Formation and ReactivityFormation and Reactivity of of

NitrenesNitrenes with Silver Catalysts for with Silver Catalysts for

CC--H Bond AminationH Bond Amination

PrasoonPrasoon SaurabhSaurabh, , KelceyKelcey Anderson, Anderson,

Joseph ScanlonJoseph Scanlon

Ripon CollegeRipon College

Why we want CWhy we want C--N bondsN bonds……

�� More chemically More chemically

reactive than Creactive than C--H H

bondsbonds

�� Important in Important in

pharmacology and pharmacology and

synthesizing synthesizing

natural productsnatural products

HO

O

HH

HHO

N

CH3

Morphine

Penicillin

Catalysts for the Formation of CCatalysts for the Formation of C--N N

BondsBonds

�� Only intramolecular amination reactionsOnly intramolecular amination reactions

H2N

O

O CH

H

2 mol%

AgNO3 and tBu3tpy

CH3CN 82°C

PhI(OAc)2

Y. Cui, C He, Angew. Chem. Int. Ed. 2004, 43, 4210-4212.

[Ag2(tBu3tpy)2(NO3)]+

[(Agbp)[(Agbp)22OTfOTf22HH22O]O]�� Intermolecular Intermolecular

ReactionsReactions

2 mol% Cat PhI=NNs

CH2Cl2 50°C

�Alkane Reactions

2 mol% CatPhI=NNs

CH2Cl2 50°C

CH

NHNs

+ PhI

+ PhI

L. Zigang, D. Capretto, R. Rahaman, C. He, Angew. Chem. Int. Ed. 2007, 46, 5184-5186.

Benefits of using Ag catalysts for Benefits of using Ag catalysts for

amination reactionsamination reactions

�� Relatively cheap by comparison to Relatively cheap by comparison to

other potential metalsother potential metals

�� LigandsLigands used are available used are available

commerciallycommercially

�� Able to react at a relatively low Able to react at a relatively low

temperaturetemperature

�� Reacts with relatively inert CReacts with relatively inert C--H H

bonds in bonds in alkanesalkanes

Research GoalsResearch Goals Part 1Part 1

�� Generation of a model system of the Generation of a model system of the disilverdisilver catalysts to determine the catalysts to determine the mechanism of formation of mechanism of formation of nitrenenitrene

�� Ag mediated generation of a Ag mediated generation of a nitrenenitrene–– SingletSinglet--triplet gaps for intermediate triplet gaps for intermediate molecules and the molecules and the nitrenenitrene

–– Calculation of enthalpy of formation of Calculation of enthalpy of formation of intermediates and intermediates and nitrenenitrene

Research Goals Part 2Research Goals Part 2

�� Determine mechanism for Determine mechanism for

uncatalyzeduncatalyzed CC--H bond aminationH bond amination

–– SingletSinglet--triplet splittingtriplet splitting

�� Determine effect of catalyst on Determine effect of catalyst on

mechanism and ratemechanism and rate

–– It is not certain that the AgIt is not certain that the Ag22PhenPhen22 dimerdimer

is the reactive species, so we will also is the reactive species, so we will also

study the study the AgPhenAgPhen form of the catalystform of the catalyst

Theoretical Methods:Theoretical Methods:

�� Density Functional: B3LYPDensity Functional: B3LYP

�� Basis sets used on all nonBasis sets used on all non--metal metal atoms: midi! and 6atoms: midi! and 6--31G(d)31G(d)

�� Stuttgart basis set and effective core Stuttgart basis set and effective core potential for Agpotential for Ag

�� In computational models,In computational models,–– Truncated Truncated tButBu33tpy to tpy to tpytpy

–– Truncated Truncated bathophenanthrolinebathophenanthroline to to phenanthrolinephenanthroline

Formation of Formation of NitreneNitrene::

�� An organic compound containing nitrogen An organic compound containing nitrogen atom with 6 valence electron with general atom with 6 valence electron with general formula:formula:

�� For studying formation of For studying formation of nitrenenitrene, , ethenediamineethenediamine (L) used as a model (L) used as a model ligandligandfor for phenanthrolinephenanthroline..

�� The similar The similar ligandligand was used for a nickel was used for a nickel complex as studied computationally by complex as studied computationally by CundariCundari and Morelloand Morello11..

Cundari T. R. ; Morello G. R. J. Org. Chem., 2009, 74 (15), pp 5711–5714

L

SingletSinglet--Triplet GapTriplet Gap

�� For For NTsNTs, triplet is favored energetically , triplet is favored energetically

over singlet by over singlet by --9.6 kcal/mol.9.6 kcal/mol.

