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Organic & Biomolecular Chemistry
Page 4 of 6
DOI: 10.1039/C8OB00745D
ARTICLE
Organic & Biomolecular Chemistry
Experimental
Conflicts of interest
There are no conflicts to declare.
General Procedure 1 (GP1) for the synthesis of sulfolenes in
hexafluoroisopropanol (HFIP)
A 75 mL glass pressure vessel was charged with a 4 : 1 v/v
mixture of HFIP (4 mL) and water (1 mL). The stirred mixture
was degassed by bubbling argon for 5 min, then 1,3-diene (2
mmol) and sodium metabisulfite (10 mmol, 5 equiv) were
added. The vessel was sealed, and the reaction mixture was
Acknowledgements
Financial support by the Welch Foundation (AX-1788), the NSF
(CHE-1455061), NIGMS (SC3GM105579), and Max and Minnie
Tomerlin Voelcker Fund is gratefully acknowledged.
stirred at 100 °C for 14 h. The reaction mixture was cooled to
room temperature and concentrated under reduced pressure
to remove HFIP. Ethyl acetate was added, and the solution was
dried over anhydrous Na2SO4. The organic phase was
concentrated under reduced pressure to afford the sulfolene
product.
Notes and references
1
(
a
)
The Chemistry of Functional Groups, Supplement S: The Chemistry of
Sulphur-Containing Functional Groups; S. Patai, Z. Rappoport, Eds.
Wiley: Chichester, 1993. ( Organosulfur Chemistry in Asymmetric
b
)
Synthesis; T. Toru, C. Bolm, Eds.; WileyꢀVCH: Weinheim, Germany,
2008.
General Procedure 2 (GP2) for the synthesis of sulfolenes in
methanol with KHSO4
2
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A 75 mL pressure vessel was charged with a 4 : 1 v/v mixture
of methanol (4 mL) and water (1 mL). The stirred mixture was
degassed by bubbling argon for 5 min, then KHSO4 (4 mmol, 2
equiv.), diene (2 mmol) and sodium metabisulfite (10 mmol, 5
equiv.) were added. The vessel was sealed, and the reaction
b
,
c
d
e
mixture was stirred at 100 °C for 14 h. The reaction mixture
f
was cooled to room temperature and concentrated. Ethyl
acetate was added, and the solution was dried over anhydrous
Na2SO4. The organic phase was concentrated under reduced
pressure to afford the sulfolene product.
Feng, B. Tang, S. H. Liang and X. Jiang, Curr. Top. Med. Chem., 2016;
16, 1200−1216.
3
4
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General Procedure 3 (GP3) for the synthesis of allylic alcohols
c
To a solution of ketone (5 mmol) in tetrahydrofuran (10 mL)
(
d
e)
was
isopropenylmagnesium bromide solution in THF (8 mmol, 1.6
equiv.) at 0 C, and the reaction mixture was stirred at room
added
1M
vinylmagnesium
bromide
or
5
(a
°
b
temperature for 12 h. Saturated solution of ammonium
chloride (3 mL) was added, and the mixture was extracted with
ethyl acetate (4 × 20 mL). The combined organic phases were
dried over anhydrous Na2SO4 and concentrated under reduced
pressure. The purity of the crude allylic alcohol was assayed by
means of 1H NMR spectroscopy with 1,4-dimethoxybenzene as
an internal standard, and the crude allylic alcohol was
immediately used for the preparation of 3-sulfolenes (GP4).
c
,
,
4
6
7
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(
a
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Heterocycles, 1985, 23, 2913−2916; (
Knight, Organosulfur Chem., 1998,
,
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3294–3296;
(
b
)
T. Nomoto and H. Takayama.
) J. Leonard, A. B. Hague and J. A.
c
2
, 229−292; (d) H. Bruyère, S.
General Procedure 4 (GP4) for the synthesis of sulfolenes
from allylic alcohol
Samaritani,, S. Ballereau, A. Tomas and J. Royer, Synlett, 2005,
1424.
9, 1421–
8
9
X.ꢀB. Wang, J.ꢀB. Du and H. Cui, Life Sci., 2014, 98, 63−67.
To a 48 mL pressure vessel charged with allylic alcohol (0.6−1
mmol) was added a 2 : 1 or 3 : 1 v/v mixture of degassed HFIP
and water (5 mL). Sodium metabisulfite (3 mmol, 3−5 equiv.)
and KHSO4 (4 mmol, 4−7.3 equiv.) were added. The vessel was
sealed, and the reaction mixture was stirred at room
temperature for 15 minutes. The reaction mixture was then
(
a
) A. S. Deeming, E. J. Emmett, C. S. RichardsꢀTaylor and M. C. Willis,
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J. Org. Chem. 2015 , 602−611.
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and M. C. Willis, Chem. Sci., 2014, , 222−228; ( ) E. J. Emmett, B. R.
Hayter and M. C. Willis, Angew. Chem., Int. Ed., 2014, 53, 10204−10208;
) A. S. Deeming, C. J. Russell and M. C. Willis, Angew. Chem., Int. Ed.
2016, 55, 747−750; ( ) A. S. Deeming, C. J. Russell and M. C. Willis,
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Wu, Angew. Chem., Int. Ed., 2016, 55, 11925−11929; ( ) E. J. Emmett, C.
b
,
4
10
(a
b
c
d
allowed to stir at 100 °C for 36 h. The reaction mixture was
5
e
cooled to room temperature, ethyl acetate was added, and the
solution was dried over anhydrous Na2SO4. The organic phase
was concentrated under reduced pressure and purified by
flash chromatography (silica gel, ethyl acetate/ hexane) to
afford the 3-sulfolene product.
(
f
,
g
h
i
S. RichardsꢀTaylor, B. Nguyen, A. GarciaꢀRubia, B. R. Hayter and M. C.
4 | Org.Biomol. Chem., 2018, 00, 1-3
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