2138
L. Doyle, F. Heaney / Tetrahedron 67 (2011) 2132e2138
ꢂ
ꢀ1
6
1
7
(
(
(
.88, N, 5.62%]; mp 110e118 C; vmax (KBr)/cm 3424, 2958, 2663,
741, 1600, 1501, 1197, 1038, 756; (300 MHz, CDCl ) 8.85 (2H, br s)
.61e7.56 (2H, m) 7.39e7.30 (3H, m) 7.27e7.22 (2H, m) 6.85e6.76
2 2
Following extraction with CH Cl optical purity was measured by
d
d
3
HPLC using a chiracel OD column, mobile phase Hexane/iso-propyl
alcohol (1:1), flow rate 1 mL/min; (þ)-5a 7.9 min; (ꢀ)-5a 9.1 min
(þ)-5b was found with 90% ee; (ꢀ)-5a was found enantiomerically
pure.
3H, m) 4.84 (1H, dd J¼8.3 and 8.3) 4.39 (1H, dd J¼7.4 and 3.9) 4.25
1H, dd J¼8.3 and 4.0) 3.92e3.85 (1H, m) 3.73e3.62 (3H, m) 3.03
1H, d J¼14.8) 2.51 (1H, d J¼14.8) 2.42e2.32 (1H, ddd J¼14.9, 12.0
and 3.8) 2.29e2.20 (1H, m) 1.98e1.95 (1H, m) 1.93e1.81 (1H, m)
Acknowledgements
1
1
1
1
.75 (1H, br d J¼18.3) 1.54e1.45 (1H, ddd J¼14.9, 9.3 and 4.7)
.28e1.2 (1H, m) 0.93 (3H, s) 0.70 (3H, s); (75.5, CDCl ) 216.7,
46.9, 146.8, 135.7, 135.6, 129.3, 129.3, 129.2, 129.2, 126.7, 126.7,
19.4, 119.2, 114.7, 114.6, 78.9, 78.8, 78.2, 59.0, 58.8, 58.3, 54.6, 54.4,
d
C
3
Financial support from the Embark Postgraduate Research
Scholarship Scheme (Grant reference number RS/2005/37) and
from the National University of Ireland, Maynooth for a John and
Pat Hume Scholarship to L.D. is gratefully acknowledged.
5
0.3, 47.9, 47.4, 42.8, 42.6, 26.9, 24.6, 19.8, 19.8.
4
7
.2.7. Preparation of the bis-salt from camphor sulfonic acid and rac-
b, 7b.2(þ)-10-CSA 5,6a-diphenylhexahydro-1H-pyrrolo[3,4-c][1,2]
Supplementary data
oxazole-1,5-diium (7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)meth-
InChIKeys of the most important compounds described in this
article.
anesulfonate. rac-7b (150 mg, 0.564 mmol) and (þ)-10-CSA
(
262 mg, 1.127 mmol) were dissolved in hot acetone (1.8 mL) and
following cooling to rt stirring continued until precipitation was
complete. The salt was filtered and dried to yield the title product as
ꢂ
ꢀ1
a dark green solid (390 mg, 95%); mp 84e96 C; vmax (KBr)/cm
415, 2960, 1744, 1600, 1415, 1154, 1038; (300 MHz, CDCl ) 12.32
3H, br) 7.63e6.91 (10H, m) 4.87 (1H, dd J¼8.3 and 8.3) 4.74 (1H, dd
J¼12.0 and 2.5) 4.45 (1H, br dd J¼8.3 and 2.6) 4.20e4.19 (1H, m)
.97 (1H, d J¼12.0) 3.94e3.74 (2H, m) 3.18 (2H, d J¼14.8) 3.71 (2H,
d J¼14.8) 2.40e2.25 (4H, m) 2.02e1.87 (4H, m) 1.77 (2H, d J¼18.4)
.62e1.53 (2H, m) 1.33e1.25 (2H, m) 0.97 (6H, s) 0.76 (6H, s);
75.5, CDCl ) 217.4, 207.8, 144.3, 144.0, 133.8, 133.6, 129.8, 129.7,
29.4, 127.2, 129.2, 117.1, 116.8, 79.4, 77.5, 60.0, 59.9, 58.4, 56.4, 56.2,
References and notes
3
(
d
d
3
1. Bertelsen, S.; Jørgensen, K. A. Chem. Soc. Rev. 2009, 38, 2178.
2
3
. MacMillan, D. W. C. Nature 2008, 455, 304.
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3
12, 8.
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5
6
. Mayer, S.; List, B. Angew. Chem., Int. Ed. 2006, 45, 4193.
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1
(
1
4
d
C
3
7
. Erkkilae, A.; Majander, I.; Pihko, P. M. Chem. Rev. 2007, 107, 5416.
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1. Lemay, M.; Ogilvie, W. W. J. Org. Chem. 2006, 71, 4663.
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9
1
9.8, 48.2, 47.8, 42.8, 42.6, 30.9, 26.9, 25.0, 19.8, 19.7.
2
4
.2.8. Classical resolution of 5a with (þ)-10-CSA. In a modification
34
1
1
1
of a literature procedure rac-5a (234 mg, 1.143 mmol) and (þ)-10-
CSA (266 mg, 1.143 mmol) were dissolved in warm acetone
(
13.5 mL). After cooling to rt stirring was continued for a further
14. Cavill, J. L.; Elliott, R. L.; Evans, G.; Jones, I. L.; Platts, J. A.; Ruda, A. M.; Tom-
2
5
kinson, N. C. O. Tetrahedron 2006, 62, 410.
