Iron-Oxo and Iron-Nitrido CompoundsRafael Navratil
Baran Group Meeting
10/31/20
Historical timeline
Acc. Chem. Res. 2007, 40, 522–531Nat. Comm. 2012, 720
J. Biol. Inorg. Chem. 2017, 185-207Chem. Rev. 2018, 2491-2553
1981 First synthetic porphyrin iron-oxo complex
2007 Highly reactive Fe(PDP) catalyst
2015 High-spin synthetic non-heme iron(IV)-oxo complex TQA
L. Que, A. Borovik, C. White, E. Solomon, K. Karlin (all USA), M. Costas (Spain), W. Nam (Korea), F. Meyer (Germany), F. Neese (Germany), S. de Visser (UK), S. Shaik (Israel)and many others....
Synthetic modelsBiological systems
N
N
N
N
OHO
Fe
OHO
SCys
O
Heme enzymes
Mononuclear non-heme enzymes (NHFe)
N
N
N
NFe
Cl
O
MesMes
Mes
Mes
Compound I
2006 Iron(VI)-nitrido complex
TauD-J
SyrB2
N
L = MeCN, OTf, Cl,...
[(TMC)Fe(O)(L)]2+/+
Fe
N
NN N
O
Mononuclear non-heme models
2+
Me
[(TQA)Fe(O)(MeCN)]2+
Fe
O
O
OH
His
O
His
Asp
Rieske dioxygenase
V
IV
IV
IV
2+
FeO
OAc
V
N
N
N
N
[(R,R-PDP)Fe(O)(OAc)]2+
1955 Discovery of an enzyme isolated from liver, later assigned as P450
Fe
O
HisAsp
HisIVO
O
-OOC
Fe
O
HisCl
HisIVO
O
-OOC
2007 (TAML)Fe(V)-oxo complex
2003 First X-ray of synthetic non-heme iron(IV)-oxo complex
2011 First evidence of Fe(V)-oxo-hydroxy intermediate
2000 Synthesis and X-ray of the first iron-oxo complex
2010 Compound I intermediate trapped and characterized
2016 Functional synthetic model of halogenase enzymes
2003 First characterization of non-heme iron-oxo enzyme TauD-J
Most active research groups:
Important reviews and books:
JACS 2018, 13988-14009ACS Catal. 2020, 12239-12255
Coord. Chem. Rev. 2013, 414-428
1985 First X-ray of P450 enzyme
1989 Raman spectra of porphyrin iron(V)-nitride
"Biomimetic High-Valent Mononuclear Nonheme Iron-Oxo Chemistry" by Klein & Quein Encyclopedia of Inorganic and Bioinorganic Chemistry, 2016, Wiley
= Iron-Oxo = Iron-Nitrido
Spin States in Biochemistry and Inorganic Chemistry, Swart & Costas (Eds.), 2016, Wiley
2+/+
N FeN N
N
O
L
IV
quintettriplet
Tetragonal geometry
O
Fe
* (dz2)
* (dxz, dyz)
nb (dxy)
* (dx2-y2)
singlet
O
Fe
* (dxz,dyz)
nb (dxy,dx2-y2)
IV
IV
S = 0 S = 1
spin state:
multiplicity: S = 2
Trigonal geometry
Iron-Oxo and Iron-Nitrido CompoundsRafael Navratil
Baran Group Meeting10/31/20
Electronic structure of iron(IV)-oxo
z
xy
Two state reactivity concept
Methods of characterization
Electron paramagnetic resonance (EPR)
Mössbauer spectroscopy - 57Fe enriched samples (100mg for 57Fe $800), absorption
of -irradiation, Mössbauer parameters are directly related to the electron density at
the iron (probe of the oxidation state) and electronic spin ground state and molecular
geometry
E
Vibrational spectroscopy (resonance Raman, FT-IR) with 18O labeling, determines the
presence and frequency of Fe=O vibration (~780-860 cm-1)
