Investigation of the Role and Form. Formation. Michael Enright

Transcription

1 Investigation of the Role and Form of Silver Catalysts in C N Bond Formation Michael Enright Ripon College

2 Importance Carbon Nitrogen Bonds Medicine Biological compounds Make C N bonds whenever we want More reactive than carbon hydrogen bonds Useful tool for chemical synthesis DNA Adenine Tylenol

3 He Group Discovery of two new silver catalysts that form C N bonds 4,4,4 tri tert butylterpyridine (t Bu 3 tpy) Bathophenanthroline (Bp) Dimer crystal structure found with Ag Ag coordination Disilver Cores in Catalysts Highlighted ht [(AgBP) 2. OTf. H 2 O]

4 He Group s Catalysts Both discovered catalysts: Had higher yields than other metal catalysts (Fe, Cu, Rh) Were easy to make at medium cost Efficient intramolecular C H amidation mediation [(AgBP) 2. OTf. H 2 O] Intermolecular reaction as well More versatility with wider range of products possible

5 Intramolecular Reaction from Amine PhI(OAc) 2 Removes Hydrogens Catalysts are believed to facilitate the removal of PhI group but do they also catalyze nitrogen insertion? Catalyst Removes PhI Group Leaves a very reactive nitrene that will react with itself to form cyclic carbamate product Nitrene

6 Goals Examine Intramolecular Amidation Reactions Uncatalyzed reaction to understand cyclic carbamate formation Effect of catalyst on reaction energetics Determine Mechanisms Catalytic Form Examine both monomer or dimer reaction energetics Determine if monomer or dimer is favored energetically Effects of Substituents on Dimer Formation and Reactivity

7 Theoretical Methods MU3C supercomputer pute and WebMO Gaussian09 program Methods: M06L densityfunctional Basis sets Nonmetals: etas 6 31G(d) Metals: sdd for basis set and effective core potential Single point calculations with SMD (Implicit Solvation Model) With experimental solvents: Dichloromethane and Acetonitrile il

8 Uncatalyzed Intramolecular Reaction Relative Energy (Kcal/mol) Nitrene Transition State Product 0.00 Bond Lengths in Angstroms Colors of atoms: Nitrogen Blue Carbon Black Oxygen Red Hydrogen White

9 Intramolecular Reaction Catalysts Ag 2 (tpy) 2 tpy=terpyridine (AgPhen) 2 Phen=Phenanthroline Ag Ag tert butyl groups removed Ligands truncated to decrease computational expense Experimentally, truncated ligands were catalytically active although less effective than full system Phenyl groups removed

10 (AgPhen) +2 2 Reaction Relative Energy (Kcal/mol) Butterfly Intermediate 4.33 Transition State Stacked (AgPhen) Carbamate Intermediate and transition state are butterfly structures, compared to stacked products Butterfly Intermediate t and N Ag bond lengths (AgPhen) 2 +2 Nitrenecarbamate Transition State

11 More Possibilities Multiple coordination sites on silver atoms Energy difference between stacked and butterfly = APh AgPhen + R = Nitrene (AgPhen) 2 +2 Possible Intermediate

12 Ag 2 (Tpy) 2 Reaction Relative Energy (Kcal/mol) Intermediate Nitrogen Coordination Products: Catalyst and Cyclic Carbamate 0.00 Nitrogen and oxygen coordination breaks catalyst apart No transition state yet found Intermediate: Nitrogen only coordination on Ag Ag axis [Ag 2 (Tpy) 2 ] o

13 A New Approach Problems with finding transition state and intermediate (AgPhen) 2 splits apart with nitrene coordination Steps to find stacked geometries: 1. Optimize catalyst alone 2. Freeze catalyst and optimize coordinated nitrene 3. Relax entire structure Result of unfrozen Frozen catalyst structure: Butterfly with optimization coordination of nitrene o 3.505

14 Monomer vs. Dimer Compare energetics of reaction with monomer vs. dimer as catalyst AgTpy + AgPhen + [Ag 2 (Tpy) 2 ] +2 (AgPhen) 2 +2

15 AgPhen + Catalyzed Reaction Rel. Energy (Kcal/mol) Solvent* Rel. Energy (Kcal/mol) AgPhen + Nitrenecarbamate Transition State Products *Dichloromethane Intermediate Transition State Products AgPhen + Nitrenecarbamate [AgPhen] + Cyclic Carbamate

16 Another Coordination? Nitrogen and Oxygen Coordinated Intermediate Nitrogen and Oxygen Coordinated Transition State Ag O Planertransition state preferred for both coordinations Nitrogen Coordinated Intermediate 1.962

17 Comparison of Coordinations Relative Energy (Kcal/mol) Solvent* Rel. Energy (Kcal/mol) Nitrogen Coordination Intermediate Nitrogen and Oxygen Coordination Intermediate Nitrogen Coordination Transition State Nitrogen and Oxygen Coordination Transition State Cyclic Carbamate and Catalyst *Dichloromethane Nitrogen Coordinated Transition State Nitrogen and Oxygen Coordinated Transition State

