3
46
D.E. Rajsfus et al. / Journal of Fluorine Chemistry 132 (2011) 339–347
1
was added and the reaction mixture was sonicated for 4 h at room
temperature. The mixture was poured into H O (25 mL) and
extracted with dichloromethane (3ꢂ 25 mL). The combined
organic extracts were washed with saturated NaHCO solution
O (2ꢂ 15 mL), and then dried over anhydrous
. The volatiles were evaporated, and the crude was dissolved
16a: Colorless oil, R
NMR (700 MHz, CDCl ):
(dd, JHF = 47.1 Hz, JHF = 24.6 Hz, 2H, H
3.637 (s, 6H, H10 and H10 ), 3.176 (m, 2H, H
(176 MHz, CDCl ): 171.9 (C and C ), 133.3 (d,
and C ), 108.9 (dd,
f
(Et
6.251 (q, J = 2.1 Hz, 2H, H
), 3.658 (m, 2H, H
2
O): 0.60. R
f
(Et
2
O, Hex 1:1): 0.28.
and H ), 4.636
and H ),
). C NMR
CF = 5.5 Hz, C
CF = 19.4 Hz, C ), 81.3 (dd,
), 51.9 (C10 and C10 ), 48.7 (dd,
and C ), 45.8 (C and C
ꢀ228.45 (td,
H
2
3
d
5
6
2
3
8
2
3
13
0
1 4
and H
3
3
(
2ꢂ 15 mL) and H
2
3
d
9
9
2
0
J
5
1
MgSO
4
6
J
CF = 208.0 Hz,
CF = 26.8 Hz, C
CF = 4.4 Hz, C
):
J
7
1
2
in a minimum of acetone and placed in the freezer overnight to
give crystals of ketal diester 13 (2.17 g, 8 mmol, 80% yield).
J
CF = 172.3 Hz,
J
8
0
2
3
19
JCF = 17.4 Hz,
J
1
4
2
3
). F NMR
1
2
3
1
3: mp: 58 8C. R
600 MHz, CDCl ): 6.275 (t, J = 2.1 Hz, 2H, H
and H ), 3.494 (m, 2H, H and H ), 3.221 (s, 3H, H10), 3.165 (m,
H, H and H ), 3.151 (s, 3H, H10
72.4 (C and C ), 132.4 (C and C
), 50.0 (C10), 48.4 (C and C
f
(acetone): 0.62. R
f
(Et
2
O): 0.51. H NMR
(188 MHz, CDCl
3
d
J
HF = 47 Hz,
J
FF = 15 Hz),
2
3
3
(
H
2
1
3
d
5
and H
6
), 3.619 (s, 6H,
ꢀ164.44 (tdquintet,
J
HF = 24.5 Hz,
J
FF = 15 Hz,
J
HF and
4
ꢀ1
0
J
HF = 2 Hz). FTIR (KBr): 1792 (m, C 55 O), 1749 (s, C 55 O) cm . MS
9
9
2
3
1
3
+
+
+
0
). C NMR (150 MHz, CDCl
), 117.2 (C ), 52.1 (C10 ), 51.6 (C
), 46.1 (C and C ). FTIR (KBr):
) m/z: 271 (MH ,
OH–CO, 34%), 207
) m/z: calcd for C13
):
d
4 3
(DCI CH ) m/z: 261 (MH , 14%), 241 (M –F, 69%), 229 (M –OCH ,
1
4
3
+
0
0
100%), 201 (M –CO
CH
3 4
, 15%). HRMS (DCI–CH ) m/z: calcd for
8
8
5
6
7
9
2
+
and C
9
0
1
4
1
2
3
12 15 2 4
C H F O (MH ) 261.0941; found, 261.0938.
ꢀ
+
1
2
(
(
747 (s, C 55 O), 1739 (s, C 55 O) cm . MS (DCI–CH
2%), 239 (MH –CH
MH –C
MH ), 271.1182; found, 271.1156. Anal. calcd for C13
7.77; H, 6.71. Found: C, 57.97; H, 6.84.