UV/vis - Soret band (~400-450 nm, - * transition in porphyrins), d-d transition at around700-900 nm in iron(IV)-oxo complexes
Nuclear resonance vibrational spectroscopy (NRVS) - detection of 57Fe vibration modes
which helps to assign the coordination sphere even in complex samples
* (dz2)E
Extended X-ray absorption fine structure (EXAFS)
Electrospray ionization mass spectrometry (ESI-MS), ideally coupled with ion spectro-scopy
* (dz2)
O
* (dx2-y2)
* (dxz)
O
* (dyz)
nb (dxy)
Theoretical calculations (DFT, ab initio) - needed for interpretation of spectroscopic data
first report JACS 1976, 859-861
Magnetic circular dichroism (MCD)
Reactivity of iron-oxo compounds
X-ray
review: J. Biol. Inorg. Chem. 2017, 185-207
Hydrogen atom transfer (HAT) from aliphatic C-H bonds
triplet
quintet
O
Fe
triplet (S = 1) and quintet (S = 2) spin statesin iron-oxos are typically close in energies
+ R H
O
Fe
H
R
O
Fe
H
R
OH
Fe+ R
E~120°
~180°
* (dxz/dyz)
* (dz2)
* path
RH
RH
* path
originates from studies on the gas phase reaction FeO+ + H2 Fe+ + H2O
reactions involving transition metals often proceed through multiple intercrossingspin states
Acc. Chem. Res. 2000, 139-145
O
FeIV+ R H
OH
FeIII+ R
oxygenrebound O
FeII
H RHAT O
FeII
H R
+
caged radical pair heteroatomrebound
R Cl/Bre- transfer
OH
FeII+ R
cage escape
R O2
R OOH
desaturation
Acc. Chem. Res. 2018, 107-117
Iron-Oxo and Iron-Nitrido CompoundsRafael Navratil
Baran Group Meeting
10/31/20
Overview of other reactions catalyzed by Cytochrome P450
FeN
NN
N
L
O
IV
H
R'
H
R
Alkene epoxidation
FeN
NN
N
L
O
IV
H
R H
R'
FeN
NN
N
L
III
O HH
R R'
SET
FeN
NN
N
L
O
IV
H
R H
R'
1,2-H-shiftR
O
R'
HH
+
Chem. Rev. 2012, 1681-1709
benzo[a]pyrene
highly carcinogenicubiquitous in car exhausts, cigarette smoke, grilled meat
O
OH
OH
DNA DNA adductswith guanine
Aromatic hydroxylation
FeN
NN
N
L
O
IVFe
N
NN
N
L
O
IV
H H
H
OH
H
OH
H
NIH shift
O
HH
OH
Dealkylation of heteroatoms
FeN
NN
N
L
O
IV
RX
Crit. Rev. Biochem. Mol. Biol. 1990, 97-153
HR'
X = O,S,N
HAT
FeN
NN
N
L
OH
IV
RX H
HR'
FeN
NN
N
L
O
IV RX H
HR'
SETET
N
NN
N
O
O
Me
Me
Me
caffeine
N
NN
N
O
O
Me
H
MeN
NN
N
O
O
Me
Me
HN
NN
N
O
O
H
Me
Me
paraxanthine(84%)
theobromine(12%)
theophylline(4%)
+ +
rebound
RX
HR'
OH
H R'
OR
XH +
Biochemistry 1972, 1961-1966
Science 1967, 1524-1530
alternative SET mechanism also proposed
N
N
N
NFe
L
O
MesMes
Mes
Mes
JACS 1981, 2884-2886
N
N
N
NFe MesMes
Mes
Mes
Majority of Cpd I synthetic analogs
are 103-106-x less reactive than
native P450 enzymes
L = MeOH
mCPBA
DCM, MeOH-78°C
Cl
Ar = 4-(Me3N)C6H4
rate of benzylic oxidationcomparable to that of P450 enzymes
N
N
N
NFe
OH2
O
ArAr
Ar
ArJACS 2009, 9640–9641
Highly reactive P450 model compound
First synthetic heme iron-oxo complex
Chem. Rev. 2018,2491-2553
Chem. Res. Toxicol.