2
6 h. A first crop of white crystals was collected (145 mg, 58%) [a]
D
15. Brazier, J. B.; Cavill, J. L.; Elliott, R. L.; Evans, G.; Gibbs, T. J. K.; Jones, I. L.; Platts,
þ76 (c 0.0023, MeOH). The mother liquor and washings were
J. A.; Tomkinson, N. C. O. Tetrahedron 2009, 65, 9961.
concentrated to x7 mL and allowed to stir at rt for 4 h after which
16. Heaney, F.; O’Mahony, C. J. Chem. Soc., Perkin Trans. 1 1998, 341; Heaney, F.;
2
5
a second crop was collected (10 mg, 4%) [
The mother liquor and washings were concentrated to x3.5 mL
and left to stir at rt for 26 h prior to collection of a third crop (11 mg,
5
a
]
D
þ74 (c 0.0072, MeOH).
Fenlon, J.; McArdle, P.; Cunningham, D. Org. Biomol. Chem. 2003, 1, 1122.
17. Heaney, F.; Doyle, L. Tetrahedron 2010, 66, 7041e7049.
1
8. ACD Labs, Calculated using Advanced Chemistry Development; Software V8.14 for
Solaris, 1994e2010. Estimated pKBHþ values; isoxazolidine (5.49þ/ꢀ0.2), N-
methylpyrrolidine (10.55þ/ꢀ0.2), N-phenylpyrrolidine (5.68þ/ꢀ0.4) and 3,5-
diphenylisoxazolidine (pKBH 4.20).
2
5
%) [
a
]
D
þ56 (c 0.0006, MeOH). Total yield of (þ)-5a$(þ)-10-CSA
based on the first two crops was 62%.
19. Katagiri, N.; Okada, M.; Morishita, Y.; Kaneko, C. Tetrahedron 1997, 53, 5725.
20. Ranganathan, D.; Ranganathan, S.; Rao, C. B.; Raman, K. Tetrahedron 1981, 37,
4
.2.9. Classical resolution of 5a with (ꢀ)-10-CSA. rac-5a (1500 mg,
629.
2
1. Fedotov, A. N.; Shishkina, I. N.; Mochalov, S. S.; Subbotin, O. A.; Shabarov, Y. S.
Zh. Org. Khim. 1987, 23, 112.
2. Lemay, M.; Ogilvie, W. W. Org. Lett. 2005, 7, 4141.
7.314 mmol) and (ꢀ)-10-CSA (3199 mg, 7.314 mmol) were dissolved
in warm acetone (58 mL). After cooling to rt stirring was continued
2
for a further 26 h after which a first crop of crystals was collected
23. Evans, G.; Gibbs, T. J. K.; Jenkins, R. L.; Coles, S. J.; Hursthouse, M. B.; Platts, J. A.;
Tomkinson, N. C. O. Angew. Chem., Int. Ed. 2008, 47, 2820.
25
(
321 mg, 20%) [
a
]
D
ꢀ74 (c 0.002, MeOH). The mother liquor and
24. Evans, G. J. S.; White, K.; Platts, J. A.; Tomkinson, N. C. O. Org. Biomol. Chem.
washings were concentrated to x49 mL and stirred continued at rt
for 69 h prior to collection of a second crop (144 mg, 9%) [
2006, 4, 2616.
2
5
a]
D
ꢀ78
25. Huanga, D.-M.; Wang, Y.-B.; Viscoc, L. M.; Taoc, F.-M. Chem. Phys. Lett. 2005, 407,
(c 0.0099, MeOH). The collection/concentration process was re-
222.
2
5
26. Nakadai, M.; Saito, S.; Yamamoto, H. Tetrahedron 2002, 58, 8167.
peated affording the following crops: third (93 mg, 6%) [
0
fifth (276 mg, 17%) [a]
D
a
]
D
þ21 (c
27. Kano, T.; Tanaka, Y.; Maruoka, K. Org. Lett. 2006, 8, 2687.
2
5
.008, MeOH), fourth (240 mg, 15%) [
a
]
D
ꢀ75 (c 0.0011, MeOH),
28. Gotoh, H.; Hayashi, Y. Org. Lett. 2007, 9, 2859; Kim, K. H.; Lee, S.; Lee, D.-W.; Ko,
25
þ36 (c 0.0014, MeOH). Total yield of
D.-H.; Ha, D.-C. Tetrahedron Lett. 2005, 46, 5991.
2
3
9. Abiko, A. Rev. Heteroat. Chem. 1997, 17, 51; Abiko, A.; Moriya, O.; Filla, S. A.;
Masamune, S. Angew. Chem., Int. Ed. Engl. 1995, 34, 793.
0. Bartoli, G.; Melchiorre, P. Synlett 2008, 1759.
(ꢀ)-5a$(ꢀ)-10-CSA (crops 1,2 and 4, all white solids) was 44%.
2
5
4
.2.10. Determination of optical purity of resolved 5a. (þ)-5a [
a
]
D
31. Lacour, J.; Linder, D. Science 2007, 317, 462.
32. Ma, Y.; Jin, S.; Kan, Y.; Zhang, Y. J.; Zhang, W. Tetrahedron 2010, 66, 3849.
2
5
þ112 (c 0.0010, MeOH) and (ꢀ)-5a [
a]
D
ꢀ110 (c 0.0064, MeOH)
3
3. Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals, 3rd ed.;
were obtained quantitatively by treatment of the corresponding
Pergamon: Oxford, 1988.
salts, (þ)-5a$(þ)-10-CSA and (ꢀ)-5a$(ꢀ)-10-CSA with 1 M NaOH.
34. Abiko, A.; Davis, W. M.; Masamune, S. Tetrahedron: Asymmetry 1995, 6, 1295.