4
+
+
3
OH, 100%), 211 (MH –CH
3
4.13. Synthesis of dimethyl 7,7-difluorobicyclo[2.2.2]oct-5-ene-2,3-
+
2
H
8
O
2
, 15%). HRMS (DCI–CH
4
H
18
O
6
dicarboxylate (17)
+
18 6
H O : C,
5
The title compound was synthesized from 0.20 g (0.84 mmol) of
1
5 following the same procedure and amounts ratio as the
0
4
.11. Synthesis of dimethyl spiro-[5-norbornene-anti-7,2 -
beforementioned fluorination procedure used to synthesis com-
pound 7. The crude was identified – by NMR – as mixture of the
product 17 (35%) and starting material 15 (65%). The desired
oxacyclopropane]-endo-2,3-dicarboxylate (14) and dimethyl 5-
oxobicyclo[2.2.2]oct-7-ene-endo-2,3-dicarboxylate (15)
product was isolated by a preparative plate runed on Et
2
O to yield
A solution of diazomethane in diethyl ether was prepared as
before and reacted with 7-oxonadic acid (5) (2.00 g, 0.010 mol) – as
described above for the synthesis of ketone diester 6. In this case,
however, the reaction mixture was stirred not for 5 min, but for 4 h
at 0 8C. The reaction mixture was worked up as before, and
evaporation of the solvent yielded 1.83 g of the yellow oil crude.
NMR analysis indicated the product mixture was comprised of 14
0.02 g (0.077 mmol, 11% yield) of 17 as a clean colorless oil.
1
17: R
6, 1 Hz, 1H, H
J = 10.5, 2 Hz, 1H, H
J = 10.5, 2 Hz, 1H, H ), 3.113 (m, 1H, H
3.632 (s, 3H, H10 or H10 ). 1.976 (tdd, J = 14.5, 7.5, 2.5 Hz, 1H, H
), 1.900 (tdd, J = 14.5, 8.5, 3.5 Hz, 1H, H
(176 MHz, CDCl ): 172.4 (C ), 171.8 (C ), 133.5 (C
), 125.6 (t, CF = 221.5 Hz, C ), 52.03 (C10 or C10
52.00 (C10 or C10 ), 45.6 (C CF = 6 Hz, C ), 41.7 (t,
), 34.0 (C ). F NMR
f
(Et
2
O): 0.57. H NMR (700 MHz, CDCl
), 6.312 (dddd, J = 8, 7, 3.5, 1.5 Hz, 1H, H
), 3.275 (qm, J = 6 Hz, 1H, H ), 3.153 (dd,
), 3.634 (s, 3H, H10 or H10 ),
or
). C NMR
), 128.3 (d,
),
3
):
d
6.443 (ddt, J = 8,
5
6
), 3.432 (dt,
2
1
0
3
4
0
8
13
H
8
0
8 8
or H
0
(
71%), 15 (25%) and 6 (4%). The mixture was separated by flash
column chromatography (Et O/Hex, 1:2–1:1) to give three pure
products: 14 (0.63 g, 2.6 mmol, 26% yield), 15 (0.42 g, 1.8 mmol;
8% yield) and 6 (0.05 g, 0.2 mmol; 2% yield). Bicyclic ketone 15 is
known [39], though only partial spectral data are reported.
3
d
9
0
9
5
3
1
J
CF = 6.5 Hz, C
6
J
7
0
2
3
0
), 42.0 (d,
J
3
2
2
2
19
1
J
CF = 24.5 Hz, C
(188 MHz, CDCl
FF = 230 Hz). FTIR (KBr): 1748 (s, C 55 O), 1212 (m), 1114 (m) cm
1
), 39.2 (t,
):
J
CF = 25 Hz, C
8
4
2
3
d
ꢀ87.35 (dm,
JFF = 230 Hz), ꢀ96.54 (dm,
1
2
ꢀ1
1
4: colorless oil. R
300 MHz, CDCl ): 6.339 (‘‘t’’, J = 2.4 Hz, 2H, H
H, H10 and H10 ), 3.589 (m, 2H, H and H ), 2.948 (s, 2H, H
m, 2H, H and H ). C NMR (176 MHz, CDCl ): 172.1 (C
and C ), 76.1 (C ), 51.7 (C10 and C10 ), 50.5 (C ), 47.6 (C
), 47.0 (C and C ). FTIR (KBr) 1791 (s, C 55 O), 1733 (s,
C 55 O) cm . MS (DCI CH ) m/z: 239 (MH , 13%), 113 (C
f
(Et
2
O): 0.68. R
f
(Et
2
O/Hex 1:1): 0.25. H NMR
and H ), 3.637 (s,
). 2.708
and C ),
J
.
+
+
+
(
6
(
1
3
d
5
6
MS (DCI CH
4
) m/z: 261 (MH , 11%), 260 (M , 15%), 241 (M –F, 61%),
+
0
229 (M –OCH
(M ) 260.0860; found, 260.0857.
