Iron-oxo and Iron-Nitrido Complexes final...BarB1, BarB2 O2,-KG, Cl--succinate,-CO 2 Me CCl3 H2N O S BarA N OMe Ph N S Me O Me CCl3 bromination also possible (JACS 2007, 13408-13409)

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


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


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

+


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


+ 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)


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


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



[(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



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



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


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


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


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

Documents

Iron-oxo and Iron-Nitrido Complexes final...BarB1, BarB2 O2,-KG, Cl--succinate,-CO 2 Me CCl3 H2N O S BarA N OMe Ph N S Me O Me CCl3 bromination also possible (JACS 2007, 13408-13409)