6
K.A. Ostrowski et al. / Applied Catalysis A: General 509 (2016) 1–7
Fig. 9. Side chains of lysine and arginine.
Scheme 5. Developed arginine catalysed assisted tandem catalysis; Conditions: 1st
step = 6 mmol, 6.67 mol% arginin, 1 mL EtOH, RT, 3 h; 2nd step = 2 eq H2O2 (35% in
water), 16 h.
Table 2
Other substrates in the new tandem aldol condensation/epoxidation.
No.
Substrate
H2O2[eq]
Yaldolcondensate
Yepoxyaldehyde
ꢀY
2.1
2.2
2.3
2.4
2
4
2
4
34
16
29
16
23
42
49
42
57
58
78
58
Scheme 6. n-Butyl amine and guanidine as not-efficient organocatalysts in the
homo aldol condensation [10].
Table 3
Conditions: 1st step = 6 mmol substrate, 6.67 mol% arginin, 1 mL EtOH, r.t., 3 h; 2nd
step = adding H2O2 (35% in water), r.t., 16 h; all results in %.
Detailed studies regarding the catalytic activity of the side chain groups of the basic
amino acids.
No.
Catalyst
[mol%]
6.67
Y3
d.r. (3)
observed (Entry 1.6). This was improved even more, since the appli-
cation of higher substrate concentrations at shorter reaction times
3 with only 4% remaining intermediate (Entry 1.7). In summary,
90% yield for the intermediate aldol condensate was obtained, from
which 97% was converted into the desired compound 3 leading
(Scheme 5).
3.1
3.2
3.3
3.4
3.5
Lysine
Arginine
nBuNH2
43
43
41
55
52
2.0
2.0
1.9
1.0
1.1
6.67
6.67
6.67
3.33
Guanidine × 1/2 CO3H2
Na2CO3
Conditions: 3 mmol 2, amino acid, 110 mol% H2O2 (35% in water), 1 mL EtOH, r.t.,
16 h; all results in %.
Other substrates, propanal (5) (Entries 2.1–2.2) and phenyl-
propionaldehyde (6) (Entries 2.3–2.4), were applied successfully
at same conditions (Table 2). Unfortunately, lower yields were
achieved. The lower activity of 6 can be explained by a bipha-
sic reaction mixture leading to a phase transfer limitation. Higher
concentrations of hydrogen peroxide did not lead to higher yields
simulating an amino acid mixture almost no yield of the aldol con-
densate 2 have been observed [10].
Then, we applied n-butyl amine and guanidine in the epoxida-
similar yields of 41–55% (Entries 3.3–3.4), if compared to the lysine
(Entry 3.1) and arginine (Entry 3.2) catalysed epoxidation with
yields of 43%. The reaction mechanism of these catalysts can be
explained by an iminium catalysis [7e]. The commercially avail-
able guanidine carbonate salt showed higher activity leading to
55% yield of the epoxy aldehyde 3 assuming an enhanced catalytic
activity, due to the carbonate activation of hydrogen peroxide [14]
analogous to the bicarbonate activation [15] (Formula 1). Na2CO3
was catalytically active in the epoxidation as well (Entry 3.5).
3.4. Amino acids with different catalytic centres in their structure
In Fig. 3 the results of the proteinogenic amino acid catalysed
epoxidation were summarised. Most of these amino acids were not
active as organocatalyst in the epoxidation, if applied in catalytic
amounts (1.67–20 mol%). Only the basic amino acids, arginine and
lysine, catalysed the epoxidation successfully. Both amino acids are
characterised by a guanidine or a butyl amine side chain (Fig. 9),
amine and guanidine salt were applied in the homo aldol condensa-
tion of butanal (1) and in the epoxidation of 2-ethylhex-2-enal (2).
Both compounds represent the side chains of lysine and arginine
(Scheme 6).
HCO−3 + H2O2 ꢀ HCO− + H2O
4
Formula 1. Equilibrium of bicarbonate and hydrogen peroxide.
On the basis of these investigations, we can divide the molecu-
lar structure of lysine and arginine in two catalytic centres, which
catalyses different reactions in the tandem catalysis (Fig. 10). The
␣-amino group is catalytically active in the homo aldol conden-
sation of aldehydes, which is described by enamine catalysis [10].
This ␣-amino group is not active as catalyst in the epoxidation,
explaining the poor to non-conversion of 2 if using the other 18
proteinogenic amino acids, which are displayed in Fig. 3. The side
chains, butyl amine and guanidine, are active in the epoxidation
n-Butyl amine and guanidine were not active in the homo
aldol condensation of 1 at given conditions, proving that only the
␣-amino function of lysine and arginine is active in the enam-
ine catalysis/homo aldol condensation. Even if acid was added
Fig. 10. Displayed different catalytic centres of lysine and arginine.