2016, 1325-1334
FeN
NN
N
L
O
IV
H
FeN
NN
N
L
O
IVH
+
Iron-Oxo and Iron-Nitrido CompoundsRafael Navratil
Baran Group Meeting
10/31/20
Non-heme iron enzymes (NHFe)
Taurine Dioxygenase (TauD)
iron coordinated by as few as two proteins residues, most commonly two His and oneAsp/Glu protein residues (so called "facial triad"), water molecules occupy 3 remainingcoordination sites and are displaced upon substrate and O2 binding
more difficult to study than heme enzymes because of lack of intense spectral featuresin comparison with porphyrins
broad scope of oxidation reaction (halogenation, hydroxylation, ring closure, desatu-ration, aromatic ring cleavage) in many biological processes, (phenylalaninemetabolism, neurotransmitters production, antibiotic biosynthesis, DNA repair,metabolism of toxins)
References:
the reactive intermediate in the catalytic cycles is a high spin (S = 2) iron(IV)-oxo species
1) -Ketoglutarate-dependent ( -KG) oxygenases
Fe
O
HisAsp/Cl
HisIV
Syringomycin Biosynthesis enzyme 2 (SyrB2)
Fe
HisAsp/Cl
His
O
O II
O
-OOCR H
Fe
HisAsp/Cl
His
H2O
H2O II
KG R+ H
OH2
O2
Fe
HisAsp/Cl
His
O
O IV
O
-OOCO O
R H
CO2
R H
O
O
-OOC
Fe
OH
HisAsp/Cl
HisIIIO
O
-OOCHAT
R
R OH/Cl
Rebound
Biochemistry 2005, 8138-8147
+ 3H2O
- 3H2O
General catalytic cycle showcased for -KG enzymes
-ketoglutarate is sacrificially oxidized, O2 is a four-electron oxidant, substrate hydro-xylation requires only two electrons
first spectroscopically characterized nonheme iron(IV)-oxo intermediate
Nature 2013, 320-323
H2NSO3
-
taurine
H2NSO3
-
SH2N
O
SyrB1
OH
SH2N
O
SyrB1
OHCl Nature 2013, 320-323
Acc. Chem. Res. 2007, 484-492
Acc. Chem. Res. 2013, 2725-2739intermediate J (TauD-J)
Biochemistry 2003, 7497-7508
catalyse mostly hydroxylation and halogenation
-methyl chlorination of L-threonine in syringomycin biosynthesis
chlorine rebound instead of oxygen, selectivity controlled by substrate approach
JACS 2004, 8108-8109JACS 2004, 1022-1023
Several enzyme families:
SyrB2
O2, -KG, Cl-
-succinate,
-CO2
high spin (S = 2) pentacoordinate complex,
v(Fe=O) = 821 cm-1, d(Fe-O) = 1.62 A
Fe
O
HisAsp
HisIVO
O
-OOC
review on Nature's halogenation catalysts: Chem. Rev. 2006, 3364-3378
An example of halogenase enzyme in biosynthesis of barbamide
JACS 2006, 3900-3901
Me
Me
H2N
O
S
BarA
BarB1, BarB2
O2, -KG, Cl-
-succinate,
-CO2
Me
CCl3
H2N
O
S
BarA
N OMe
Ph
N S
Me
O
Me
CCl3
bromination also possible (JACS 2007, 13408-13409)
Acc. Chem. Res. 2007, 475-483
PNAS 2009, 17723-17728
J. Biol. Inorg. Chem. 2017, 185-207
sulfite metabolism in bacteria
Nat. Prod. Rep. 2020, 1065-1079
OH
H2N
O+ SO3
2-
ACS Catal. 2013, 2362-2370Nat. Prod. Rep. 2018, 622-632
2) Biopterin-dependent aromatic amino acid hydroxylases
naphtalenedioxygenase
O2, NADH
OH
OH
Iron-Oxo and Iron-Nitrido CompoundsRafael Navratil
Baran Group Meeting
10/31/20
3) Rieske dioxygenases
cis-dihydroxylation of aromatic compounds
first identified as enzymes involved in arene degradation
Fe
OH2
N
His
O
OAsp
II
electrons from NADH are transfered first to [2Fe-2S] cluster,which donates them to the NHFe center in the catalytic cycle
HN
HisO
