3754
D. P. Sant’Ana et al. / Tetrahedron Letters 50 (2009) 3753–3755
O
a nitrogen atmosphere until starting material disappeared (12a:
O
i
O
O
O
O
O
O
O
ii
12h; 12b: 5h; and 19: 2h). The cooled solution was partitioned be-
tween dichloromethane and water. The organic layer was washed
with water (3 times), dried, filtered, and evaporated. The material
obtained was purified by silica gel chromatography, except for 5,
which was purified by basic alumina.
80%
OH
77%
Br
OH
OBz
O
(+/-)-15
iii
(+/-)-14
13
iv
O
O
O
60% for the
two steps
O
4. 5-Deoxypterocarpen 4a
OH
O
O
I
OMe
vi
(+/-)-17
1H NMR (CDCl3), d (ppm): 7.64 (1H, d, J = 7.4 Hz); 7.48 (2H, m);
7.28–7.16 (5H, m); 3.07 (2H, t, J = 7.8 Hz); 2.92 (2H, t, J = 7.6)—13C
NMR (CDCl3), d (ppm): 155.2(C); 151.6(C); 135.8(C); 128.3(C);
128.9(CH), 127.6(C); 127.5(CH); 126.7(CH); 123.9(CH); 122.6(CH);
120.4(CH); 119.0(CH); 113.9(C); 111.3(CH); 28.56(CH2);
19.20(CH2)—MS: m/z = 220.
O
(+/-)-16
v
82%
O
O
O
O
O
vii
81%
O
I
O
89%
OMe
OTs
O
19
(+/-)-18
5. 9-Methox-5-deoxypterocarpen 4b
I
OMe
1H NMR (CDCl3), d (ppm): 7.59 (1H, d, 3J = 7.4 Hz); 7.35 (1H, d,
J = 8.6 Hz); 7.29–7.14 (3H, m); 7.07 (1H, d, 4J = 2.4 Hz); 6.88 (1H,
dd, 3J = 8.6 Hz, J = 2.4 Hz); 3.87 (3H, s); 3.08 (2H, t, J = 8.0 Hz);
O
O
O
O
O
viii
O
2.92 (2H, t, J = 7.8)—13C NMR (CDCl3),
d (ppm): 157.9(C);
O
100%
O
O
156.2(C); 150.9(C); 135.2(C); 127.9(CH), 127.8(C); 126.9(CH);
126.7(CH); 121.8(C); 119.2(CH); 119.8(CH); 114.1(C); 111.4(CH);
96.35(CH); 55.69(CH3); 26.6(CH2); 19.34(CH2)—MS: m/z = 250.
5
6
OMe
OMe
Scheme 2. Synthesis of 5 and 6 through intramolecular Heck reaction of 19. (i)
MCPBA, NaHCO3 0.5 M, CH2Cl2, 0 °C to rt, 1.5 h; (ii) NBS, H2O, DMSO, 0 °C to rt,
15 min; (iii) NaH (2 equiv) THF, rt, 20 min; (iv) 11b, rt, 12 h; (v) TsCl, pyridine,
CHCl3 1:3, rt, 12 h; (vi) tBuOK, THF 0 °C to rt, 1 h; (vii) Pd(AcO)2 (5 mol %) TBACl,
NaHCO3, DMF, 100 °C, 2 h; (viii) DDQ, THF, t.a., 2 h.
6. 1,3-Dioxolo-9-methoxypterocarpen 5
1H NMR (CDCl3), d (ppm): 7.21 (1H, d, J = 8.6 Hz); 7.05 (1H, d,
J = 2.0 Hz); 6.97 (1H, s); 6.87 (1H, dd, J = 8.6 Hz, J = 2.0 Hz); 6.51
(1H, s); 5.93 (2H, s); 5.48 (2H, s); 3.86 (3H)—13C NMR (CDCl3), d
(ppm): 157.7(C); 156.3(C); 149.2(C); 147.9(C), 147.6(C); 142.2(C);
119.2(C); 118.6(CH); 111.8(CH); 109.6(C); 106.0(C); 101.3(CH2);
100.3(CH); 99.3(CH); 99,6(CH); 66.4(CH2); 55.8(CH3)—MS: m/
z = 296.
with tBuOK furnished the corresponding key intermediates, olefins
12a and 12b. These compounds cyclized to the corresponding 5-
desoxipterocarpens 4a and 4b in the presence of 5 mol % of
Pd(OAc)2.16 A similar strategy was described by Santosh and co-
workers for the synthesis of pterocarpans through radical cycliza-
tion promoted by nBu3SnH.17
Our next goal was the synthesis of pterocarpen 5 and coume-
stan 6 (Scheme 2). Chromene 13, required for this synthesis, was
prepared from sesamol, as described in the literature.18 Under
the same conditions used for epoxidation of 7, 13 led exclusively
to benzoate 14. Alternatively, chromene 13 led to bromohydrin
15 regioselectively by reaction with NBS in DMSO/H2O.
