Page 3 of 4
Journal Name
Organic & Biomolecular Chemistry
DOI: 10.1039/C4OB02602K
and extending the reaction time, a higher enantioselectivity could
Due to the enantioenriched 2-amino-3-cyano-4H-chromenes
be achieved (92% ee) without any loss of the yield. Further, we synthesized via our methodology hold potential as antitumor
examined the solvent effect of the reaction (Table 1, entries 12- agents, we tried to scale up the reaction (Scheme 2). To our
14). Polar solvents such as diethyl ether gave poor delight, under 2 mol% catalytic amount, 6mmol 1a (1.512g) and
enantioselectivity. DCM and Chloroform led to moderate yields 9 mmol malononitrile (2a, 0.621g) was able to generate 4a in
and enantioselectivities. Toluene was found to be the ideal 95% yield and 90%ee.
solvent for this reaction. Reducing catalyst loading to 5 mol%
and 2 mol% led to only a slight loss of the enantioselectivity
(Table1, entries 15 - 16).
In conclusion, we have developed a chiral bifunctional-
organocatalyzed formal 4+2 reaction of ortho-quinone methides
and malononitrile, providing 2-amino-3-cyano-4H-chromenes,
a class of potential anti-cancer agents, in excellent yields and
enantioselectivities. Employed as catalyst, quinine is the best
choice for our reaction, which represents excellent generality
for a diversity of ortho-quinone methides, and leads to high
yields and enantioselectivity. Significantly, we also managed to
scale up the reaction with excellent results. Further studies will
be continued on constructing complex molecules from ortho-
quinone methides.
This work was supported by the Fundamental Research Funds
for the Central Universities (WK2060190041).
Notes and references
Department of Chemistry, University of Science and Technology of
China, Hefei, 230026, China.
†Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/c000000x/
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With the optimized reaction condition in hand, we then
examined the scope of the substrates (Table 2). Generally, for
2. W. Kemnitzer, J. Drewe, S. C. Jiang, H. Zhang, Y. Wang, J. H. Zhao,
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enantioselectivity ranging from 90 to 94% ee.
electron-withdrawing group exhibited much higher reactivity (3e
3g). Thiophenyl and naphenyl substituted -QMs also tolerated
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o
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H
aryl-chromene, which holds great potential as antitumor agent,
could also be synthesized with excellent yield and
enantioselectivity (4j). 4H-4-Vinyl chromene 4k was obtained as
well with 98% yield and 91% ee. The absolute configuration of
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4b was determined by X-ray analysis of its single crystal.
This journal is © The Royal Society of Chemistry 2012
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