Jeff Turner Dr Scanlon Dr. Scanlon Ripon College

Transcription

1 Jeff Turner Dr Scanlon Dr. Scanlon Ripon College

2 Importance of Nitrene Insertion Carbon Nitrogen bonds are useful in a chemical synthesis. Biomolecules Pharmaceuticals i l Specialized materials Formation of these bonds has been a staple of chemical research Nitrene

3 Use of Gold in Formation of C N Bonds He group has investigated the use of AuCl3 in formation of C N bonds in wide variety of systems. Determining i the mechanism of C H bond to C N bond conversion will allow for the design of better catalysts. Historically the use of gold catalysts in the formation of carbon nitrogen bonds has not been as developed as other metals.

4 Experimental Background Reaction was attempted by He group variety of catalysts, solvents, and conditions. High yields with AuCl3 and dichloromethane as solvent Functional group chemoselectivity favors insertion at aromatic position instead of usual benzylic position. 1 1

5 Experimental Background Use of 1,3,5 tri isopropyl benzene yielded insertions at aromatic and benzylic positions.

6 Experimental Background Very weak benzylic C H bonds encourages formation of carbon gold(iii) bond. Deuterium replacement on hydrogen indicated AuCl3 inserted into benzylic and aromatic positions. Kinetic isotope effect indicates that C H bond breaking is not rate determining step.

7 Experimental Background Mechanism of nitrene insertion not determined by He group, but catalytic cycle and reaction pathway was proposed.

8 Research Goal Determine the mechanism of nitrene insertion onto aromatic position on mesitylene. Determine the mechanism of nitrene insertion i onto benzylic and aromatic positions of 1,3,5 tri isopropyl benzene. Determine how AuCl 3 can catalyze reactions at 2 positions and its behavior throughout the cycle.

9 Computational ti methods used Gaussian Theory: M06-2X Basis Sets: midi! (non metallic atoms and iodine*), sdd (gold), 6 311G(d,p) (non metallic atoms except iodine) ECP: sdd (Gold) Solvation model: SMD Dichloromethane Auto method used to speed up calculations.

10 Possible Mechanism of Reaction Aromatic Insertion PhINNs =N-(p-nitrophenylsulfonyl)imino]phenyliodinane Reactants Hydrogen transfer Aryl gold intermediate PhINNs Complex + HCl PhINNs Nitrene inserted product Catalyst regeneration Nitrene inserted intermediate Nitrene insertion AuCl3 HCl

11 Energetics of formation Gold ldcomplexation Species Relative Gas Phase Energy (Kcal/mol) Relative Solvation Energy (Kcal/mol) Relative 6 311G(d,p) Gas Phase Energy (Kcal/mol) Reactants AuCl 3 complexation Hydrogen transfer HCl ejection Aryl gold intermediate Dissociation of chlorine hydrogen to form HCl. Axial displacement of aromatic C H bond to incoming gold species. The formation of Aryl gold ld type intermediates has been previously shown experimentally 1 Reactants AuCl 3 Complexation Hydrogen Transfer Ejection of HCl Aryl gold intermediate +

12 Formation of Mes AuCl 2 NNs Stepwise Species Relative Gas Phase Energy Relative Solvation Energy Relative 6 311G(d,p) Gas (Kcal/mole) (Kcal/mole) Phase Energy (Kcal/mole) Aryl gold intermediate PhINNs Complex PhINNs directly complexes to gold. This refutes our original hypothesis of a transition state where we have a concerted dissociation of phenyl iodide and formation of gold nitrogen bond. Aryl Gold Intermediate PhINNs Complex

13 Formation of the Bridging Nitrene Species Relative Gas Phase Energy (Kcal/mol) Relative Solvation Energy (Kcal/mol) Relative Gas Phase 6 311G(d,p) Energy (Kcal/mol) PhINNs Complex TS-Nitrene insertion Insertion of Nitrene Phenyl Iodide behavior strongly supported that it is still associated through insertion, then dissociate after transition state. This is due to an inability to find a nitrene inserted intermediate with phenyl iodide still complexed. to the system, along with a transition state showing dissociation through the process. PhINNs Complex TS Nitrene Insertion Inserted Nitrene A

14 Formation of the product Species Relative Gas Phase Energy Relative Solvation Energy Relative gas phase 6 311G(d,p) (Kcal/mol) (Kcal/mol) Energy (Kcal/mol) Bridging Nitrene HCL complexation TS-Hydrogen transfer to nitrene Intermediate prior to catalyst dissociationi Final Product Bridging Nitrene HCL complexation HCl HCl Complexation Intermediate Transition State Final Product Intermediate prior to catalyst dissociation Hydrogen Transfer Catalyst Regeneration -AuCl 3

