922
P. S. Koranne et al. / Tetrahedron: Asymmetry 18 (2007) 919–923
4
5
. Evans, D. A.; Woerpel, K. A.; Hinman, M. M.; Faul, M. M. reaction was quenched with water and extracted using
J. Am. Chem. Soc. 1991, 113, 726.
0
2 2
CH Cl . The resulting diastereomers 2 and 2 were easily
. (a) Uozumi, Y.; Kato, K.; Hayashi, T. J. Am. Chem. Soc.
separated by silica gel column chromatography.
1
997, 119, 5063; (b) Uozumi, Y.; Kato, K.; Hayashi, T. J.
11. The required diastereomer was identified based upon com-
0
Org. Chem. 1998, 63, 5071; (c) Uozumi, Y.; Kyota, H.; Kato,
K.; Ogasawara, M.; Hayashi, T. J. Org. Chem. 1999, 64,
plexation studies of the two diastereomers 2d and 2d . The
major diastereomer 2d formed a single species upon com-
1
620; (d) Hayashi, T.; Yamasaki, K.; Mimura, M.; Uozumi,
plexation with Pd(OCOCF
2d was unable to coordinate in a bidentate fashion to
3
)
2
. While, the minor diastereomer
0
Y. J. Am. Chem. Soc. 2004, 126, 3036.
6
7
8
. For the Pd-sparteine catalyzed Wacker-type cyclization, see:
palladium as observed in NMR experiment and GPC
1
(
a) Trend, R. M.; Ramtohul, Y. K.; Ferreira, E. M.; Stoltz, B.
analysis. For the other hybrid ligands, the analogy in
H
M. Angew. Chem., Int. Ed. 2003, 42, 2892; (b) Trend, R. M.;
Ramtohul, Y. K.; Stoltz, B. M. J. Am. Chem. Soc. 2005, 127,
NMR analyses and TLC behaviour was used to identify the
required diastereomer.
1
7778.
12. Analytical data for both the diastereomers of ligands:
*
*
0 0 0 0
. (a) Hosokawa, T.; Miyagi, S.; Murahashi, S.-I.; Sonoda, A. J.
Chem. Soc., Chem. Commun. 1978, 687; (b) Hosokawa, T.;
Uno, T.; Inui, S.; Murahashi, S.-I. J. Am. Chem. Soc. 1981,
(R ,S )-3 ,3a ,4 ,5,5 ,6-Hexahydro-4H-spiro[2,1-benzisoxazole-
0
1
7,6 -cyclopenta[c]isoxazole] 2a: H NMR (CDCl
3
, 270 MHz) d
1.60–2.45 (m, 7H), 2.50–2.72 (m, 1H), 2.84–2.88 (m, 2H), 3.95–
13
1
03, 2318; (c) Hosokawa, T.; Okuda, C.; Murahashi, S.-I. J.
3.97 (m, 2H), 4.55–4.56 (m, 1H), 8.12 (t, J = 1.4 Hz, 1H).
C
Org. Chem. 1985, 50, 1282.
. For reports on the Pd-catalyzed tandem cyclizations, see: (a)
Hegedus, L. S.; Allen, G. F.; Olsen, D. J. J. Am. Chem. Soc.
NMR (CDCl , 68 MHz) d 18.3, 20.1, 27.7, 34.7, 39.0, 44.9,
3
54.6, 75.3, 114.0, 153.4, 163.8, 175.5. FAB-HRMS calcd for
+
C H N O [M+H ]: 219.1134. Found: 219.1150. Mp 167 ꢁC
12
15
2 2
29
1
980, 102, 3583; (b) Doi, T.; Yanagisawa, A.; Nakanishi, S.;
Yamamoto, K.; Takahashi, T. J. Org. Chem. 1996, 61, 2602;
c) Coperet, C.; Negishi, E. Org. Lett. 1999, 1, 165; (d) Ohno,
(recrystallization from hexane/ether). ½aꢁ ¼ ꢀ134 (c 0.11,
D
3
CHCl ) (first peak of HPLC).
*
*
0 0 0 0
(
(R ,R )-3 ,3a ,4 ,5,5 ,6-Hexahydro-4H-spiro[2,1-benzisoxazole-
0
0
1
H.; Miyamura, K.; Mizutani, T.; Kadoh, Y.; Takeoka, Y.;
Hamaguchi, H.; Tanaka, T. Chem. Eur. J. 2005, 11, 3728; (e)
Tietze, L. F.; Sommer, K. M.; Zinngrebe, J.; Stecker, F.
