LETTER
Pseudo C2-Symmetric 2-Methyl Substituted 1,3-Diols
31
were purified by flash chromatography (SiO2; pentane–
Et2O) to afford the alkenes (S,S)-3.
References
Analytical data of compound (S,S)-3e: [ ]D24 = –94.6 (1.04,
CHCl3); 1H NMR (300 MHz, CDCl3): = 1.40 (s, 6 H,
CH3), 1.83 (m, 2 H, CHHCO), 2.04 (m, 2 H, CHHCO), 2.65
(ddd, J = 13.9, 9.5, 7.1 Hz, 2 H, CHHPh), 2.86 (m, 2 H,
CHHPh), 4.26 (m, 2 H, CHO), 4.78 (t, J = 1.8 Hz, 2 H,
CH2C), 7.14–7.30 (m, 10 H, ArH); 13C NMR (75 MHz,
CDCl3): = 25.0 (CH3), 31.4 (CH2Ph), 34.3 (CH2CO), 69.2
(CO), 100.4 (CCH3), 103.9 (CH2C), 125.8 (pCH), 128.3,
128.5 (CH, mCH), 142.1 (CPh), 152.9 (CCH2); MS (CI,
methane) m/z = 337 [M++1], 279, 278, 262, 261, 173, 133,
131, 117(100); IR (CHCl3): 3085, 3061, 3026, 2986, 2953,
2933, 2860, 1944, 1870, 1803, 1745, 1652, 1604, 1584,
1544, 1496, 1455, 1432, 1411, 1378, 1323, 1281, 1226,
1183, 1159, 1115, 1087, 1057, 1031, 1000, 970, 957, 896,
865, 819, 802, 750, 700, 652, 622, 582, 518, 486 cm–1; Anal.
Calcd for C23H28O2: C, 82.10; H, 8.39. Found: C, 81.97; H,
8.65.
(1) (a) Omura, S.; Tamaka, H. In Macrolide Antibiotics:
Chemistry, Biology, Practice; Omura, S., Ed.; Academic
Press: New York, 1984, 351. (b) Rychnovsky, S. D. Chem.
Rev. 1995, 95, 2021.
(2) (a) Mahrwald, R.; Ziemer, B. Tetrahedron 1999, 55, 14005.
(b) Anwar, S.; Bradley, G.; Davis, A. P. J. Chem. Soc.,
Perkin Trans. 1 1991, 1383. (c) Bloch, R.; Gilbert, L.;
Girard, C. Tetrahedron Lett. 1988, 29, 1021. (d) Evans, D.
A.; Chapman, K. T.; Carreira, E. M. J. Am. Chem. Soc. 1988,
110, 3560. (e) Narasaka, K.; Pai, F.-C. Tetrahedron 1984,
40, 2233. (f) Delas, C.; Moïse, C. Synthesis 2000, 251.
(g) Mascarenhas, C. M.; Duffey, M. O.; Liu, S.-Y.; Morken,
J. P. Org. Lett. 1999, 1, 1427. (h) Bodnar, P. M.; Shaw, J.
T.; Woerpel, K. A. J. Org. Chem. 1997, 62, 5674.
(i) Collum, D. B.; Still, W. C.; Mohamadi, F. J. Am. Chem.
Soc. 1986, 108, 2094. (j) Ichinose, N.; Mizuno, K.; Tamai,
T.; Otsuji, Y. J. Org. Chem. 1990, 55, 4079. (k) Kitamaru,
M.; Ohkuma, T.; Inoue, S.; Sayo, N.; Kumobayashi, H.;
Akutagawa, S.; Ohta, T.; Takaya, H.; Noyori, R. J. Am.
Chem. Soc. 1988, 110, 629.
(9) Rychnovsky, S. D.; Rogers, B.; Yang, G. J. Org. Chem.
1993, 58, 3511.
(10) (a) Tebbe, F. N.; Parshall, G. W.; Reddy, G. S. J. Am. Chem.
Soc. 1978, 100, 3611. (b) Pine, S. H.; Shen, G. S.; Hoang, H.
Synthesis 1991, 165.
(11) Petasis, N. A.; Bzowej, E. I. J. Am. Chem. Soc. 1990, 112,
6392.
(12) Osborn, J. A.; Jardine, F. H.; Young, J. F.; Wilkinson, G. J.
Chem. Soc. A 1966, 1711.
(3) (a) Enders, D. In Asymmetric Synthesis, Vol.3; Morrison, J.
D., Ed.; Academic Press: New York, 1984, 275. (b)Enders,
D.; Klatt, M. In Encyclopedia of Reagents for Organic
Synthesis, Vol. 1; Paquette, L. A., Ed.; Wiley: Chichester,
1995, 178. (c) Enders, D.; Gatzweiler, W.; Jegelka, U.
Synthesis 1991, 1137.
(4) Enders, D.; Bockstiegel, B.; Gatzweiler, W.; Jegelka, U.;
Dücker, B.; Wortmann, L. Chimica Oggi 1997, 15, 20.
(5) Synthesis of 4,6-disubtituted 2,2-Dimethyl-1,3-dioxan-5-
ones (S,S)-2: t-Butyllithium (11 mmol, 15% in pentane) was
added dropwise to a solution of SAMP-hydrazone (S)-1 (10
mmol) in anhyd THF (40 mL) at –78 °C. After stirring for 2
h the mixture was cooled to –100 °C and the electrophile (11
mmol; dissolved in 1 mL anhyd THF), was added slowly.
