LETTER
A New Method to Prepare 3-Alkyl-2-hydroxy-1,4-naphthoquinones
1553
O
O
O
OH
H
O
O
EtOH
H
H
O
H
H
+
H
+
+
– H2O
O
H
O
O
OH
H
O
O
H
O
O
O
H
O
OH
+ CO2 + H2O
H
O
O
Scheme 2 Proposed mechanism for the reduction of o-quinone methide by formic acid in water
vation energy. In summary, the DFT calculations Acknowledgment
provided further evidence for the reduction of quinone
methides by formic acid, preferentially with one interven-
ing water molecule.
Thanks are due to the CNPQ (National Council of Research of Bra-
zil), CAPES and FAPERJ-PRONEX (E-26/171.512.2010), for fun-
ding this work. S. B. Ferreira and D. R. da Rocha thanks FAPERJ
for their doctoral fellowship.
References
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Figure 2 Optimized transition structures for reduction of o-QM by
formic acid without (a) and with (b) the participation of one water
molecule. Selected distances are given in Å.
In summary, this article describes the development of an
alternative synthetic pathway for the reduction of the in-
termediate o-quinones methides in situ to perform selec-
tive C-alkylation of lawsone, producing the
corresponding 1,4-naphthoquinone 6a–g in moderate to
good yields. This one-pot methodology was used in the
synthesis of the natural product lapachol (1), which was
obtained in 78% yield. Previous reports in literature
showed the obtained compound 1 in 32% (after 3 steps)27
and 43% (involving the use of palladium as catalyst and
excess of reagents),28 which indicates that our reaction
method is the most efficient method to date.
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Supporting Information for this article is available online at
Synlett 2011, No. 11, 1551–1554 © Thieme Stuttgart · New York