Angew. Chem., Int. Ed. 2005, 44, 257; (f) Lee, P. H.; Lee, K.;
Kang, Y. J. Am. Chem. Soc. 2006, 128, 1139; (g) Lautens, M.;
Alberico, D.; Bressy, C.; Fang, Y.-Q.; Mariampillai, B.;
Wilhelm, T. Pure Appl. Chem. 2006, 78, 351; (h) Yip, K.-T.;
Yang, M.; Law, K.-L.; Zhu, N.-Y.; Yang, D. J. Am. Chem.
Soc. 2006, 128, 3130.
7,6 -cyclopenta[c]isoxazole] 2a : H NMR (CDCl
3
, 270 MHz)
d 1.60–2.72 (m, 10H), 2.85–3.92 (m, 1H), 4.25–4.35 (m, 1H),
13
4.55–4.62 (m, 1H), 8.12 (t, J = 1.08 Hz, 1H). C NMR
(CDCl , 68 MHz) d 18.4, 20.6, 25.9, 33.7, 38.8, 44.9, 54.6,
3
+
75.3, 114.1, 153.4, 163.0, 174.0. FAB-MS [M+Na ]: 219.2.
*
*
0
0
0
0
0
(R ,S )-3,3 -Diethyl-3 ,3a ,4 ,5,5 ,6-hexahydro-4H-spiro[2,1-
0
1
benzisoxazole-7,6 -cyclopenta[c]isoxazole] 2b:
H NMR
(CDCl , 270 MHz) d 0.87 (t, J = 7.29 Hz, 3H), 1.20 (t,
3
J = 7.29 Hz, 3H), 1.25–1.40 (m, 1H), 1.60–2.45 (m, 9H),
1
3
9
. Structures with various combinations of ring size such as
spiro[4.4]nonane, spiro[4.5]decane and spiro[4.6]undecane
having unsubstituted isoxazole and isoxazoline moieties were
2.60–2.72 (m, 4H), 3.82–3.93 (m, 1H), 4.38–4.44 (m, 1H).
C
NMR (CDCl , 68 MHz) d 10.3, 11.4, 18.6, 19.5, 20.2, 22.8,
3
23.7, 34.4, 39.2, 45.5, 56.9, 84.8, 108.7, 165.1, 167.8, 174.8.
Anal. Calcd for C16H N O : C, 70.04; H, 8.08; N, 10.21.
22 2 2
*
optimized using HF/6-31G . The optimized structures of
these spiro skeletons, in which five membered spiro ring
bearing isoxazoline unit, showed the N–N distance of 3.76,
Found: C, 69.68; H, 8.05; N, 9.96. FAB-HRMS Calcd for
+
C H N O [M+H ]: 275.1760; found, 275.1730. Mp 106 ꢁC
1
6
23
2
2
2
D
9
˚
*
*
3
4
.35 and 3.87 A, respectively, for the R ,S diastereomer, and
.21, 4.01, 4.32 A, respectively, for the R ,R diastereomer.
(recrystallization from hexane/ether). ½aꢁ ¼ ꢀ186 (c 0.10,
˚
*
*
3
CHCl ) (first peak of HPLC).
*
*
0 0 0 0 0
1
0. Concise procedure for the synthesis of hybrid ligands: (a)
(R ,R )-3,3 -Diethyl-3 ,3a ,4 ,5,5 ,6-hexahydro-4H-spiro[2,1-
0
0
1
Diethyl malonate (3) was added to a suspension of 60% NaH
benzisoxazole-7,6 -cyclopenta[c]isoxazole] 2b :
H NMR
(
1 equiv) in THF at 0 ꢁC. Alkenyl bromide 4 (1 equiv) was
(CDCl , 270 MHz) d 0.87 (t, J = 7.56 Hz, 3H), 1.18 (t,
J = 7.56 Hz, 3H), 1.22–1.58 (m, 2H), 1.6–1.78 (m, 2H), 1.80–
3
added to the solution and allowed to warm to rt. After
completion, the reaction was quenched with saturated aq
NH
2.45 (m, 6H), 2.46–2.62 (m, 4H), 4.11–4.18 (m, 1H), 4.38–4.47
1
3
4
Cl and extracted with EtOAc. Mono alkenylated prod-
3
(m, 1H). C NMR (CDCl , 68 MHz) d 10.5, 11.5, 18.7, 19.5,
uct was obtained from the organic layer, after column
chromatography. The second alkylation of the mono alken-
ylated compound was carried out in a similar manner using
alkynyl iodide 5 (1 equiv) to give 6. (b) Diester 6 was reduced
20.5, 20.6, 23.8, 29.7, 33.7, 39.1, 44.3, 56.5, 84.2, 109.0, 164.0,
+
168.0, 173.1. FAB-MS [M+H ]: 275.
