Bis(acylsilanes)
J . Org. Chem., Vol. 66, No. 13, 2001 4547
(dd, J CF ) 281.7, J CF ) 274.6); 19F NMR δ -106.3 (d, 2F, J AB
4. These compounds can be subjected to a facile and
effective defluorosilylation. The overall process consti-
tutes a total synthesis of cyclic 6- and 7-membered
2-fluoro-1,3-diketones 8, with the regiospecific introduc-
tion of fluorine being concomitant with the ring construc-
tion. Such a method may be of interest, in addition to
the direct fluorination of 1,3-diketones by electrophilic
fluorination reagents, for the synthesis of elaborated
substituted derivatives.
) 84.0), -121.0 (d, 2F, J AB ) 84.0); IR (film) 1772 cm-1
.
2,2-Diflu or o Ald ols 4; Gen er a l On e-P ot P r oced u r e. To
a solution of bis(acylsilane) 1b-i (10.0 mmol, 1.00 equiv) in
CH2Cl2 (30 mL) at -10 °C were added trifluoromethyltrim-
ethylsilane (CF3SiMe3) (13.0 mmol, 1.30 equiv) then tetrabu-
tylammonium difluorotriphenylstannate (DFTPS) (0.5 mmol,
0.05 equiv). The mixture was stirred for 30 min at room
temperature. Lewis acid (0.1-2.0 equiv, see Table 2) was then
added. After 1 day of stirring at room temperature, the mixture
was filtered through Celite then hydrolyzed with an aqueous
solution of NaHCO3 (100 mL). The aqueous phase was
extracted with CH2Cl2 (4 × 50 mL). The combined organic
phases were dried over MgSO4, filtered, and concentrated in
vacuo. The residue was chromatographed on silica gel using
petroleum ether/AcOEt (90/10) to give the desired 2,2-difluoro
aldol 4b-i (Table 2).
Exp er im en ta l Section
General methods are described in ref 20. CF3TMS was
provided by Bayer company (Leverkusen). Bu4N+Ph3SnF2- was
prepared according to a reported procedure.11
Gen er a l Tw o-Step P r oced u r e, via Diflu or oen oxysi-
la n es 2. To a solution of the bis(acylsilane) 1 (4.56 mmol, 1.00
equiv) in CH2Cl2 (15 mL) at -10 °C were added trifluorom-
ethyltrimethylsilane (CF3SiMe3) (5.74 mmol, 1.26 equiv) and
then tetrabutylammonium difluorotriphenylstannate (DFTPS)
(0.02 mmol, 0.05 equiv). After stirring for 1 h at room
temperature, the mixture was hydrolyzed with water (20 mL).
The aqueous phase was extracted with CH2Cl2 (3 × 40 mL).
The combined organic phases were dried over MgSO4, filtered,
and concentrated in vacuo. The residue was chromatographed
on silica gel using petroleum ether/diethyl ether (97/3) to give
the mono(difluoroenoxysilane) 2a ,c-e,g and the bis(difluo-
roenoxysilane) 3c,g (Table 1). To a solution of mono(difluo-
roenoxysilane) 2c-e,g (1.00 mmol, 1.00 equiv) in CH2Cl2 (3
mL) was added BiCl3 (0.4 or 4.0 equiv, see Table 1) at room
temperature. After stirring for 1 day at room temperature, the
mixture was filtered through Celite, then hydrolyzed with an
aqueous solution of NaHCO3 (15 mL). The aqueous phase was
extracted with CH2Cl2 (4 × 10 mL). The combined organic
phases were dried over MgSO4, filtered, and concentrated in
vacuo. The residue was chromatographed on silica gel using
petroleum ether/AcOEt (90/10) to give the desired 2,2-difluoro
aldol 4c-e,g (Table 1). The aldols are described in the next
section.
2,2-Diflu or o-3-h yd r oxy-3-(ter t-bu tyld im eth ylsilyl)-cy-
1
cloh exa n on e (4c). Oil; H NMR δ 0.15 (s, 6H), 1.01 (s, 9H),
1.75 (brs, 1H), 1.8-2.0 (m, 1H), 2.1-2.3 (m, 3H), 2.5-2.7 (m,
2H); 13C NMR δ -6.6, -6.5, 18.1, 20.6, 27.3, 31.0 (d, J CF
7.9), 38.6, 75.2 (t, J CF ) 33.5), 117.1 (dd, J CF ) 259.9, J CF
252.0), 199.5 (t, J CF ) 27.6); 19F NMR δ -106.6 (d, 1F, J AB
)
)
)
257.5), -123.2 (d, 1F, J AB ) 257.5); IR (film) 3470, 1752 cm-1
MS (CI, NH3) m/e (%) 282 (M + 1 + 17), 132 (100).
