Organocatalysis by Hydrogen Bonding Networks
283
that the crucial feature is the reduction of activation energy by effective
hydrogen bonding to the transition state of a reaction, whereas substrate
binding alone is not sufficient.
2
Case Studies
2.1
Epoxidation and Baeyer–Villiger Oxidation with Hydrogen
Peroxide in Fluorinated Alcohol Solvents
The epoxidation of olefins with hydrogen peroxide is dramatically accelerated in fluorinated alcohols as solvents (Berkessel and Andreae
2001; Neumann and Neimann 2000, Sheldon et al. 2001) For example,
in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as solvent, Z-cyclooctene
is fully converted to the corresponding epoxide by 50% aqueous hydrogen peroxide at 60 °C within minutes. In 1,4-dioxane as solvent, only
a few percent of product are formed under the same conditions. In fact,
the acceleration in HFIP is in the range of 10
5 -fold (Berkessel and Adrio
2004). A thorough kinetic analysis revealed that the fluorinated alcohol
solvent had a kinetic order of 2–3, indicating the involvement of 2–3
molecules of HFIP (Berkessel and Adrio 2006; Berkessel et al. 2006).
Both the olefin substrate and the oxidant showed first order dependence
of rate on concentration. An investigation of the aggregation behavior of
HFIP, by determination of its hitherto unknown crystal structure, proved
the existence of H-bonded and endless helices, as shown in Fig. 1. DFT
calculations on the H-bond donor ability of HFIP aggregates indicated
that the clustering of the HFIP monomers leads to cooperatively enhanced H-bond donor ability (Berkessel et al. 2006).
According to our quantum chemical analysis, the oxygen transfer
from hydrogen peroxide to the substrate olefin, in the presence of HFIP,
proceeds through a single transition state. Hydrogen bonding by the
fluorinated alcohol solvent significantly reduces the activation barrier
(Berkessel and Adrio 2006; for a DFT-study involving only one HFIP
molecule see Neumann et al. 2003). We were able to localize transition
states comprising up to four molecules of HFIP. However, as the activation entropy becomes more and more unfavorable the more molecules
of HFIP are involved, the overall optimal free energy of activation is
found for 2–3 HFIPs (Fig. 2) which coincides with our kinetic results
283
that the crucial feature is the reduction of activation energy by effective
hydrogen bonding to the transition state of a reaction, whereas substrate
binding alone is not sufficient.
2
Case Studies
2.1
Epoxidation and Baeyer–Villiger Oxidation with Hydrogen
Peroxide in Fluorinated Alcohol Solvents
The epoxidation of olefins with hydrogen peroxide is dramatically accelerated in fluorinated alcohols as solvents (Berkessel and Andreae
2001; Neumann and Neimann 2000, Sheldon et al. 2001) For example,
in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as solvent, Z-cyclooctene
is fully converted to the corresponding epoxide by 50% aqueous hydrogen peroxide at 60 °C within minutes. In 1,4-dioxane as solvent, only
a few percent of product are formed under the same conditions. In fact,
the acceleration in HFIP is in the range of 10
5 -fold (Berkessel and Adrio
2004). A thorough kinetic analysis revealed that the fluorinated alcohol
solvent had a kinetic order of 2–3, indicating the involvement of 2–3
molecules of HFIP (Berkessel and Adrio 2006; Berkessel et al. 2006).
Both the olefin substrate and the oxidant showed first order dependence
of rate on concentration. An investigation of the aggregation behavior of
HFIP, by determination of its hitherto unknown crystal structure, proved
the existence of H-bonded and endless helices, as shown in Fig. 1. DFT
calculations on the H-bond donor ability of HFIP aggregates indicated
that the clustering of the HFIP monomers leads to cooperatively enhanced H-bond donor ability (Berkessel et al. 2006).
According to our quantum chemical analysis, the oxygen transfer
from hydrogen peroxide to the substrate olefin, in the presence of HFIP,
proceeds through a single transition state. Hydrogen bonding by the
fluorinated alcohol solvent significantly reduces the activation barrier
(Berkessel and Adrio 2006; for a DFT-study involving only one HFIP
molecule see Neumann et al. 2003). We were able to localize transition
states comprising up to four molecules of HFIP. However, as the activation entropy becomes more and more unfavorable the more molecules
of HFIP are involved, the overall optimal free energy of activation is
found for 2–3 HFIPs (Fig. 2) which coincides with our kinetic results