G. Cabrera et al. / Tetrahedron Letters 42 (2001) 5867–5869
5869
was isolated by evaporation of the organic phase. The
yields of crude methoxyolefins were uniformly high and
1991, 279; (b) Miller, R. D.; McKean, D. R. Tetrahedron
Lett. 1982, 23, 323.
the lower yields of purified product listed in Table 1 are
2. Gothelf, K. V.; Jorgensen, K. A. Chem. Commun. 2000,
1449.
1
due to evaporation losses. Regioselectivity (by
H
9
NMR) was uniformly higher than 95%. Methanol
elimination leading to the formation of the less substi-
tuted methoxyolefin, which is likely to be determined by
steric factors, is the preferred reaction pathway even in
those cases (as for the conversion of 9 to 23) in which
the alternative mode of elimination would lead to a
particularly stable conjugated olefin. The elimination
conditions are compatible with the presence of other
functional groups: aliphatic chlorides (10 and 11), a
double bond (12), and, quite surprisingly, acetals (13
and 14) are stable to TIBA; thus, bifunctional com-
pounds 24–28 could be readily prepared. Phenylac-
3. (a) Denmark, S. E.; Guagnano, V.; Dixon, J. A.; Stolle, A.
J. Org. Chem. 1997, 62, 4610; (b) Nagaoka, H.; Iwashima,
M.; Abe, H.; Yamada, Y. Tetrahedron Lett. 1989, 30,
5919; (c) Verkruijsse, H. D.; Brandsma, L.; von, R.;
Schleyer, P. J. Organomet. Chem. 1987, 332, 99; (d) Chav-
darian, C. G.; Heathcock, C. H. J. Am. Chem. Soc. 1975,
97, 3822.
4. Taherirastgar, F.; Brandsma, L. Chem. Ber./Recueil 1997,
130, 45.
5. Matsubara, S.; Ukai, K.; Mizuno, T.; Utimoto, K. Chem.
Lett. 1999, 825.
6. Gassman, P. G.; Burns, S. J.; Pfister, K. B. J. Org. Chem.
etaldehyde
dimethyl
acetal
and
2-phenyl-
1993, 58, 1449. See also Ref. 1.
propionaldehyde dimethylacetal were completely inert
to elimination, even under forcing conditions (18 h,
reflux). Acetals containing a nitrile or an ester (such as
methyl 4,4-dimethoxypentanoate or the corresponding
nitrile) gave complex mixtures upon exposure to TIBA.
7. Sugimura, T.; Tai, A.; Koguro, K. Tetrahedron 1994, 50,
1164.
8. Rychnovsky, S. D.; Lee, J. L. J. Org. Chem. 1995, 60,
4318.
1
9. Selected spectroscopic properties of products; H NMR
(
200 MHz, benzene-d ); 20 7.2–7.0 (m, 5H), 3.90 and 3.85
6
A few ketals from ketones other than methyl ketons
were also studied (15–19). The aliphatic ketal 15 and
the aromatic one 16 were converted to the respective
methoxyolefins 29 and 30 under conditions similar to
those used for ketals of simple methyl ketons; the
aromatic acetal 17, on the other hand, underwent a
much more rapid elimination and the conditions had to
be optimized to avoid further reaction of the desired
elimination product 31. The elimination occurred with
a low degree of stereoselectivity and, except for the
halogenated derivative 30, the preferred product had
the methoxy group cis to the vinyl hydrogen, as estab-
lished by means of NOESY experiments. A very high
regioselectivity was observed in the reaction of cyclo-
hexanone derivative 18, in which the acetal group is
flanked by a methylene and a methyne, the less substi-
tuted olefin 32 being the preferred product. The elimi-
nation from steroidal ketone 19 to give 33 was,
however, non-regioselective, probably due to the similar
hindrance of the two carbon atom a to the ketal.
