COMMUNICATIONS
49.48, 71.57, 111.49, 126.16, 127.80, 128.80, 144.44, 144.82; calcd for
C14H22OSi: C 71.73, H 9.46; found: C 71.33, H 9.55.
than for 13: a small pseudoaxial group minimizes allylic strain
with the existing stereogenic center (Scheme 2). Thus, this
allylic transfer reaction led to the formation of a cis
tetrahydropyran with high diastereoselectivity through the
stereochemical model 12.
Having been successful in forming bridged pyran ring 11,
we tried to extend this approach to intramolecular allylic
transfer reactions.[15] We were surprised that 7 f and 7h did not
cyclize on treatment with a variety of Lewis acids and
modified substrates. After surveying numerous reaction
conditions, we were gratified to find that the use of Sn(OTf)2
and Me3SiSPh in the intramolecular allylic transfer reaction
led to the formation of 11 as the sole product (Scheme 2, e).
The use of catalytic amounts of TMSSPh was crucial,
presumably as a result of the formation of a thioketal
intermediate, which formed a oxocarbenium ion under
mediation of the tin catalyst.
In summary, we have described herein a new synthetic
strategy for the stereoselective synthesis of tetrahydropyrans
with an exocyclic double bond by means of a catalytic
asymmetric sequential allylic transfer reaction in a very
general and efficient way, which promises to be widely
applicable. We believe that the products can serve as synthetic
intermediates for useful substances.
Received: August 10, 2001 [Z17701]
[1] General discussions: a) Lewis Acids in Organic Synthesis, Vol. I, II
(Ed. H. Yamamoto), Wiley, VCH, Weinheim, 2000; b) Y. Yanagisawa
in Comprehensive Asymmetric Catalysis, Vol. II (Eds. E. N. Jacobsen,
A. Pfaltz, H. Yamamoto), Springer, Heidelberg, 1999, pp. 965 979;
c) S. E. Denmark, N. G. Almstead in Modern Carbonyl Chemistry
(Ed.: J. Otera), Wiley-VCH, Weiheim, 2000, pp. 299 402.
[2] For an excellent review, see: D. J. Berrisford, C. Bolm, K. B. Sharpless,
Angew. Chem. 1995, 107, 1159 1170; Angew. Chem. Int. Ed. Engl.
1995, 34, 1059 1070.
[3] a) E. M. Vogl, H. Groger, M. Shibasaki, Angew. Chem. 1999, 111,
1671 1680; Angew. Chem. Int. Ed. 1999, 38, 1571 1577; b) K.
Mikami, M. Terada, T. Korenaga, Y. Matsumoto, M. Ueki, R.
Angelaud, Angew. Chem. 2000, 112, 3676 3701; Angew. Chem. Int.
Ed. 2000, 39, 3532 3556.
[4] a) C.-M. Yu, H.-S. Choi, W.-H. Jung, H.-J. Kim, J. Shin, Chem.
Commun. 1997, 761 762; b) C.-M. Yu, H.-S. Choi, W.-H. Jung, S.-S.
Lee, Tetrahedron Lett. 1996, 37, 7095 7098.
[5] a) C.-M. Yu, S.-K. Yoon, H.-S. Choi, K. Baek, Chem. Commun. 1997,
763 764; b) C.-M. Yu, H.-S. Choi, S.-K. Yoon, W.-H. Jung, Synlett
1997, 889 890.
[6] C.-M. Yu, S.-K. Yoon, K. Baek, J.-Y. Lee, Angew. Chem. 1998, 110,
2505 2506; Angew. Chem. Int. Ed. 1998, 37, 2392 2395.
[7] a) C.-M. Yu, S.-K. Yoon, S.-J. Lee, J.-Y. Lee, S. S. Kim, Chem.
Commun. 1998, 2749 2750; b) C.-M. Yu, S.-J. Lee, M. Jeon, J. Chem.
Soc. Perkin Trans. 1 1999, 3557 3558; c) C.-M. Yu, M. Jeon, J-Y. Lee,
J. Jeon, Eur. J. Org. Chem. 2001, 6, 1143 1148.
[8] For some efforts towards the synthesis of natural products that contain
tetrahydropyran groups, see: a) D. A. Evans, V. J. Cee, T. E. Smith,
K. J. Santiago, Org. Lett. 1999, 1, 87 90; b) S. D. Rychnovsky, C. R.
Thomas, Org. Lett. 2000, 2, 1217 1219.
[9] a) G. E. Keck, K. H. Tarbet, L. S. Geraci, J. Am. Chem. Soc. 1993, 115,
8467 8468; b) G. E. Keck, D. Krishnamurthy, J. Am. Chem. Soc. 1995,
117, 2363 2364.
[10] a) A. Takuwea, H. Saito, Y. Nishigaichi, Chem. Commun. 1999, 1963
1964; b) D. L. J. Clive, C. C. Paul, Z. Wang, J. Org. Chem. 1997, 62,
7028 7032; c) G. Majetich, H. Nishidie, Y. Zhang, J. Chem. Soc.
Perkin 1 1995, 453 457.
[11] To remove the proton source, all volatile materials were evaporated
from the BINOL TiIV complex, but the catalytic ability decreased
sharply. For a discussion on the role of additional alcohol in chiral
Lewis acid reactions, see: H. Ishitani, Y. Yamashita, H. Shimizu, S.
Kobayashi, J. Am. Chem. Soc. 2000, 122, 5403 5404.
[12] a) M. Santelli, J.-M. Pons, Lewis Acids and Selectivity in Organic
Synthesis, CRC, Boca Raton, 1995, pp. 91 225; b) I. E. Marko, J.-M.
