Communication
RSC Advances
Fig. 1 Single-crystal X-ray structure of compound 3i (a) and 3n (b).
high mechanical energy from local high pressure, friction,
shear strain and so on.14
Acknowledgements
It is worthy to point out that herein solvent-free ball milling
promoted reactions afforded the corresponding THQs 3 exclu-
sively in cis-(2e, 4e) conguration based on HPLC analysis of the
resulted reaction mixtures. The high diastereoselectivity may be
ascribed to high local concentration of the reactants under this
mechanochemical and solvent-free condition, which may result
in an enhanced second-order reaction rate and thus prefer to
selective formation of products via kinetic control.15 There is a
fact that when the reaction for synthesis of tetrahydroquino-
lines 3i was performed by reuxing in organic solvents such as
CH2Cl2 and THF, minor trans-diastereomer was detected. The
cis-(2e, 4e) conguration is indicated by the diagnostic coupling
constants of the relevant protons on the saturated THQ ring
from 1H NMR analysis. That is, the large vicinal coupling
constants J2a,3a and J3a,4a ¼ 9.9–12.0 Hz for this form indicate an
axial–axial relationship, and the aryl groups on C-2 and C-4 are
both pseudoequatorial and thus located in cis-conguration.16
In addition, this stereochemistry was further unambiguously
conrmed by single-crystal X-ray diffraction analysis of two
selected examples 3i and 3n (Fig. 1), showing that the substit-
uents in the saturated part of the tetrahydroquinoline occupy
the equatorial positions, strongly conrming that the reaction
was highly diastereoselective.17
In summary, under mechanochemical ball-milling at room
temperature, the FeCl3 promoted Diels–Alder cycloaddition
reactions of styrene with in situ generated N-aryl aldimines in
absence of any solvent afforded exclusively cis-2,4-diphenylte-
trahydroquinolines in good to excellent yields within 90
minutes. The isolation work up just involves washing the
resulting reaction mixture with water and recrystallization in
EtOH–H2O. This novel protocol exhibits the advantages of high
diastereoselectivity, short reaction time, free use of organic
solvent, low cost, employment of cheap, easily available and
nontoxic catalyst, and simple work-up procedure. These merits
make this protocol a very efficient and green alternative to
traditional methods for synthesis of these kinds of compounds,
and even can presumably be extended to the construction of
other heterocyclic skeletons.
We are grateful to nancial support from National Natural
Science Foundation of China (21242013).
Notes and references
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