in this cyclization. → Ad inhibits racemization.
2. C-H breakage is big rate determining step. → Radical Stepwise Mechanism
3. Radical is not generated. → Concerted Direct C-H Insertion

 Benzylic substrate → Stepwise Mechanism Stronger C-H substrate → Direct C-H Insertion
T. A. Betley et al. Science, 2013, 340, 591.

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Another strategy to make Nitrene Radical
StrategyMechanism

J. I. van der Vlugt et al. JACS, 2014, 136, 11574.

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Another strategy to make Nitrene Radical

 Mechanism

J. I. van der Vlugt et al. JACS, 2014, 136, 11574.

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4. Summary and Future of N radical

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Reactivity of N Radicals
 Intramolecular Reaction

T. A. Betley et al. Science, 2013, 340, 591.

 Intermolecular Dehydrogenation

X. P. Zhang et al. ACIE, 2010, 49, 10192

Are there more reactive N radicals?
H. Grutzmacher et al. ACIE, 2007, 46, 3567.

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Bis-Nitrene Complex (N Radical Future ) Stronger Oxidizing nature of iminoiodane promotes bis-nitrene species.
 This nitrene radical species would show higher reactivity
B. de Bruin et al. JACS, 2015, 137, 5468.

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More Reactive N Radicals (N Radical Future )B. de Bruin et al. JACS, 2015, 137, 5468.

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Appendix

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Appendix 1 (Isotropy and Anisotropy in EPR spectra)

Organic Radical: isotropy
Metallic Radical: anisotropy

シュライバー アトキンス
無機化学 上 第四版

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Appendix 2A (Aminyl Radical Generation by using Leaving Group)

T. H. Warren et al., ACIE, 2010, 49, 904.

T. H. Warren et al., ACIE, 2010, 49, 8850.

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Appendix 2B (C-H Amination through Copper Amides)

 Aminyl radical promotes benzyl and also cyclohexane C-H bond cleavage.
T. H. Warren et al., ACIE, 2010, 49, 8850.

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Appendix 2C (C-H Amination through Copper Amides)

 Proposed Mechanism

Benzyl C-H Bond is activated by Aminyl Radical.
T. H. Warren et al., ACIE, 2010, 49, 8850.

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Appendix 3 (First Example of Nitrene Radical)

 Nitrene moiety gets electron from Metal and made radical complex
 Nitrene is stabilized by electron donation from metal.

T. H. Warren et al. JACS, 2005, 127, 11248

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Appendix 4 (Computational Study for substrate Scope (Slide 20))c, d: High Na-Nb bond energy disturbs reaction. (TS1)b: Electron withdrawing PhSO2 group decreases radical reactivity. (TS2)
B. de Bruin et al. JACS, 2011, 133, 12264.

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Appendix 5A (EPR spectra with hydrogen bond)Figure . Left: Disappearance of signals of 1P2 with simultaneous appearanceof new signals characteristic for 3P2troc. Right: Spectrum around g = 2.00
showing the cobalt and nitrogen hyperfine structure of species 3P2troc inbenzene-d6.

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Appendix 5B (EPR spectra with hydrogen bond) Spin Density on N radical evaluated by hyperfine coupling By using hydrogen bonding, radical density on N increases.
B. de Bruin et al. JACS, 2011, 133, 12264.

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Appendix 6 (Nitridyl Radical)

Nitridyl Radical
K. Wieghardt et al. JACS, 1999, 121, 4859.

Nitridyl Radical
J. I. van der Vlugt et al. ACIE, 2015, 54, 7055.