Plancher, Tetrahedron Lett. 1999, 40, 5259 5262; I. E. Marko, D. J.
Bayston, Tetrahedron Lett. 1993, 34, 6595 6598; I. E. Marko, A.
Mekhalfia, D. J. Bayston, H. Adams, J. Org. Chem. 1992, 57, 2211
2213.
[13] For applications of MNTf2 (M Al, Si, Ti, Li, Sc) in Lewis acid
catalyzed reactions, see: a) A. Marx, H. Yamamoto, Angew. Chem.
2000, 112, 182 184; Angew. Chem. Int. Ed. 2000, 39, 178 181; b) B.
Mathieu, L. Ghosez, Tetrahedron Lett. 1997, 38, 5497 5500; c) K.
Mikami, O. Kotera, Y. Motoyama, M. Sakaguchi, M. Maruta, Synlett
1996, 171 172; d) L. Ghosez, C. Mineur, P. A. Grieco, S. T. Handy,
Synlett 1995, 565 567.
[14] TMSNTf2 can be readily prepared by the reaction of allyltrimethyl-
silane with HNTf2, according to a literature procedure (ref. [13b]).
[15] For a racemic synthesis of 11a, see: G. A. Molander, D. C. Shubert, J.
Am. Chem. Soc. 1987, 109, 6877 6878.
Experimental Section
6:[16] (R)-BINOL and Ti(OiPr)4 (1:1) in the presence of 4-ä molecular
sieves at 458C in PhCF3 for 2h afforded ( R)-BINOL TiIV complex.
1,1,1,3,3,3-Hexafluoro-2-propanol (2 equiv) was added to the resulting
mixture. The solution was stirred at 458C for an additional 2h and the
volatile materials were evaporated under high vacuum (ꢀ0.5 mmHg) in a
Schlenk tube. Freshly distilled PhCF3 was added.
Typical procedure (Table 1, entry 1): A flame-dried Schlenk flask that
contained (R)-BINOL (57.3 mg, 0.2mmol) and activated powdered 4-ä
molecular sieves (1.0 g) was evacuated, carefully purged with nitrogen
three times, and then charged with dry PhCF3 (2mL) followed by freshly
distilled Ti(OiPr)4 (freshly prepared, 0.5m in PhCF3, 0.4 mL, 0.2mmol).
The mixture was allowed to proceed at 458C for 2h. After cooling to 23 8C,
1,1,1,3,3,3-hexafluoro-2-propanol (68 mg, 0.4 mmol) was added. The result-
ing solution was warmed to 458C and heated for 2h. The solution was
cooled to 238C and concentrated under vacuum (ꢀ0.5 mmHg) in a Schlenk
tube. The vacuum line was equipped with a drying tube (CaSO4). Freshly
distilled PhCF3 (3 mL) was added, the homogeneous solution of 6 was
cooled to À208C in a dry ice/CCl4 bath, and treated with benzaldehyde
(R1 Ph, 0.44 g, 4.0 mmol) in PhCF3 (1 mL). The temperature was kept
below À208C, while 4 (1.67 g, 4.0 mmol) in PhCF3 (2mL) was added
dropwise through a gas-tight syringe to this mixture over 20 min along the
wall of the flask by using a syringe pump. After stirring for 12h at À208C,
aqueous NaHCO3 (5 mL) was added to the reaction mixture, which was
then diluted with CH2Cl2 (20 mL). The molecular sieves were removed by
filtration, and the aqueous layer was extracted with CH2Cl2 (ꢀ20 mL).
After the combined organic solution was dried over anhydrous Na2SO4, the
solvents were removed under reduced pressure. Column chromatography
(15% EtOAc in hexanes) afforded 5a (R1 Ph, 0.835 g, 3.56 mmol, 89%)
as a colorless liquid. Rf 0.26 (15:1 hexane/EtOAc); [a]2D0 27.08 (c
1.230, CHCl3); 96% ee determined by means of HPLC on a Daicel OD-H
column [hexane/iPrOH 97:3; tr(major) 12.4 min, tr(minor) 14.2min];
FTIR (neat): nÄ 3404.7 (br), 3069.9, 2953.6, 1631.7, 1250.0, 848.3 cmÀ1
;
[16] This is a stoichiometric representation. We do not know the exact
structure and aggregation at this moment, although we observed a
signal at d 5.45 [m, 1 ppm downfield shift relative to (CF3)2CHOH]
for (CF3)2CHOTi with no peaks for isopropoxy group according to the
500 MHz NMR spectrum of 6.
1H NMR (500 MHz, CDCl3): d 0.03 (s, 9H; Si(CH3)3), 1.59 (ddd, J 0.92,
13.42, 13.42 Hz, 1H; (CH3)3SiCHH), 1.63 (ddd, J 0.92, 13.42, 13.42 Hz,
1H; (CH3)3SiCHH), 2.29 (d, J 1.83 Hz, 1H; OH), 2.34 (dd, J 9.46,
13.73 Hz, 1H; HOCHCHHC C), 2.37 (ddd, J 0.92, 3.97, 13.73 Hz, 1H;
HOCHCHHC C), 4.75 (d, J 0.91 Hz, 1H; C CHH), 4.78 (d, J
0.91 Hz, 1H; C CHH), 4.80 (dd, J 0.92, 3.97 Hz, 1H; HOCH),
7.33~7.39 (m, 5H; Ph); 13C NMR (125 MHz, CDCl3): d À0.95, 26.93,
Angew. Chem. Int. Ed. 2002, 41, No. 1
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