Abstract
A concise, simple two-step method for the preparation of [4+3] cycloadducts from ketones
using Koser"s reagent and trifluoroethanol-triethylamine has been developed. This
sequence affords yields similar to those obtained using the α-halo and α-mesyloxyketones,
but with the advantages of simplicity in preparation and stability of the intermediates.
Key words
cycloaddition - ketones - cations - sonication - sulfonyl
References
1a </A>
Rigby JH.
Pigge FC.
Organic Reactions
Vol. 51:
John Wiley & Sons, Inc.;
New York:
1997.
p.351-478
1b </A>
Cha JK.
Oh J.
Curr. Org. Chem.
1998,
2:
217
1c </A>
Harmata M.
Tetrahedron
1997,
53:
6235
<A NAME="RS07901ST-2">2 </A> For a discussion of various methods for the halogenation of ketones, see:
House HO.
Modern Synthetic Reactions
2nd Ed.:
W. J. Benjamin Inc.;
Menlo Park, CA:
1972.
p.459-478
<A NAME="RS07901ST-3">3 </A> This alternative has been most extensively explored by Föhlisch and co-workers.
For examples, see:
Föhlisch B.
Herrscher I.
Chem Ber.
1986,
119:
524 ; and further papers from this group
<A NAME="RS07901ST-4">4 </A> One similar variation that has been reported is the use of β-keto trifluoromethanesulfones.
This option has been used in a number of intramolecular cycloadditions reported by
the Harmata and co-workers. For examples, see:
Harmata M.
Acc. Chem. Res.
2001,
34:
595
5a </A>
Tuncay A.
Dustman JA.
Fisher G.
Tuncay CI.
Suslick KS.
Tetrahedron Lett.
1992,
33:
7647
5b </A> For a review of the use and preparation of α-tosyloxy and mesyloxy ketones,
see:
Moriarty RM.
Prakash O.
Organic Reactions
Vol. 54:
John Wiley & Sons, Inc.;
New York:
1999.
p.273-418
6 </A>
We have noted that chromatographic purification of the tosyloxyketones is generally
unnecessary. Trituration with hexanes is sufficient to remove virtually all of the
iodobenzene by-product and afford the products as white, crystalline solids with melting
points identical to those reported in the literature. Further, in our studies using
a standard sonication cleaning bath, the yield of the reaction is very dependent upon
the location in the bath (and thus, the strength of the sonication). Optimization
in terms of the location of the flask may be necessary to reproduce the yields reported
here and in ref.
[5
<A NAME="RS07901ST-7">7 </A>
Representative Procedure : To 0.650 g (1.67 mmol) of [hydroxy(tosyloxy)iodo]benzene in a dry round-bottom flask
under argon were added 2 mL of cyclohexanone and 15 mL of acetonitrile. The flask
was placed in an ultrasound cleaning bath filled with warm (55 °C) water to a depth
of 2 inches. The reaction mixture was sonicated for 15 minutes, during which time
the suspension cleared to a yellowish-brown solution. After removal of the volatiles
in vacuo, the residue was dissolved in methylene chloride (15 mL) and washed with
saturated aqueous NaHCO3 (3 × 5 mL). The organic layer was dried with magnesium sulfate and concentrated in
vacuo. The residue was then triturated with minimal hexane (2 mL) at ice-bath temperatures
to afford 0.375 g (89%) of a pale yellow solid.
<A NAME="RS07901ST-8">8 </A> For the first report of these now-standard conditions, see:
Föhlisch B.
Gehrlach E.
Herter R.
Angew. Chem. Int. Ed. Engl.
1982,
21:
137
<A NAME="RS07901ST-9">9 </A>
Jin S.
Choi J.-R.
Oh J.
Lee D.
Cha JK.
J. Am. Chem. Soc.
1995,
117:
10914
<A NAME="RS07901ST-10">10 </A>
Representative Procedure : To 0.1928 g (0.7194 mmol) of 2-tosyloxycyclohexanone in 0.72 mL of furan was added
0.72 mL of 2,2,-trifluoroethanol at 0 °C under argon. The mixture was stirred and
187 µL (1.35 mmol) of triethylamine was added slowly and the reaction was allowed
to warm to room temperature. After 4 hours, TLC indicated complete consumption of
starting material. The reaction mixture was diluted with water (10 mL) and extracted
with diethyl ether (5 × 5 mL). The combined organics were washed with saturated aqueous
NaHCO3 , dried with magnesium sulfate, and concentrated in vacuo. The resulting residue was
purified by chromatography (elution with 1:4 ethyl acetate-hexanes) to afford 70.8
mg (60%) of the cycloadduct as a pale yellow solid.
<A NAME="RS07901ST-11">11 </A>
All compounds exhibited spectroscopic data consistent with that reported in the literature.
<A NAME="RS07901ST-12">12 </A> For the first report using these conditions, see:
Herter R.
Föhlisch B.
Synthesis
1982,
976
