LETTER
Ring-Opening of Monoprotected Epoxy Diols
437
(4) (a) The starting epoxy diols can be prepared in optically
active form, see: Katsuki, T.; Sharpless, K. B. J. Am. Chem.
Soc. 1980, 102, 5974. (b) Because this reiterative approach
is substrate controlled and highly stereoselective, this is the
only instance in which chirality needs to be introduced.
(5) Sasaki, M.; Tanino, K.; Miyashita, M. J. Org. Chem. 2001,
66, 5388.
(6) (a) Rychnovsky, S. D.; Skalitzky, D. J. Tetrahedron Lett.
1990, 31, 945. (b) Evans, D. A.; Rieger, D. L.; Gage, J. R.
Tetrahedron Lett. 1990, 31, 7099.
13C NMR (500 MHz, CDCl3): δ = 80.5, 75.4, 74.9, 67.1,
65.1, 36.4, 17.9, 11.6, 3.5. Anal. Calcd for C16H32O3Si: C,
63.95; H, 10.73. Found: C, 63.94; H, 10.73.
Alkynyl Substitution of Epoxy Alcohols with
Diethylalkynyl Aluminum (Protocol II, Alanate
Procedure); General Procedure: A flame-dried flask
equipped with a dry-ice condenser was charged with
anhydrous toluene (protocol IIA; 23.0 mL) and the flask was
cooled to 0 °C. Then, n-BuLi (3.1 mL, 6.9 mmol, 4.0 equiv)
was added and an excess of propyne gas was bubbled
through the solution. After stirring for 30 min, Et2AlCl (3.8
mL, 6.9 mmol, 4.0 equiv) was added at 0 °C. In a separate
flash, a solution of the lithium alkoxide of the epoxy alcohol
was prepared from the alcohol (0.26 g, 1 mmol, 1.0 equiv) in
toluene (7.7 mL, 0.15 M final solution) and n-BuLi (0.6 mL,
1.7 mmol, 1.1 equiv), and the mixture was stirred at 0 °C for
30 min. The alane reaction mixture was cooled to –78 °C and
the lithium alkoxide solution was transferred by using a
double-ended needle and stirred overnight while reaching
r.t. The reaction was quenched by the slow addition of 5% aq
H2SO4 at 0 °C. The reaction mixture was transferred to a
separatory funnel and the phases were separated. The
aqueous layer was extracted with hexane (3 × 20 mL) and
the combined organic extracts were dried over MgSO4. The
solvent was removed in vacuo and the crude product was
purified by column chromatography (hexane–EtOAc, 5:1).
Compound 5b (for all other compounds, see the Supporting
Information): 1H NMR (500 MHz, CDCl3): δ = 3.93 (dd,
J = 9.8, 3.2 Hz, 1 H), 3.85–3.77 (m, 3 H), 3.72 (ddd, J = 8.3,
5.6, 2.7 Hz, 1 H), 2.87 (d, J = 3.6 Hz, 1 H), 2.82 (br s, 1 H),
(7) Taylor, R. E. Nat. Prod. Rep. 2008, 25, 854.
(8) Alkynyl Substitution of Epoxy Alcohols with
Diethylalkynyl Aluminum (Protocol I, Alane
Procedure); General Procedure: A flame-dried flask,
equipped with a dry-ice condenser, was charged with 12.0
mL of toluene (protocol IA) or dichloromethane (protocol
IB) and cooled to 0 °C. Then, n-BuLi (2.1 mL, 4.6 mmol, 3.8
equiv) was added and an excess of propyne gas was bubbled
through the solution. After stirring for 30 min, Et2AlCl (2.6
mL, 4.6 mmol, 3.8 equiv) was added and the mixture was
stirred for 3 h at 0 °C. To the reaction mixture was added
epoxide (0.30 g, 1.2 mmol, 1.0 equiv) and the mixture was
stirred overnight. The reaction was quenched by the slow
addition of 5% aq H2SO4 (9.2 mL) at 0 °C. The reaction
mixture was transferred to a separatory funnel and the phases
were separated. The aqueous phase was extracted with
hexane (3 × 10 mL) and the combined organic extracts were
dried over MgSO4. The solvent was removed in vacuo and
the crude product mixture was purified by column
chromatography (hexane–EtOAc, 4:1).
Compound 6b (for all other compounds, see the Supporting
Information): 1H NMR (500 MHz, CDCl3): δ = 4.02 (dd,
J = 9.9, 4.2 Hz, 1 H), 3.91–3.70 (m, 4 H), 2.75 (dtq, J = 9.4,
6.6, 2.4 Hz, 1 H), 1.77 (d, J = 2.4 Hz, 3 H), 1.11 (m, 21 H).
2.65 (m, 1 H), 1.65 (d, J = 2.4 Hz, 3 H), 1.10 (m, 21 H). 13
C
NMR (125 MHz, CDCl3): δ = 80.3, 75.9, 73.8, 65.6, 64.5,
37.5, 17.9, 11.9, 3.5. Anal. Calcd for C16H32O3Si: C, 63.95;
H, 10.73. Found: C, 63.66; H, 10.96.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 433–437
Prieto, José A.
