1. Polymer Supported Reagents & Catalysts
Contents
Polymer reagent : oxidation reagent, bromination,..
Polymer catalyst : C-C coupling catalyst

2. Polymeric Supports in Organic Chemistry
Solid-Phase Synthesis
(Peptides, DNA, ...)
Supported Reagents &
Catalysts during Synthesis
Rapid Development of Combinatorial Chemistry
Advantages of Supported Reagents
Easy separation of polymer and its bound component
Recycling possible (especially for expensive catalysts)
Can use high concentrations of reagents
Easier chemistry than solution-phase synthesis

3. Basic Concept of Solid Phase
Organic Synthesis
Catalyst or

4. Polymer Supported Reagents
Oxidation
Reduction
Nucleophilic reaction
C-C bond formation
Amide bond formation
Reagent
filtration
substrate
product
- Example of polymer supported oxidant
Dihydroxylation of alkene
Oxidation of alcohol
C-OH
C=O
Epoxidation & oxidation of amine

5. Polymeric Reagents for amide bond formation
reddish orange
60-99% yield
dark brown
R-COCl,
R-CO2H
R’-NH2
Yoon-Sik Lee et al. Tetrahedron Lett., 44, 2003,

6. Polymeric Scavenger Scavenger Acidic A(excess) + B Basic A-B + A
Nuclophilic
filtration
A-B
Electrophilic

7. Polymeric Oxidant : IBX reagent
IBX (o-iodoxybenzoic acid)
Efficient, selective, mild and environmentally safe oxidizing agent
Synthesis of carbonyl compounds from primary or secondary alcohols
No oxidative cleavage (1,2-diols)
Insoluble in organic solvent (except DMSO) thru inter H-bonding
DMP
IBX
IBX amide
IBX is mild oxidizing agent that convert primary or secondary alcohol to aldehyde or ketone.
In history of ibx, periodinane was prepared by Dess & Martin group in 1983, then O-iodoxybenzoic acid was prepared by Frigerio group in In 2003, zhdankin group reported 2-iodoxybenzoic acid ester type ibx.
(1983)
Dess & Martin
(1994)
Frigerio et al.
(2003)
Zhdankin & Tykwinski

8. Solubility Problem of IBX
Rxn in ionic liquid/water
Rxn at elevated temp.
Liu et al.
Org. Lett. (2003)
More et al.
Org. Lett. (2002)
β-cyclodextrin
Water-soluble
derivative of IBX
With catalyst
Thottumkaraa et al.
T. L. (2002)
Surenda et al.
J. Org. Chem. (2003)
IBX amide
Zhdankin et al.
Angew. Chem. (2003)
Polymer supported IBX

9. Rxn at High Temp or with Catalyst
Rxn at elevated temperature
- Jesse D. More et al. Org. Lett. 2002, 4,
Solvent: EtOAc, CHCl3, DCE, toluene, THF
Decomposition problem
With catalyst
- K. Surendra et al. J. Org. Chem. 2003, 68, β
Supramolecular catalysis

10. Soluble IBX Derivatives (I)
Water-soluble derivatives
- A. P. Thottumkaraa et al. Tetrahedron Lett. 2002, 43,
Solvent: Water/THF (3:2)
Temp.: ℃
Oxidant: 1.5 eq.
Rxn time: 3–12 h
Only electronically active
substrate were oxidized

11. Soluble IBX Derivatives (II)
IBX amide
- V. V. Zhdankin et al. Angew. Chem., Int. Ed. 2003, 42, 2194–2196
R-NH2: amino acid
Reactivity similar to IBX
Pseudo cyclic structure (intramolecular secondary I•••O bonds):
- partially replace the intermolecular I•••O secondary bonds that afforded the polymeric
structure of other reported iodylarenes
soluble

