G. P. More, S. V. Bhat / Tetrahedron Letters 54 (2013) 4148–4149
4149
O
enantiomeric excess (ee %) of (S)-(+)-4-hydroxy-b-ionone 2 and
(S)-(+)-4-hydroxy-b-damascone 5 was determined using chiral
HPLC on chiracelÒ OD analytical column and was found to be
89% and 84% respectively.
In summary, we have achieved a convenient asymmetric syn-
thesis of (S)-4-hydroxy-b-damascone and (S)-4-hydroxy-b-ionone
through PPL catalysed trans-esterification.
OH
Anhy. K2CO3
m-CPBA
5°C
89%
MeOH
reflux
62%
O
O
O
6
7
( )-2
OAc
OH
Lipase, n-hexane
MS 4Å, vinyl acetate
OH
O
O
O
(R)-3
(S)-2, ee 89%
( )-2
Acknowledgments
Scheme 1. Synthesis of (S)-(+)-4-hydroxy-b-ionone from
a
-ionone.
Authors are grateful to Kelkar Education Trust, Mumbai for
encouragement and financial support. We are also thankful to
the Department of Chemistry and Sophisticated Analytical Instru-
mentation Facility, Indian Institute of Technology, Bombay for
NMR spectral data.
OH
O
Anhy. K2CO3
m-CPBA
MeOH
5°C
81%
reflux
79%
O
O
O
O
8
9
References and notes
( )-5
OH
OAc
OH
Lipase, n-hexane
MS 4Å, vinyl acetate
O
O
( )-5
(R)-10
a-damascone.
(S)-5, ee 84%
Scheme 2. Synthesis of (S)-(+)-4-hydroxy-b-damascone from
minor products (cumulative total ꢂ9%).16 Two of these were
isolated from whole cell systems and were identified as 3-hydro-
xy-4-oxo-b-damascone and 3,4-epoxy-b-damascone. The other
two products observed by GC were not produced in sufficient
quantity to be characterized. Dehydrated decalone of (S)-4-hydro-
xy-b-damascone also represents valuable key intermediate for the
elaboration of other trans-decalins.17
We report herein a new asymmetric synthesis of (S)-(+)-4-hy-
droxy-b-ionone 2 (Scheme 1) and (S)-(+)-4-hydroxy-b-damascone
5 (Scheme 2) starting from
a-ionone and a-damascone respec-
tively through pig pancreatic lipase (PPL) catalysed trans-
esterification.
Thus, the epoxidation of
a-ionone (6) with m-CPBA at 5 °C for
19. General procedure. A mixture of ( )-4-hydroxy-b-damascone 5 (1 g, 4.8 mmol),
dry lipase (357 mg), activated molecular sieves 4 Å (286 mg), and vinyl acetate
(825 mg, 9.6 mmol) in dry n-hexane (18 ml) was stirred at room temperature
for 26 h. Reaction was monitored by GC and terminated at ꢂ50% conversion.
The reaction mixture was filtered and the filtrate was concentrated in vacuo.
The residue was purified further by silica gel column chromatography and
elution with a mixture of ethyl acetate and hexane (0.2:9.8) yielded (R)-10
(472 mg, 39%) and (S)-5 (503 mg, 51%).
1 h in CH2Cl2 yielded 4,5-epoxide (7), which was subjected to a
5 °C base catalysed rearrangement by refluxing with K2CO3 in
methanol for 4 h to give ( )-2. The latter compound was subjected
to the PPL catalysed trans-esterification18 to give (S)-(+)-4-hydro-
xy-b-ionone 2, which was purified by silica gel column chromatog-
raphy.19 The structure of (S)-(+)-2 was supported by IR, 1H and
13C NMR spectral values.20 The presence of axial –OH group at
C-4 position in (S)-(+)-2 was indicated by peak at d 4.03 (1H, t,
J = 4.8 Hz) in 1H NMR spectrum.
Similarly synthesis of (S)-(+)-4-hydroxy-b-ionone 2 was also achieved.
20. Analytical data for (S)-(+)-4-hydroxy-b-ionone (2) IR (CHCl3, c
max, cmꢀ1): 3449,
3055, 2967, 2935, 1664, 1266, 739; 1H NMR (400 MHz, CDCl3, d, ppm): 7.21 (d,
J = 16.4 Hz, 1H), 6.14 (d, J = 16.4 Hz, 1H), 4.03 (t, J = 4.8 Hz, 1H), 2.34 (s, 3H),
1.98–1.62 (m, 4H), 1.85 (s, 3H), 1.07 (s, 3H), 1.04 (s, 3H); 13C NMR (100 MHz,
CDCl3, d, ppm): 198.8, 143.1, 138.9, 134.6, 132.8, 69.6, 34.7, 28.7, 28.2, 27.5,
27.2, 18.4; GCMS: 208 (M+), 193, 175, 165, 151, 137, 123, 109, 91, 77, 65, 55,
43; chiral HPLC (MeCN:H2O—8:2), kmax 254 nm, flow rate: 0.8 ml/min), tR = 4.2
With the use of similar procedure (S)-(+)-4-hydroxy-b-damas-
cone 5 from
a-damascone was synthesized. The epoxidation of
a-damascone (8) with m-CPBA at 5 °C for 1 h in CH2Cl2 yielded
4,5-epoxide (9), which was subjected to a base catalysed rear-
rangement by refluxing with K2CO3 in methanol for 4 h to give
( )-5. The latter compound was subjected to the PPL catalysed
trans-esterification18 to give (S)-(+)-4-hydroxy-b-damascone 5,
which was purified by silica gel column chromatography. The pres-
ence of axial –OH group at C-4 position in (S)-(+)-5 was indicated
by peak at d 3.98 (1H, t, J = 5.0 Hz) in 1H NMR spectrum.19 The
structure of (S)-(+)-5 was supported by IR, 1H and 13C NMR spectral
values, which are identical with those of sample reported earlier
through hydroxylation of b-damascone with CYP101C1.16 The
(major isomer), tR = 5.7 (minor isomer), ee = 89%, ½a 20
ꢁ
¼ 6:4 (c = 1, EtOH).
Analytical data for (S)-(+)-4-hydroxy-b-damascone (5) IR (CHCl3,
c
max, cmꢀ1):
3410, 2937, 1692, 1643, 1442, 1364, 1291, 1172, 1136, 1079, 1023; 1H NMR
(300 MHz, CDCl3, d, ppm): 6.76 (dq, J = 15.7, 6.9 Hz, 1H), 6.14 (dq, J = 15.7 Hz,
1.5 Hz, 1H), 3.98 (t, J = 5 Hz, 1H), 2.01–1.94 (m, 1H), 1.92 (dd, J = 6.9, 1.6 Hz,
3H), 1.79–1.70 (m, 1H), 1.69–1.62 (m, 1H), 1.63 (s, 3H), 1.43 (ddd, J = 13.1,7.5,
3.1 Hz, 1H), 1.02 (s, 6H); 13C NMR (75 MHz, CDCl3, d, ppm): 18.0, 18.5, 27.7,
28.4, 28.9, 33.9, 34.7, 68.9, 131.2, 133.9, 143.4, 146.7, 201.2; GCMS: 208 (M+),
193, 175, 139, 121, 105, 91, 69, 55, 41; chiral HPLC (MeCN:H2O—8:2), kmax
254 nm, flow rate: 0.8 ml/min), tR = 4.1 (major isomer), tR = 5.6 (minor isomer),
ee = 84%, ½a 20
¼ 3:7 (c = 1.8, EtOH).
ꢁ