Asp-O
NNH
His
Fe
S
S
Fe
Cys
CysHis
III
IInon-heme iron center
Rieske center
Proposed catalytic cycle
Science 2003, 1039-1042
Fe
O
O
OH2His II
Asp
His
Fe
O
OO
OHHis III
Asp
His
O2e-, H+
-H2O
rearrangement
Fe
O
OO
OHHis V
Asp
His
Fe
O
OO
OHis IV
Asp
His
Fe
O
OO
OHis
Asp
His
Fe
O
OO
OHHis
Asp
His
IV
evidence of enzymaticFe(V) intermediates
is lacking
III
Fe
O
O
OH2His II
Asp
His
OH2
-H2O
OH
OH
e-, H+
H2O
Naph
no direct evidence for Fe(V) intermediate
X-ray study: Structure 1998, 571
Prolyl 4-hydroxylase
Naph
Crit. Rev. Biochem. Mol. Biol. 2010, 106-124
catalyzes the single most prevalent posttranslational modification in humans,hydroxylation of proline, which is a major component of collagen (the most abundantprotein in animals and the major component of connective tissue)
N
PH4
O2, -KG
-succinate,-CO2
O N O
HO
N
NN
N
NH2
DNA
Me
N
NN
N
NH2
DNA
OH
N
NN
N
NH2
DNA
O
HH+
AlkBO2, -KG
-succinate,-CO2
Nature 2002, 174-178
AlkB
enzyme isolated from E. coli that repaires alkylated nucleobases in DNA and RNA
analogous enzymes also found in humans (ABH2 and ABH3)
Chem. Rev. 1996, 2659-2756; Biochemistry 2006, 11030-11037
HO
COOH
NH2
NH
HN
HO
NH
N
O
NH2
tetrahydropterin
O2FeII
NH
HN
N
N
O
NH2
O
OFeIII
NH
HN
N
N
O
NH2
O
H
Fe
O
IV+
tyrosine hydroxylase(TyrH)
HO
COOH
NH2 N
H
R RR
HO NH2
COOHphenylalanine hydroxylase(PheH)
serotonin precursormelatonin precursor
tryptophan hydroxylase(TrpH)
FeN
N N
NN
2+
O
H
NH
NH2 O
HO2C
NHO
HHO2C
SH IPNS
O2H
N
NH2 O
HO2C
N
S
CO2H
H
O
Isopenicilin N
4) Isopenicillin-N-synthase (IPNS)
found in fungi and bacteria
Synthetic non-heme iron(IV)-oxo complexes
Iron-Oxo and Iron-Nitrido CompoundsRafael Navratil
Baran Group Meeting10/31/20
[(TMC)FeIV(O)(MeCN)]2+
Science 2003, 1037-1039
Science 2000, 938-941
developed to better understand, to interpret and to model spectroscopic and reactivitydata on natural iron-oxo species and, ultimately, chemists wanted to mimic highreactivity of natural iron-oxo complexes in a flask
[(H3buea)FeIII(O)]2-
sextet spin state S = 5/2
first characterized terminal iron-oxo
so far around 70 synthetic complexes have been made, which enabled to generatea set of spectroscopic data which helps in interpreting data on enzymatic systems
Fe
N
O
NN
N
analogous Fe(IV)-oxo prepared10 years later, see JACS 2010, 12188
NH
O
tBu HNO
HN
O
tBu
tBu-
III
X-Ray
first terminal iron(IV)-oxo
Fe(IV)-oxo proposed in the reaction of [(cyclam-ac)Fe(OTf)2]+ with O3 at -80°C
Inorg. Chem. 2000, 5306-5317
prepared in 90% by reacting Fe(II) complexwith PhIO in MeCN at -40°C
however, most tetragonal iron(IV)-oxo complexes adopt triplet spin state (S = 1),while non-heme enzymatic iron-oxos adopt quintet state (S = 2), only trigonalsynthetic iron(IV)-oxo complexes adopt the same spin state as enzymes
representative examples:
+
N FeN N
N
O
L
[(TMC)FeIV(O)(L)]+
IV
L = OTf, N3, Cl, NCO,NCS, OH
first complex to oxidizecyclohexane
very stable
t1/2 = 60 h at 25°C
JACS 2004, 472-473ANIE 2005, 3690-3694
[(N4Py)FeIV(O)]2+
PNAS 2003, 3665-3670
FeN
N N
NN
2+
O
Me
IV IV
[(TPA)FeIV(O)(MeCN)]2+
LFeII + CH3COOOH in ACN
at -40°C
oxidation of thioanisole
