Synthesis and Reactivity of Manganese and Iron Complexes with Methylated Derivatives of Bis(2-pyridylmethyl)-1,2- ethanediamine (bispicen) Christian R.

Synthesis and Reactivity of Manganese and Iron Complexes with Methylated Derivatives of Bis(2-pyridylmethyl)-1,2-ethanediamine (bispicen)

Christian R. GoldsmithAuburn UniversityDepartment of Chemistry & Biochemistry

Conversion of Alkane C-H to C-X Bonds

• Chief industrial method for halogenating aliphatic C-H bonds is free radical halogenation

• Halogen radicals abstract hydrogen atom from alkane

• Cl2 or Br2 serves as halogen source as well as oxidant

• Lack of regioselectivity problematic

2

RCH3 + Cl. + HClRCH2.

+ Cl---ClRCH2. RCH2Cl + Cl.

3

Bio-Inspiration: SyrB2 Halogenase

• The halogenase SyrB2 uses a mononuclear non-heme iron active site to halogenate aliphatic C-H bonds using O2 and Br/Cl-

• Crystal structure differs from non-heme iron oxygenases in that Br/Cl atom ligates iron

• Similar mechanism to -ketoglutarate dependent hydroxylases proposed

• Active FeIV(O)(Cl) species proposed to abstract H atom from L-threonine substrate

Blasiak, L. C.; Vaillancourt, F. H.; Walsh, C. T.; Drennan, C. L. Nature 2006, 440, 368-371

Br/Cl Fe

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Postulated Enzymatic MechanismOH2

FeII

NHis

Cl ONHis O

O

COO-

FeII

NHis

Cl ONHis O

O

R'

H3CR

FeIII

NHis

Cl O

NHis O

O

R'

H3CR

OO

FeIV

NHis

ClNHis

H2CR

O

O R'

O

FeIII

NHis

ClNHis

OH

O R'

O

O2

RCH3

H2O

Cl-

RCH2Cl

H

H2CR.

Previous Successes

• TPA system reported by Que’s group (Leising, R. A. et al. J. Am. Chem. Soc. 1991, 113, 8555)

• Iron(II) bispidine catalyst reported by Comba’s group (Comba, P. & Wunderlich, S. Chem. Eur. J. 2010, 16, 7293)

• Common features: relatively rigid ligands, t-butyl hydroperoxide serves as oxidant

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Comba, P.; Wunderlich, S. Chem. Eur. J. 2010, 16, 7293-7299

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Parent Ligand- Bispicen

• N,N-Bis(2-pyridylmethyl)-1,2-ethanediamine• Binds metal ions in cis- conformation• Easy to make• Easy to modify– Steric bulk (pyridine rings/amines)– Electronic perturbations Bispicen

HNNH

NN

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Methylated Bispicen Syntheses (LMen)

R = H: LMe2R = Me: LMe4

R = H: LMe1R = Me: LMe3

Yields from commercial materials:67% (LMe4) and 77% (LMe3)LMe2, LMe2’ and LMe1 previously made

Coates, C. M. et al. manuscript submitted

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Metal Complex Syntheses• Mix ligands, MnCl2 or FeCl2, and acetonitrile (MeCN)

• Heat to dissolve everything, then cool• Many compounds crystallize, allowing structural

characterization• Compounds prepared in yields ranging from 41% to 96%• Lowest yields with tetramethylated bispicen derivative (LMe4)

[Mn(LMe4)Cl2][Fe(LMe4)Cl2]

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• All compounds high-spin as assessed by M-L bond lengths and magnetic susceptibility

• Unexpectedly, all three conformational possibilities seen!

[M(LMen)Cl2] Structural Analysis

[Mn(LMe1)Cl2]: cis- [Mn(LMe3)Cl2]: cis-

[M(LMen)Cl2] Structural Analysis

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• trans conformer seen with LMe2’ ligand, despite steric clash between 6-methyl groups on pyridine rings

• Pyridine rings tilt in opposite directions to relieve strain

• Significant distortion from octahedral geometry

• Overall geometry best described as pentagonal bipyramidal with missing vertex

[Mn(LMe2’)Cl2]: trans

Solution Dynamics• Structures not conserved in solution• EPR spectra of manganese complexes not consistent with

single mononuclear species• 1H NMR spectra of structurally characterized iron

compounds also inconsistent with crystal structures• At higher temperatures, 1H NMR resonances broaden and

coalesce

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EPR spectrum of [Mn(LMe2)Cl2] in DMF at 50 K

NN

NN

CH3 CH3LMe2 =

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[M(LMen)Cl2] Electrochemistry

• M(III/II) potentials generally increase with methylation

• Methylation weakens ability of ligand to act as -donor

• Potentials of iron compounds more strongly impacted by ligand perturbations

CV of [Mn(LMe4)Cl2] in MeCN

Mn-N Bond Lengths• Average M-N bond distances generally increase with

methylation• Comparison complicated by different conformers, crystal

packing• cis- conformation appears to allow closer approach of

one of the methylpyridines and the non-methylated amine N(4)

