Beilstein J. Org. Chem. 2020, 16, 2338–2345.
Table 2: Enamine-catalyzed nitro-Michael reaction with hierarchically assembled helicates.a
Entry
catalyst
mol %
T
t
[d]
yield
[%]
dr
[°C]
1
2
3
4
5
6
7
8
9
b
13a-H2
25
15
15
15
7.5
15
15
15
15
rt
rt
rt
0
2
3
3
7
1
3
3
3
3
45c
0
52:48c
–
Li4[(13a)1(2)5Ti2]
Li4[(13b)1(2)5Ti2]
Li4[(13b)1(2)5Ti2]
Li4[(13b)1(2)5Ti2]
Li4[(13c)1(2)5Ti2]
Li4[(13d)1(2)5Ti2]
Li4[(13b)1(4)5Ti2]
Li4[(13b)1(5)5Ti2]
88
71
48
0
83:17
87:13
65:35
–
70
rt
rt
rt
rt
0
–
13
27
80:20
80:20
aNo enantioselectivity was achieved. bReaction was performed in DMSO-d6 (0.26 M) due to solubility limitations of the free ligand with 3 equiv of
propanal. cValues determined by integration of the crude NMR spectrum of the reaction.
Catalysis at the “statistical” helicates was carried out with tivity. A reasonable diastereoselectivity of 60% de was ob-
5
equivalents of propanal (14) in order to gain a higher conver- served for both catalysts. The limited solubility of these com-
sion. Beside a significant control over the diastereomeric ratio plexes caused a significant reduction of the yield at room tem-
no enantioselectivity was achieved with helicates as catalysts. perature and due to this the reaction was not performed at lower
Catalysts at concentrations of 15 mol % were used in CDCl3 at temperatures.
room temperature and 0 °C with three or seven days of reaction
time. The conversion was controlled by NMR spectroscopy and Conclusion
TLC. The helicate Li4[(13a)1(2)5Ti2] did not lead to any An optimization of the Diels–Alder reaction taking place in the
conversion at room temperature (Table 2). The catalyst periphery of hierarchically assembled helicates was carried out.
Li4[(13b)1(2)5Ti2] with an ethyl-substituted amine worked well It was based on the elucidated induction pathway showing that
resulting in 88% yield and 66% de at room temperature. The the stereoselectivity was due to the proximity of the chiral units
diastereomeric excess increased slightly to a maximum of 74% of ligand 2 to the diene unit. The helicity of the helicate did not
de (dr 87:13) at 0 °C. A dramatic decrease to 30% de was ob- have a significant influence. After optimization of solvent,
served by lowering the catalyst loading to 7.5 mol % while in- chiral ligand, and substituent at the dienophile stereoselectivity
creasing the temperature to 70 °C. No enantioselectivity was was nearly tripled. Up to 58% ee was achieved in the
observed using the helicate Li4[(13b)1(2)5Ti2] as catalyst. The Diels–Alder reaction in chloroform with the indanyl-substi-
helicates Li4[(13c)1(2)5Ti2] and Li4[(13d)1(2)5Ti2] with an iso- tuted chiral ligand 4-H2 and N-benzylmaleimide (8e) as the
propyl-substituted ethylamine and a cyclic secondary amine dienophile.
ligand as catalytically active unit showed no conversion in the
nitro-Michael reaction. Solubility problems were the supposed In addition, the transition from the stoichiometric Diels–Alder
reason for this observation. Thus, the amine ligand 13b-H2 reaction to a catalytic nitro-Michael reaction was described
seemed to be an appropriate component to make helicates from utilizing secondary amine ligands as catalysts. Only amine
ligand mixtures which possess catalytic activity.
ligand 13b-H2 seemed suitable in the catalysis with the corre-
sponding statistical helicates. With other complexes solubility
Exchange of the chiral ligand 2 by other chiral ones resulted in problems arose. Li4[(13b)1(2)5Ti2] was the most efficient cata-
the corresponding complexes Li4[(13b)1(4)5Ti2] and lyst discussed in this study and provided good yields of up to
Li4[(13b)1(5)5Ti2], but did not lead to a control of enantioselec- 88% at room temperature. Suitable diastereoselectivities were
2343