1. Investigating Substrate
Reactivity in Hydroacylation
Reactions with Rhodium
Catalysts
Geno Schneider
Dr. Joe Scanlon
Ripon College

2. Outline
 Background
 Hydroacylation
 Previous Studies
 Chirality
 Potential Energy Surfaces
 Results
 Conclusions
 Ongoing and Future Research
 Acknowledgments
 References

3. Hydroacylation
 Alkene and aldehyde react to form a new carbon-
carbon bond
 Intramolecular hydroacylation requires a catalyst

4. Previous Research
 Stanley Group at Iowa State
 Found unique substitution effects and high
enantioselectivity

5. Previous Research
 Tested many substituents and ligands
 Found as a backbone in narcotics

6. Previous Research
 Dr Sargent et. al
 Computational Study on simple system
 Brian Schumacher and Dr. Joe Scanlon
computationally studied Dr. Stanley's system
 Mechanism Changes from Sargent
 Additional Intermediate found

7. Chirality

8. Potential Energy Surfaces
 Depict relative energies
 Reaction alternates between intermediates(local
minima) and transition states(local maxima).
 Determine mechanisms of reactions
-65
-55
-45
-35
-25
-15
-5
DeltaH(kcal/mol)
Reaction Coordinate
PES

9. Mechanism

10. Dr. Sargent
 Recreated Sargent’s system with two methods
 H-coordination Intermediate was found in both cases
0
10
20
30
DeltaE(kcal/mol)
Reaction Coordinate
PES
M06L
B3LYP
Sargent
6-HcoordTS
I6
Hcoord
Hcoord-7aTS
I7a
Sargent’s
TS

11. Enantioselective Reaction
 Intramolecular Hydroacylation catalyzed by
[Rh(BINAP)]

12. Enantioselectivity
 Different side of alkene coordinating to Rh, allowing for R or S
enantiomers to be formed.
 Pathway of R vs S Enantiomers
H
R2
LRh(I)
R1
O
H
R2
R1
R2
O
H
R2
R1
R Enantiomer S Enantiomer

13. -65
-55
-45
-35
-25
-15
-5
5
DeltaH(kcal/mol)
Reaction Coordinate
PES
S Enantiomer
R Enantiomer
I2
SM
I1
TS1
I3
TS2
TS3
I4
TS4
I5
TS5
ΔH
kcal/mol
TS1 TS2 TS3 TS4 TS5
R-S 2.9 11.1 -3.1 -0.5 3.0

14. 3.90A
2.52A
S Enantiomer, Transition State 2
2.13A
2.70A
R Enantiomer, Transition State 2
Distance to catalyst phenol rings

15. S Enantiomer, Transition State 2
Dihedral Angle=6.65
R Enantiomer, Transition State 2
Dihedral Angle= -16.40
Dihedral angle

16. Cyclopentene and
Cyclohexene

17. -25
-15
-5
5
DeltaH(kcal/mol)
Reaction Coordinate
PES
Cyclohexane
Cyclopentane
I2
SM
I1
TS1
I3
TS2
TS3
I4
TS4
I5
TS5
ΔH
kcal/mol
TS1 TS2 TS3 TS4 TS5
CH-CP 1.7 1.4 4.1 NA -7.2

18. Future Work
 Finish Cyclopentene pathway.
 Analyze geometry to explain differences in energy.

19. Acknowledgements
 MU3C Cluster
 National Science Foundation
 Knop Scholarship Fund
 Ripon College Chemistry Department
 Dr. Joe Scanlon

20. References
1. Beletskiy, E. V.; Sudheer, Ch.; Douglas, C. J. Cooperative Catalysis Approach to
Intramolecular Hydroacylation. J. Org. Chem, 2012, 77, 5884-5893.
2. Ghosh, A.; Stanley, L. M. Enantioselective hydroacylation of N-vinylindole-2-
carboxaldehydes. Chemical Communication 2014, 50, 2765-2768.
3. Dempsey Hyatt, I. F.; Anderson, H. K.; Morehead, Jr. A. T.; Sargent, A. L. Mechanism of
Rhodium-Catalyzed Intromolecular Hydroacylation: A Computational Study. Organometallics
2007, 27, 135-147.
4. Pawley, R. J.; Huertos, M. A.; Lloyd-Jones, G. C.; Weller, A. S.; Willis, M. C. Intermolecular
Alkyne Hydroacylation. Mechanistic Insight from the Isolation of the Vinyl Intermediate That
Precedes Reductive Elimination. Organometallics 2012, 31, 5650-5659.
5. Gao, J.; Wang, F.; Meng, Q.; Li, M. Density Functional Computations of Rh(I)-Catalyzed
Hydroacylation of Ethene or Ethyne. Journal of Theoretical and Computational Chemistry,
2008, 7, 1041-1053.