Table 1. Fluorous Selenide Mediated Eliminationsa
a
With the exception of 6, all dimesylates and alkenes were as described in the literature1,2,11,12 or were identical to commercial samples. b Unless otherwise
stated 0.2 molar equiv of 1 was used (see Typical Procedure). c 0.4 molar equiv of 1 was used (see text).
mediated radical chain reactions.3,4 We have also reported a
protocol for the dehydrogenation of ketones and esters using
a selenenyl chloride derived from 1. For solubility reasons
FC-72 in the jacketed continuous extractor, which permitted
recovery of the pure diselenide and greatly facilitated the
chromatgraphic purification of the alkene. As is evident from
Table 1, the alkenes were obtained in good yield in all cases
and the diselenide was recovered efficiently. We then turned
to the development of a catalytic variant on this protocol by
reducing gradually the amount of diselenide employed.
Eventually, we settled on the use of 0.2 molar equiv of 1 in
0.02 M ethanolic solution with the use of a 10-fold excess
(wrt 1) of sodium borohydride. The results presented in
Table 1 indicate that these conditions were satisfactory in
every instance but one; in the case of the nucleoside 2′,3′-
dimesylate 8, the yield was depleted by the formation of
several byproducts, one of which was identified as 12. On
the grounds that these byproducts arise by competing
5
the fluorous chains in 1 were limited to six carbons, resulting
in a fluorine content of 52%, which is below the nominal
minimum of 60% usually considered necessary for ready
extraction into fluorous solvents.6 We therefore termed
these diselenides “minimally” fluorous and developed a
convenient protocol for their recovery involving brief
continuous extraction of the organic solvent by the fluorous
-8
1
3
4
phase in a water-jacketed continuous extractor. Curran has
termed such minimally fluorous substances “light” fluorous
reagents and has presented an alternative protocol for their
9
recovery involving chromatography over fluorous silica gel.
N
intramolecular S 2 attack by the base on the 2′-O-mesylate
and then elimination (and desilylation), the amount of 1 was
doubled to 0.4 equiv, which effectively restored the yield to
(10) Although we have not attempted any demonstration, we assume
that the true nucleophile is the arylseleno(triethoxy)borate: Miyashita, M.;
Hoshino, M.; Yoshikoshi, A. Tetrahedron Lett. 1988, 29, 347
A protocol for elimination was readily developed in which
an orange ethanolic solution of 1 was reduced with excess
(
11) Habich, D.; Barth, W. Synthesis 1988, 943.
12) Lin, T. S.; Luo, M. Z.; Liu, M. C. Tetrahedron Lett. 1994, 35, 3477.
(
NaBH
4
under an inert atmosphere to give a colorless solution
(13) Typical Procedure for the Catalytic Reaction. In a typical
experiment the diselenide (1) (18.6 mg, 0.02 mmol) was placed in a three-
necked round-bottom flask carrying a sidearm addition tube containing
NaBH4 (7.4 mg, 0.2 mmol). Deoxygenated ethanol (1 mL) was added, and
the mixture was cooled to 0 °C under an Ar atmosphere. The NaBH4 was
then added slowly (H2 evolution) until the orange solution turned colorless.
After 1 h the dimesylate 2 (41 mg, 0.1 mmol) dissolved in THF (1 mL)
was added, and the reaction mixture was heated to reflux for a period of
5-6 h. After cooling to room temperature, the reaction mixture was diluted
with CH2Cl2 (5 mL), washed with water, and concentrated in vacuo. The
extracts were taken up again in CH2Cl2 (5 mL) and partitioned with FC 72
10
of the selenide, followed by addition of the dimesylate and
refluxing until completion (5-6 h). After aqueous work up
the organics were partitioned between dichloromethane and
(
(
(
(
(
3) Crich, D.; Hao, X. Org. Lett. 1999, 1, 269.
4) Crich, D.; Hao, X.; Lucas, M. Tetrahedron 1999, 55, 14261.
5) Crich, D.; Barba, G. R. Org. Lett. 2000, 2, 989.
6) Horvath, I. T. Acc. Chem. Res. 1998, 31, 641.
4
7) de Wolf, E.; van Koten, G.; Deelman, B.-J. Chem. Soc. ReV. 1999,
(15 mL) in the continuous extractor for 2 h. The fluorous diselenide (1)
2
8, 37.
was recovered by evaporation of the FC 72 phase (14.1 mg, 76%) and the
olefin (3) by flash chromatography over silica gel using 25% EtOAc-
hexane as eluent (31 mg, 74%).
(
(
8) Curran, D. P. Angew. Chem., Int. Ed. Engl. 1998, 37, 1174.
9) Curran, D. P.; Luo, Z. J. Am. Chem. Soc. 1999, 121, 9069.
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Org. Lett., Vol. 2, No. 25, 2000