LFeII + PhIO in MeCN, rtexchange of MeCNwith anionic ligand
highly stabilizing hydrogen bonds
[(TMG3tren)FeIV(O)]2+
Fe
N
O
NN
N
Me2N
NMe2
IVMe2N
NMe2NMe2
NMe2
2+
first high spin (S = 2) iron-oxocomplex, albeit in trigonal geometry
ANIE 2009, 3622-3626
t1/2 ~ 30 s at 25°C
comparatively reactive to N4Py complex
Fe
N
N N
NL
2+
O
IV
N
NNMe Me
MeL = MeCN or vacant
triplet spin (S = 1)
t1/2 = 2 min at -40°C
Chem. Sci. 2011, 1039-1045
[(Me3NTB)FeIV(O)(L)]2+
LFeII + mCPBA in ACN at -40°C
very reactive, >1800x more than N4Py andcomparable to TQA (next page)
2+
N FeN N
N
O
N
IV
Me
Nat. Commun. 2012, 720; Coord. Chem. Rev. 2013, 414-428; ANIE 2016, 7632-7649reviews:
Nature 1997, 827-830
t1/2 = 10 h at 25 °C
X-ray, UV/vis, Mössbauer, ESI-MS
triplet spin state (S = 1)
DFT predicted that high spin triplet Fe(IV)-oxo species are better oxidants than thosewith triplet spin state; howewer, synthesis of quintet state complexes is challenging
FeN
N N
NCl/Br
+
O
IV
spectroscopic parameters resemble those of TauD-J
Iron-Oxo and Iron-Nitrido CompoundsRafael Navratil
Baran Group Meeting10/31/20
recent report on preparation and spectroscopy of ligated (TMC, TPA, N4Py, TQA)Fe(III)-oxo complexes in the gas phase, see JACS 2018, 14391-14400
FeN
N N
NN
2+
O
Me
IV
first tetragonal high spin (S = 2) iron(IV)-oxo complex
JACS 2015, 2428-2431
highly reactive, oxidizes alkanes and alkenescyclohexane oxidation rate comparable to that of TauD-J
Synthetic non-heme iron(V)-oxo complexes
nBu4NCl/BrMeCN, -40 °C
so far the best electronic and functional model for TauD-J
JACS 2016, 2484-2487
electronic and functional model for SyrB2 and CytC3halogenases
t1/2 = 15 min at -40°C
t1/2 = 5 min at -40°C
first example for C–H bond halogenation by syntheticiron(IV)-oxo-halide complex
reproduce Mössbauer parameters of halogenases
Iron(III)-oxo complexes
implicated in iron(IV)-oxo chemistry, formal one-electron reduction product
reports scarce - H3buea (previous page and JACS 2014, 17398-17401
N N
N N
O
O
O
O
Fe
O
Science 2007, 835-838
VN N
N N
N
O
O
O
O
Fe
OV
reviews: ANIE 2020, 7332-7349; Acc. Chem. Res. 2015, 2612-2621
JACS 2014, 9524-9527
LFeII + 2-(tBuSO2)PhIO in MeCN at -40°C
relevant to the postulated Rieske dioxygenase intermediate, Fe(V)(O)(OH),Fe(V)-oxo isoelectronic to Fe(IV)-oxo porphyrin radical cation (Cpd I),generally highly reactive, which limits their accesibility and spectroscopic studies
NFe
N S
S
II
N
SiMe2
Me
Me
Me
Activation of O2 by a non-heme FeII complex
relevant to thiolate-ligated iron centers (e.g., IPNS, cystein dioxygenase)
O2
2-MeTHF-135 °C
NFe
N S
S
O
IV
N
SiMe2
Me
Me
Me
NFe
N
S
S
III
N SiMe2
Me
Me
Me
N
Fe
N
S
S
III
NMe2Si
Me
Me
Me
O O
h or warm to -105 °C
2-MeTHF
JACS 2019, 17533-17547 dark greenpale
orange
Fe(IV)-oxo does HAT fromO-H bonds at -135 °C
Tetra-Amido Macrocyclic Ligand (TAML) complexes
shorter d(Fe=O) than that inFe(IV)-oxo complexes
[(TAML)FeV(O)]-
stable at -60 °C stable at 25 °C[(bTAML)FeV(O)]-
[(TQA)FeIV(O)(MeCN)]2+
[(TQA)FeIV(O)(Cl/Br)]+
N N
N N
N
O
O
O
O
Fe
OV
O2N
[(NO2bTAML)FeV(O)]-
H
[(NO2bTAML)FeIII(Cl)]2- (1-2 mol%)
mCPBA (2.5 eq.)
