2460
A. Dittoo et al.
LETTER
8 was treated under acidic conditions. Thus, when 8 was In conclusion, the total synthesis of (+)-dodoneine has
treated with 80% aqueous AcOH, at 60 °C for 24 hours, been accomplished in eight steps from commercially
(+)-dodoneine 9 was isolated in 70% yield (Scheme 2).8 available ester 1 with an overall yield of 21.4%. The key
Gratifyingly, the 1H and 13C NMR spectra of 9 are in total bond-forming event involves an enantioselective allyl-
agreement with those of the natural (+)-dodoneine. The titanation, a 1,4-addition of a hemiacetal to an unsaturated
HRMS and optical rotation confirmed that compound 9 is ester, a cross-metathesis reaction, and a Still–Gennari-
indeed (+)-dodoneine.
modified Horner–Wadsworth–Emmons reaction. The
route detailed herein is flexible and can be used to synthe-
size isomers for SAR studies.
O
O
1) TBSCl
imidazole
H
CH2Cl2
OMe
Acknowledgment
TBSO
2) DIBAL-H
toluene, –78 °C
88%
HO
We are indebted to Prof. J.-M. Coustard for providing us with the
NMR spectra of natural (+)-dodoneine.
1
2
(S,S)-Ti-I
Et2O
–78 °C, 3 h
97%
O
References and Notes
OEt
OH
HG-II (5 mol%)
OH
O
(1) Ouedraogo, M.; Carreyre, H.; Vandebrouck, C.; Bescond, J.;
Raymond, G.; Guissou, I.-P.; Cognard, C.; Becq, F.;
Potreau, D.; Cousson, A.; Marrot, J.; Coustard, J.-M. J. Nat.
Prod. 2007, 70, 2006.
CH2Cl2, r.t., 2 d
Ar
Ar
OEt
80%
4
3 >96% ee
PhCHO
t-BuOK
THF
(2) The allyltitanium complex (S,S)-Ti-I was prepared
according to: Hafner, A.; Duthaler, R. O.; Marti, R.; Rihs,
G.; Rothe-Streit, P.; Schwarzenbach, F. J. Am. Chem. Soc.
1992, 114, 2321.
(3) The ee of 3 and its S absolute configuration were determined
by 1H NMR after derivatization with (S)- and (R)-
methoxyphenylacetic acids. See: (a) Dale, J. A.; Mosher,
H. S. J. Am. Chem. Soc. 1973, 95, 512. (b) Trost, B. M.;
Belletire, J. L.; Godleski, S.; McDougal, P. G.; Balkovec,
J. M. J. Org. Chem. 1986, 51, 2370. (c) Seco, J. M.; Quiňoà,
E.; Riguera, R. Tetrahedron: Asymmetry 2001, 12, 2915.
(4) Evans, D. A.; Gauchet-Prunet, J. A. J. Org. Chem. 1993, 58,
2446.
68%
Ph
Ar = TBSOC6H4
0 °C, 2 h
Ph
DIBAL-H
toluene, –78 °C
O
O
O
O
O
O
O
94%
Ar
OEt
(syn/anti = 98:2)
Ar
H
5
6
O
P
70%
(CF3CH2O)2
OEt
7
KHMDS, 18-C-6
THF, –78 °C, 2 h
(5) Cossy, J.; BouzBouz, S.; Hoveyda, A. H. J. Organomet.
Chem. 2001, 624, 327.
O
Ph
(6) Kingsbury, J. S.; Harrity, J. P. A.; Bonitatebus, P. J. Jr;
Hoveyda, A. H. J. Am. Chem. Soc. 1999, 121, 791.
(7) Still, W. C.; Gennari, C. Tetrahedron Lett. 1983, 24, 4405.
(8) Compound 9: Rf = 0.23 (PE–EtOAc, 2:8); [a]D20 +48.1
(c = 0.34, CHCl3) {Lit.1 [a]D20 +40.2 (c = 0.40, CHCl3)}. IR
(neat): 3311, 2920, 1698, 1515 cm–1. 1H NMR (400 MHz,
CDCl3): d = 7.05 (app dt, J = 8.5, 2.5 Hz, 2 H), 6.88 (app dt,
J = 9.5, 4.1 Hz, 1 H), 6.76 (app dt, J = 8.5, 2.5 Hz, 2 H), 6.02
(dt, J = 9.8, 1.9 Hz, 1 H), 5.32 (br s, 1 H), 4.65 (dddd, J = 7.7,
7.7, 7.7, 5.3 Hz, 1 H), 3.87 (m, 1 H), 2.67 (m, 2 H), 2.38 (m,
2 H), 2.00 (dt, J = 15.7, 8.2 Hz, 1 H), 1.90 (br s, 1 H, OH),
1.79 (m, 3 H). 13C NMR (100 MHz, CDCl3): d = 164.6 (s),
154.3 (s), 145.8 (d), 133.9 (s), 129.8 (2 × d), 121.5 (d), 115.7
(2 × d), 77.4 (d), 69.0(d), 42.4 (t), 39.7 (t), 31.2 (t), 29.8 (t).
MS (EI, 70 eV): m/z (%) = 262 (5), 150 (2), 133 (10), 120
(9), 108 (27), 107 (100), 94 (14), 77 (49), 67 (23), 53 (22).
HRMS (ESI): m/z [M + Na]+ calcd for C15H18O4Na:
285.10987; found: 285.10973.
aq AcOH
60 °C, 24 h
OH
O
O
O
70%
EtO2C
8
HO
TBSO
9
(Z/E = 90:10)
(+)-dodoneine
N
N
Ti
O
O
Ph
Ph
O
Cl
Cl
Ru
O
Ph
Ph
O
HG-II
(S,S)-Ti-I
Scheme 2
Synlett 2008, No. 16, 2459–2460 © Thieme Stuttgart · New York