Chemo-enzymatic asymmetric total synthesis of penienone

Article abstract of DOI:10.1016/j.tetlet.2009.07.043

An asymmetric synthesis of penienone has been accomplished from (R)-5-hydroxymethyl-2-cyclohexenone by adopting a linear strategy. Lipase-PS-catalyzed enzymatic kinetic resolution (EKR) and Julia-Kocienski olefination followed by substrate-directed anioni

Full text of DOI:10.1016/j.tetlet.2009.07.043

Tetrahedron Letters 50 (2009) 5392–5394
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Tetrahedron Letters
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Chemo-enzymatic asymmetric total synthesis of penienone
*
Tridib Mahapatra, Rajib Bhunya, Samik Nanda
Department of Chemistry, Indian Institute of Technology, Kharagpur 721 302, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An asymmetric synthesis of penienone has been accomplished from (R)-5-hydroxymethyl-2-cyclohexe-
none by adopting a linear strategy. Lipase-PS-catalyzed enzymatic kinetic resolution (EKR) and Julia–
Kocienski olefination followed by substrate-directed anionic hydroxymethylation have been successfully
employed to achieve the target molecule.
Received 19 May 2009
Revised 7 July 2009
Accepted 9 July 2009
Available online 12 July 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Penienone and penihydrone, the cyclohexane-based fungal
metabolites have been isolated in 1997 by Kimura et al., from
the metabolite of the fungus Penicillium sp. no. 13, and these were
found to have plant growth regulatory activity.1 Their structures
have been elucidated on the basis of NMR and CD spectral studies.
To date two asymmetric syntheses of (ꢀ)-penienone and one
asymmetric synthesis of (+)-penihydrone have been reported in
the literature. The first synthesis of both the molecules is reported
by Sato and co-workers, in which an efficient cuprate addition of
(1E,3E)-hepta-1,3-dienyl group to chiral 5-substituted-2-cyclo-
hexenone has been accomplished.2 Meyers and Waterson, in
2000 reported the asymmetric synthesis of (ꢀ)-penienone by
employing bicyclic chiral lactams as a homoenolate equivalent to
access a properly substituted chiral 5-substituted-2-cyclohexe-
none which is the core structure of penienone.3 We have recently
developed a chemo-enzymatic strategy for the synthesis of chiral
5-hydroxymethyl-2-cyclohexenone in both enantiomeric forms.
Retrosynthetic analysis of penienone reveals that it can be easily
accessed from (R)-5-hydroxymethyl-2-cyclohexenone by func-
tional group manipulation (Scheme 1).
The starting compound (R)-5-hydroxymethyl-2-cyclohexenone
(3) has been prepared by lipase-catalyzed (Burkohedria cepacica, Li-
pase-PS) kinetic resolution of the parent racemic compound (1).4 In
the irreversible trans-esterification reaction with vinyl acetate as
the acylating agent the fast reacting (S)-enantiomer is converted
to the corresponding acetate (2) (yield = 47%, ee = 99%) whereas
the slow reacting enantiomer yielded (R)-5-hydroxymethyl-2-
cyclohexenone (3) in 48% yield (ee = 98%).5 The acetate group in
the (S)-enantiomer is deacetylated with PPL (Porcine pancreatic
lipase) to afford (S)-5-hydroxymethyl-2-cyclohexenone (4) in 82%
yield. The primary hydroxyl group is oxidized with PCC (pyridini-
um chlorochromate) to yield the (S)-ketoaldehyde (5).6 The race-
mization of (S)-ketoaldehyde to the corresponding racemic
mixture (1) is achieved by treatment with catalytic DBU (1,8-
diazabicyclo-undec-7-ene) in tetrahydrofuran7 at room tempera-
ture. Chemoselective reduction of the aldehyde functionality is
achieved with NaCNBH3 in methanol. So by a three-step methodol-
ogy the undesired (S)-5-hydroxymethyl-2-cyclohexenone (2) has
been
racemized
to
( )-5-hydroxymethyl-2-cyclohexenone
(Scheme 2). This can be used again in the initial kinetic resolution
step.
