LETTER
Desymmetrizing Asymmetric Epoxidations of Bis(cis-configured) Divinylcarbinols
37
(6) (a) Herunsalee, A.; Isobe, M.; Pikul, S.; Goto, T. Synlett
1991, 199. (b) Hatakeyama, S.; Satoh, K.; Takano, S.
Tetrahedron Lett. 1993, 34, 7425. (c) Esumi, T.; Fukuyama,
H.; Oribe, R.; Kawazoe, K.; Iwabuchi, Y.; Irie, H.;
Hatakeyama, S. Tetrahedron Lett. 1997, 38, 4823.
(d) Nishioka, T.; Iwabuchi, Y.; Irie, H.; Hatakeyama, S.
Tetrahedron Lett. 1998, 39, 5597. (e) Masaki, H.;
Maeyama, J.; Kamada, K.; Esumi, T.; Iwabuchi, Y.;
Hatakeyama, S. J. Am. Chem. Soc. 2000, 122, 5216.
(f) Bayer, A.; Svendsen, J. S. Eur. J. Org. Chem. 2001, 1769.
(7) Berkenbusch, T.; Brückner, R. Synlett 2003, 1813.
(8) Spivey, A. C.; Woodhead, S. J.; Weston, M.; Andrews, B. I.
Angew. Chem. Int. Ed. 2001, 40, 769.
159.43 and 159.44 (2 × Cpara). Anal. Calcd (%) for C23H28O6
(400.5): C, 68.98; H, 7.05. Found: C, 69.16; H, 7.16.
(13) The diastereomeric composition of monoepoxidation
product 1b was determined by comparing the integrals over
the following 1H NMR signals (300 MHz, CDCl3): d = 3.02
[dd, J3,4 = 7.5 Hz, J3,2 = 4.1 Hz, 3-H (anti-1b7)] vs. d = 3.07
[dd, J3,4 = 7.4 Hz, J3,2 = 4.5 Hz, 3-H (syn-1b)]. ‘ds >98:2’
means that the mentioned 1H NMR signal of the minor
diastereomer could not be detected.
(14) The ee of monoepoxidation product syn-1b was determined
by HPLC. Column: Chiralpak OD-H; eluent: n-heptane–
i-PrOH 200:1; flow rate: 1.0 mL/min; UV detector: 210 nm;
tR = 24.5 min for syn-1b; tR = 27.8 min for ent-syn-1b.
(15) Analytical Data for cis,cis-2,3-5,6-Bisepoxy-1,7-bis[4-
methoxybenzyl)oxy]-4-heptanol (syn,syn-5).
(9) The diastereomeric compositions of monoepoxidation
product 1a were determined by comparing the integrals over
the following 1H NMR signals (300 MHz, CDCl3): d = 2.99
[dd, J3,4 = 7.5 Hz, J3,2 = 4.3 Hz, 3-H (anti-1a7)] vs. d = 3.07
[dd, J3,4 = 7.4 Hz, J3,2 = 4.5 Hz, 3-H (syn-1a)]. ‘ds >98:2’
means that the mentioned 1H NMR signal of the minor
diastereomer could not be detected.
Colorless solid (mp 90–91 °C). 1H NMR (499.9 MHz,
CDCl3/TMS): d = 2.53 (br d, JOH,4 = 5.4 Hz, OH), 3.13 (dd,
J3,4 or J5,4 = 6.0 Hz, respectively, J3,2 or J5,6 = 4.5 Hz,
respectively, 3-H, 5-H), 3.27 (ddd, J2,1-H(A) or J6,7-H(A) = 5.5
Hz, respectively, J2,3 = J2,1-H(B) or J6,5 = J6,7-H(B) = 4.6 Hz,
respectively, 2-H, 6-H), 3.63–3.72 (m, 1-H2, 4-H, 7-H2),
3.79 (s, 2 × OCH3), AB signal (dA = 4.42, dB = 4.50,
JAB = 11.4 Hz, 2 × Ar-CH2), AA¢BB¢ signal centered at
d = 6.87 und 7.24 (2 × C6H4). 13C NMR (125.7 MHz,
CDCl3/CDCl3): d = 55.33 (C-2, C-6), 55.60 (2 × OCH3),
56.98 (C-3, C-5), 66.74 (C-4), 67.54 (C-1, C-7), 73.12
(2 × benzylic CH2), 113.96 (2 × Cmeta), 129.57 (2 × Cortho),
129.64 (2 × Cipso), 159.48 (2 × Cpara). Anal. Calcd (%) for
C23H28O7 (416.5): C, 66.33; H, 6.78. Found: C, 66.14; H,
6.83.
