1. Bijay Bhattarai Faculty Advisor Debra D. Dolliver Kevin Shaughnessy University of Louisiana System Academic Summit 2013 04/13/2013 SUZUKI COUPLING OF N-ALKOXYIMIDOYL HALIDES

2. Oxime Oxime Ether

3. Conventional method for the synthesis of diaryl oxime ether A. Rosenthal, Can. J. Chem. 1960,38, 2026.

4. Suzuki Coupling Reaction -Palladium catalyzed cross-coupling between organoboron compounds and organic halides -Formation of carbon-carbon bonds N. Miyaura, A. Suzuki, J. Chem. Soc. Chem Commun. 1979, 19, 867

5. Mechanism of Suzuki coupling reaction S.Kotha, K. Lahiri, D. Kashinath, Tetrahedron. 2002, 58, 9637. Oxidative Addition Reductive Elimination Transmetalation

6. Imidoyl Halide Our Research Group

7. STEP 1: Hydroxamate Synthesis Path 1 Path 2 Path 2 Preparation of Starting Material Fisher, L.E.; Caroon, J.M.; Stabler, S.R.; Lundberg, S.; Muchowski, J.M. J. Org. Chem., 1993, 58, 3643- 3647.

8. STEP 2: Tosylate Synthesis

9. STEP 3: Halide Synthesis

10. Reaction Optimization Ligands PPh 3 dppf PH(t-Bu) 3 BF 4 SPhos No ligand Solvent MeOH THF THF/H 2 O Concentration of Reaction Bases K 2 CO 3 Cs 2 CO 3 KOH

11. Reaction Optimization Ligands PPh 3 dppf PH(t-Bu) 3 BF 4 SPhos No ligand Solvent MeOH THF THF/H 2 O Concentration of Reaction Bases K 2 CO 3 Cs 2 CO 3 KOH

12. Reaction Optimization Ligands PPh 3 dppf PH(t-Bu) 3 BF 4 SPhos No ligand Solvent MeOH THF THF/H 2 O Concentration of Reaction Bases K 2 CO 3 Cs 2 CO 3 KOH

13. Suzuki cross coupling reaction of N-alkoxybenzimidoyl halide with trifluoroborate salt or boronic acid Compound ArR' R Y Isolated Yield 1ZPhp-OCH 3 Ph CH 3 BF 3 K88% Php-OCH 3 PhCH 3 B(OH) 2 100% 2ZPhp-ClPh CH 3 BF 3 K75% Php-ClPhCH 3 B(OH) 2 81% 3Z Pho-CH 3 Ph CH 3 BF 3 K84% 4ZPhp-CH 3 Ph CH 3 BF 3 K99% Php-CH 3 PhCH 3 B(OH) 2 93% 5Z Php-NO 2 Ph CH 3 BF 3 K72% 6Z Phm-NO 2 PhCH 3 BF 3 K70% 7Z PhmesitylCH 3 BF 3 K0% 8Z Php-CH 3 Phi-PrBF 3 K98% 9Z Ph CH 3 BF 3 K94% 10ZPhPhCH=CHCH 3 B(OH) 2 89% 11ZPhp-vinylPhCH 3 B(OH) 2 82% 12ZPhp-piperidineCH 3 B(OH) 2 0% Compound ArR' R Y Isolated Yield 1Ep-OCH 3 PhPh CH 3 BF 3 K79% 2Ep-ClPhPh CH 3 BF 3 K93% 4Ep-CH 3 PhPh CH 3 BF 3 K85% 5Ep-NO 2 PhPhCH 3 B(OH) 2 97% 6Em-NO 2 PhPhCH 3 B(OH) 2 96% 8Ep-CH 3 PhPh i-Pr BF 3 K99% p-OCH 3 Php-CH 3 CH 3 BF 3 K83% p-CH 3 Php-CH 3 CH 3 BF 3 K86% Dolliver, D.D. et al. J. Org. Chem., 2013

14. 43

15. 93(99) 85 (85) 79 100(88)

16. 81(75) 97 73

17. 96 70 (99) (98)

18. (84) 0 89 82

19. 0

20. How do you prove that you synthesized single geometric isomer?  Retention Time in GC  NMR- 1) 13 CNMR 2)Proton NMR  X-ray crystallography

21. H-NMR Z-isomer E-isomer

22. C- NMR E-isomer Z-isomer

23. Further Characterization: Entry N-alkoxyimidoyl halide reactant Boronic acid reactant X-ray crystal structure of product 1 2 Dolliver et al. In progress

24. Conclusion: o We developed a new synthetic route of oxime ether from benzimidoyl iodide and boronic acid or trifluoroborate salt. o 1% Palladium Catalyst- Low catalytic loading o Characterized single geometric isomers by HNMR and CNMR o Single geometric isomers of crystalline compounds were confirmed by X-ray crystallography

25. Acknowledgements ACS-PRF UR grant NSF-RUI grant -Dr. Debra Dolliver -Dr. Kevin Shaughnessy- Univ. of Alabama -Dr. Steven Raders- Univ. of Alabama -Dolliver’s Research Group -Shaughnessy’s Research Group- Univ. of Alabama -Dr. Artie S. McKim- Gaylord Chemical Company -Dr. Frank Fronczek- LSU -NSF-REU – Univ. of Alabama -LSU