;
2,2-Diflu or o-3-h yd r oxy-3-(ter t-b u t yld im et h ylsilyl)-4-
m eth yl-cycloh exa n on e (4d ). Ma jor Dia ster eom er . White
solid: mp 80-82 °C; 1H NMR δ 0.19 (s, 6H), 1.02 (s, 9H), 1.12
(d, 3H, J HH ) 6.9), 1.68 (brs, 1H), 1.7-1.8 (m, 1H), 2.03 (m,
1H), 2.4-2.5 (m, 2H), 2.70 (m, 1H); 13C NMR δ -4.1, -3.9,
17.3, 18.8, 27.6, 29.6, 36.3 (d, J CF ) 4.2), 37.1, 75-76, 116.5
(dd, J CF ) 258.9, J CF ) 250.5), 199.5 (t, J CF ) 29.5); 19F NMR
δ -107.2 (d, 1F, J AB ) 255.6), -118.5 (d, 1F, J AB ) 255.6); IR
(KBr) 3368, 1755 cm-1; MS (CI, NH3) m/e (%) 297 (M + 1 +
17), 260 (100), 211.
Min or Dia ster eom er . Oil; H NMR δ 0.22 (d, 3H, J HF
1.9), 0.27 (d, 3H, J HF ) 1.2), 1.02 (s, 9H), 1.33 (dd, 3H, J HH
1
)
)
7.6, J HF ) 3.8), 1.6-1.7 (m, 1H), 1.82 (brs, 1H), 2.4-2.5 (m,
2H), 2.5-2.6 (m, 1H), 2.8-3.0 (m, 1H); 13C NMR δ -5.2, 15.9
(d, J CF ) 8.4), 18.5, 27.9, 28.1, 34.5, 36.1 (d, J CF ) 8.4), 78.3
(dd, J CF ) 30.5, J CF ) 28.4), 117.2 (dd, J CF ) 257.8, J CF
)
1-(ter t-Bu tyld im eth ylsilyl)-5-(ter t-bu tyld im eth ylsilyl-
253.6), 199.2 (dd, J CF ) 27.4, J CF ) 25.3 Hz); 19F NMR δ -103.5
(d, 1F, J AB ) 263.2), -117.3 (d, 1F, J AB ) 263.2).
1
oxy)-6,6-d iflu or o-h ex-5-en -1-on e (2c). Oil; H NMR δ 0.12
(s, 3H), 0.13 (s, 3H), 0.18 (s, 6H), 0.93 (s, 18H), 1.72 (tt, 2H,
J HH ) 7.2, J HH ) 6.9), 2.0-2.1 (m, 2H), 2.61 (t, 2H, J HH ) 7.2);
13C NMR δ -7.0, -4.8, 18.0, 18.2, 18.7, 25.5, 26.4, 28.0, 48.7,
CF2CO unvisible, 129.4 (dd, J CF ) 281.7, J CF ) 274.5), 246.7;
2,2-Diflu or o-3-h yd r oxy-3-(tr is-isop r op ylsilyl)-cyclo-
1
h exa n on e (4e). White solid: mp 62-64 °C; H NMR δ 1.17
(d, 18H, J HH ) 6.9), 1.31 (sept, 3H, J HH ) 6.9), 1.79 (brs, 1H),
1.8-1.9 (m, 1H), 2.1-2.3 (m, 3H), 2.5-2.7 (m, 2H); 13C NMR
δ 11.4, 19.1, 19.3, 20.4, 31.9 (d, J CF ) 9.9), 38.5, 76-78 (C4),
116.7 (dd, J CF ) 260.6, J CF ) 248.9), 199.8 (dd, J CF ) 28.2,
J CF ) 25.8); 19F NMR δ -105.9 (d, 1F, J AB ) 251.8), -122.6
(d, 1F, J AB ) 251.8); IR (KBr) 3474, 1750 cm-1; MS (CI, NH3)
m/e (%) 324 (M + 1 + 17), 287, 271 (100), 132. Anal. Calcd for
19F NMR δ -106.2 (d, 1F, J AB ) 87.7), -120.9 (d, 1F, J AB
)
87.7); IR (film) 1755, 1647 cm-1
.