15 Reaction Pathway Mesitylene Species Relative Energy (Kcal/mol) Relative Solvation Energy (Kcal/mol) Relative 6 311G(d,p) Gas Phase Energy (kcal/mole) Reactants Catalyst complexation TS-Hydrogen transfer HCl ejection Aryl Gold intermediate PhINNs Complex TS-Nitrene insertion Inserted nitrene Mes-NNs-AuCl 2 (HCl) TS-Hydrogen transfer to nitrene Mes-NHNs-AuCl Mes-NHNs Thermodynamic behavior is fairly extreme in certain cases, with up to 50 kcal/mol energy gains (Aryl gold to PhINNs complex), and 60 kcal/mol energy difference to the product from the catalytic regeneration process (Mes NHNs AuCl 2 to Mes NHNs) Data implies stability of the Mes NHNs AuCl 3 complex before the catalyst is regenerated, thus suggesting that it does not reform. Reaction was completed by He group within one day, leading us to believe that the energy barriers in reality are not as high as they are computationally predicted. Use of 6 311G(d,p) reduces, but does not eliminate anomalous behavior (see well barrier flip between inserted nitrene and Mes NNs AuCl 2 (HCL).

16 Benzylic Insertion of Nitrene Reaction that occurs in addition to aromatic insertion onto 1,3,5 tri isopropyl benzene when treated with same reagents. For the reaction to occur, a weak C H bond on the benzylic and neighboring aromatic C H position was found to be required by He group 1. Reaction hypothesized to follow general pathway of aromatic insertion following gold complexation. AuCl 3 PhINNs + PhI

17 Proposed Mechanism of Benzylic Insertion Reactants TS-Gold Transfer Aryl Gold Specie -HCl PhINNs

18 Proposed Mechanism of Benzylic Insertion Continued PhINNs Complex TS-Nitrene insertion Nitrene inserted Intermediate t PhI HCl -AuCl 3

19 Gold Transfer Transition State Search Mechanism currently unknown The most promising path of catalyst complexation involves attachment to the aromatic carbon, then transferring to the benzylic position by either of these two methods. Direct Swing - HCl dissociation and direct movement of gold from aromatic to benzylic position. Riding the pi-way HCl dissociation and movement of gold species along benzene pi orbitals to benzylic position Alternatively, the catalyst could complex onto the carbon bonded to isopropyl group, and attack either the aromatic hydrogens, or the benzylic hydrogen, then migrate to either of these positions.

20 1,3,5 5tri isopropyl isopropyl benzene aromaticinsertion insertion ofnitrene nitrene. A mechanism has been found and it is the same as the mesitylene pathway. Key difference in potential energy surface from mesitylene is that HCl complexation to inserted nitrene is that t the 1,3,5 Tri isopropyl ii benzene group has almost no energy barrier, while it is significant in mesitylene (6 311G(d,p) calculations) AuCl 2 Complexed Species Gas Phase Solvation Intermediate (Kcal/mol) (Kcal/mol) Reactants Gold Complexed Intermediate Hydrogen transfer to chlorine HCL ejection intermediate AuCl2 Complexed Intermediate PhINNs complex Product Nitrene insertion Nitrene inserted intermediate HCL complexation Hydrogen transfer to nitrogen Catalyst regen intermediate Products

21 Concluding remarks Mechanism of nitrene insertion determined for aromatic mesitylene and 1,3,5 tri isopropyl benzene. Our understanding of gold catalytic behavior is not complete in the benzylic system, open to shifts in hypothesized mechanistic pathway based on data acquired. We suggest three possible mechanistic pathways. Thermodynamic anomalies (high energy difference in regards to experimental data) exist on minimal basis set use in mesitylene and aromatic 1,3,5 insertions, particularly during nitrene insertion and catalytic reformation. With mesitylene, use of 6 311G(d,p) reduced some, but not completely eliminate these. The most alarming was the switch from a well to a barrier in the complexation of HCl to the nitrene in mesitylene.

22 Future Plans Determine exact mechanism of benzylic migration of gold catalyst, either through direct swing, pi way, or complexation. Complete large basis set calculations for other projects. Obtain hypothesized transition states for benzylic Obtain hypothesized transition states for benzylic pathway.

23 Acknowledgements Dr. Scanlon Ripon College Chemistry Department MU3C Trustee Grant: Ripon College

24 References Gold(III) Catalyzed Nitrene Insertion into Aromatic and Benzylic C H groups; Li Zigang; Cappretto, David A.; Rahaman, Ronald O.; He, Chuan; Journal of the American Chemical Society; Volume 129; Issue 40; Pages ; Journal; 2007 Ring Expansions in the Reactions of Transition Metal Carbon Bonded Chelate Complexes; Bennett, M.A.; Hitchcock, P.B.; Hoskins, Kathleen; Kneen, W.R.; Mason, R.; Nyholm, R.S.; Robertson, G.B.; Towl, A.D.C.; Journal of the American Chemical Society; Volume 93; Issue 18; Pages ; Journal; 1971 The Chemistry of Organic Gold Compounds. III. Direct Introduction of Gold into the Aromatic Nucleus; M.S., Kharasch; h Horace, Isbell; bll Journal of the American Chemical Society; Volume 53; Pages ; Journal; 1931