The primary hydroxyl group in 3 was protected as its TBDPS
(tert-butyl diphenylsilyl) ether by treatment with imidazole and
TBDPS–Cl to afford compound 6 in 90% yield. The keto protection
in compound 6 was problematic in our hands and after the failure
of numerous literature procedures, we achieved the desired trans-
formation by a three-step protocol as described by Smith.8 Bromin-
ation and dehydrobromination of compound 6 with Br2–CCl4/Et3N
afforded (R)-2-bromo-5-(tert-butyl-diphenyl-silanyloxymethyl)-
cyclohex-2-enone (7) in 88% yield.9 Compound 7 when refluxed
with ethylene glycol and PPTS (pyridinum para-toluene sulfonate)
in benzene afforded the corresponding ketal 8 in 72% yield. Debro-
mination of 8 was achieved by treatment with n-BuLi at ꢀ78 °C
and quenching with NH4Cl to afford compound 9 in 78% yield.
Deprotection of the TBDPS group was achieved by treatment of 9
with TBAF (tetrabutylammonium fluoride) in tetrahydrofuran10
to yield alcohol 10.11 Oxidation of 10 with TPAP/NMO (tetrapropyl
ammonium perruthenate/N-methyl morpholine-N-oxide)12 in the
presence of powdered molecular sieves afforded the aldehyde 11
in 88% yield.13 Wittig olefination of aldehyde 11 with phospho-
Substrate directed
hydroxymethylation
O
O
O
EKR
OH
OH
OH
(-)-penienone
(R)-5-hydroxymethyl-2-cyclohexenone
Scheme 1. Retrosynthetic analysis of penienone.
Julia-Kocienski olefination
* Corresponding author.
E-mail address: snanda@chem.iitkgp.ernet.in (S. Nanda).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.07.043

T. Mahapatra et al. / Tetrahedron Letters 50 (2009) 5392–5394
5393
O
achieve the total synthesis of (ꢀ)-penienone. An organocatalytic
asymmetric variant of the aldol reaction was first tried with com-
pound 15 and formaldehyde in the presence of (S)-proline.21 After
the usual work-up and purification (ꢀ)-penienone was obtained in
30% yield only. The unusual low yield of this organocatalytic aldol
reaction forced us to adopt a different strategy for the introduction
of the required hydroxymethyl functionality. Base-induced, sub-
strate-directed hydroxymethylation was attempted.22 Hence when
compound 15 was treated with LiTMP (lithium tetramethylpiperi-
dide) at ꢀ78 °C and the generated enolate was treated with ben-
zotriazol-1-yl-methanol at the same temperature, (ꢀ)-penienone
was obtained in 70% yield. The other diastereomer epi-penienone
was obtained in 15% yield. The stereochemical course of the reac-
tion was governed by the presence of the bulky (1E,3E)-hepta-1,3-
dienyl moiety. The overall yield of (ꢀ)-penienone was 16% starting
O
O
Lipase-PS
OAc
+
OH
OH
3, (R); ee = 98%
OAc
1
2, (S); ee = 99%
NaCNBH3/MeOH
PPL
O
O
1) PCC, DCM
H
OH
2) DBU, THF, RT
4
O
5
Scheme 2. Synthesis of (R)-5-hydroxymethyl-2-cyclohexenone by lipase-catalyzed
kinetic resolution and recycling of the (S)-enantiomer.
O
O
O
O
O
O
O
Br
Br
a
b
c
d
e
3
6
7
8
9
OTBDPS
OH
OTBDPS
OTBDPS
OTBDPS
O
O
O
O
f
g
H
CHO
10
11
OH
12
S
h
i
+
SH
OH
SO2BT
O
N
13
BT-SH
O
O
O
OH
j
H
k
nPr
nPr
nPr
14
15
(-)-penienone
Scheme 3. Reagents and conditions: (a) TBDPS–Cl, imidazole, DMF, 90%; (b) Br2–CCl4, Et3N, 0 °C, 2 h, 88%; (c) (CH2OH)2, PPTS, benzene, reflux, 48 h, 72%; (d) n-BuLi, ꢀ78 °C to
rt, NH4Cl, 78%; (e) TBAF/THF, 90%; (f) TPAP, NMO, MS (4 Å), rt, 6 h, 88%; g) n-BuLi, ꢀ78 °C; 1E,3E-hepta-1,3-dienylphosphoniumbromide; (h) Ph3P, DIAD (diisopropylazo-
dicarboxylate), THF, rt; (NH4)6Mo7O24ꢁ4H2O, H2O2, 78%; (i) LHMDS, ꢀ78 °C, 1 h, then add 7, 2 h, 70%; (j) PTSA, CHCl3, 2 h, 0.1 equiv I2, 100 W tungsten lamp, 2 h; 88%; (k)
LiTMP, benzotriazol-1-yl-methanol, 70%.
