Download pdf file

Research Interests of the Straub Group
Our research covers several topics of organometallic chemistry.
1) Investigation of the mechanism of the copper-catalyzed azide alkyne reaction
(Huisgen Sharpless triazole click reaction), particularly the origin of the secondorder dependence of the reaction rate on the copper concentration.[1]
Cu2
+e
H
+ HCCR
[Cu]
Cu
R
+H
- triazole
R'
N N
N
R'
[Cu]
[Cu]
R
[Cu]
R
strain-free
µ-alkenylidine
dicopper complex
- H + Cu
- Cu
R'
N
+ R'N3
N N
C
[Cu] C
[Cu]
R'
R
N
N
N N
C
[Cu] C
R
highly strained
six-membered cycle
with bend sp-carbon
N
[Cu]
N
R
[Cu]
We isolated a copper(I) triazolide complex,[2] a so far only proposed intermediate
in click chemistry.
The triazolide complex is formed at RT from an organoazide and an acetylide
complex. The triazolide is thermally stable in the solid state and in solution, but it
is rapidly protonated by e.g. acetic acid. Apparently, N2 elimination from the
triazolide ligand does not occur with the substitution pattern present in this click
intermediate.
In a quantum-chemical model study, we identified thermodynamically stable
dinuclear and tetranuclear copper acetylide structures as reasonable starting
catalysts.[1] Mononuclear model species and aqua complexes have to be considered as irrelevant, high-energy species. Bridging acetylides are predicted to be
both more thermodynamically stable as well as more reactive from a kinetic perspective. The favored (green) pathway comprises two copper atoms binding to
an evolving sp2 carbon in the rate-determining step. In the disfavored (red) alternative, a highly ring-strained sp-type carbon in a six-membered cycle would be
enforced, thereby increasing the formation barrier by an additional >30 kJ mol-1.
N N
H
N
CH3
‡
H3C
Cu
Cu
‡
N N
H
Cu
Cu
N
N
N
Favored Pathway
N
N
Higher Barrier
by >30 kJ mol-1
Additives such as phenanthroline are proposed to increase the efficiency of
CuAAC click reactions by – among other reasons – inhibit copper acetylide
aggregation.
[1] B. F. Straub*, Chem. Commun. 2007, 3868-3870.
[2] C. Nolte, P. Mayer, B. F. Straub*, Angew. Chem. 2007, 119, 2147; Angew.
Chem. Int. Ed. 2007, 46, 2101.
2) Synthesis of non-homoleptic tertiary phosphines, tailoring ligands for transition
metal catalysis in organic synthesis. A didactic and aestethic phosphine synthesis is the preparation of the “3-2-1 phosphine” depicted below.[3]
P(OPh)3
1) 9-Anthryllithium,
THF, < -78°C
P
2) 1-Naphthyllithium
3) PhLi, RT
one-pot, isolated 66 %
[3] J. Keller, C. Schlierf, C. Nolte, P. Mayer, B. F. Straub, Synthesis 2006, (2),
354.
3) We develop novel coinage metal catalysts inspired by the ethene receptor
protein ETR1.[4] The latter is responsible for the recognition of traces of the plant
hormone ethene by plants, leading to e.g. stress responses or fruit ripening. The
core of ETR1 is an uncharged copper(I) imidazole thiolate unit, stabilized against
cluster formation by steric shielding due to the protein backbone.
S
Cu
N
CH2
CH2
N
Figure 1. Ethene receptor protein ETR1
We tailor chelating, electron-rich monoanionic thiolate ligands with sterically demanding substituents to mimic the electronic and steric situation of the active
protein site.
[4] a) F. I. Rodríguez, J. J. Esch, A. E. Hall, B. M. Binder, G. E. Schaller, A. B.
Bleecker, Science 1999, 283, 996;
b) A. B. Bleecker, H. Kende, Annu. Rev. Cell. Dev. Biol. 2000, 16, 1.
