HomKaT Practicum Instructions 2015

Experimental Procedures for the Practicum
Homogeneous Catalysis
Subject: synthesis of supramolecular ligands, preparation and NMR study of
Rhodium complexes with the synthesized ligands and application of the
complexes as catalysts in asymmetric hydrogenation.
Ligands: UreaPhos ligands. When two ligands are binding to one metal center,
these monodentate ligands can form bidentate ligands through hydrogenbonding with the urea functionality.
Catalytic reaction: Hydrogenation of methyl 2-acetamidoacrylate and dimethyl
itaconate in the synthesis robot.
Schedule of the Practicum:
Day one: synthesis of the Ligands
Day two: Preparation and NMR studies of the Rhodium catalysts
Day three: Catalysis
Day One: Preparation of the Ligands

General remarks: Ligands/complexes are sensitive to moisture (water, air
humidity) and oxygen so all the manipulations have to be carried out under an
inert atmosphere with strict exclusion of water. Urea alcohols and amberlyst
should be azeotropically dried with toluene before use and all solvents are
distilled over an appropriate drying agent and degassed before use. A failure to
do so may result in the decomposition/oxidation of the ligands and therefore to
the failure in the practicum.
1) Preparation of the UreaPhos ligands1
According to Reek et al., Chem Comm, 2007, 864-866
General Procedure:
To a 50 mL Schlenk-flask add 0.6 mmol of urea-alcohol 1 and 500 mg of
amberlyst. Add 2-3 mL of toluene and evaporate it in vacuum (use water bath) in
order to azeotropically remove any traces of water. Add 15 ml of dry
tetrahydrofurane (THF) and cool the reaction mixture down to 0C. In a separate
Schlenk-flask dissolve 0.6mmol of BINOL-PCl 2 in 4 mL dry THF and cool down
the solution to 0C. Add the solution of 2 to the reaction mixture of 1 using a
syringe and stir the resulting mixture for 1 hour at 0C. Stir it for additional 1
hour at room temperature to ensure the total conversion of BINOL-PCl. Filter the
resulting mixture (this step can be done even under air, if it is done rapidly) and
collect the filtrate in a Schlenk-flask. Evaporate the solvent from the filtrate
under vacuum. The ligand 3 will be obtained as a foam. Make an NMR sample of
your product in dry CDCl3.
What is the role of amberlyst?
Important: These ligands will be used for catalysis. In order to avoid

decomposition/oxidation, the sample has to be stored under inert atmosphere in
a Schlenk-flask (use Parafilm) at -15C.
Day Two: Preparation of the Rhodium Complexes

In this part of the practicum, Rhodium-complexes of your ligands will be studied
using NMR. Both homo- and heterocomplexes will be analyzed.
For UreaPhos:
a)
Preparation of the homocomplex:
In a Schlenk-flask, dissolve 0.01 mmol of Rh(COD) 2BF4 and the ligand in 5 mL of

dichloromethane (DCM) in ratio Rh:L = 1:2 and stir for 20 min at room
temperature. Remove the solvent under high vacuum. Wash the solid residue
with hexane (2-3 times) and dry well under vacuum. Add 0.8 ml of dry CDCl 3. Fill
the NMR tube under nitrogen atmosphere.
b)
Preparation of the heterocomplex:
In a Schlenk-flask, dissolve 0.01 mmol of your ligand and 0.01 mmol of one of
your colleagues ligand in 3 mL of DCM. In another Schlenk-flask, dissolve 0.02
mmol of Rh(COD)2BF4 in 2 mL of DCM. Add dropwise the solution of metal to the
solution of ligand via syringe and stir it for 30 min. Remove the solvent under
high vacuum. Wash the solid residue with hexane (2 times) and dry well under
vacuum. Add 0.8 ml of dry CDCl3. Fill the NMR tube under nitrogen atmosphere.
NMR Analysis will be done by the assistants.
Day Three: Catalysis

These experiments will first take place at the practicum laboratory and then at
the laboratory E-1.05 where the synthesis robot and the glove box are located.
The library of ligands will be evaluated in the asymmetric hydrogenation of two
substrates: Methyl 2-acetamidoacrylate and dimethyl itaconate. One lab will test
the first substrate, and the other lab will test the other.
Scheme 3. Catalytic hydrogenation of methyl 2-acetamidoacrylate and of

dimethyl itaconate
The ligands, Rhodium and the substrates will be placed in a 96-well plate (this
will be done in a glove bag to enable working under a nitrogen atmosphere).
Both homo- and heterocomplexes of the UreaPhos ligands library will be
evaluated (see figure below).
Figure 1. 96-well plate for performing parallel reactions in the synthesis robot
(left), and the distribution of the samples on the plate (right).
The complexes are formed in situ by mixing stock solutions of ligands,

Rh(COD)2BF4 and substrates (on the scheme above). L1-L1 is the homocomplex
of the ligand L1, and L1-L2 is a heterocomplex.
The conditions of the catalysis will be the following:
- Solvent: Dichloromethane, volume: 1ml
- Catalyst concentration = 5 M
- Ratio Rh/L = 1:2 for UreaPhos, ratio Rh/L= 1:1 for IndolPhos
- Substrate concentration = 0.1 mM
- Conditions: 10 Bar H2 pressure; 2 hours; room temperature.
Procedure:
Preparation of the UreaPhos stock solution
In a Schlenk-flask, make a 0.025 mM solution of your ligand in dry
dichloromethane (0.2 mmol in 8 ml of DCM) and keep it under nitrogen.
Hydrogenation using UreaPhos homocomplexes as catalysts
In the glove bag, add the stock solutions of the UreaPhos ligand (400 l), the
Rhodium precursor (100 l) and the substrates (500 l) on the 96-well plate
using micropipettes.
Hydrogenation using UreaPhos heterocomplexes as catalysts
In the glove box, add the stock solutions of both UreaPhos ligands (200 l + 200
l), the Rhodium precursor (100 l) and the substrates (500 l) on the 96-well
plate using micropipettes.
The detailed procedure for the preparation of the plate will be given and
explained on the day of the practicum.
After depressurization of the reaction vials, samples will be taken out for chiral
GC analysis. For that, 100l of the reaction mixture will be diluted in 900 l of
DCM in a GC vial. Remember to correctly name the vials.

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Experimental Procedures for the Practicum

Day One: Preparation of the Ligands

According to Reek et al., Chem Comm, 2007, 864-866

Important: These ligands will be used for catalysis. In order to avoid

Day Two: Preparation of the Rhodium Complexes

Preparation of the homocomplex:

In a Schlenk-flask, dissolve 0.01 mmol of Rh(COD) 2BF4 and the ligand in 5 mL of

Preparation of the heterocomplex:

Day Three: Catalysis

Scheme 3. Catalytic hydrogenation of methyl 2-acetamidoacrylate and of

The complexes are formed in situ by mixing stock solutions of ligands,

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