1-(ter t-Bu tyld im eth ylsilyl)-5-(ter t-bu tyld im eth ylsilyl-
oxy)-6,6-d iflu or o-2-m eth yl-h ex-5-en -1-on e (2d ). Oil; 1H
NMR δ 0.11 (s, 6H), 0.17 (s, 3H), 0.19 (s, 3H), 0.91 (s, 18H),
0.93 (d, 3H, J HH ) 8.8), 1.1-1.3 (m, 1H), 1.8-1.9 (m, 1H), 2.0-
2.1 (m, 2H), 2.94 (m, 1H); 13C NMR δ -6.53, -6.46, -4.8, 13.9,
16.7, 17.9, 25.4, 26.5, 26.6, 26.8, 49.4, 112.7 (dd, J CF ) 42.0,
J CF ) 14.1), 153.5 (dd, J CF ) 282.6, J CF ) 275.7), 249.8; 19F
NMR δ -106.2 (d, 1F, J AB ) 87.7), -120.8 (d, 1F, J AB ) 87.7);
C
15H28F2O2Si: C, 58.79; H, 9.21. Found: C, 58.54; H, 9.23.
2,2-Diflu or o-3-h yd r oxy-3-(ter t-bu tyld im eth ylsilyl)-cy-
1
cloh ep ta n on e (4 g). White solid: mp 53-55 °C; H NMR δ
0.12 (s, 3H), 0.16 (s, 3H), 1.00 (s, 9H), 1.5-2.2 (m, 7H), 2.4-
2.7 (m, 2H); 13C NMR δ -6.4, -6.1, 18.3, 20.9, 21.8, 27.6, 33.5
(d, J CF ) 9.8), 38.6, 71.6 (dd, J CF ) 35.4, J CF ) 32.5), 121.3
IR (film) 1763, 1640 cm-1
.
1-(Tr is-isopr opylsilyl)-5-(tr im eth ylsilyloxy)-6,6-diflu or o-
h ex-5-en -1-on e (2e). Oil; 1H NMR δ 0.17 (s, 9H), 1.08 (d, 18H,
J HH ) 7.2), 1.25 (sept, 3H, J HH ) 7.3), 1.70 (tt, 2H, J HH ) 7.3,
J HH ) 6.9), 2.0-2.1 (m, 2H), 2.58 (t, 2H, J HH ) 7.3); 13C NMR
δ 0.03, 10.7, 17.9, 18.5, 28.0, 50.0, 112.8, 153.6 (dd, J CF ) 281.7,
J CF ) 274.5), 246.6; 19F NMR δ -106.5 (d, 1F, J AB ) 83.9),
-121.2 (d, 1F, J AB ) 83.9); IR (film) 1763, 1640 cm-1. Anal.
Calcd for C18H36F2O2Si2: C, 57.09; H, 9.58. Found: C, 56.88;
H, 9.57.
2,6-Bis(ter t-bu tyld im eth ylsilyloxy)-1,1,7,7-tetr a flu or o-
h ep t-1,6-en e (3c). Oil; 1H NMR δ 0.14 (s, 12H), 0.94 (s, 18H),
1.72 (quint, 2H, J HH ) 7.2), 2.0-2.1 (m, 4H); 13C NMR δ -4.9,
18.0, 22.4, 25.5, 28.0, 112.4 (dd, J CF ) 42.2, J CF ) 14.1), 153.6
(dd, J CF ) 255.0, J CF ) 252.0), 200.8 (dd, J CF ) 31.5, J CF
)
25.6); 19F NMR δ -104.8 (d, 1F, J AB ) 251.8), -108.2 (d, 1F,
J AB ) 251.8); IR (film) 3507, 1736 cm-1; MS m/e (%) 278 (M+),
261, 127 (100).
2,2-Diflu or o-3-h ydr oxy-3-(ter t-bu tyldim eth ylsilyl)-5 (or
6) -p h en yl-cycloh ep ta n on e (4h ). Oil. Isomeric mixture of
four compounds (66/22/8/4). IR (film): 3517, 1738, 1466 cm-1
.
HRMS: calcd. for C19H28F2O2Si m/e ) 354.1827; found 354.1832.
F ir st Isom er (66%). 1H NMR (500 MHz) δ 0.18 (m, 6H),
1.00 (s, 9H), 1.81 (brs, 1H), 2.0-2.2 (m, 3H), 2.6-3.1 (m, 4H),
7.2-7.3 (m, 5H); 13C NMR (125 MHz) δ -6.41, -6.0, 18.4, 27.6,
29.4, 38.4, 38.5, 41.6 (d, J CF ) 9.8), 72.3 (dd, J CF ) 36.7, J CF
)
32.5), 121.0 (t, J CF ) 253.3), 126.3, 126.5, 128.7, 147.5, 200.2
(t, J CF ) 30.8); 19F NMR δ -105.2 (d, 1F, J AB ) 251.7), -107.6
(d, 1F, J AB ) 251.7); GCMS (CI, NH3, retention time: 9.31)
m/e (%) 372 (M + 1 + 17), 335 (M + 1), 132, 52 (100).
(20) Bouillon, J .-P.; Didier, B.; Dondy, B.; Doussot, P.; Plantier-
Royon, R.; Portella, C. Eur. J . Org. Chem. 2001, 187.