nium ylide derived from (E)-1-bromo-hex-2-ene at ꢀ78 °C affor-
ded the undesired compound 12 instead of the desired compound
14. The formation of 12 can be explained as follows. During the
from compound 3 (Scheme 3). Our synthesized (ꢀ)-penienone
shows comparable spectral characteristic values as those reported
in the literature.1–3,23,24
preparation
of
the
Wittig
ylide
1E,3E-hepta-1,3-dien-
In conclusion we have described an efficient asymmetric syn-
thesis of the natural enantiomer of (ꢀ)-penienone by adopting an
enzymatic kinetic resolution–racemization protocol and Julia–
Kocienski olefination strategy followed by substrate-directed anio-
nic hydroxymethylation strategy.
ylphosphoniumbromide, the presence of some triphenylphosphine
causes deketalization14 and subsequent olefination yielded com-
pound 12 in 70% yield (E,E/E,Z = 3:1). The installation of the re-
quired
1E,3E-hepta-1,3-dienyl
group
was
successfully
accomplished by a Julia–Kocienski protocol.15 The desired sulfone
(13)16 was prepared from (E)-2-hexenol17 and 2-mercaptobenzo-
thiazole by a standard method.18 The sulfone was subjected to
the olefination reaction with aldehyde 11 in the presence of
LHMDS (lithiumhexamethyldisilazide) to afford compound 14.
The ketal moiety in 14 was removed by treating the compound
with PTSA (para-toluenesulfonic acid) in CHCl3 to afford compound
15 (mixture of geometrical isomers) in 95% yield. The undesired E,Z
component in compound 15 was photoisomerized to the desired
E,E component19 by treatment of 0.1 equiv I2.20 After successful
installation of the (1E,3E)-hepta-1,3-dienyl moiety in a stereocon-
trolled way the remaining task is to introduce the required
Acknowledgements
We are thankful to DST (New Delhi, India) for providing finan-
cial support (DST fast track scheme and IRPHA). Two of the authors,
T.M. and R.B. are thankful to CSIR (New Delhi, India) for research
fellowship.
References and notes
1. Kimura, Y.; Mizuno, T.; Shimada, A. Tetrahedron Lett. 1997, 38, 469–472.
2. Hareau, G. P.-J.; Koiwa, M.; Hikichi, S.; Sato, F. J. Am. Chem. Soc. 1999, 121, 3640–
3650.
hydroxymethyl group at the
a-carbon in a stereoselective way to
3. Waterson, A. G.; Meyers, A. I. J. Org. Chem. 2000, 65, 7240–7743.

5394
T. Mahapatra et al. / Tetrahedron Letters 50 (2009) 5392–5394
16. 2-[((E)-Hex-2-ene)-1-sulfonyl]-benzothiazole (13): to
4. (a) Barral, K.; Courcambeck, J.; Pepe, G.; Balzarini, J.; Neyts, J.; De Clercg, E.;
Camplo, M. J. Med. Chem. 2005, 48, 450–456; (b) Hatcher, M. A.; Peleg, S.; Dolan,
P.; Kensler, T. W.; Sarjeant, A.; Posner, G. H. Bioorg. Med. Chem. 2005, 13, 3964–
3976; (c) Yu, S.-H.; Chung, S.-K. Tetrahedron: Asymmetry 2004, 15, 581–584; (d)
Smith, A. B.; Hale, K. J.; Laakso, L. M.; Chen, K.; Riera, A. Tetrahedron Lett. 1989,
30, 6963–6966; (e) Linde, R. G.; Egbertson, M.; Coleman, R. S.; Jones, A. B.;
Danishefsky, S. J. J. Org. Chem. 1990, 55, 2771–2776.