18 AgTpy + Reaction Nitrogen and Oxygen Coordination Rel. Energy (Kcal/mol) Solvation* Rel. Energy (Kcal/mol) Intermedate Transition State Cyclic carbamate and AgTpy Nitrogen only coordination with AgTpy + investigation unsuccessful *Acetonitrile Non planar Transition State Agtpy + Nitrenecarbamate Agtpy + Nitrenecarbamate Transition State

19 Dimer Formation [Ag 2 Phen 2 ] +2 with 2,9 methyl substitution He Group Disrupt dimer formation with added substituent groups No reaction with substituents observed Is the dimer formation or the reaction hindered? Look at reactivity and formation of substituted catalysts Substituted monomer reactivity with nitrene Dimer formation with substituent groups Ag Ag [Ag 2 Phen 2 ] +2 mesityl substitution

20 2,9 Methyl Substitution Monomer 2,9 Methyl Groups Rel. E (Kcal/mol) Solvent* Rel. E (Kcal/mol) AgPhen + 2,9 Methyl Nitrenecarbamate Intermediate AgPhen + Nitrenecarbamate Transition State Products: Cyclic carbamate + AgPhen + 2,9 Methyl Transition state of isomeric shift not nitrogen insertion * Dichloromethane AgPhen + 2,9 Methyl Substitution Hydrogen Waggle Transition State Vector Depiction of Hydrogen Waggle

21 Monomer Substitution Pathway ay for unsubstituted monomer reaction found No transition states found for monomer with substituents btit t AgPhen + 2,9 Methyl hlsubstitution i Hindered d This could indicate substituents block reaction due to sterics AgPhen + Mesityl Substitution

22 Dimerization with Substitutions Mesityl substituted dimer not found yet Dimethyl substituted yielded no valid transition state [Ag 2 Phen 2 ] +2 with mesityl substitution (Not Optimized) [Ag 2 Phen 2 ] +2 with 2,9 methyl substitution Ag Ag bond length Ag Ag bond length 3.215

23 Is Dimerization Favored? ΔE 2 Monomer Dimer Example: 2 AgPhen + ΔE (AgPhen) +2 2 Positive ii values favor monomer, negative dimer Ligand Type ΔE (Kcal/mol) Solvent* ΔE (Kcal/mol) Tpy Phenanthroline Unsubstituted Phenanthroline 2,9 Substituted * Tpy Acetonitrile Phen Dichloromethane

24 Conclusions Monomer reaction for both AgTpy + and AgPhen + favored and mechanism found Relative energy barrier: 25K 2.5 Kcal/mol lnitrogen coordination i 12 Kcal/mol Nitrogen and Oxygen coordination 7 Kcal/mol Uncatalyzed Multiple coordination possibilities (N vs N and O) Dimer formation of 2,9 9 Methyl substitution unfavorable in gas phase, but favorable in solution

25 Future Work Continue search for dimer transition states Freeze sections of molecules to enable optimization of nitrene coordination to catalyst Freeze catalyst from splitting with nitrogen coordination Find coordinated stacked structure before complete optimization Compare energies of butterfly and stacked conformations for (AgPhen) 2+ 2 species Examine substitution reactions with different orientations, coordinations, and solvation calculations Intermolecular amination with (AgPhen) 2+ 2

26 Acknowledgements Dr. Joe Ripon College Knop Shl Scholarship hi Program MU3C NSF Funding for Computer Cluster

27 Citations Cui, Y.; He, C. A Silver Catalyzed Intramolecular Amidation of Saturated C H Bonds. Angew. Chem. Int. Ed. 2004,, 43,, Cui, Y.; He, C. Efficient Aziridination of Olefins Catalyzed by a Unique Disilver(I) Compound. J. Am. Chem. Soc. 2003, 125, Cundari, T. R.; Morello, G. R.; A computational Study of Metal Mediated Decomposition of Nitrene Transfer Reagents. J. Org. Chem. 2009, 74, Klotz, K. L.; Slominski, L. M.; Riemer, M. E.; Phillips, J. A.; Halfen, J. A. Mechanism of the Iron Mediated Alkene Aziridination Reaction: Experimental and Computational Investigations. Inorg. Chem. 2009, 48, Halfen, J.A. Recent Advances in Metal Mediated Carbon Nitrogen Bond Formation Reactions: Aziridination and Amidation. Current Organic Chemistry. 2005, 9, Li, Z.; Capretto, D. A.; Rahaman, R.; He, C. Silver Catalyzed Intermolecular Amination of C H Groups. Angew. Chem. Int. Ed. 2007, 46, Li, Z.; He, C. Recent Advances in Silver Catalyzed Nitrene, Carbene, and Silyene, ;, y,, y Transfer Reactions. Eur. J. Chem. 2006, a