enantioselective catalysis in aqueous micellar...
TRANSCRIPT
Enantioselective Catalysis in Aqueous Micellar Media
Caitlin McMahon March 29, 2013
Organic Reactions in Water
• Organic solvents are expensive, toxic, and environmentally unfriendly
• Water provides cheap, safe, “green” alternative
• Can influence rate and selectivity – hydrophobic effect
• Possible catalyst recycling
• Problem: solubility, incompatibility
Outline
• Introduction to micelles
• Micelles in catalysis
• Chiral catalysts with added surfactant
• Chiral catalysts = surfactants
• Chiral surfactant environments
• Surfactants – hydrophilic head group and hydrophobic tail
• Examples:
• Micelles – aggregation of amphiphilic surfactants
Oehme, G. et al. Angew. Chem. Int. Ed. 2005, 44, 7174-7199.
What are Micelles?
Uses for Micelles • Soaps/detergents
• Micellar Liquid Chromatography
De Villiers, et al. Nanotechnology in Drug Delivery. Springer, 2009.
Yao, S. et al. Green Chem., 2009, 11, 132-137.
• Drug Delivery
Micelles in Organic Reactions • Allow for solubilization of nonpolar reagents in water
• Create high effective concentration of reactants
• “microreactors”; “nanoenvironments”
Oehme, G. et al. Angew. Chem. Int. Ed. 2005, 44, 7174-7199.
• Micelles can act as enzyme mimics
• Proximity of substrates at micelle surface – mimics enzyme active site
• Hydrolysis – micellar Cu2+ and Zn2+ complexes as protease mimics
Yu, X. et al. Coord. Chem. Rev. 2009, 253, 2166-2177
Metalloenzyme Models
Modes of Micellar Catalysis 1. Reagent is amphiphilic and forms a micelle which changes reaction
2. Reactants intercalate into and interact with micelle
3. Micelle is comprised of catalytically active surfactants
Oehme, G. et al. Angew. Chem. Int. Ed. 2005, 44, 7174-7199.
Reactions Catalyzed by Micelles
Reactions Catalyzed by Micelles • Hydrogenation
• Surface-crosslinked micelles (SCMs)
• Prefers terminal, linear alkenes of certain chain length
Zhao, Y. et al. Chem. Commun. 2012, 48, 9998-10000.
.
Reactions Catalyzed by Micelles • Diels Alder
• Ionic liquid micelles
rate increased x4 in ionic liquid compared with pure water
• Hydroformylation
• Compare to Ruhrchemie/Rhone-Poulenc
process in H2O – only propene
Zirbs, R. et al. Chem. Commun. 2012, 48, 5013-5015
Strukul et al. Adv. Synth. Catal. 2010, 352, 2251 – 2262
Chiral Catalysts in Micelles
• Asymmetric Baeyer-Villiger oxidation
• Adding surfactant enables solubilization in H2O without catalyst modification
Strukul et al. Green Chem. 2009, 11, 1517.
Chiral Catalysts in Micelles • Asymmetric epoxidation
Strukul et al. Adv. Synth. Catal. 2007, 349, 797 – 80
Chiral Catalysts in Micelles • Asymmetric Transfer Hydrogenation (ATH) of Imines & Iminiums
• Noyori Conditions:
• Aqueous Micellar Media:
• Synthesis of biologically active β-carboline alkaloids
Yu, B. et al. Chem. Commun., 2006, 1766-1768
Chiral Surfactant Catalysts • Organocatalytic Asymmetric Aldol
• Water is more versatile • Temperature:
• Low catalyst loading:
Barbas, C.F. and Mase, N. Org. Biomol. Chem., 2010, 8, 4043-4050
50 °C
DMSO 99% yield, 52% ee
H2O 99% yield, 90% ee
1 mol % catalyst
DMSO no reaction
H2O 91% yield, 91% ee
Chiral Surfactant Catalysts
• Organocatalytic Michael Addition
Anionic surfactant with catalytic counteranion
• Cheng et. al. Chem. Commun., 2006, 3687–3689.
Chiral Surfactant Catalysts • Isotetronic acid synthesis
• Previous – organic solvent:
• Aqueous micellar media:
Landais et al. Chem. Commun. 2007, 4782-4784.
Li et al. Angew. Chem. Int. Ed., 2012.,51, 13159-13162.
Reaction at Micelle Surface
• Fluorescence Studies
• Reaction Model
Li et al. Angew. Chem. Int. Ed., 2012.,51, 13159-13162.
Chiral Surfactant Catalysts • Asymmetric transfer hydrogenation of aliphatic ketones
Deng et al. JACS, 2012, 134, 18522-18525.
R1 R2
yield (%)
ee (%)
n-hex Me 92 90
n-dec Me 93 94
Me 95 84
Ph Me 97 97
Model for Enantioselectivity
Deng et al. JACS, 2012, 134, 18522-18525.
Chiral Surfactant Environments
• Asymmetric reduction with chiral amino acid-based cationic surfactants
• Chiral surfactants used as protecting agents of rhodium nanoparticles for hydrogenation
• Low levels of enantioinduction
Das et al. Langmuir. 2005, 21, 23, 10399.
Roucoux et al. ChemSusChem. 2012, 5, 91-101.
Summary
• Water = safe, “green”, alternative solvent
• Micelles – efficiently catalyze many types of reactions in aqueous media
• Hydrolysis, hydrogenation, aldol, Diels-Alder, oxidation, etc.
• Possibilities for enantioinduction • Chiral catalyst interacting with micelle
• Chiral surfactant catalysts
• Chiral surfactant environments
• Prof. Erik Alexanian
Alexanian Group:
• Kayla Le
• Andy Brusoe
• Valerie Schmidt
• Ben Giglio
• Brendan Lainhart
• Njamkou Noucti
• Ryan Quinn
• Alex Venning
• James Lancaster
• Patrick Bohan
• Frank Tillman
Acknowledgements
Chiral Surfactants
• Micelle principle – use of β-cyclodextrin as catalyst support