Selectivity in an Encapsulated Cycloaddition Reaction Jian Chen and Julius Rebek,Jr. Org. Lett....
-
Upload
emilie-edrington -
Category
Documents
-
view
217 -
download
1
Transcript of Selectivity in an Encapsulated Cycloaddition Reaction Jian Chen and Julius Rebek,Jr. Org. Lett....
Selectivity in an Encapsulated Cycloaddition Reaction
Jian Chen and Julius Rebek,Jr.
Org. Lett. 2002, 4, 327-329
Tobe laboratoryShintaro Itano
Contents
• Introduction
Self-assembly
Cage-shaped molecular complexes
Previous work
Purpose of this work
• Results and discussion
1,3-Dipolar cycloaddition
1H NMR Measurement
Equilibrium constant and reaction rate
• Conclusion
Self-assembly• Self-assembly
the spontaneous and reversible organization of molecular units into ordered structures by non-covalent interactions.
Non-covalent interactions• hydrogen-bonding• dipole–dipole interaction• van der Waals interaction • metal–ligand coordination
O
O
OO
H
H
Lackinger, M.; Griessl, S.; Markert, T.; Jamitzky, F.; Heckl, W. M.J. Phys. Chem. B 2004, 108, 13652–13655.
Cage-shaped molecular complexes• Cage-shaped molecular complexes
The supramolecules formed by self-assembly via weak intermolecular interaction and having a cavity encapsulating guest molecules reversibly.
Yoshizawa, M.; Tamura, M.; Fujita, M. Science 2006, 312, 251–254.
2
Kang, J.; Rebek, J., Jr. Nature 1997, 385, 50-52.
Previous work: Capsule complex
The authors reported that the compound 1 dimerizes hydrogen bondings between edges. This cylindrical capsule 2 have a large cavity where two aromatic guest molecules can be accommodated.
1 2
CH3
Guest molecule
Heinz, T.; Rudkevich, D. M.; Rebek, J., Jr. Nature 1998, 394, 764-766.
Purpose of this workThe interior of molecular cage complexes becomes a space to stabilize reactive intermediates and to create new forms of stereoisomerism.
The authors investigated the ability of their capsule complex to accelerate a 1,3-dipolar cycloaddition with regioselectivity.
2
Accelerate?Regioselective?
1,3-Dipolar cycloaddition• 1,3-DipoleThe neutral molecules which have a resonance forms as foll.
• 1,3-Dipolar cycloadditionThe reaction between a 1,3-dipole and alkenes or alkynes to form a five-membered ring.
X Y Z X Y ZY ZX
X Y Z R1 R2X Y Z
R1 R2
YX Z
R1 R2
Guest moleculesThey chose phenylacetylene 3 and phenylazide 4 as the guest molecules. These compounds react to give a mixture of regioisomeric triazoles 5 and 6 equally in organic solvent.
N N
NN
NNH
H
N NN
H
N
H
N NN N
N
H
1,4-isomer 5
1,5-isomer 6
3 4
But, at ambient temperature the reaction rate is very slow. Rate constant k = 4.3 x 10-9 M-1 s-1
half life: several years (at 1 M each component)
1H NMR measurementAccelerating a 1,3-dipolar cycloaddition
t = 0
t = 1540 min
t = 4320 min
t = 8500 min
50 mM 25 mM
5 mM
2
in
CD3
D
CD3
D
D3C
D
N N NH
3 4
Mesitylene-d12
1 H NMR measurementRegioselectivity
・ Addition of DMF-d7 to
A: in mesitylene-d12
B:
in mesitylene-d12
C: in mesitylene-d12
N N
N
H
N N NH
3 4
Only 1,4-isomer was produced.
(●): 1,4-isomer’s peaks (▼): 1,5-isomer’s peaks
Selectivity of guest molecules
H
3
or
2
Triazole compound
N N N
H
H
N N N
3 + 7 + 2 3 + 8 + 2
The various encapsulated species
There are four encapsulated species in the solution; homocapsules 9 and 10, heterocapsule 11 and encapsulated 1,4-isomer 12.
NH resonance
1H NMR measurementAssignment of NH resonance
A: At t = 0 incubating
in mesitylene-d12
B: At t = 8500 min for incubating
in mesitylene-d12
C: in mesitylene-d12
N N NH
3 4
N N NH
3 4
(c) NH resonance of 11(d) NH resonance of 9(e) NH resonance of 10(f) NH resonance of 12(g) ortho-protons of the phenyl rings of encapsulated 1,4-isomer 5 in complex 12
NH resonance
1H NMR measurementAssignment of NH resonance
(c) NH resonance of 11(d) NH resonance of 9(e) NH resonance of 10(f) NH resonance of 12(g) ortho-protons of the phenyl rings of encapsulated 1,4-isomer 5 in complex 12
Equilibrium constant
KD = [11]2/[9][10]
KD: Equilibrium constant[x]: concentrations of x
・ Prediction by the statistical distribution
KD = 4・ Experimentally determined value
KD = 9 3
Experimentally observed value is larger than predicted value. The space of 11 is better occupied or there is a weak attractive force between the occupants.
Prediction by the statistical distribution
HN
N
N
H
N
N
N
N
N
N
H H
N
N
N
10 11 9
1 : 2 : 1
KD = [11]2/[9][10] = 22/1 ・ 1 = 4
Reaction rate
v = kcat[3][4]v: reaction ratekcat: reaction rate constant
・ Observed initial reaction rate in 2 1.3 x 10-9 M s-1
・ Calculated reaction rate outside 2 5.4 x 10-12 M s-1
・ Volume of the cavity of 2 ~450 Å
・ Reactant concentration in 2 3.7 M
・ Estimated reaction rate in 2 ~6 x 10-8 M s-1
Reaction rate
v = kcat[3][4]v: reaction ratekcat: reaction rate constant
・ Estimated rate is larger than initial rate actually observed.
・ Reactants’ positions of 2 are not ideal for the transition state.
・ Reaction rate in 2 is 240 times faster than it outside 2.
Conclusion
• 1,3-Dipole cycloaddition was accelerated by the capsule complex 2.
• In the capsule complex 2, only 1,4-isomer was formed.
• Equilibrium constant KD was bigger than the prediction. It suggest that the space in 11 is better occupied or there is a weak attractive force between the occupants.
• The actual observed reaction rate is slower than the estimated rate, but 240 times faster than the calculated rate outside 2.