L. Borén et al. / Tetrahedron Letters 50 (2009) 3237–3240
3239
OH
resulting mixture was stirred at 0 °C for 1.5 h and then at rt over-
night. Water was added and the aqueous phase was extracted with
diethyl ether. The combined organic layers were dried over MgSO4
and concentrated. Purification by silica gel column chromatogra-
phy (pentane/EtOAc 2:1 to EtOAc) afforded the dimesylate (R,R)-
11a (807 mg, 79%) as a white solid.
OAc
K2CO3
R
DYKAT
R
R
R
(78-82%)
MeOH:H2O
(4:1), rt
OH
OAc
1a R = Me
1b R = Et
(R,R)-10
(81-97%)
OH
OMs
MsCl, Et3N
THF
R
R
R
R
(iii) The dimesylate (R,R)-11a (170 mg, 0.62 mmol), NaHNTs
(357.5 mg, 1.86 mmol), and Cs2CO3 (202 mg, 0.62 mmol) were
added to a flame-dried round bottom flask. Dry DMF (4 mL) was
added and the resulting mixture was heated at 50 °C for 24 h and
was then allowed to cool to rt. Water (10 mL) was added and the
mixture was extracted with EtOAc (5 ꢀ 20 mL). The combined or-
ganic phases were washed with water and brine, dried over MgSO4,
and concentrated. Purification by silica gel column chromatogra-
phy (pentane/EtOAc 4:1 to EtOAc) afforded pyrrolidine (S,S)-12a
(112 mg, 71%) as a white solid. The ee and diastereomeric ratio
were determined by chiral GC; >99% ee, trans:cis 96:4. 1H NMR
(CDCl3, 400 MHz): d 1.19 (6H, d, J = 6.4 Hz, 2 ꢀ CH3), 1.49–1.54
(2H, m, CH2), 2.04–2.18 (2H, m, CH2), 2.41 (3H, s, CH3), 4.02 (2H,
m, 2 ꢀ CH), 7.24-7.28 (2H, m, Ar–H), 7.69–7.76 (2H, m, Ar–H).
13C NMR (CDCl3, 100 MHz): d 21.3, 21.5, 31.2, 56.2, 127.0, 129.4,
139.9, 142.6.
OH
OMs
(R,R)-11
(R,R)-1
(72-79%)
DMF, 50 o
(65-71%)
C
NaHNTs,
Cs2CO3
R
R
N
Ts
(S,S)-12a R = Me
(S,S)-12b R = Et
trans:cis 96:4
>99% ee
trans:cis 93:7
>99%ee
Scheme 5. Synthesis of pyrrolidines.
OAc
Cl
Spectral data are in accordance with those previously
reported.26
10d'
OR
Acknowledgments
Figure 3. Diol derivative 10d0 with different protecting groups.
Financial support from the Swedish Foundation for Strategic Re-
search, the Swedish Research Council, and the K & A Wallenberg
Foundation is gratefully acknowledged. We thank Amano Europe
Ltd for a gift of PS-C ‘Amano’ II and Johnson Matthey (New Jersey,
verted to enantiomerically pure pyrrolidines. This synthetic ap-
proach toward various piperidine derivatives is currently being
studied in our laboratory.
USA) for a gift of Ru3(CO)12
.
3. Procedure for the dynamic kinetic asymmetric
transformation (DYKAT) of 1,4-diols
Supplementary data
(R,R)-2,5-Diacetoxyhexane (10a). In a general procedure, en-
zyme (CALB)24 (2.5 mg), Na2CO3 (106 mg, 1.0 mmol), and ruthe-
nium catalyst 9 (16 mg, 0.025 mmol) were added to a flame-
dried Schlenk tube under argon. The Schlenk tube was evacuated,
filled with argon and toluene (1 mL), placed in a preheated oil bath
Supplementary data associated with this article can be found, in
References and notes
(50 °C), and a solution of tBuOK (0.5 M in THF, 50 lL, 0.025 mmol)
was added. The mixture was stirred for 6 min and then diol 1a
(118 mg, 1.0 mmol) was added, and after an additional 4 min, iso-
propenyl acetate (330 lL, 3 mmol) was added. The mixture was
stirred at 50 °C for 24 h then filtered and concentrated. Purification
by silica gel column chromatography (pentane:EtOAc 4:1 to EtOAc)
afforded 10a (165 mg, 82%) as an oil. The ee and diastereomeric ra-
tio were determined by chiral GC; >99% ee, anti:syn = 94:6. 1H NMR
(CDCl3, 400 MHz): d 1.21 (6H, d, J = 6.3 Hz, 2 ꢀ CH3), 1.43–1.69 (4H,
m, 2 ꢀ CH2), 2.03 (6H, s, 2 ꢀ CH3), 4.90 (2H, m, 2 ꢀ CH). 13C NMR
(CDCl3, 100 MHz): d 19.9, 21.3, 31.7, 70.5, 170.7. Spectral data are
in accordance with those previously reported.25
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15. Substrate 1a was previously used in a highly selective DYKAT, see Ref. 6.
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(ii) (R,R)-1a (440 mg, 3.7 mmol) was dissolved in dry THF
(40 mL) and cooled to 0 °C. Et3N (1.8 mL, 12.7 mmol) was added
followed by dropwise addition of MsCl (0.98 mL, 12.7 mmol). The
17. This corresponds to an E-value of >400.