5
994
S. Genovese et al. / Tetrahedron Letters 51 (2010) 5992–5995
the use of chloramine T as the source of chloronium ion in place of
NaClO, performing the reaction using the same conditions as de-
scribed above. Results are summarized in Table 1.
2.2.1. 4-Chloro-5-phenyldihydro-2(3H)-furanone (2)
Yellow solid (mp: 65–66 °C); IR (neat, cm ): 1727, 1180; 1
À1
H
4
13
NMR;
C NMR (50.1 MHz, CDCl
3
) d 24.86, 28.36, 46.69, 78.72,
+
+2
Also employing chloramine T in our procedure is safe, clean, and
not expensive in practical and economical terms, and provides a
5 7 2
177.10; GC/MS: M = 134, M = 136. Anal. Calcd for C H ClO : C,
44.63; H, 5.24; O, 23.78. Found: C, 44.58; H, 5.27; O, 23.77.
4
valuable alternative to the method developed by Damin et al. In fact
our yields are significantly improved and the use of toxic solvents
such as benzene as well as any kind of chromatographic purification
2.2.2. 5-(Chloromethyl)-dihydro-2(3H)-furanone (4)
À1
Pale yellow solid (mp: 122–124 °C); IR (neat, cm ): 1792,
1
5
is not required. It is noteworthy that our synthetic process is charac-
1142; H NMR; (200 MHz, CDCl
3
) d 2.89 (dd, J = 5.5, 18.1 Hz,
7
terized by better yields than that developed using CeCl
3
Á7H
2
O as
1H), 3.17 (dd, J = 7.2, 18.1 Hz, 1H), 4.45 (ddd, J = 5.3, 7.2, 4.9 Hz,
1
3
the Lewis acid. Moreover, only 0.2 equiv of the catalyst, instead of
a 1:3 ratio between the substrate and the lanthanide, is needed to
efficiently promote the conversion of acids into lactones.
1H), 5.59 (d, J = 4.4 Hz, 1H), 7.43 (m, 5H); C NMR (200 MHz,
CDCl ) d 38.0, 57.7, 87.4, 125.1, 129.0, 129.2, 135.7, 172.7; GC/
MS: M = 197, M = 199. Anal. Calcd for C10
3
+
+2
2
H10ClO : C, 61.08; H,
When comparing results obtained with the use of chloramine T
4.61; O, 16.27. Found: C, 61.09; H, 4.56; O, 16.21.
and NaClO under Yb(OTf)
were obtained employing the first reactant. This could be due to
the fact that chloramine T has by far a greater solubility in CH Cl
than NaClO, being at the same time soluble in H O, thus facilitating
its reaction with alkenoic acids. So it may be hypothesized that an
effective reaction occurring at the interface between H O and the
3
catalysis, it is evident that better yields
2.2.3. 4-(Chloromethyl)-2-oxetanone (6)
À1
2
2
White–yellow solid (mp: 39–40 °C); IR(neat, cm ): 1750,
1
11 13
+
2
1730; H NMR;
C NMR (200 MHz, CDCl
3
) d 41.3, 45.7, 69.8,
+2
167.2; GC/MS: M = 120, M = 122. Anal. Calcd for C10
H
10ClO : C,
2
2
39.86; H, 4.18; Cl, 29.41; O, 26.55. Found: C, 39.84; H, 4.23; O,
26.51.
chlorinated solvent could be claimed as the key step leading to
the desired adducts. The same mechanistic considerations given
above could explain the formation of chloronium ion and ring clo-
sure, while the enhancement of the electrophilic features of the
chlorine atom linked to the sulfonamide moiety of chloramine T,
2.2.4. 6-Chloro-3,7-dimethyl-7-octenoic acid (8)
À1
Pale yellow solid (mp: 112–114 °C); IR (neat, cm ): 3500,
1
7 13
1710; H NMR;
3
C NMR (200 MHz, CDCl ) d 17.13, 20.09, 29.05,
+
3
+
may be due to a strong coordination of Yb on the oxygen atoms
of the –SO – moiety which could account for the great reactivity of
alkenoic acids employed in this second methodology.
Also in the latter case Yb(OTf) was recovered and recycled in
34.30, 40.73, 64.30, 115.15, 142.08, 178.33; GC/MS: M = 204,
+
2
2
M
2
= 206. Anal. Calcd for C10H17ClO : C, 58.68; H, 8.37; O, 15.63.
Found: C, 58.60; H, 8.35; O, 15.65.
