1314
T. Yakura et al.
LETTER
(6) Hooz, J.; Layton, R. B. J. Am. Chem. Soc. 1971, 93, 7320;
mixture of 3, 2d and 2b in quantitative yield (Table 1, en-
try 7).15
Hooz, J.; Layton, R. B. Can. J. Chem. 1973, 51, 2098;
Hashimoto, S.; Shinoda, T.; Ikegami, S. Tetrahedron Lett.
1986, 27, 2885; Yoshino, T.; Okamoto, S.; Sato, F. J. Org.
Chem. 1991, 56, 3205.
The ester congener 1b,8c,9 upon treatment with 2.2 equiv
of Me3Al in toluene at -78 °C for 30 min, gave the 3,4-cis
adduct 2e as a sole diasteroisomer but only in 22% yield,
along with 22% of unreacted 1b (Table 1, entry 8). The
spectroscopic data of 2e were identical to those of a race-
mic authentic sample.8a Use of 4 equiv of Me3Al increased
the yield to 51% (Table 1, entry 9). As expected, no reac-
tion took place when the cyclopentenone 1c was treated
with Me3Al under the same conditions.
(7) Pappo, R.; Collins, P. W. Tetrahedron Lett. 1972, 2627;
Collins, P. W.; Dajani, E. Z.; Bruhn, M. S.; Brown, C. H.;
Palmer, J. R.; Pappo, R. Tetrahedron Lett. 1975, 4217;
Caddick, S.; Delisser, V. M. Tetrahedron Lett. 1997, 38, 2355.
(8) (a) Yakura, T.; Yamada, S.; Kunimune, Y.; Ueki, A.; Ikeda,
M. J. Chem. Soc., Perkin Trans. 1 1997, 3643. (b) Yakura, T.;
Yamada, S.; Azuma, M.; Ueki, A.; Ikeda, M. Synthesis 1998,
973. (c) Yakura, T.; Ueki, A.; Kitamura, T.; Tanaka, K.;
Nameki, M.; Ikeda, M. Tetrahedron 1999, in press.
One possible rationalization for the high diastereoselec-
tivity obtained in the reaction of 1a or 1b with R3Al is
based on the assumption of 1:2 complex A or B, respec-
tively. Thus, the first alane combines with the keto and
sulfonyl or ester groups as a Lewis acid to activate the
enone 1a or 1b. The second R3Al makes the chelation be-
tween R3Al and an oxygen atom of the TBDMSO group
at C-4 to form the intermediate A or B.16 The alkyl group
is then transfered intramolecularly from the coordinated
R3Al to give the 3,4-cis adducts 2a–e.17 The nucleophilic-
ity of the alkyl group of the resulting ate-complex is
(9) Yakura, T.; Ueki, A.; Morioka, Y.; Kurata, T.; Tanaka, K.;
Ikeda, M. Chem. Pharm. Bull. 1998, 46, 1182.
(10) A typical procedure for the conjugate addition of
trialkylaluminum: A 1.0 M solution of Me3Al in hexane (0.63
mL, 0.63 mmol) was added to a solution of 1a (100 mg, 0.28
mmol) in toluene (6 mL) at -78 °C under a nitrogen
atmosphere. The mixture was stirred at the same temperature
for 30 min and quenched with sat. aq. NH4Cl. The mixture was
allowed to warm to room temperature and extracted with
EtOAc. The extract was washed with brine, dried (MgSO4),
and concentrated. The residue was chromatographed on silica
gel (hexane/EtOAc, 10:1) to give 2a (89 mg, 86%) as colorless
crystals: mp 111-113.5 ¡C (from hexane); [a]D24 -96.9 (c 1.08,
CHCl3); IR (CCl4) n 1760, 1320, 1140 cm-1; 1H NMR d: 0.02,
0.05 (both 3H, s, SiMe), 0.82 (9H, s, t-Bu), 1.30 (3H, d, J = 6.8
Hz, 3-Me), 2.31 (1H, dt, J = 16.8. 1.0 Hz, one of 5-H2), 2.54
(1H, dd, J = 16.8, 3.9 Hz, one of 5-H2), 2.96 (1H, dqd, J = 10.0,
6.8, 3.5 Hz, 3-H), 3.48 (1H, d, J = 10.0 Hz, 2-H), 4.31 (1H, t,
J = 3.7 Hz, 4-H), 7.54-7.61 (2H, m, ArH), 7.65-7.71 (1H, m,
ArH), 7.86-7.91 (2H, m, ArH). Anal. Calcd for C18H28O4SSi:
C, 58.66; H, 7.66. Found: C, 58.87; H, 7.51.
known to be higher than for a noncoordinated R3Al.2a,18
A
bulky alane such as triisobutylaluminum would retard the
formation of the intermediate A to reduce the yield of the
conjugate addition. The high reactivity of diethyl(trimeth-
ylsilylethynyl)aluminum to the enones would allow the
reaction to proceed through non-chelated intermediate C,
in which the nucleophile attacked from the less-hindered
side to afford the 3,4-trans isomer 3. In ether, complex-
ation of R3Al with ether would make it unable to form the
intermediate A.
(11) In contrast, treatment of 1a with lithium dimethylcuprate gave
the 2,3-trans-3,4-trans isomer, (2S,3R,4S)-4-(TBDMSoxy)-3-
methyl-2-phenylsulfonylcyclopentanone (4), in 90% yield as
a single diastereoisomer. Desulfonylation of 4 with SmI2
produced 5.8a
TMS
R
Et
Al
R
R
O
R
O
S
Et
R
O
R
O
Al
Al
O
O
S
O
O
Ph
Ph
OMe
SO2Ph
Me CuLi
2
SmI2
O
O
Et
Al
1a
(90%)
(88%)
TBDMSO
R
TBDMSO
R
Et
TMS
TBDMSO
TBDMSO
Me
TBDMSO
Me
Al
Al
A
B
4
5
C
R
R
R
R
(12) Molander, G. A.; Hahn, G. J. Org. Chem. 1986, 51, 1135.
(13) The 1H NMR data of H-2 and H-4 protons of 2a-d, 3, and 4.
References and Notes
(1) Perlmutter, P. Conjugate Addition in Organic Synthesis;
Pergamon Press: Oxford, 1992.
(2) (a) Yamamoto, H. In Organometallics in Synthesis: A
Manual; Schlosser, M. Ed.; John Wiley & Sons: Chichester,
1994; p 509. (b) Maruoka, K.; Yamamoto, H. Tetrahedron
1988, 44, 5001.
(3) Kabalka, G. W.; Daley, R. F. J. Am. Chem. Soc. 1973, 95,
4428.
(4) Schwartz, J.; Carr, D. B.; Hansen, R. T.; Dayrit, F. M. J. Org.
Chem. 1980, 45, 3053; Flemming, S.; Kabbara, J.; Nickisch,
K.; Neh, H.; Westermann, J. Synthesis 1995, 317, and
references cited therein.
(5) Takemoto, Y.; Kuraoka, S.; Hamaue, N.; Iwata, C.
Tetrahedron: Asymmetry 1996, 7, 993; Kabbara, J.;
Flemming, S.; Nickisch, K.; Neh, H.; Westermann, J.
Tetrahedron 1995, 51, 743, and references cited therein.
Synlett 1999, No. 8, 1313–1315 ISSN 0936-5214 © Thieme Stuttgart · New York