Jacobsen Catalyst

C344

Overview

• Asymmetric catalysis• Lab overview• Organometallic reactions• Chiral GC analysis• Optical Activity

Asymmetric Catalysis

H3CO

H3CO

COOH

NHCOCH3

H3CO

H3CO

COOH

NHCH2OCH3

H2 CHIRALCATALYST

L-DOPA

Asymmetric Synthesis

• Stereoselectivity • Diastereomeric

excess• Enantiomeric

excess• From JOC, 2013, 78, 4762-4778.

91% ee

Lab Overview

O*

NaOCl

N

Mn

N

O

t-Bu

t-Bu

O

Cl

t-Bu

t-Bu

Lab 1

• Formylation reaction

• Isolate chiral salt during reflux

• May not get to silica column of aldehyde

OH

t-Bu

t-Bu

NH3

NH3

O2C

O2C

OH

OH

O

OH

t-Bu

t-Bu

NH2

NH2

HO2C

HO2C

OH

OH

+

MgCl2, TEA, (CH2O)n

THF, heat

glacialacetic acid

Lab 2

• Imine formation• Lowest yielding reaction• Optical activity

N

N

OH

t-Bu

t-Bu

OH

t-Bu

t-Bu

OH

t-Bu

t-Bu

NH3

NH3

O2C

O2C

OH

OH

K2CO3

O

Lab 3

• Jacobsen’s catalyst

• Air, moisture stable!

• You do not need optical activity data

N

Mn

N

O

t-Bu

t-Bu

O

Cl

t-Bu

t-Bu

N

N

OH

t-Bu

t-Bu

OH

t-Bu

t-Bu

1. Mn(OAc)2.4H2O

2. LiCl

Lab 4

• Finally getting to the point!• Bleach: a green, stoichiometric catalyst• Full characterization, with optical activity• Submit sample for chiral GC• Lab 5 can be used to catch up, finish

characterization data

O*

NaOCl

Jacobsen's catalyst

Organometallic Chemistry

• Mechanism: Wikipedia

Enantiomeric Excess

• Maybe due to radical mechanism• Calculations of ee

Chiral GC

• Basics of separation• Cyclodextrin column• Calculating ee• But which peak is which?

Optical Activity

• Chiral compounds bend plane polarized light

• Angle depends on concentration, path length, solvent, temperature, wavelength of light, which enantiomer

• Specific rotation

[a]20D = +66.4o (H2O)

The specific rotation of sucrose is reported:

D = sodium D-line = 589 nm

Calculation

• Specific rotation is calculated from observed rotation by [a] = a / (c . l)– C (concentration) is in grams/mL– L (pathlength) is in decimeters

• Most samples are determined at more dilute concentrations (g/ 100mL)

• Dilution does affect rotation, so to compare to literature, you must obtain data at same concentration they did

Example

• Reported data: Compound A has a reported specific activity [a]23

D = 93o (c = 1.9, CH2Cl2)• To repeat the experiment, you mixed 190 mg of

compound in 10mL of methylene chloride at 23o C and used a sodium lamp and standard tube.

• You obtained a rotation of 1.6o

• What is the ee of your compound?– Answer: 90% ee (Mixture is 95% to 5%)