20% aq. K2HPO4 in MeCN
2-12h
OH
OH
H
AcO
OH
OH
OR
O
H
H
OOAc
H
OH
cis 77% (3°:2° 99:1)trans 27% (3°:2° 38:62)
C7C3
51% (C7:C3 4:1)
OH
BzO
O
O
N
MeO
MeO
OOMe
OMe
HO
NHBoc
80% (3°:2° 15:1)
C1
C8
68%
80%
90%
H
OHHO
O
H
38%
51% (3°:2° 4:1)
R = Ac 41%(C1:C8 3:1)
R = TBDPS 65%(C1:C8 100:0)
OL 2017, 746-749
Iron-Oxo and Iron-Nitrido CompoundsRafael Navratil
Baran Group Meeting10/31/20
FeN
N N
NHO
2+
O
V
[(5tips3TPA)FeV(O)(OH)]2+
TIPS TIPS
TIPS
Nat. Comm. 2019, 901
[(5tips3TPA)FeII(OTf)2] (1 mol %)
H2O2 (1.5 eq.), Mg(ClO4).6H2O (2.2 eq.)
MeCN, 0 °C, 1 hR R
2+
Nat. Chem. 2011, 788-793
LFeIIH2O2
LFeIII OOH
NFe
N
NV
N
Me
Me
OOH
H2O
H
OO
Fe
O
H
L
H
III
H
O
Fe
O
L VH2O
water-assisted mechanism
Iron(V)-oxo-hydroxo species
early experiments in 90's suggested that these intermediates might be involvedin stereospecific hydrocarbon hydroxylation, first example:
JACS 1997, 5964-5965
[(TPA)FeII(MeCN)2](ClO4)2H2O2, ACN, rt
OH
OH O
>99% retention of stereochemistry
O
4:1Fe cat.H2O2
+
Fe cat.H2O2
-substitution on Py of the ligand lowers alcohol/ketone selectivity and increasesselectivity towards alkene syn-dihydroxylation (vs. epoxidation)
FeN
N N
NTfO
OTf
NFe
N
NII
N
Me
Me
OTf
OTf
R R
R
R
+
OHO OHFe cat.H2O2
TPA catalyst (R = H)6-Me3TPA catalyst (R = Me)
PyTACN (R = H)6-MePyTACN (R = Me)
MeCN, rt30 min
TPA
PyTACN
II
1.2 : 17 : 11 : 15.5 :1
JACS 2002, 3026-3035; Chem. Eur. J. 2008, 5727-5731
tetradentate ligands with cis coordination sites yield both syn-diols and epoxides,trans configuration favours epoxidation exclusively
OH
Fe
O
L V
low spin iron-hydroperoxidestrong Fe-O and weak O-O
favours O-O cleavage
What is the reactive intermediate? Both H2O2 and H2O are incorporated in products,iron(IV)-oxo complexes are significantly less reactive
iron(V)-oxo-hydroxy intermediate were first postulated in
1999, first evidence was reported in 2011 from cryo-ESI-MS
and 18O labeling experiments
other catalytic systems for iron-catalyzed syn-dihydroxylation:
JACS 2010, 13229-13239
MeO2CCO2Me
OH
R'R
OH
N FeN Cl
ClIII
N
N
Ph OMe
O
Fe(IV)-oxo-hydroxo or Fe(V)-dioxoproposed to be the catalytic species
Oxone (2 eq.), NaHCO3 (6 eq.)
(0.7-3.5 mol %)
Ph OMe
O
MeCN, H2Ort, 5 min
limited to electron poor alkenes
OH
OH
gram scale
(+ epoxidation/overoxidation/C=C clevage)
(diol : epoxide)
92% (11 : 1)
OO92% (40 : 1)
74% (8 : 1)
89% (9 : 1)
90% (-)
37% (-)
N
O
O
68% (44 : 1)
99% (23 : 1)O
94% O
O
77
81%
JACS 2017, 12821-12829
tBu
53% (-)
syn-diol incorporates one O from H2O and one from H2O2
R = H or Me
catalyst design:bulky TIPS groups facilitate product releaseMg salt binds the syn-diol product
shown Fe(V)(OH) intermediate trapped andspectroscopically characterized
Iron-Oxo and Iron-Nitrido CompoundsRafael Navratil
Baran Group Meeting
10/31/20
2+
FeNCMe
NCMe
II
N
N
N
N
2SbF6-
Science 2007, 783-787
early reports showed that addition of AcOH to an iron catalyst improves yields ofalkene epoxidation
Fe cat. (5 mol %)H2O2 (1.2 eq.)AcOH (0.5 eq.)