*
*
0
0
0
0
0
0
(R ,S )-3,3 ,3 -Trimethyl-3 ,3a ,4 ,5,5 ,6-hexahydro-4H-spiro-
0
1
[2,1-benzisoxazole-7,6 -cyclopenta[c]isoxazole] 2c: H NMR
(CDCl , 270 MHz) d 1.26 (s, 3H), 1.53 (s, 3H), 1.70–2.40 (m,
11H), 2.40–2.80 (m, 2H), 3.60–3.64 (m, 1H). C NMR
with LiAlH
4
as usual to produce the diol. (c) The diols were
3
13
converted into dialdehydes by Swern oxidation. To a solution
of (COCl) (3.8 equiv) in CH Cl was slowly added a solution
(CDCl , 68 MHz) d 10.9, 18.4, 20.1, 22.2, 22.9, 26.3, 34.1,
2
2
2
3
of DMSO (5.8 equiv) in CH
2
Cl
2
at ꢀ78 ꢁC and stirred for
39.7, 45.2, 61.9, 87.7, 109.5, 163.1, 164.8, 176.2. Anal. Calcd
4
0 min. A solution of the diol in CH
2
Cl was added and
2
for C15
H, 7.60; N, 10.53. FAB-HRMS calcd for C H N O
2
20 2 2
H N O : C, 69.20; H, 7.74; N, 10.76. Found:C, 68.83;
further stirred for 40 min. Et N (9 equiv) was then added and
3
15 21
2
+
allowed to stirred at rt for 1.5 h. After quenching with
[M+H ]: 261.1603; found, 261.1587. Mp 101 ꢁC (recrystalli-
zation from hexane/ether). ½aꢁ ¼ ꢀ202 (c 0.095, CHCl
29
D
saturated aq NH
CH Cl to give crude dialdehyde. (d) The dialdehyde was
dissolved in pyridine and treated with NH OHÆHCl
4
Cl, the reaction mixture was extracted with
3
)
2
2
(first peak of HPLC).
*
*
0
0
0
0
0
0
(R ,R )-3,3 ,3 -Trimethyl-3 ,3a ,4 ,5,5 ,6-hexahydro-4H-spiro-
2
0
0
1
(
6
10 equiv) at 0 ꢁC. The reaction mixture was stirred at rt for
days with additions of additional NH OHÆHCl (5 equiv) per
day. The reaction mixture was diluted with CH Cl and
[2,1-benzisoxazole-7,6 -3cyclopenta[c]isoxazole]
NMR (CDCl , 270 MHz) d 1.23 (s, 3H), 1.53 (s, 3H), 1.7–
2.4 (m, 8H), 2.25 (s, 3H), 2.40–2.80 (m, 2H), 3.84 (t,
2c : H
2
3
2
2
1
3
washed with 1 N HCl, saturated NaHCO3 and brine.
Dioxime 7 was obtained from the organic layer after
purification by silica gel column chromatography. (e) Finally,
a solution of dioxime 7 in CH Cl was treated with aq NaOCl
J = 9.45 Hz, 1H). C NMR (CDCl , 68 MHz) d 11.1, 18.7,
3
20.5, 20.9, 22.3, 27.0, 33.5, 39.9, 44.3, 61.7, 87.5, 109.9, 163.4,
+
163.9, 174.5. FAB-MS [M+H ]: 261.
*
*
0
0
0
0
0
0
(R ,S )-3 ,3 -Diisopropyl-3 ,3a ,4 ,5,5 ,6-hexahydro-4H-spiro-
0
2
2
1
(
2.3 equiv) at 0 ꢁC and the mixture stirred overnight at rt. The
[2,1-benzisoxazole-7,6 -cyclopenta[c]isoxazole] 2d: H NMR