Organic Letters
Letter
Scheme 2. Derivatization of 3-Bromofuranoindole 6b
ASSOCIATED CONTENT
* Supporting Information
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S
Experimental procedures, spectral data, and copies of all new
compounds. This material is available free of charge via the
AUTHOR INFORMATION
Corresponding Authors
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Author Contributions
∥These authors contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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We are grateful for financial support from the National Natural
Science Foundation of China (Grant Nos. 21202187 and
21372239).
protecting groups on indole, carbamate (Cbz and Alloc) was
found to be tolerated in this reaction, affording the furoindoline
in excellent enantioselectivity (Scheme 1, 6b and 6c). While
employing strong electron-withdrawing substituents such as Ts,
the corresponding furoindoline was obtained only in moderate
enantioselectivity (89% ee, Scheme 1, 6d). The substituent on
the indole ring was evaluated next, and either electron-rich or
electron-deficient substituents were perfectly compatible with
the reaction conditions, delivering the cyclization product in
excellent enantioselectivities (94−98.5% ee, Scheme 1, 6g and
6l). In particular, 2-substituted tryptophols were also found to
be suitable substrates, providing furoindoline with two
continuous quaternary carbon centers in excellent diastereose-
lectivity and enantioselectivity (Scheme 1, 6q and 6s).
However, only low enantioselectivity (17% ee) was obtained
due to steric hindrance when a phenyl group was put on C-2 of
the indole ring (Scheme 1, 6r). The absolute configuration of
3-bromofuroindoline 5 was determined to be (3R,8S) by X-ray
crystallographic analysis of 6g and 6q.10
Gram-scale asymmetric synthesis of 3-bromofuroindoline 6b
was also implemented to show the practical application of this
reaction (Scheme 2), which afforded 6b in excellent
enantioselectivity. The bromide of 3-bromofuroindoline 6b
provided a versatile handle for further transformations to
deliver important intermediates for synthesizing furoindoline
alkaloids. Hydration in the presence of CF3CO2Ag11 in ionic
liquid solvent produced 3-hydroxylfuroindole 7 in quantitative
yield, which is the core structure of (+)-madindoline. Removal
of bromide mediated by AIBN/Bu3SnH smoothly gave
furoindoline 8 with a slight loss of chiral purity. Friedel−
Craft reactions of bromofuroindoline 6b using toluene or
allylstannane resulted in 3-arylfuroindoline 9 and 3-allylfur-
oindoline 10, respectively, with retention of chiral purities.12
In summary, a highly asymmetric bromocyclization of
tryptophol was described by using chiral anionic phase-transfer
catalyst and DABCO-derived brominating reagent salt.
Enhancement of reaction rate and enantioselectivity was
observed by addition of a catalytic amount of DABCO-derived
bromine complex. This reaction provided a direct synthesis of
chiral 3-bromofuroindoline from tryptophol in excellent
enantioselectivities, and currently, application of this method-
ology in the synthesis of indole alkaloids is under investigation
in our laboratory.
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