(10) All new compounds gave satisfactory 1H NMR and 13
C
NMR spectra and provided correct combustion analyses (C
and H 0.4%).
(11) The ee of monoepoxidation product syn-1a was determined
by HPLC. Column: Chiralpak AD; eluent: n-heptane–
i-PrOH 90:10; flow rate: 1.0 mL/min; UV detector: 238 nm;
tR = 48.2 min for syn-1a; tR = 53.4 min for ent-syn-1a.
(12) Synthesis of cis-(2R,3S,4R)-2,3-Epoxy-1,7-bis[(4-
methoxybenzyl)oxy]-5-hepten-4-ol (syn-1a).
At –20 °C, L-(+)-DiPT (51 mL, 57 mg, 0.24 mmol, 1.1 equiv)
and t-BuOOH (4.43 M in CH2Cl2, 100 mL, 0.44 mmol, 2.0
equiv) were added to a suspension of Zr(Oi-Pr)4·i-PrOH (84
mg, 0.22 mmol, 1.0 equiv) and 4 Å MS (140 mg, powdered)
in CH2Cl2 (4.5 mL). The mixture was stirred for 1 h at
–20 °C before a solution of divinylcarbinol 2a (85 mg, 0.22
mmol) in CH2Cl2 (2.0 ml) was added slowly. After stirring
at –20 °C for 4 h, the reaction was quenched at –20 °C with
a solution (1.0 mL) prepared from NaOH (30 g), NaCl (5 g),
and H2O (90 mL). The cooling bath was removed and the
mixture stirred for 2 h at r.t. t-BuOMe (10 mL) was followed
by Na2SO4 for drying. After filtration through a pad of
Celite® excess t-BuOOH was removed by azeotropic
distillation with toluene (2 × 5 mL). The residue was
purified by flash chromatography20 (cyclohexane–EtOAc,
5:2) to afford syn-1a (56 mg, 63%) in the early fractions and
a 68:32-mixture of syn,syn-5/syn-1a [33 mg, composed of 10
mg syn-1a (11%) and 23 mg syn,syn-5 (25%)] thereafter,
both samples being colorless liquids. The total yield of syn-
1a was 74% and its ee value 82.0% (by HPLC11). Sample of
98.3% ee from the time resolved experiment (Figure 1; 16 h,
44% yield): [a]D20 –8.7 (c 0.8, CHCl3), [a]36520 –33.1 (c 0.8,
CHCl3). 1H NMR (499.9 MHz, CDCl3/TMS): d = 2.67 (br s,
OH), 3.07 (dd, J3,4 = 7.4 Hz, J3,2 = 4.5 Hz, 3-H), 3.25 (ddd,
J2,1-H(A) = 6.5 Hz, J2,3 = J2,1-H(B) = 4.2 Hz, 2-H), AB signal
(dA = 3.50, dB = 3.65, JAB = 11.4 Hz, in addition split by
JA,2 = 6.6 Hz, JB,2 = 3.7 Hz, 1-H2), 3.79 (s, 2 × OCH3), AB
signal (dA = 4.02, dB = 4.06, JAB = 12.8 Hz, in addition split
(16) This study was effected starting with 1.56 mmol 2a in 48 mL
CH2Cl2. After the indicated times, 8 mL aliquots were
removed from the reaction mixture and worked up
extractively as described in ref. 12. After assessing the yields
of the constituents of the crude product17 the latter was flash-
chromatographed20 for obtaining pure samples of syn-1a for
ee determination.11
(17) The overall weights of the crude products and their 1H NMR
spectra allowed determining the yields of the constituents
syn-1a, 2a, and 5 of these mixtures.
