Combinatorial Chemistry: Carbon-Carbon-Bond Building/Formation

14 Pages·2006·0.15 MB·English

Combinatorial Chemistry:
Carbon-Carbon-Bond
Building/Formation
Presented by Dominik Grögel
Contents
1.Resins
2.Types of Reaction
2.1 Condensation
2.2 Cycloaddition
2.3 Carbon - Alkylation
2.4 Olefin Formation
2.5 Pd-catalysed Couplings
3. Applications
4. Conclusion
5. References
1. Resins and Linkers
Merrifield
Rinkamide SASRIN
(X=NH)
Furthermore: Safety Catch, trityl, HMPA, traceless, MBHA
2. Types of Reaction
2.1 Condensation
Claisen
(cid:132)
Resins/Linkers: Merrifield, Rinkamide
O
O O O
MeO
H H
N N
O O
Knoevenagel
(cid:132)
Resins/Linkers: Wang, SASRIN, Merrifield
Mannich
(cid:132)
Resins/Linkers: 2-chlorotrityl, Merrifield, Wang
Lit.: Reference [1]
2.2 Cycloaddition
Important tool for constructing cyclic systems of different
ring-size.
[2+2] Cycloaddition
(cid:132)
O
R OR
O
OR ² ³
³
Cl
O
N R
N R ² N
H O
N R
H
β-Lactam
Resins: SASRIN, MBHA
(cid:131)
[4+2] Cycloaddition
→Diels-Alder reaction
Resins: Merrifield or PS carboxylic acid resin
Lit.: Reference [1]
2.3 Carbon-Alkylation
(cid:132) Aldoladdition
O
OTMS O OH
R H
²
R
S S R
Lewis-Acid
²
R
O
O
R X
N Ph
O N Ph
BEM P O
Ph
R Ph
(cid:132) Alkylation of the α-carbon of benzophenone imines:
→ synthesis of unnatural aminoacids on the resin
→ synthesis of unusual peptides
(cid:132) Resins: Merrifield, Rink Amide, etc.
Lit.: Reference [1]
2.4 Olefin-Formation
Wittig
(cid:132)
Ylid-based reactions have been successfully
transformed to the solid phase
O
O
Ph P
3
O O
O
(cid:131)
Cross Metathesis
Si
R Si R
Ru
Lit.: Reference [1]
2.5 Pd-catalysed Reactions I
The three „classical“ Pd-catalysed C-C-bond
building reactions have been successfully
transformed to solid-phase chemistry:
Heck
(cid:132)
Stille
(cid:132)
Suzuki
(cid:132)
Also: Sonogashira-Hagihara
2.5 Pd-catalysed Reactions II
Stille:
(cid:132)
In most cases the aryl-halide is bound to the polymer. The
aryl/vinyl-stannane must be aded.
Resins/Linkers: Rink, Wang, HMPA, traceless
Heck:
(cid:132)
There is no difference in reactivity if the alkene or the aryl-
halide is bound to the resin.
Resins/Linkers: Wang, Rink, THP, trityl
Suzuki:
(cid:132)
Both polymer-bound aryl-halide and polymer-bound boronic
acid give satisfactory results (like Heck).
Resins/Linkers: Wang, Rink amide, SafetyCatch, THP, traceless
Lit.: Reference [1]
2.5 Pd-catalysed Reactions III
Another possibility: Pd is bound to
the polymer
Angew. Int. Ed. 2006, 45
Polyionic gel beads build a highly
polar microenvironment, which
can be used for:
Efficient metal scavenging
(cid:132)
Active heterogenous catalyst
(cid:132)
preparation
Pd-particle size ranged from 3 to
10 nm
Lit.: Reference [4]