(2m, 2H), 3.25 (s, 3H), 2.83 and 2.41 (2m, 2×2H); 21 3.93
and 3.85 (2m, 2×1H), 3.24 (s, 3H), 2.15 (t, J=7.2 Hz, 2H),
1.56 (m, 2H), 1.22 (m, 6H), 0.85 (m, 3H); 22 3.90 and 3.79
(2m, 2×1H), 3.19 (s, 3H), 2.41 (s, 4H); 23 7.48–7.15 (m,
5H), 3.90, 3.85 (2m, 2H), 3.42 (s, 2H), 3.15 (s, 3H); 24 3.81
and 3.79, 3.15 (s, 3H), 3.16 (m, 2H), 2.12 and 1.72 (2t,
J=7.0 Hz, 2×2H); 25 3.82 and 3.85 (2m, 2×1H), 3.21 (s,
3H), 3.13 (m, 2H), 1.98 (m, 2H), 1.50 (m, 4H); 26 5.68–
5.89 (m, 1H), 5.03–4.94 (m, 2H), 3.83 and 3.80 (2m,
2×1H), 3.19 (s, 3H), 2.13–2.28 (m, 4H); 27 4.81 (t, J=6
Hz, 1H), 4.04, 3.92 (2m, 2H), 3.22 (s, 3H), 3.18 (s, 6H),
2.59 (d, J=6 Hz, 2H); 28 4.60 (q, 5.3 Hz, 1H), 3.97 and
3.86 (2m, 2×1H), 3.55 (m, 2H), 3.38 (m, 2H), 3.23 (s, 3H),
2.32 (t, J=7.2 Hz, 2H), 1.88 (m, 2H), 1.25 (d, J=5.3 Hz,
3H), 1.24 (t, J=6.8 Hz, 3H); 29 (Z:E=3:1); Z: 4.28 (t,
J=8.0 Hz, 1H), 3.25 (s, 3H); E: 4.48 (t, J=8.0 Hz, 1H),
3.29 (s, 3H); 30: Z: 5.63 (s, 1H), 3.03 (s, 3H); E: 5.18 (s,
1H), 3.03 (s, 3H); 31 (Z:E=5:1); Z: 4.62 (t, J=8.0 Hz,
1H), 3.35 (s, 3H); E: 5.28 (t, J=8.0 Hz, 1H), 3.32 (s, 3H);
32: 4.46 (t, J=3.8 Hz, 1H), 3.25 (s, 3H), 2.35 (m, 1H), 2.03
2
(
m, 2H), 1.25–1.75 (m, 4H), 1.19 (d, J=6.9 Hz, 3H); 33 D :
3
13
In conclusion, TIBA can bring about the regio- and
chemoselective elimination of methanol from 2,2-
dimethoxyalkanes; the reaction is efficient, occurs under
mild conditions, is compatible with other functional
groups (most noteworthy, aldehyde acetals are not
affected by the reagent), and affords valuable products
such as 2-methoxy-1-alkenes from readily prepared
starting materials.
C(2)-H 4.45; D : C(4)-H 4.23; C NMR (50 MHz, ben-
zene-d ); 20: 165.1, 140.4, 130.7, 130.6, 129.9, 129.5, 129.0,
6
128.0, 83.6, 56.0, 43.3; 21: 164.7, 80.2, 54.3, 35.4, 32.0,
29.1, 27.7, 22.9, 14.2; 22: 163.4, 80.2, 54.3, 33.2; 23: 163.2,
139.3, 130.7, 128.5, 126.8, 80.9, 56.4, 42.3; 24: 162.6, 81.3,
54.3, 44.1, 32.3, 30.4; 25: 163.5, 80.5, 54.4, 44.2, 34.1, 32.0,
24.3; 26: 163.7, 138.3, 114.7, 80.6, 54.3, 34.7, 31.3; 27:
160.3, 102.4, 82.9, 54.4, 52.3, 39.3; 27: 164.0, 99.59, 80.58,
64.18, 60.39, 54.35, 32.18, 31.90, 28.21; 29 (Z:E=3:1); Z:
156.7, 98.3, 53.5, 32.4, 21.2, 20.4, 16.1, 13.8. E: 154.8,
111.7, 55.9, 33.7, 20.7, 18.6, 15.6, 13.7; 30: Z: 158.85,
References
90.37, 79.67. E: 158.85, 79.66, 57.23; 31 (Z:E=5:1) Z:
47.5; E: 146.9; 32: 159.43, 92.64, 53.59, 32.63, 31.91,
24.48, 20.79, 14.32; 33 D : C(2) 91.30; D : C(4)-H 4.23;
C(4) 81.85.
1
2
3
1
. For general references about the use of enol ethers, see: (a)
Katritzky, A. L.; Bayyuk, S. I.; Rachwal, S. Synthesis
.