4) We investigate mechanisms of transition metal catalyzed reactions by
DFT model calculations. Convential experimental methods are often not suited
to gain information about reactive intermediates or transition states that are
neither the rate- nor the selectivity-determining step.
a) Palladium-catalyzed cyclopropanation of alkenes by CH2N2
R
R
H
N2
+
+ N2
[Pd]
H
Predicted mechanism:
Pd
palladium(0) alkene complex
resting state
+/- C2H4
catalyst resting state
formation
+ C2H4
Pd
+ CH2N2
product release
+/- CH2N2
Pd
Pd C
H2
preequilibria
N2
Pd CH2
N2
+/- C2H4
N2
Pd
rate-determining
transition state:
N2 elimination
Pd CH2
- N2
reductive
elimination
Pd
short-lived
palladium(II) intermediate
Pd
Pd
Pd
[5] B. F. Straub, J. Am. Chem. Soc. 2002, 124, 14195.
H
H
active carbene species
cis-rearrangement
4b) Reppe’s Nickel-catalyzed Ethyne Tetramerization
Ni(CN)2, CaC2
4
H
H
THF
Predicted mechanism:
Ni
+ C2H2
Ni
- C2H2
Ni
+ C2H2
Ni
- C2H2
- C2H2
+ C2H2
Ni
Ni
+ C2 H2
Ni
Ni
[6] W. Reppe, O. Schlichting, K. Klager, T. Toepel, Justus Liebigs Ann. Chem.
1948, 560, 1.
[7] B. F. Straub, C. Gollub, Chem. Eur. J. 2004, 10, 3081.
4c) Gold-catalyzed Benzannulation
In Y. Yamamoto’s benzannulation reaction,[8] it remains unclear whether gold(III)
or reduced gold(I) species are the active catalyst.
O
Ph
Ph
Me
+
O
Me
H
cat. AuCl3
Me
CH2Cl2
Me
In our DFT study,[9] both AuCl and AuCl3 are predicted to feature almost identical
overall Gibbs free activation energies. Surprisingly, no direct [4+2] cycloaddition
step can be located, but a pathway comprising a [3+2] cycloaddition with
subsequent rearrangements.
Predicted mechanism (X = 1 or X = 3):
ClxAu
H
AuClx
H
O
O
H
H
O
H
+ C2H2
H
O
H
O
AuClx
AuClx
AuClx
H
O
O
H
H
[8] (a) N. Asao, K. Takahashi, S. Lee, T. Kasahara, Y. Yamamoto, J. Am. Chem.
Soc. 2002, 124, 12650. (b) N. Asao, T. Nogami, S. Lee, Y. Yamamoto, J. Am.
Chem. Soc. 2003, 125, 10921. (c) N. Asao, K. Sato, Y. Yamamoto, Tetrahedron
Lett. 2003, 44, 5675. (d) G. Dyker, D. Hildebrandt, J. Liu, K. Merz, Angew. Chem.
2003, 115, 4736; Angew. Chem. Int. Ed. 2003, 42, 4399.
[9] B. F. Straub, Chem. Commun. 2004, 1726.
4d) The origin of the differences of metathesis activity of ruthenium carbene
complexes (first generation versus second generation Grubbs catalysts) is due to
the electronic and steric stabilization of active and inactive carbene conformations.[10] Strongly electron-donating spectator ligands L such as N-heterocyclic
carbenes stabilize the active carbene conformation and facilitate the [2+2]
cycloaddition to a ruthenacyclobutane intermediate. Alkene ligand rotation in the
alkene carbene complexes is rapid and the alkene ligand conformations are
almost degenerate.
[10] (a) B. F. Straub, Angew. Chem. 2005, 117, 6129; Angew. Chem. Int. Ed.
2005, 44, 5974; (b) B. F. Straub*, Adv. Synth. Catal. 2007, 349, 204.
