1,2-Addition of 2-[(Trimethylsilyl)oxy]furan to Aldehydes
J . Org. Chem., Vol. 63, No. 15, 1998 5171
Ta ble 3. TMSOF Ad d ition to Va r iou s Ach ir a l
Ald eh yd es, in th e P r esen ce of Ti(IV):(R)-Bin ol a t -20 °C
in CH2Cl2
Sch em e 1
entry
Ra
yield (%) syn/anti ratio eeb (%) [abs config]c
1
2
3
4
5
n-C7H15
n-C7H15
n-C12H25
n-C12H25
Ph
95
70:30
53:47
60:40
70:30
70:30
57 [S,S]
87 [S,S]
80 [S,S]
90 [S,S]
54 [ND]
50d
80
20d
70
a
b
R of RCHO. Enantiomeric excess of the major isomer was
determined using the chiral shift reagent [Eu(hfc)3], by 1H NMR
d
analysis. c Of threo product. In Et2O.
pure (4S,5S)-5-hydroxy-hepadecan-4-olide, namely (+)-
muricatacin. Recrystallization of muricatacin14 should
allow us to increase the ee (Scheme 1).
tivity of the reaction (entry 21), but gave poor ee (10%).
This suggested that the reaction is auto-induced. How-
ever, more experiments are needed to confirm this
explanation. Next we decided to study the reaction with
various aldehydes, and the results are tabulated in Table
3.
In conclusion, these results describe the first enanti-
oselective addition of TMSOF on achiral aldehydes, to
form the expected butenolides in a highly enantiomeric
pure form. This reaction finds an application to the
synthesis of natural muricatacin, but allows single-step
preparation of chiral building blocks which possess two
contiguous stereogenic centers substituted by two hy-
droxyls whose absolute configurations are under catalyst
control. The structure of the catalyst remains unknown;
however, a tentative schematic view has been given by
Bach15 in which (R)-Binol displaced (Oi-Pr) ligands.
Further development of this reaction in which aldehydes
are replaced by different electrophiles is now under
investigation in our laboratory.
Addition of TMSOF in CH2Cl2 to aliphatic aldehydes
gave excellent results in terms of chemical yield and
enantioselectivity. However, the aromatic aldehyde gave
a lower ee. In contrast when the reactions were run in
Et2O, the enantioselectivity was in all cases better, albeit
the addition occurred in moderate yields and some of the
starting material (aldehyde) was recovered. Absolute
configurations of the adducts on aliphatic aldehydes were
determined, after hydrogenation of the double bonds, by
comparisons of the sign of specific rotations of the reduced
products with related compounds.10,11 In the case of
benzaldehyde, we assume that the major aldol product
has the 4R,5R configurations since the sign of the specific
rotation is opposite to those of the aliphatic aldol prod-
ucts. This inverse inductive effect has already been
observed in a related case by Shibasaki.3d We then
applied this new methodology to the efficient and rapid
synthesis of natural muricatacin, a natural metabolite
of the bioactive annonaceous acetogenins.12 Since the
discovery of this cytotoxic hydroxy-butyrolactone, about
17 different total syntheses were reported in the
literature.4b,13 Therefore, TMSOF was added to trideca-
nal in the presence of (R)-1,1′-bi-2-naphthol (Binol) 8, at
-20 °C in CH2Cl2 as described above. 1H NMR analysis,
in the presence of Eu(hfc)3, of the mixture of butenolides
showed that the major threo product was obtained with
80% ee. This is probably due to the steric hindrance of
the long aliphatic chain (compare entries 1 and 3, Table
3) which cannot be seen as an extanded chain but rather
as a “bowl”. When the reaction was run in Et2O, it is
noteworthy that the major threo product was obtained,
in this case with 90% ee. The resulting mixture of the
aldols was then hydrogenated over palladium, and flash
chromatography on silica gel allowed us to isolate the
Exp er im en ta l Section
Gen er a l P r oced u r es. 1H and 13C NMR spectra were
recorded at 200 MHz and 50 MHz, respectively, using CDCl3
as solvent and internal reference. EI-MS were obtained at an
ionization potentiel of 40 eV, CI-MS with NH3, and otherwise
as indicated. Toluene and THF were distilled over sodium-
benzophenone, and CH2Cl2 over CaH2 immediately prior to
use. Molecular sieves (4 Å) were dried at 100 °C for a
minimum of 12 h prior to use. Aldehydes were obtained
commercially and used without purification. Chiral ligands
1, 2, 3, and 8 were purchased from Aldrich, and compounds
4-7 were synthesized as previously reported.16 SiO2 (from
Riedel-de Hae¨n, 230-400 mesh) was used for the purifications
by flash chromatography.