a solution of DIAD
(1.28 mL, 6.5 mmol) in 20 mL of dry THF were added benzothiazole-2-thiol
(1 g, 6 mmol), E-2-hexen-1-ol (0.5 g, 5 mol) and TPP (1.5 g, 6 mmol) at 0 °C. The
reaction mixture was allowed to attain room temperature for 4 h, after that it
was evaporated and the crude product was taken in 50 mL of ether, washed
successively with 1 N NaOH (20 mL), water and brine. The organic layer was
dried over anhydrous MgSO4 and evaporated under reduced pressure. The
crude sulfide (110 mg, 0.44 mmol) was taken in 5 mL of ethanol and treated
with ammonium molybdate (54 mg, 0.044 mmol) and 0.5 mL of 30% H2O2. The
reaction mixture was stirred at room temperature overnight. After that, the
solution was evaporated and purified through silica-gel chromatography (1:3;
hexane/EtOAc) to afford the sulfone 13 in 82% yield.
5. The enantioselectivity of the lipase-PS-catalyzed trans-esterification step was
measured by chiral HPLC (OJ-H, hexane:2-propanol/9:1) of the benzoate
derivative of (R)-1 and (S)-1.
6. (R)-5-oxo-cyclohex-3-ene-carbaldehyde (5):1H NMR (CDCl3, 400 MHz), d: 9.63
(s, 1H, –CHO), 6.92 (dt, J = 10.0, 3.6 Hz, 1H, olefinic-H), 6.0 (d, J = 10.0 Hz, 1H,
olefinic-H), 3.0 (m, 1H, –CH–CHO), 2.7–2.6 (m, 4H, ring-H).13C NMR (CDCl3,
100 MHz), d: 200.55, 196.34, 147.25, 130.30, 46.53, 36.73, 24.50.
1H NMR (CDCl3, 400 MHz), d: 8.3 (m, 1H, Ar–H), 8.1 (m, 1H, Ar–H), 7.7–7.5 (m,
2H, Ar–H), 5.8 (m, 1H, olefinic-H), 5.5 (m, 1H, olefinic-H), 4.3 (d, J = 7.2 Hz, 2H,
–CH2–SO2–), 2.1 (q, J = 7.6 Hz, 2H), 1.4 (m, 2H), 0.85 (t, J = 7.2 Hz, 3H).13C NMR
(CDCl3, 100 MHz), d: 165.25, 152.58, 143.34, 141.03, 136.76, 127.59, 125.34,
122.32, 114.31, 58.51, 34.48, 21.66, 13.28.
7. Peng, J.; Clive, D. L. J. J. Org. Chem. 2009, 74, 513–519.
8. Smith, A. B., III; Branca, S. J.; Guaciaro, M. A.; Wovkulich, P. M.; Korn, A. Org. Syn.
Coll. 1990, 7, 271.
9. (R)-2-Bromo-5-(tert-butyl-diphenyl-silanyloxymethyl)-cyclohex-2-enone
(compound 7): a solution of compound 6 (2 g, 5.5 mmol) in 4 mL of carbon
tetrachloride is prepared in a two-necked round-bottomed flask. The solution
is cooled to 0 °C with an ice bath and a solution of bromine (0.3 mL in 4 mL of
CCl4, 6 mmol) is added dropwise for 15 min. A solution of 1.2 mL of Et3N
(8.25 mmol) in 4 mL of CCl4 is then added dropwise with vigorous stirring. The
stirring is continued for an additional 2 h at room temperature. The resulting
dark suspension is washed with dil. HCl (2 ꢂ 10 mL), saturated NaHCO3
(20 mL) and brine solution. The resultant solution is dried over MgSO4, and the
solvent is evaporated under reduced pressure. The compound is purified by
chromatography.1H NMR (CDCl3, 400 MHz), d: 7.65 (m, 4H, Ar–H), 7.5–7.3 (m,
7H, Ar–H and olefinic-H), 3.6 (m, 2H, –CH2–OTBDPS), 2.8–2.6 (m, 2H, ring-H),
2.5–2.4 (m, 3H, ring-H), 1.0 (s, 6H).13C NMR (CDCl3, 100 MHz), d: 191.17 (C@O),
150.01, 135.47, 133.05, 129.82, 127.76, 123.54, 66.16 (CH2), 40.99 (CH2), 37.54
(CH), 31.03 (CH2), 26.78 (CH3), 19.23 (C).