After further stirring for 2 h the reaction mixture was
allowed to warm to r.t. over 15 h. The mixture was quenched
with pH 7-buffer solution (2 mL) and diluted with Et2O(80
mL). The organic layer was washed with pH 7-buffer
solution (10 mL) and brine (2 10 mL). The combined
organic layers were dried (MgSO4) and concentrated in
vacuo. The resulting monoalkylated SAMP-hydrazone was
alkylated again at the '-position as described above. The
obtained 4,6-disubtituted SAMP-hydrazone was dissolved
in dichloromethane (50 mL) and flushed with ozone
(60 Lh–1) at –78 °C for 15 min. The reaction mixture was
allowed to warm to r.t. and flushed with argon. After
removal of the solvent under reduced pressure the crude
products were purified by flash chromatography (SiO2;
pentane–Et2O) to afford 4,6-disubtituted 2,2-dimethyl-
1,3-dioxan-5-ones (S,S)-2.
(13) Mislow, K.; Siegel, J. J. Am. Chem. Soc. 1984, 106, 3319.
(14) Marshall, J. A.; Crute, T. D. I. I. I.; Hsi, J. D. J. Org. Chem.
1992, 57, 115.
(15) Synthesis of 4,6-disubstituted 2,2,5-Trimethyl-1,3-dioxanes
(S,S)-4: The methylenated 1,3-dioxan-5-ones (S,S)-3
(0.5 mmol) and chlorotris(triphenylphosphine)rhodium(I)
(10 mol%) were dissolved in anhyd benzene (10 mL) and
vigorously stirred at r.t. under hydrogen atmosphere (1 atm)
for 4 h. The solvent was removed under reduced pressure
and the residue was filtered through silica gel, washed with
pentane–Et2O (10:1), filtered through florisil®, washed with
pentane and dried in vacuo to give (S,S)-4 as colorless oils.
Analytical data of compound (S,S)-4e: [ ]D24 = –2.8 (1.03,
CHCl3); 1H NMR (400 MHz, CDCl3): = 0.78 (d,
J = 6.9 Hz, 3 H, CH3CH), 1.36 (d, J = 7.1 Hz, 6 H, CH3C),
1.60 (m, 2 H, CHHCO), 1.79 (m, 3 H, CHHCO, CHCH3),
2.56 (m, 2 H, CHHPh), 2.81 (m, 2 H, CHHPh), 3.22 (dt,
J = 8.2, 3.8 Hz, 1 H, CHO), 3.85 (m, 1 H, CHO), 7.15–7.29
(m, 10 H, ArH); 13C NMR (100 MHz, CDCl3): = 11.7
(CH3CH), 24.0 (CH3C), 25.1 (CH3C), 32.2, 32.3, 32.4, 36.2
(4 C, CH2), 40.1 (CHCH3), 68.4 (CHO), 74.0 (CHO), 100.5
(CCH3), 125.5, 125.6 (2 C, pCH), 128.1, 128.1, 128.2 (4
C, CH, mCH), 142.0 (2 C, CPh); MS (EI, 70 eV): m/z = 338
[M+], 323, 146, 134, 131, 117, 104, 92, 91(100); IR (CHCl3):
3513, 3085, 3062, 3026, 2985, 2936, 2875, 2674, 1943,
1870, 1804, 1746, 1713, 1622, 1604, 1585, 1496, 1455,
1432, 1380, 1361, 1279, 1227, 1192, 1161, 1130, 1062,
1038, 997, 961, 941, 910, 871, 800, 749, 700, 618, 573, 514,
480 cm–1; Anal. Calcd for C23H30O2: C, 81.61; H, 8.93.
Found: C, 81.17; H, 9.00.
(6) (a) Wittig, G.; Schöllkopf, U. Chem. Ber. 1954, 87, 1318.
(b) Enders, D.; Thiebes, C. Synthesis 2000, 510.
(7) Maercker, A. Angew. Chem., Int. Ed. Engl. 1987, 26, 972;
Angew. Chem. 1987, 99, 1002.
(8) Synthesis of the exo-Methylene Derivatives (S,S)-3: t-
Butyllithium (26.4 mmol, 15% in n-pentane) was added
dropwise to a suspension of methyltriphenylphosphonium
bromide (26.4 mmol) in dry THF (125 mL) at –78 °C and
stirring was continued for 15 min. Then the mixture was
allowed to warm to r.t. over 30 min and cooled again to
–78 °C. Ketone (S,S)-3 (4.4 mmol; dissolved in 8 mL dry
THF), was added and the reaction mixture was allowed to
warm to r.t. over 15 h. The mixture was quenched with water
(10 mL) and the aq layer was extracted with diethyl ether
(3 20 mL). The combined organic layers were dried
(MgSO4) and concentrated in vacuo. The crude products
(16) Synthesis of (3S,5S)-4-Methyl-1,7-diphenylheptane-3,5-
diol (S,S)-5: TFA (0.05 mL) was added to (S,S)-4e
(0.3 mmol) in THF (2 mL) and water (1 mL). The mixture
was stirred at r.t. until the reaction was completed (TLC
control). Concd NH3 (0.5 mL) and water (1.5 mL) were
added and the aq layer was extracted with CH2Cl2
(3 10 mL). The combined organic layers were dried
(MgSO4) and concentrated in vacuo. The crude product was
purified by flash chromatography (SiO2; pentane–Et2O 1:1)
Synlett 2002, No. 1, 29–32 ISSN 0936-5214 © Thieme Stuttgart · New York