3
the same way as described above. The reaction affording com-
pound (2) employing chloramine T was repeated three more times
leading to the desired product in 61%, 61%, and 63%, respectively.
In conclusion, in the present work we disclosed an easy and
environmentally sound method for the synthesis of chlorinated
lactones starting from differently unsaturated acids and a different
2.2.5. 6-(Chloromethyl)-tetrahydro-2H-pyran-2-one (10)
Yellow solid (mp: 85–87 °C); IR (neat, cm ): 1740, 1170; 1
À1
H
4
13
NMR;
79.12, 171.25; GC/MS: M = 148,
ClO
21.57.
C NMR (200 MHz, CDCl
3
) d 18.10, 25.21, 29.51, 46.41,
+
+2
M
= 150. Anal. Calcd for
C H
6 9
2
: C, 48.50; H, 6.11; O, 21.54. Found: C, 48.56; H, 6.13; O,
3
source of chloronium ion effectively promoted by Yb(OTf) .The
simple work-up procedure, mild reaction conditions, and from
good to satisfactory yields make our methodology a valid and
alternative contribution to the existing processes in the field of
the synthesis of chlorinated lactones.
2.2.6. 4-Chloro-5-ethyldihydro-2(3H)-furanone (12)
White solid (mp: 78–80 °C); IR (neat, cm ): 1772, 1168; 1
À1
H
7
13
NMR;
C NMR (200 MHz, CDCl
3
) d 10.0, 26.6, 39.7, 42.7, 89.4,
+
+2
173.5; GC/MS: M = 148, M = 150. Anal. Calcd for C
6 9 2
H ClO : C,
Further investigation into the scope and other applications of
48.50; H, 6.11; O, 21.54. Found: C, 48.57; H, 6.09; O, 21.51.
3
Yb(OTf) promoted reactions are now in progress in our laborato-
ries and will be reported in due course.
2.2.7. 5-(Chloromethyl)-4-methyldihydro-2(3H)-furanone (14)
Yellow solid (mp: 78–79 °C); IR (neat, cm ): 1722, 1185; 1
À1
H
7
13
NMR;
1
4
C NMR (200 MHz, CDCl
3
) d 13.1, 32.1, 32.9, 41.7, 80.9,
75.6; GC/MS: M = 148, M = 150. Anal. Calcd for C ClO : C,
8.50; H, 6.11; O, 21.54. Found: C, 48.52; H, 6.09; O, 21.59.
The degree of purity of each product listed in the Table 1 was
2
2
. Experimental
+
+2
6
H
9
2
.1. Synthesis of chlorinated lactones with sodium
hypochlorite. General procedure
analyzed by GC/MS with a Hewlett Packard 6890 gas chromato-
graph equipped with a 12.5 mm  0.25 mm MetSil column couplet
to HP Chem Station Software. The carrier gas was helium at a pres-
2 2 2
Toa stirredsolutionofalkenoicacid(2 mmol)ina1:1CH Cl /H O
mixture (10 mL), 0.2 mmol of Yb(OTf)
3
(0.2 mmol) was added. The
2
sure of 3.5 kg/cm , and the column temperature was programed
resulting mixture was vigorously stirred for 10 min at room temper-
ature. A solution of NaClO (2 mmol, 10–13% available chlorine) was
then added dropwise for 30 min. The reaction was monitoredby TLC.
After the appropriate time (see Table 1) the reaction mixture was
from 50 to 270 °C at 10 °C/min. The chromatogram was obtained
by using a reporting integrator. Mass spectra were obtained from
a GC/MS system operating in the EI mode at 70 eV, equipped with
a 12.5 mm  0.25 mm MetSil column and an HP5973 Mass selec-
tive detector, by using the same chromatographic conditions re-
ported above. The column was connected to the mass
spectrometer insource through an open-split interface heated at
washed with a saturated solution of Na
CH Cl
(3 Â 5 mL). The combined organic layers were dried over
anhydrous Na SO and the solvent evaporated to dryness. The de-
sired product was then obtained after crystallization from n-hexane.
2 2 3
S O and extracted with
2
2
2
4
1
13
2
50 °C. H and C NMR spectra were recorded by using the same
general procedure as already reported in Ref. 12.
2
.2. Synthesis of chlorinated lactones with chloramine T.
General procedure
Acknowledgments
The same procedure as above was done but with the use of
chloramine T (2 mmol) instead of NaClO.
Financial support from MIUR PRIN 2008 ‘‘A Green Approach to
Process Intensification in Organic Synthesis” is gratefully acknowl-