�� Optimizing a triplet Optimizing a triplet PhIPhI--NTsNTs ((nitrenenitrene

precursor) leads to Iprecursor) leads to I--N bond breaking.N bond breaking.

NTs

Model Model LigandLigand Vs Actual Vs Actual LigandLigand::

77.078.2N-Ag-N/°

2.2652.318Ag-N/Å

AgPhenAgL

Uncoordinated

Coordinated Nitrene

176.4138.9N2-Ag-N3/°

98.2146.2N1-Ag-N3/°

78.274.4N1-Ag-N2/°

2.0162.159Ag-N3/Ǻ

2.192.369Ag-N2/Ǻ

2.1212.313Ag-N1/Ǻ

Agphen-NTsLAg-NTs

N1

N3

LAg-NTs

N2

Agphen

N1

N2

Energy Diagram of Intermediates of Energy Diagram of Intermediates of NitreneNitrene FormationFormation

�� Atoms in parenthesis are coordinated to silverAtoms in parenthesis are coordinated to silver

�� Many possible intermediates foundMany possible intermediates found

�� Similar structures and relative energies as found by Similar structures and relative energies as found by CundariCundari’’ssnickel systemnickel system

UncatalyzedUncatalyzed Intramolecular Intramolecular

ReactionReaction

0.00Product

89.81TS (Singlet)

83.00Nitrene (Singlet)

70.65Nitrene (Triplet)

Rel. E. (kcal/mol)

1.35

1.20

UncatalyzedUncatalyzed Intermolecular Intermolecular

ReactionReaction

0.00Product

83.21TS (Singlet)

88.05Reactant Singlet

78.45Reactant Triplet

Rel. E. (kcal/mol)1.07

1.50

[[AgPhenAgPhen]]++ Catalyzed ReactionCatalyzed Reaction

0.00[AgPhen]+ and Product

38.54TS Singlet

26.22[Ag(Phen)(nitrene)]+ Triplet

35.60[Ag(Phen)(nitrene)]+ Singlet

Rel. E. (kcal/mol) 1.671.14

[Ag[Ag22(tpy)(tpy)22]]+2+2 Catalyzed ReactionCatalyzed Reaction

0.00[Ag2(tpy)2]+2 + Product

49.90TS (singlet)

56.17[Ag2(tpy)2(nitrene)]+2 (singlet)

46.02[Ag2(tpy)2(nitrene)]+2 (triplet)

Rel. E. (kcal/mol)

ConclusionConclusion

�� EthenediamineEthenediamine does a good job as a model does a good job as a model ligandligandfor for phenanthrolinephenanthroline..

�� Desired product LAgDesired product LAg33NTs is not the lowest energy NTs is not the lowest energy species so perhaps the reaction goes through an species so perhaps the reaction goes through an intermediate.intermediate.

�� For For uncatalyzeduncatalyzed reactions, there are barrier reactions, there are barrier heights of 5heights of 5--19 kcal/mol.19 kcal/mol.

�� [[AgPhenAgPhen]]++ lowered the barrier to 3lowered the barrier to 3--12 kcal/mol.12 kcal/mol.

�� [Ag[Ag22(tpy)(tpy)22]]+2+2 had a barrier of approximately 4 had a barrier of approximately 4

kcal/mol.kcal/mol.

�� Spin crossing could be a possibility for these Spin crossing could be a possibility for these systems.systems.

Future researchFuture research

�� Determine full reaction pathway for Determine full reaction pathway for nitrenenitreneformation by locating transition states connecting formation by locating transition states connecting intermediates to intermediates to nitrenenitrene complexcomplex

�� Replace model Replace model ligandsligands with experimental with experimental ligandsligandsfor studying for studying nitrenenitrene formationformation

�� Model the full [(AgPhen)Model the full [(AgPhen)22]]+2+2 dimerdimer system for Csystem for C--

H bond aminationH bond amination

�� Explore different methods (M06L) and larger Explore different methods (M06L) and larger basis setsbasis sets

�� Investigate singlet reaction surfaces that have a Investigate singlet reaction surfaces that have a transition state lower in energy than reactant transition state lower in energy than reactant minimumminimum

AcknowledgementsAcknowledgements

�� Dr. Joseph ScanlonDr. Joseph Scanlon

�� Ripon College Chemistry DepartmentRipon College Chemistry Department

�� Midwest Undergraduate Midwest Undergraduate

Computational Chemistry Consortium Computational Chemistry Consortium

(MU3C)(MU3C)

�� Minnesota Supercomputing InstituteMinnesota Supercomputing Institute

�� Rachel Rachel VandenVanden BergBerg