12. Preparation of IBX Reagent Resin
IBX-ester resin
IBX-amide resin
In our strategy, we will use three classes of polymer supports. PS gel type bead, macroporous bead, surface grafted bead. Also we Classified hydroxy bead and amino bead according to functional group. First step is coupling. Polymer bound iodoacid was prepared from functionalized beads and 2-iodobenzoic acid using DIC coupling and BOP coupling.
Second step is activation. In other words oxidation. In this step we used tetrabutylammonium oxone in dichloromethane containing the same equivalent of methanesulfonic acid or DMDO(dimethyl dioxirane) as activating agents.
Polymer support: BTCore™-OH *, BTCore™-NH2
* Yoon-Sik Lee et al. Tetrahedron Lett. 1997, 38, 591–594
Oxone : potassium peroxymonosulfate, 2KHSO5 KHSO4 K2SO4

13. FT-IR Spectra (coupling)
Coupling of 2-Iodobenzoic acid to BTCoreTM-OH
hydroxy
carbonyl
It’s a FT-IR spectrum of ester type bead after coupling reaction. As you can see, after coupling reaction Hydroxy peak of hydroxy bead disappeared and carbonyl peak appeared.
1724 cm-1
Appearance of 1655 cm-1 (C=O stretch of amide)

14. Activation (step 2) Bu4N-Oxone, MeSO3H (5eq. each) / DCM, 30℃, 20 h
IBX ester
resin
Bu4N-Oxone, MeSO3H (5eq. each)
In activation step, we used three different methods. Method A, tetrabutylammonium oxone in dichloromethane containing the same equivalent of methanesulfonic acid. Method B, tetrabutylammonium oxone in dichloromethane without methanesulfonic acid. Method C DMDO,dimethyldioxirane. Using method A and C, Iodinated polymer was oxidised. But Method B oxidation was not occurred. The addition of methane sulfonic acid forms Caro’s acid(monoperoxysulfuric acid) in situ, which is a stronger oxidant than Oxone alone.
The loading level of polymer supported IBX was determined by titration using benzyl alcohol.
/ DCM, 30℃, 20 h
IBX amide
resin

15. FT-IR Spectrum (activation) Activation of BTCore™- 2-Iodobenzamide
Activation of BTCore™-2-iodobenzoate
activation
This slide shows FT-IR data of Prepared BT-Core-Iodobenzoate using method A. tetrabutylammonium oxone and methanesulfonic acid actvation.The progress of oxidation was measured by a shift the acid carbonyl to broad carbonyl peak approximately. according to reaction time increase, reaction is progressed.
Characteristic peak
C=O: 1674 cm-1
I=O: cm-1
Activation of BTCore™- 2-Iodobenzamide
- peak shift (C=O of amide) : 1655 cm-1  1620 cm-1

16. Determination of Loading Level - Titration by benzyl alcohol
oxidant resin
RT, 18hr
excess
100mg of resin / 1mL of DCM
GC-Mass Analysis
To determine loading level of polymer supported IBX reagent, we used 3 equivalent of benzyl alcohol and enough reaction time. After reaction the benzyl alcohol and benzaldehyde mixture was analyzed by GC-MS, then we calculate loading level of oxidant bead using peak area ratio.
BTCore™-IBX ester
(from 2.1 mmol/g )
(from 0.91 mmol/g )
BTCore™- IBX amide
Loading Level of resin
1.1 mmol/g (HL)
0.65 mmol/g (SL)
0.98 mmol/g

17. Time Course (benzyl alcohol oxidation)
at 25℃ in DCM (100mg of resin / 1 mL)
BTCore™- IBX ester
2eq. of resin (SL) (▲)
2eq. of resin (HL) (■)
4eq. of resin (HL) (□)
BTCore™- IBX amide
1.2eq. of resin (○)
2eq. of resin (●)
BTCore™- IBX amide exhibited
fast oxidation of benzyl alcohol

18. Bromination using IBX Amide resin
* Yoon-Sik Lee et al. SYNLETT. 2005, 2, 279–282
TEAB ( Tetraethylammonium Bromide )
In our method, BT-IBX amide used as oxidant and TEAB as bromide source.
Et4NBr3 * : Mild brominating agent
IBX amide resin : Oxidizing agent
* S. Kajigaeshi et al., J. Chem. Soc., Perkin Trans , 897.

