Scheme 4a
a Reagents and conditions: (a) (i) Ac2O, pyr, room temperature; (ii) aqueous AcOH, room temperature, 95%; (b) (i) SOCl2, Et3N, CH2Cl2,
room temperature; (ii) cat. RuCl3, NaIO4, aqueous CH3CN, room temperature; (iii) NaOMe, MeOH, room temperature; (iv) aqueous H2SO4-
Et2O, room temperature, 83%; (c) (i) MOMCl, i-Pr2NEt, CH2Cl2, room temperature; (ii) 10% Pd/C, H2, EtOH, room temperature; (iii)
Dess-Martin periodinane, CH2Cl2, room temperature; (iv) dimethyl-1-diazo-2-oxopropylphosphonate, K2CO3, MeOH, room temperature;
61% for 3, 35% for 16 (in 10 steps from 12); (d) (Ph3P)2PdCl2, CuI, Et3N, room temperature; 79% for 17, 84% for 18; (e) (i) (Ph3P)3RhCl,
H2, benzene-EtOH (6:1), room temperature; (ii) BF3‚Et2O, Me2S, 0 °C, 56% for 1, 68% for 2.
group as a methoxymethyl (MOM) ether; (2) hydrogenolysis
of the benzyl group; (3) Dess-Martin oxidation; (4) instal-
lation of the terminal acetylene by using Bestmann’s
procedure.15
scopic and physical properties of the synthetic material 1
were found to differ from those of natural jimenezin. In
particular, the coupling constant value between H-19 and
H-20 of the synthetic product was clearly different from that
of the natural one: J ) 6.3 Hz (synthetic) vs J ) 2.3 Hz
(natural). In addition, the natural product contained two
multiplets at δ 3.90 (H-16), and 3.94 (H-19), which were
observed at 3.77, and 3.82 ppm, respectively, in the 1H NMR
spectrum of the synthetic product. The four signals for C-16
and C-19-21 of the synthetic material deviated by 0.4-1.0
ppm compared with the respective signals of the natural
compound in the 13C NMR spectrum. These results suggested
a difference in the stereochemistry around the THF ring.
In reexamining the NMR data reported,2 we estimated that
the relationship between H-19 and H-20 of natural jimenezin
should be threo, suggesting an epimer 2 bearing a cis THF
ring. Disconnection of the structure 2 can revert it to two
fragments 16 and 4; hence the R-alcohol 12 was regarded
as an ideal starting material (Scheme 4). According to the
procedure described in the synthesis of 3, the chromato-
graphically pure 19R-alcohol 12 was transformed into the
terminal acetylene derivative 16 in 35% overall yield. The
coupling reaction of 16 with 4 gave the enyne 18 in 84%
yield. Finally, reduction and deprotection of 18 afforded 2,19
whose physical and spectral data ([R]D,20 1H and 13C NMR)
were identical with those of the natural jimenezin.
The complete carbon skeleton of 1 was assembled by
joining 3 and 4 under Hoye’s conditions,16 to give enyne 17
in 79% yield. This underwent regioselective reduction with
Wilkinson’s catalyst to give a fully protected jimenezin, in
which all of the MOM groups were subsequently cleaved
by BF3‚Et2O in methyl sulfide17 to give 1.18 The spectro-
(15) Muller, S.; Liepold, B.; Roth, G. J.; Bestmann, H. J. Synlett 1996,
521.
(16) (a) Hoye, T. R.; Hanson, P. R.; Kovelsky, A. C.; Ocain, T. D.; Zang,
Z. J. Am. Chem. Soc. 1991, 113, 9369. (b) Hoye, T. R.; Hanson, P. R.
Tetrahedron Lett. 1993, 34, 5043. (c) Hoye, T. R.; Tan, L. Tetrahedron
Lett. 1995, 36, 1981. (d) Hoye, T. R.; Ye, Z. J. Am. Chem. Soc. 1996, 118,
1801.
(17) Naito, H.; Kawahara, E.; Maruta, K. Maeda, M.; Sasaki, S. J. Org.
Chem. 1995, 60, 4419.
(18) Physical and spectroscopic data for 1: [R]D25 -0.8° (c 1.40, MeOH);
IR (film) 3700-3100, 2925, 2854, 1744, 1655, 1466, 1320, 1204, 1068,
953 cm-1 1H NMR (400 MHz) δ 7.18 (ddd, J ) 1.7, 1.5, 1.5 Hz, 1H),
;
5.05 (dddq, J ) 6.8, 1.5, 1.5, 1.5 Hz, 1H), 3.82 (m, 2H), 3.77 (ddd, J )
6.8, 6.6, 6.3 Hz, 1H), 3.37 (ddd, J ) 6.3, 6.1, 6.1 Hz, 1H), 3.26 (ddd, J )
9.3, 9.0, 4.9 Hz, 1H), 3.16 (ddd, J ) 10.5, 6.3, 2.0 Hz, 1H), 3.01 (ddd, J
) 9.0, 9.0, 2.2 Hz, 1H), 2.53 (dddd, J ) 15.1, 3.4, 1.7, 1.5 Hz, 1H), 2.39
(dddd, J ) 15.1, 8.3, 1.5, 1.5 Hz, 1H), 2.10-1.25 (m, 49H), 1.43 (d, J )
6.8 Hz, 3H), 0.88 (t, J ) 6.8 Hz, 3H); 13C NMR (100 MHz) δ 174.6, 151.8,
131.2, 82.9, 82.2, 81.3, 79.7, 78.0, 74.1, 70.9, 70.0, 37.4, 33.5, 33.3, 32.7,
32.0, 31.9, 29.7, 29.6, 29.5, 29.4, 28.9, 28.1, 25.6, 25.5, 22.7, 19.1, 14.1;
HR-MS (FAB) calcd for C37H67O7 [M + H]+ 623.4887, found 623.4890.
Org. Lett., Vol. 1, No. 12, 1999
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