This compound was transformed, in one pot, to alcohol 17 as a
mixture of epimers (3:1) at the benzylic carbon by reacting with
sodium hydride in THF in the presence of phenol 9b.19 It seems
reasonable to accept that epoxide 16 is an intermediate in this
transformation.
7. 1,3-Dioxolo-9-methoxycoumestan 6
1H NMR (CDCl3), d (ppm): 8.03 (1H, d, J = 2.2 Hz); 7.32 (1H, s);
7.21 (1H, d, 4J = 0.6); 7.12 (1H, dd, J = 2.2 Hz, J = 0.6 Hz); 7.03
(1H,s); 6.15 (2H,s); 3.89 (3H)—13C NMR (CDCl3),
d (ppm):
159.3(C); 156.4(C); 151.1(C); 150.4(C); 145.2(C), 132.5(C);
121.7(CH); 120.2(C); 116.6(C); 113.3(CH); 106.3(C); 102.4(CH2);
100.0(C); 99.2(CH); 99.1(CH); 99.6(CH); 55.9(CH3)—MS: m/z = 310.
Acknowledgments
We thank CAPES, FAPERJ, FINEP, and CNPq for financial support
and CNPq for fellowships to the authors. We also thank Professor
Alcides J. M. da Silva for the sample of chromene 13.
Alcohol 17 (mixture of epimers) was tosylated leading to 18
(mixture of epimers).
The desired key intermediate, olefin 19, was formed when 18
reacted with tBuOK in THF at rt. Pterocarpen 5 was obtained from
19 through an intramolecular Heck reaction in the presence of
5 mol % of Pd(OAc)2.16 Finally, coumestan 6 was prepared in quan-
titative yield by oxidation of 5 with DDQ in THF.
References and notes
1. Lerner, L. J.; Holthaus, F. J.; Thompson, C. R. Endocrinology 1958, 63, 295–318.
2. Jordan, V. C. Pharmacol. Rev. 1984, 36, 245–276.
In conclusion, the strategy described herein allowed the prepara-
tion of 5-deoxypterocarpens 4a,b, a pterocarpen (5), and a coume-
stan (6) in 40%, 31%, 27%, and 27% overall yield, respectively,
starting from olefins 9 and 13. The use of this strategy to prepare
new compounds, including naturally occurring pterocarpens, ptero-
carpans, and coumestans is under investigation in our laboratory.
3. Shelly, W.; Draper, M. W.; Krishnan, V., et al Obstet. Gynecol. Surv. 2008, 63,
163–181.
4. Miller, C.P.; Collini, M.D.; Morris, R.L.; Singhaus, R.R., Jr. US Patent 2006/
0004087 A1.
5. Veitch, N. C. Nat. Prod. Rep. 2007, 24, 417–464.
6. Bickoff, E. M.; Livingston, A. L.; Booth, A. N. Arch. Biochem. Biophys. 1960, 88,
262–266.
7. Kaushik-Basu, N.; Bopda-Waffo, A.; Talele, T. T.; Basu, A.; Costa, P. R. R.; da Silva,
A. J. M.; Sarafianos, S. G.; Nöel, F. Nucleic Acids Res. 2008, 36, 1482–1496; Pôças,
E. S. C.; Touza, N. A.; Pimenta, P. H. C.; Leitão, F. B.; Netto, C. D.; da Silva, A. J. M.;
Costa, P. R. R.; Noël, F. Bioorg. Med. Chem. 2008, 16, 8801–8805; da Silva, A. J. M.;
Coelho, A. L.; Simas, A. B. C.; Moraes, R. A. M.; Pinheiro, D. A.; Fernandes, F. F. A.;
Arruda, E. Z.; Costa, P. R. R.; Melo, P. A. Bioorg. Med. Chem. 2004, 14, 431–435; da
Silva, A. J. M.; Melo, P. A.; Silva, N. M. V.; Brito, F. V.; Buarque, C. D.; de Souza, D.
3. General procedure for intramolecular Heck reactions
A mixture of Pd(AcO)2 (5 mol %), NaHCO3 (2.5 equiv), TBACl
(1 equiv), olefins 12a, 12b or 19 in DMF was heated to 100 °C under