CH2Cl2 Rep r esen ta tive P r oced u r e. As a typical proce-
dure, preparation of (+)-2,3-deshydromuricatacin from tride-
canal is given as follows: (R)-1,1′-bi-2-naphthol (114 mg, 0.4
mmol) and Ti(Oi-Pr)4 (59 µL, 0.2 mmol) are stirred in 4 mL of
CH2Cl2 at room temperature for 1 h. To this red-brown colored
solution is added tridecanal (198 mg, 1 mmol) in 3 mL of CH2-
Cl2, the temperature is brought to -20 °C, and then 2-[(tri-
methylsilyl)oxy]furan (0.25 mL, 1.5 mmol) is added. After
stirring 1.5 h at this temperature, 5 mL of NH4Cl are added
followed by 5 mL of 1 M HCl, and the reaction mixture is
stirred at 20 °C for 1 h. After extraction of the organic layer
with 3 × 5 mL of EtOAc, the combined organic phases are
dried over MgSO4, filtered, and concentrated under vacuum.
Then purification by flash chromatography on silica gel
(cyclohexane/EtOAc: 60/40) led to 212 mg (80%) of the threo/
erythro (60/40) mixture of the expected butenolides, (4S,5S)-
and (4S,5R)-5-(1′ hydroxytridecanyl)furan-2(5H)-one or 2,3-
deshydromuricatacin (for ee of major diastereomer, see Table
3).
(12) Rieser, M. J .; Koslowski, J . F.; Wood, K. V.; McLauglin, J . L.
Tetrahedron Lett. 1991, 32, 1137-1141.
(13) For recent reviews (on isolation and synthesis) on annonaceous
acetogenins, see: (a) Cave´, A.; Cortes, D.; Figade`re, B.; Hocquemiller,
R.; Lapre´vote, O.; Laurens, A.; Leboeuf, M. Recent Advances in the
acetogenins of Annonaceae. In Phytochemical potentiel of Tropical
Plants; Downum, K. R., Romeo, J . T., Stafford, H. E., Eds.; Plenum
Press: New York, 1993; pp 167-202. (b) Figade`re, B. Acc. Chem. Res.
1995, 28, 359-365. (c) Cave´, A.; Figade`re, B.; Laurens, A.; Cortes, D.
In Progress in the Chemistry of Natural Products; Herz, W., Eds.;
Springer-Verlag: Wien, Austria; New York, 1997; Vol. 70, pp 81-288.
(d) Figade`re, B.; Cave´, A. Studies in Natural Products Chemistry. In
Stereoselective Synthesis; Atta-ur-Raman, Ed.; Elsevier: Amsterdam,
1996; Vol. 18, pp 193-227; for the more recent paper on this topic,
see: (e) Peyrat, J .-F.; Mahuteau, J .; Figade`re, B.; Cave´, A. J . Org. Chem.
1997, 62, 4811-4815.
CH2Cl2 w it h Molecu la r Sieves 4 Å. R ep r esen t a t ive
P r oced u r e. (R)-1,1′-Bi-2-naphthol (28.5 mg, 0.1 mmol) and
(14) However, the reaction was run on 1 mmol scale and did not
allow us to recrystallize (+)-muricatacin.
(15) Bach, T. Angew Chem., Int. Ed. Engl. 1994, 33, 417.
(16) Mukaiyama, T.; Iwasawa, N.; Stewens, R. W.; Haga, T. Tetra-
hedron 1984, 40, 1381-1390.