4e) In ruthenium-carbene catalyzed enyne metathesis,[11] ruthenacyclobutenes
are not intermediates in the catalytic cycle, but only transient structures with the
lifetime of a molecular vibration.[12]
R'
R
[Ru]=CHPh
H +
R'
R
PCy3
Cl
Ru CHPh
[Ru]=CHPh =
Cl
Mes N
N Mes
Cl
Ru CHPh
Cl
PCy3
H
Cy = cyclo-C6H11
Ph = C6H5
Mes = 2,4,6-Me3C6H2
PCy3
All relevant steps of the catalytic cycle have been modelled for both the intra- and
intermolecular reaction of alkene and alkyne substrate.
[11] (a) S. T. Diver, A. J. Giessert, Chem. Rev. 2004, 104, 1317; (b) S. T. Diver,
A. J. Giessert, Synthesis 2004, 466; (c) C. S. Poulsen, R. Madsen, Synthesis
2003, 1; (d) M. Mori, Top. Organomet. Chem. 1998, 1, 133.
[12] J. J. Lippstreu, B. F. Straub, J. Am. Chem. Soc. 2005, 127, 7444.
R N
R N
N R
Cl
H
Ru
H
- PR'3
Cl
PR'3
Cl
+ C2H4
+ PR'3
N R
Cl H
active catalyst
Ru
H
Cl
R N
+ C2H2
- C2H2
-
Cl
ethyne
association
+
N R
product
Cl
H π complex
Ru
H
Cl
N R alkyne π complex
Cl
H
Ru
H
slow irreversible
alkyne
insertion
R
no
ruthenacyclobutene
local minimum
Cl
N R
R N
Ru
Cl
dead-end
equilibrium
- PR'3
- C2H2
Cl
N R
H
Cl
Cl
+ C2H2
N R
Cl
Ru
R N
N R
Cl
H
Ru
Cl
competing
alkyne
N R polymerization
Ru
Cl
R N
PR'3
Cl
η3-allyl
ruthenium
derivative
N R
Cl
Ru
+ PR'3
Ru
R N
Ru
Cl
+ C2H4
Cl
Cl
Ru
- C2H4
N R
N R
R N
H
ethene
association
R N
H
R N
Cl
Ru
cisoid-transoid
isomerization
[2+2]
cycloaddition
Cl
Cl
N R
N
Cl
[2+2] cycloreversion,
R N
N R
Cl
Ru
R N
rapid alkene metathesis
- C2H4
R N
R N
N R
Cl H
Ru
H
Cl
computed model complexes:
R = R' = Me
experimental catalyst:
R = mesityl;
R' = Cy
N R precatalyst
Cl H
- PR'3
Ru
H
Cl
+ PR'3
PR'3
R N N R + substrate
Cl
- product
H2C Ru
R N NR
N
N
R
Cl
R
Cl
H
- substrate
Cl + product
Ru
H2C Ru
H
Cl
Cl
R N
[2+2] cycloreversion,
rate-limiting step
N R
R N
[2+2] cycloaddition
Ru Cl
Cl
Cl
N R
Cl
Ru
R N
Cl
H
model complexes
R = R' = Me
+ C2H4
R N
- C 2H 4
experimental catalyst
R = Mes;
R' = Cy
N R
Cl
Ru
N R
Cl
Ru
Cl
+ C 2H 4
R N
H
Cl
- C 2H 4
N R
Cl
Ru
Cl
- PR'3
+ PR'3
+ PR'3
R N
N R
Cl
Ru
Cl
R'3P
Cl
Ru
[2+2] cycloreversion
[2+2] cycloaddition
R N
N R
R N
- PR'3
R N
N R
Cl
Ru
Cl
catalyst resting state
R N
H
N R
Cl
Ru
Cl
R N
H
N R
Cl
Ru
Cl
PR'3
irreversible alkyne insertion