19. Results of Bromination
entry
IBXa:TEAB
Time (h)
Substrate
Product
Yieldb (%) 1
3:3
0.5
82.8 2
4:4
51.6 3 95 4
1:1
2.5
94.5
(1 : 6.4)
a IBX : IBX amide resin (0.99mmol/g) , b isolated yields

20. Oxidation of Sulfides & Phosphites
entry
oxidant
(eq)
t (h)
substrate
product
conversiona (%) 1 2 3
99% 6 15 4
1.2
0.25
P(OEt)3
O=P(OEt)3 5
4.5
P(OPh)3
O=P(OPh)3
a GC-MS analysis; 100 mg of resin / 1.5 mL of DCM

21. Regeneration of IBX Amide Resin
Oxidant resin
Loading capacity (a.u.)
(0.59 mmol/g)
Initial 1 2 3 4 5 6 7 8 9
Benzyl alcohol (3 eq.) oxidation
: RT, 18h
reuse (#)
Regeneration: Bu4N-Oxone, MeSO3H (5eq. each) / DCM at RT for 20h
Oxidative activity was maintained during 9 times oxidation & regeneration

22. Macroporous PS-supported IBX amide
Advantages of MPS (Macroporous Polystyrene)
Less solvent diffusion problem.
Large surface area.
Much broader solvent system.
Less swellable.
Applicable to Pack-bed reactor flow-system.
Synthetic Scheme
i) 2-iodobenzoic acid, DIC, HOBT, DIEA, DMF, rt, 6h; ii) NBu4SO5H, MeSO3H, DCM, rt, 10~12 h.

23. Solvent-friendly MPS-IBX amide
Comparison of several solvents
MPS-IBX amide
A gel type of PS-IBX amide
Using 2 equiv of oxidant at rt and methoxybenzyl alcohol as the substrate.
DCM (□), ACN (♦), THF (■), acetone (▲) and diethyl ether (+).
Conversion (%) was determined by 300MHz 1H NMR spectroscopy.

24. IB-Core Resin Preparation of imidazolium-bound Core (IB-Core) bead
1) CHCl3
50℃
5hr
PF6-
immiscible with styrene
and water. +
2) NaPF6
Acetone
25℃
2 days
1.3 eq
[MVBIM][PF6-]
- Polymerization Time : 20 hours
- Polymerization Temperature : 70 º C
- RPM : 200 ~ 300
PF6-
water
Suspension polymerization
PF6-
oil
Tetrahedron Lett. 2004, 45, , J. W. Byun, Y. S. Lee
Tetrahedron Lett. 2004, 45, , J. H. Kim, Y. S. Lee

25. IB-Core Resin
FE-SEM & CLSM images of imidazolium-bound Core (IB-Core) bead
20 ㎛
20 ㎛

26. IB-Core Resin Immobilization of Pd for Suzuki C-C coupling Pd(OAc)2
1, 2, 4 eq
Cs2CO3
H2O/DMF
50 ℃, 2 h
IB-1 (0.23 mmol/g)
IB-NHC-Pd complex

27. IB-Core Resin Suzuki C-C coupling reaction using IB-NHC-Pd complex
(1 mol%)
Ph-B(OH)2 , 50℃
DMF/ H2O
=1/1
Entry R X
Base
Time
(h)
Isolated
Yield
(%) 1 OH I
Na2CO3 95 2
OCH3 94 3
CH3 4 Br 6 93 5 92
CHO 7
COOH 8

28. IB-Core Resin Reusability of IB-NHC-Pd complex Isolation yield(%)
(1 mol %)
Ph-B(OH) eq
Na2CO eq
for 1 h at 50℃
Isolation yield(%)
The number of recycling