JACS 2001, 7194-7195
Fe(PDP) catalyst
$76/100 mg (Strem)
Fe(S,S-PDP)
3x
51%>99:1 dr
MeCN, rt30 min
R OH MeO2C OH
60%
RO
O
O
OH
R = Br 46%R = OAc 53%
N
H
F3C
O
OH
33%R = H 57%R = OAc 43%
OPivOPiv
HO
2+
FeNCMe
NCMe
II
N
N
N
N
CF3
CF3
F3C
F3C
(R,R)-Fe(CF3-PDP)
O
O
H
OHHO
O
H
54% (SM 2x recycled)
H
AcO
HO
OH
OAcOO
H
H
AcO
H
O
OAcOO
O
3 factors influence site selectivity:
directed C-H oxidation:
Fe(S,S-PDP)H2O2, AcOH
52% (SM 1x recycled)
EWG
RH H
R
electronic
R = H, Me, BG = bulky group
site with sterically moreaccessible C-H preferred
site activated through hyper-conjugation, relief of 1,3-diaxial interactions, torsinalstrain
BG
RH H
RBG H
H
site with most electron-rich C-H preferred
steric stereoelectronic
Carboxylate-assisted mechanism
JACS 2007, 15964-15972;Nat. Chem. 2011, 216-222; ACS Catal. 2015, 2702-2707; ACS Catal. 2016, 5399-5404
LFeIIH2O2
LFeIII OOH
H2O
OO
Fe
O
H
LIII
O
Fe
O
L VRCO2H
O
R
R
OH
Substrate vs. catalyst control
JACS 2013, 14052-14055
bulky groups enhance sensitivity to steric effect
O
O
H
OHHO
O
H54%
Fe(PDP)H2O2, AcOH
Fe(CF3-PDP)H2O2, AcOHO
O
H
HO
O
H
O
O
H
HO
O
H
O
52%
Fe(PDP)H2O2, AcOH
AcO
AcOOH
Fe(CF3-PDP)H2O2, AcOH
4 days47%
O
O
H
HO
O
H
OHengineered P450
92%
AcO
2°:3° = 1:3
66% (19% ketone)
O
51% (28% alcohol)NH
O
NHNs
H
MeO2C
H H
NH
O
NHNs
H
MeO2C
O
NH
O
NHNs
OH
MeO2C
Fe(PDP) 2°:3° = 1:1Fe(CF3-PDP) 2°:3° = 9:1
2°:3° = 2:1Fe cat.H2O2AcOH
2°
3°
Science 2010, 566-571
Cunninghamella echinulate
Perspective on late stage functionalization(inc. Fe(PDP)): JACS 2018, 13988-14009
prediction of reactive site
JACS 2012, 18695-18704
Iron-Oxo and Iron-Nitrido CompoundsRafael Navratil
Baran Group Meeting
10/31/20
OH
OH
1. TsCl, Py2. Me2CuLi.LiI, Et2O
Et
Et
Ph
Me
Cl
O
Et
Et
O
Ph
Me
H
HAlMe3, DIPEA
CH2Cl2
1. KHMDS, THFthen EtI
2. H2O2, NaOHMeOH
3. O3,CH2Cl2then NaClO2, NaH2PO4t-BuOH, isobutylene
51% (3 steps)
Et
EtH
O
H
H
OHO
O
Et
59% (2 steps)
gracilioether F
65%
Fe(PDP)H2O2, MeCN
9% (48% RSM)
Et
Et
O
H
H
O
EtO
O
ANIE 2014, 14522-14526
Me
Me
MeO2C
Me
HHO
O
1. SmI22. SeO2
52% (2 steps)
Me
Me
MeO2C
Me
H
OH
O
Fe(PDP)H2O2, AcOH
MeCN60%
mitrephorone B
Me
Me
MeO2C
Me
O
O
O
mitrephorone A
JACS 2019, 19589-19593
O
O H
H
Fe(PDP)H2O2, AcOH
MeCN
O
O H
H
cyanthiwigin
OH
O
O H
H
Fe(CF3-PDP)H2O2, AcOH
MeCN
22% 57% (C13:C12 2:1)
O
JOC 2018, 3023-3033
13
12
JACS 2017, 18428-18431
OH
O
TESO
OAc
H
O
TESO
OAc
O
Fe(PDP)H2O2
+
28%
O
O
TESO
OAc
O
Cp2TiCl, Zn
71%
43%
OO
O
OH
3 steps
scaparvin C
scaparvin B
scaparvin D
1 step
review on aplication of nonenzymatic catalysts: Chem. Rev. 2017, 11894-11951
tolerance of alkenes, arenes and basic nitrogens is generally poor in C-H oxidations
JACS 2015, 14590-14593
TfO
NMeH
TfO
NMeH
O
TfO
NMeH
HO
45%ketone/alcohol 2.5:1
+
H
HH
HAcO
42%alcohol:ketone 6:1
1. HBF4, DCM2. Fe(CF3-PDP)
H2O2, AcOH
JACS 2017, 14586-14591
N
NHtBu
H
HH
HO
Me
O
MeOTf
N
NHtBu
H
HH
HMeO
Me
O
TfON
NHtBu
H
HH
HO
Me
O
O
32% (3 steps)