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Compound M-N(1) M-N(2) M-N(3) M-N(4) M-N avg

[Mn(LMe1)Cl2], unit A 2.278(3) 2.290(3) 2.342(3)* 2.307(3) 2.304

[Mn(LMe1)Cl2], unit B 2.273(4) 2.293(3) 2.391(4)* 2.311(4) 2.317

[Mn(LMe2)Cl2] 2.278(2) 2.278(2) 2.366(2)* 2.366(2)* 2.322

[Mn(LMe2’)Cl2] 2.4222(11)* 2.4182(10)* 2.2868(10) 2.2874(11) 2.354

[Mn(LMe3)Cl2], unit A 2.377(4)* 2.439(4)* 2.344(4)* 2.256(4) 2.355

[Mn(LMe3)Cl2], unit B 2.307(5)* 2.458(5)* 2.343(5)* 2.263(5) 2.343

[Mn(LMe4)Cl2] 2.4757(10)* 2.4703(10)* 2.3298(10)* 2.3386(10)* 2.404

[Fe(LMe2)Cl2] 2.195(4) 2.195(4) 2.278(4)* 2.278(4)* 2.237

[Fe(LMe4)Cl2] 2.4069(18)* 2.4236(19)* 2.2689(18)* 2.2639(19)* 2.341

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Chlorination Activity- [Fe(LMe2)Cl2]

• Hydrocarbon chlorination seen when peracid used as terminal oxidant

• Metal systems cannot chlorinate cyclohexane but can mildly chlorinate allylic and benzylic substrates

• [FeIV(LMe2)(O)Cl2] seen by optical and mass spectroscopies in absence of substrate, vanishes in under 30 s at RT

• Reactions run for 60 min under N2 at 22 °C with MCPBA as terminal oxidant; no additional chloride added

• Organic products identified and quantified by GC and 1H NMR

BDE of weakest C-H bond(s): 88 85 83

Goldsmith, C. R.. et al. manuscript in preparation

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Regioselecivity?

• With single equivalent of MCPBA, [Fe(LMe2)Cl2] chlorinates ethylbenzene (15% yield) but not toluene or cumene

• With 10 equiv MCPBA, yield of above chlorination reaction with ethylbenzene increases to 83% but with oxygenated byproducts (30% of oxidized substrate)– Toluene chlorinated (20%) with excess oxidant – Cumene still untouched

• Comparable ethylbenzene reaction with [Mn(LMe2)Cl2] yields 1-chloroethylbenzene in 2% yield

{with excess oxidant}

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Conclusions• The bispicen framework is more flexible than previously

thought and is able to accommodate metal ions in at least three distinct conformations: cis-, cis-, and trans– EPR and NMR demonstrate that these solid-state

structures are not exclusively maintained in solution• The M(III/II) potentials generally increase with ligand

methylation, consistent with steric effects weakening the -donation from the N-donors to the metal ion

• The [Fe(LMe2)Cl2] reacts with MCPBA to chlorinate benzylic substrates via an [FeIV(LMe2)(O)Cl2] species, albeit poorly

– Iron outperforms manganese– The oxidant seems to have a preference for activating C-

H bonds on secondary carbons (ethylbenzene)– Flexibility of ligand may facilitate its degradation

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AcknowledgementsPersonnel

• Dr. Cristina M. Coates (AU, now at Nicholls State University)• Dr. John D. Gorden (AU)• Prof. Thomas E. Albrecht-Schmitt (University of Notre Dame)• Prof. Evert Duin (AU)• Kenton Hagan (Huntington College)• Casey A. Mitchell (AU)

Funding• Auburn University• AU Cell and Molecular Biosciences Program (NSF EPS-

0814103)• American Chemical Society-Petroleum Research Fund

[Fe(LMe2)(O)Cl2]

• 0.32 mM [Fe(LMe2)Cl2] + 0.36 mM MCPBA in MeCN

• Intermediate observed at 5 s (scan B in UV/vis)• Associated with transient feature in MS with m/z ratio of 412

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Chlorination of Toluene Derivatives

Catalyst Substrate Alcohol CarbonylChloride

None Toluene 0 mM 0 mM0 mM

FeCl2 Toluene 0 0.89.1

[Fe(LMe2)Cl2] Toluene 0 0.92.0

[Fe(LMe4)Cl2] Toluene 0.9 1.02.0

None Ethylbenzene 7.7 0 0FeCl2 Ethylbenzene 6.0 0 17.7

[Fe(LMe2)Cl2] Ethylbenzene 3.3 0 8.3

[Fe(LMe4)Cl2] Ethylbenzene 0 0 6.0

None Cumene 5.0 n/a0

FeCl2 Cumene 42.0 n/a8.9

[Fe(LMe2)Cl2] Cumene 0 n/a0

[Fe(LMe4)Cl2] Cumene 0 n/a0