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