(18) This experiment was performed before we learnt to prepare
epoxy alcohol syn-1a as enantioselectively as documented in
Table 1 and Figure 1.
(19) Method: (a) Hatakeyama, S.; Satoh, K.; Takano, S.
Tetrahedron Lett. 1993, 34, 7425. (b) Esumi, T.;Fukuyama,
H.; Oribe, R.; Kawazoe, K.; Iwabuchi, Y.; Irie, H.;
Hatakeyama, S. Tetrahedron Lett. 1997, 38, 4823.
(c) Nishioka, T.; Iwabuchi, Y.; Irie, H.; Hatakeyama, S.
Tetrahedron Lett. 1998, 39, 5597.
(20) Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43,
2923.
(21) Analytical Data for (2S,4R)-1-[4-Methoxybenzyl)oxy]-6-
heptene-2,4-diol [(2S,4R)-7].
Colorless liquid. [a]D20 = –7.7 (c 0.92, CHCl3) when
prepared from anti-6 the ee of which was 96.8% (by HPLC).
1H NMR (499.9 MHz, CDCl3/TMS): AB signal (dA = 1.55,
dB = 1.63, JAB = 14.4 Hz, in addition split by JA,4 = 8.9 Hz*,
4
by JA,6 = 5.9 Hz, JA,5 = 1.2 Hz, JB,6 = 6.2 Hz, 4JB,5 = 1.5 Hz,
JA,2 = 3.5 Hz*, JB,2 = 8.5 Hz**, JB,4 = 2.8 Hz**, 3-H2),
7-H2), 4.27 (br dd, J4,5 = J4,3 = 7.8 Hz, 4-H), 4.39–4.51 (m,
2 × Ar-CH2), AB signal (dA = 5.66, dB = 5.78, JAB = 11.3
Hz, in addition split by JA,4 = 8.2 Hz, JB,7-H(A) = JB,7-H(B) = 5.9
Hz, A: 5-H, B: 6-H), AA¢BB¢ signal centered at d = 6.87 and
d = 7.24 (2 × C6H4). 13C NMR (125.7 MHz, CDCl3/CDCl3):
d = 55.33 (2 × OCH3), 56.00 (C-2), 58.93 (C-3), 65.83 (C-
7), 66.79 (C-4), 67.79 (C-1), 72.41 and 73.02 (2 × benzylic
CH2), 113.92 and 113.96 (2 × Cmeta), 129.52 and 129.56
(2 × Cortho), 129.78 (2 × Cipso), 130.24 (C-5), 130.38 (C-6),
d = 2.20–2.31 (m, 5-H2), 2.54 and 2.79 (2 × br s, 2 × OH),
AB signal (dA = 3.38, dB = 3.47, JAB = 9.5 Hz, in addition
split by JA,2 = 7.7 Hz, JB,2 = 3.7 Hz, 1-H2), 3.80 (s, OCH3),
3.92–3.98 (m, 4-H), 4.12 (mC, 2-H), 4.49 (s, Ar-CH2), 5.09–
5.14 (m, 7-H2), 5.82 (dddd, J6,7-H(Z) = 16.3 Hz, J6,7-H(E) = 11.0
Hz, J6,5-H(A) = J6,5-H(B) = 7.2 Hz, 6-H), AA¢BB¢ signal
centered at d = 6.88 and 7.25 (C6H4); *,** assignments
interchangeable. 13C NMR (125.7 MHz, CDCl3/CDCl3):
d = 38.78 (C-3), 42.20 (C-5), 55.35 (OCH3), 67.93 and 67.99
Synlett 2006, No. 1, 33–38 © Thieme Stuttgart · New York