Y. Cai, B. P. Roberts / Tetrahedron Letters 45 (2004) 1485–1488
1487
EWG
EWG
18
EWG
EWG
EWG
step A
EWG
EWG
step B
O
OTBS
19
OTBS
OTBS
EWG
EWG
EWG
O
O
EWG
20
Scheme 3.
The ketene acetals 4 and 19 have not been reported
previously. Compound 4: bp 98–100 ꢁC/0.05 mm Hg;
culations (MMX force field) to be less favourable
thermodynamically by 4.5 kJ molÀ1
.
1
NMR (throughout, 500 MHz for H, 125.7 MHz for 13C;
CDCl3 solvent, J in Hz); dH 0.19 (6H, s, SiMe2), 0.94 (9H,
s, But), 1.62 (6H, m, Ad), 1.92 (6H, m, Ad), 2.16 (3H, br s,
Ad), 3.51(8) (1H, d, J 1.1, @CHAHB), 3.52(4) (1H, d, J
1.1, @CHAHB); dC )4.8, 18.1, 25.7, 30.9, 36.2, 42.3, 74.6,
77.5, 156.9. Found: C, 69.9; H, 10.6. C18H32O2Si requires
C, 70.1; H, 10.5. Compound 19: bp 90–92 ꢁC/1.0 mm Hg;
dH 0.19 (6H, s, SiMe2), 0.38 (4H, m, 2CH2), 0.93 (9H, s,
But), 1.11 (1H, m, CH), 1.25 (6H, s, 2Me), 3.47 (1H, d, J
1.1, @CHAHB), 3.52 (1H, d, J 1.1, @CHAHB); dC )4.9,
1.8, 18.0, 21.0, 25.1, 25.7, 73.3, 79.7, 157.6. Found: C, 65.6;
H, 10.9. C14H28O2Si requires C, 65.6; H, 11.0.
O
H
13
CO2Me
R (or S)
MeN
11
O
9
H
H
H
O
5
3NMe
O
7
1
S (or R)
H
21
Although the yield of 21 is so far only moderate, this
type of metal- and halogen-free reaction is of significant
interest in that it involves the formation, in a single pot
from two readily obtained starting materials, of a
cyclopentane ring and four new C–C bonds in a stereo-
controlled manner. Moreover, the highly functionalised
molecules that result from these alkylation–carboxy-
methylation and annulation reactions should be readily
amenable to further elaboration, making this chemistry
of potential use in the synthesis of complex molecules.
6. (a) Chick, W. H.; Ong, S. H. Chem. Commun. 1969, 216–
217; (b) Griller, D.; Roberts, B. P. J. Chem. Soc., Perkin
Trans. 2 1972, 747–751.
7. Cai, Y.; Roberts, B. P.; Tocher, D. A. Org. Biomol. Chem.,
in preparation.
8. Fischer, H.; Radom, L. Angew. Chem., Int. Ed. 2001, 40,
1340–1371.
9. Di-tert-butyl peroxide could also be used as initiator, but
the yield was lower than with DTAP.
10. Representative procedure: 1-Adamantoxy-1-(tert-butyl-
dimethylsiloxy)ethene 4 (616 mg, 2.0 mmol), N-methyl-
maleimide (267 mg, 2.4mmol), di-tert-amyl peroxide (70 mg,
0.40 mmol) and dry chlorobenzene (4 mL) were added to a
dry, argon-filled flask, containing a magnetic stirrer bar
and equipped with a condenser. The flask was immersed in
an oil bath, pre-heated to 140 ꢁC, and the reaction mixture
was stirred at reflux under argon for 3 h. The solvent was
removed by rotary evaporation and methyl iodide (1.14 g,
8.0 mmol) and dry THF (2 mL) were added to the residue
and the resulting solution was cooled in an ice-water bath
before addition of tetrabutylammonium fluoride (1 M in
THF, 2.2 mL). The solution was stirred at 0 ꢁC for 2 h
before saturated aqueous NH4Cl solution (10 mL) was
added. The mixture was extracted with CH2Cl2
(3 · 10 mL), the combined extracts were dried (MgSO4)
and the solvent was removed under reduced pressure. The
residue was purified by flash chromatography on silica gel,
using light petroleum (bp 40–60 ꢁC)–diethyl ether–CH2Cl2
(16:4:5) as eluent, to give the methyl ester 10 (422 mg,
66%), which was recrystallised from hexane–CH2Cl2; mp
115–117 ꢁC; dH 1.49 (3H, dd, J 12.0 and 1.8, Ad), 1.64
(3H, d, J 12.3, Ad), 1.71 (3H, d, J 12.3, Ad), 1.83 (3H, dd,
References and notes
1. Cai, Y.; Roberts, B. P. Tetrahedron Lett. 2003, 44, 4645–
4648.
2. Sakaitani, M.; Ohfune, Y. J. Org. Chem. 1990, 55, 870–
876.
3. Recupero, F.; Bravo, A.; Bjorsvik, H.-R.; Fontana, F.;
Minisci, F.; Piredda, M. J. Chem. Soc., Perkin Trans. 2
1997, 2399–2406.
4. Kruppa, G. H.; Beauchamp, J. L. J. Am. Chem. Soc. 1986,
108, 2162–2169.
5. Silyl ketene acetals RO(TBSO)C@CH2 were prepared
from the acetate esters ROC(@O)CH3 by treatment with
lithium diisopropylamide in THF at )78 ꢁC, followed by
quenching of the lithium enolate with ButMe2SiCl in the
presence of hexamethylphosphoramide at )78 ꢁC and
subsequent warming to room temperature, see: Danishef-
sky, S.; Vaughan, K.; Gadwood, R.; Tsuzuki, K. J. Am.
Chem. Soc. 1981, 103, 4136–4141.