, 100%). HRMS (DCI–CH
) m/z: calcd for C12
H
14
F
O
2
3
8
3
4
2
4
1
3
+
0
1
4
3
d
9
9
32.8 (C
and C
5
6
7
0
8
1
4
2
3
Acknowledgements
ꢀ
+
1
+
+
4
6
H
9
O
2
, 33%),
2
(
07 (MH –OMe, 66%). HRMS (DCI–CH
4
14 5
) m/z: calcd for C12H O
We acknowledge the kind and generous support of the Ethel
and David Resnick Chair in Active Oxygen Chemistry.
+
MH ) 239.0919; found, 239.0924.
5: mp: 102 8C. R (Et O): 0.38. R
300 MHz, CDCl ): 6.565 (t, J = 7.2 Hz, 1H, H
H, H ), 3.654 (s, 3H, H10 or H10 ), 3.650 (s, 3H, H10 or H10
dt, J = 6.6, 1.2 Hz, 1H, H ), 3.352 (m, 1H, H ), 3.322 (bd, J = 1.5 Hz,
), 3.294 (bd, J = 2.1 Hz, 1H, H ) 2.133 (bt, J = 3.3, Hz, 2H,
208.5 (C ), 172.1 (C ), 171.0 (C ),
), 52.0 and 51.9 (C10 and C10 ), 50.6 (C ), 46.6
), 39.1 (C ), 35.4 (C ). FTIR (KBr): 1745 (s, C 55 O), 1731
s, C 55 O) cm . MS (DCI CH ) m/z: 239 (MH , 94%), 207 (M –OCH
1
1
f
2
f
(Et
2
O/Hex 1:1): 0.11. H NMR
(
1
(
1
H
1
(
(
3
d
8
), 6.335 (t, J = 7.2 Hz,
), 3.480
0
0
7
Appendix A. Supplementary data
1
4
H, H
6
5
1
3
3
). C NMR (75 MHz, CDCl
), 126.9 (C
), 43.3 (C
3
):
d
2
9
0
9
35.2 (C
8
7
0
1
C
5
6
ꢀ
3
4
1
+
+
4
3
,
References
+
+
1
00%), 196 (M –CO–CH
CH ) m/z: calcd for C12
Anal. calcd for C12
0.87; H, 6.07; O, 33.43.
2
, 34%), 113 (C
6
H
9
O
2
, 31%), HRMS (DCI–
(MH ) 239.0919; found, 239.0918.
14 5
H O : C, 60.50; H, 5.92; O, 33.58. Found: C,
+
4
H
14
O
5
[1] T.J. Narita, Polym. Sci. A: Polym. Chem. 42 (2004) 4101–4125.
[2] S.M. Grayson, B.K. Long, S. Kusomoto, B.P. Osborn, R.P. Callahan, C.R. Chambers,
C.G. Willson, J. Org. Chem. 71 (2006) 341–344.
6
[3] D.P. Sanders, E.F. Connor, R.H. Grubbs, R.J. Hung, B.P. Osborn, T. Chiba, S.A.
MacDonald, C.G. Willson, W. Conley, Macromolecules 36 (2003) 1534–1542.
4
.12. Synthesis of anti-7-fluoro syn-7-fluoromethyl-nadic dimethyl
[4] A. Haimerl, U.S. Patent 0103318 (1 August 2002).
[
[
[
5] M.A.B. Meador, A.A. Frimer, U.S. Patent 6303744 (16 October 2001).
6] M. Hudlicky, Org. React. 35 (1988) 513–641.
7] W. Dmowski, K. Piasecka-Maciejewska, J. Fluorine Chem. 104 (2000) 273–276.
ester (16a)
The title compound was synthesized from 14 (0.40 g, 1.68 mmol)
[8] G.S. Lal, G.P. Pez, R.G. Syvret, Chem. Rev. 96 (1996) 1737–1755.
9] S. Stavber, M. Zupan, Tetrahedron 42 (1986) 5035–5043.
10] D.D. Tanner, P. Van Bostelen, J. Am. Chem. Soc. 94 (1972) 3187–3195.
11] M. Zupan, A. Gregorcic, A. Pollak, J. Org. Chem. 42 (1977) 1562–1566.
[
followingthe same proceduredescribed above forthe preparation of
compound 7. NMR analysis of the reaction product showed it to be
very clean 16a (0.13 g, 0.5 mmol, 30% yield).
[
[
[12] S.A. Shackelford, Tetrahedron Lett. 18 (1977) 4265–4268.