August 1998
SYNLETT
883
i
It was essential for the success of the present method to use dry-TBAH
which is prepared from commercially available 40wt% reagent by
azeotropic removal of water with DME and toluene (entry 1).
Na SO and concentrated. To the residue was added Pr O-Hex (1:1)
2 4 2
and an insoluble recovered camphorsultam was filtered off. The filtrate
was concentrated and the residue was purified by silica gel
chromatography (EtOAc:Hex, 5:95) to afford (2S)-hexyl-4-pentenoic
As a major side reaction in our system, lactone 4 was isolated from the
residue of concentrated acidic aqueous layer after work-up. The lactone
can be derived from an intermediate 3 via intramolecular epoxidation
(Scheme 2).
20
acid 2 (397 mg, 82%) as a colorless oil.
Acknowledgments: Financial support from the Ministry of Education,
Science and Culture of the Japanese Government is gratefully
acknowledged. We thank the analytical group of the Process Research
Laboratory of Ono Pharmaceutical Co. for measurements of the
analytical data.
References and Notes
Scheme 2
1) Oppolzer, W.; Moretti, R. Tetrahedron Lett. 1989, 30, 5603.
2) Hanessian, S.; Yang, R. ibid. 1996, 37, 5273.
3) Oppolzer, W.; De Brabander, J. ibid. 1997, 38, 1539.
4) Csuk, R.; Schröder, C. Tetrahedron: Asymmetry 1997, 8, 1411.
5) Jurczak, J.; Jezewski, A. ibid. 1997, 8, 1741.
6) Perlmutter, P.; Bond, S. J. Org. Chem. 1997, 62, 6397.
7) Leahy, J. W.; Brzezinski, L. J. J. Am. Chem. Soc. 1997, 117, 4317.
8) Oppolzer, W. Tetrahedron 1987, 43, 1969.
To suppress the side reaction, addition of excess 2-methyl-2-butene was
effective in giving carboxylic acid 2 in maximum yield (entry 2, c.f.
entry 7 in Table 1).
As another application of the new method, we attempted hydrolyses of
hindered esters and amides. Dry-TBAH was very effective for these
hydrolyses and the results are shown in Table 3. These yields were
15
superior to those obtained by the previous technique.
9) See for another recently approach: Naito, T.; Miyata, O. Synlett
1994, 637.
10) Oppolzer, W.; Kingna, A, J. Helv. Chim. Acta 1989, 72, 1337.
11) Harlow, G. A. Analytical Chem. 1956, 28, 787.
12) Cluett, M. L. ibid. 1959, 31, 610.
13) This result agrees with Evans’ explanation for the regio-selectivity
of lithium hydrogen peroxide hydrolysis: Evans, D. A.; Britton, T.
C. Tetrahedron Lett. 1987, 28, 6141.
14) Boeckman, R. K. Jr.; Connell, B. T. J. Am .Chem. Soc. 1995, 117,
12368.
15) See for hydrolysis using aqueous TBAH:
a) Schuda, P .F.; Phillips, J. L. J. Org. Chem. 1986, 51, 2742.
b) Manchand, P. S.; Micheli, R. A. Tetrahedron. 1992, 48, 9391.
c) Myers, A. G.; Yang, B. H. J. Am. Chem. Soc. 1997, 119, 6496.
16) Gassman, P. G.; Schenk, W. N. J. Org. Chem. 1977, 42, 918.
17) Gassman, P. G.; Hodgson, P K. G. J. Am. Chem. Soc. 1976, 98,
1275.
Interestingly, di-(-)-menthyl bicyclo[2.2.2.]octane-2,3-di-carboxylate
was selectively converted to corresponding half ester (entry 2). This
18 Robbins, M. D.; Vaughn, H. L. J. Org. Chem. 1975, 40, 1187
19
19 A typical procedure for hydrolysis with dry-TBAH: Aqueous
tetrabutylammonium hydroxide (40% w/w, 0.28 ml, 0.42 mmol)
was azeotropically concentrated four times with DME- toluene (4
ml, 1:1). To the residue was added a solution of di-(-)-
menthylbicyclo[2.2.2.]octane-2,3-dicarboxylate (100 mg, 0.21
mmol) in THF (0.4 ml) at room temperature. The resulting
may have been caused by the electronic repulsion of the naked
carboxylate anion under our anhydrous condition.
In conclusion, the dry-TBAH with hydrogen peroxide system showed
mild and powerful removal potency for Oppolzer’s sultam. Dry-TBAH
was also very effective for hydrolysis of sterically hindered esters and
amides.
mixture was stirred for 1h, diluted with H O and reverse extracted
2
i
with Pr O. The aqueous layer was acidified with 2N aqueous HCl
and extracted with Pr O. The organic layer was washed with
2
i
A typical procedure for removal of camphorsultam:
2
To
a
solution
of
N-(2’S)-hexyl-4’-pentenoyl-(1S)-(-)-2,10-
H O, brine, dried over Na SO and concentrated. The residue was
2 2 4
camphorsultam 1 (1.00 g, 2.62 mmol) and 2-methyl-2-butene (0.83 ml,
purified by silica gel chromatography (EtOAc:Hex, 1:9) to afford
1
7.8 mmol) in DME (10 ml) was added dropwise 30% aqueous hydrogen
the half ester (66 mg, 93%) as a colorless amorphous solid.
H
o
peroxide (0.54 ml, 5.3 mmol) at
0
C, followed by aqueous
NMR (300MHz, CDCl ) 4.69 (dt, 1 H, J = 10.9, 4.3 Hz), 3.19 (d,
3
tetrabutylammonium hydroxide (40% w/w, 3.4 ml, 5.3 mmol). After
stirring for 2h, the reaction was quenched with 1.5N aqueous Na SO
(3.5 ml), then the cooling bath was removed. The mixture was further
1 H, J = 6.9 Hz), 3.02 (dd, 1 H, J = 7.0, 2.0 Hz), 2.13 (d, 2 H, J =
15.0 Hz), 2.03 (d, 1 H, J = 10.5 Hz), 1.86 (m, 1 H), 1.70-1.40 (m,
13 H), 1.00 (m, 3 H), 0.90 (d, 3 H, J = 7.5 Hz), 0.89 (d, 3 H, J =
7.5 Hz), 0.74 (d, 3 H, J = 7.5 Hz); MS (FAB) m/z 337 (M+1), 319,
199, 181, 153, 139; IR (KBr) 2950, 2870, 1727, 1701, 1458, 1422,
1387, 1372, 1339, 1304, 1271, 1240, 1192, 1103, 1080, 1040,
2
3
stirred for 1h and concentrated in vacuo. The residue was acidified with
i
2N aqueous HCl and extracted twice with EtOAc- Pr O (1:3). The
2
combined organic layers were washed with H O, brine, dried over
2