1. Fe(CF3-PDP)H2O2, AcOH
2. NaI
OH
N
Iron-Oxo and Iron-Nitrido CompoundsRafael Navratil
Baran Group Meeting
10/31/20
+
N FeN N
N
R
R
R
N3
O
III
Science 2011, 1049-1052
Fe ClBPh
N
N
N
N
N tBu
tBu
NtBu
1. NaN3
2. hFe NBPh
N
N
N
N
N tBu
tBu
NtBu
FeCp2BArF24
-78 °C, Et2OFe NBPh
N
N
N
N
N tBu
tBu
NtBu
+
O
- e-
2+
N FeN N
N
Me
Me
Me
N3
O
IV
O
R = Me
h
2+
N FeN N
N
Me
Me
Me
N
O
VI
O
- N2
- N2
h
- N2
R = H +
N FeN N
N
Me
Me
Me
N
O
V
O
Science 2006, 1937-1941First iron(VI) compound (except for FeO42- salts)Iron-nitrido complexes
proposed as key intermediates of challenging reaction - nitrogen atom transfer(JACS 1985, 6427-6428), nitrogen fixation (reduction of N2 to NH3 by nitrogenase en-zyme, Acc. Chem. Res. 2009, 609-619), and Haber-Bosch ammonia synthesis(ANIE 1990, 1219-1227)
terminal nitrido ligand is bound to an iron center in a high oxidation state (+4,+5,+6)
only a few iron-nitrides have been generated and characterized because of their highlyreactive and thermally instable nature, particularly in tetragonal geometry
all studied iron-nitrides are simple synthetic models
First spectroscopic report
preparared by photolysis of iron-azides (photooxidation) at low temperatures thatcompetes with dissociation of azido radical (photoreduction) and dissociation of azideanion (redox-neutral process), their ratio depends on temperature and irradiationwavelength (Int. Rev. Phys. Chem. 2014, 521-553)
77 K
reviews: Dalton Trans. 2012, 1423-1429; Nat. Commun. 2012, 720
JACS 1988, 4044-4045
resonance Raman spectrum with v(FeN) at 876 cm-1
N
N
N
NFe
N
PhPh
Ph
Ph
V
prepared by photolysis of [(TPP)Fe(N3)] in frozen DCM at 30 K
JACS 1999, 4859-4876
+
N FeN N
N
H
H
HH
N3
N3
III
4 K or 77 K
+
N FeN N
N
H
H
HH
N
N3
V
Hg-lamp/419 nm
time-resolved FT-IR study in MeCN at room temp. with 532-, 355- and 266-nm lasersshowed that no photooxidation occurs in visible range, photooxidation is efficient onlyat 355 and 266 nm
ANIE 2013, 13067-13071
gas phase temperature-depedent photodissociation experiments showed that tetragonaliron(III)-azides adopt two, thermally interconverting, electronic spin states (doublet andsextet), which control the outcome of photolysis process
JACS 2008, 4285-4294
2+
NH2 Fe
NH2 NH2
NH2
N
N
V
Generation and reactions of iron-nitride in the gas phase
prepared by collisional activation of iron-azide precursor
transfers nitrogen to buta-1,3-diene
alkyne-nitrile metathesis in reaction with alkynes
Helv. Chim. Acta 2008, 1430-1434
Study on iron-azide photochemistry
only doublet iron(III)-azides (prevalent at low temperatures) undergo desired photooxida-tion to iron(V)-nitrides
recent report on stable iron(VI)compound, see Science 2020, 356–359
ANIE 2017, 14057-14060
characterized byMössbauer and EXAFS
EPR and Mössbauer
IV VIII
Fe(V)-nitride reacts with H2O at -78°C to yield NH3
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