17. (E)-2-Hexen-1-ol was prepared from n-butanal by Horner–Wittig olefination
with triethylphosphonoacetate followed by DIBAL-H reduction.
18. Blakemore, P. R.; Kocienski, P.; Morley, A.; Muir, K. J. Chem. Soc, Perkin Trans. 1
1999, 955–968.
19. (R)-((1E,3E)-5-Hepta-1,3-dienyl)-cyclohex-2-enone (15).1H NMR (CDCl3,
400 MHz), d: 7.0 (m, 1H, olefinic-H), 6.1–5.97 (m, 3H, olefinic-H), 5.65 (dd,
J = 14.8, 7.2 Hz, 1H, olefinic-H), 5.5 (dd, J = 14.8, 7.2 Hz, 1H, olefinic-H), 2.85 (m,
1H, ring-H), 2.5 (m, 2H), 2.3–2.0 (m, 4H), 1.48 (q, J = 7.2 Hz, 2H), 0.92 (t,
J = 7.2 Hz, 3H).13C NMR (CDCl3, 100 MHz), d: 199.11 (C@O), 149.36, 134.60,
132.84, 130.39, 129.84, 129.75, 43.96 (CH2), 38.02 (CH), 34.71 (CH2), 32.16
(CH2), 22.43 (CH2), 13.74 (CH3).½a D28
ꢀ50.6 (c 1.0, MeOH).HRMS (ESIMS) calcd
ꢃ
for C13H18ONa (M+Na)+ 213.1249, found 213.1261.
20. Watanabe, Y.; Lida, H.; Kibayashi, C. J. Org. Chem. 1989, 54, 4088–4097.
21. Casas, J.; Sunden, H.; Cordova, A. Tetrahedron Lett. 2004, 45, 6117–6119.
22. Deguest, G.; Bischoff, L.; Fruit, C.; Marsais, F. Org. Lett. 2007, 9, 1165–1167.
23. (5S,6R)-5-((1E,3E)-Hepta-1,3-dienyl)-6-hydroxymethyl-cyclohex-2-enone
(penienone): to a stirred solution of n-BuLi (0.28 mL, 0.17 mmol) in anhydrous
THF (4 mL) was added dropwise 2,2,6,6-tetramethylpiperidine (0.026 mL,
0.17 mmol) at ꢀ10 °C. The solution was allowed to stir at 0 °C for 30 min and
was then cooled to ꢀ78 °C. Compound 15 (30 mg, 0.16 mmol) in anhydrous
THF (2 mL) was added dropwise and stirred for an additional 1 h. Benzotriazol-
1-yl-methanol (48 mg, 0.32 mmol) in anhydrous THF (3 mL) was added
dropwise over 10-min period and kept for 2 h at this temperature. The
reaction mixture was quenched with water (10 mL) and extracted with diethyl
ether (50 mL) and was then washed successively with 4 N NaOH (15 mL) and
brine (15 mL). The organic layer was dried over Na2SO4, filtered and
concentrated in vacuo. The product was purified by flash chromatography
(1:5; hexane/EtOAc) to afford 24 mg (70%) of (ꢀ)-penienone.
10. Hanessian, S.; Lavallee, P. Can. J. Chem. 1975, 53, 2975.
11. (R)-1-(1,4-Dioxa-spiro-[4.5]-dec-9-en-7-yl)-methanol(10):
compound
9
(1.21 g, 2.98 mmol) was taken in dry THF (30 mL). TBAF (1 M in THF,
2.98 mL) was added to it, and the reaction mixture was stirred for 3 h at
room temperature. After that, THF was evaporated, and water (20 mL) was
added to it, the reaction mixture was extracted with EtOAc (2 ꢂ 50 mL), the
organic layer was washed with NaHCO3 and brine and dried (Na2SO4). It was
purified by flash chromatography (1:1; hexane/EtOAc) to afford 375 mg of
compound 10 (90%).1H NMR (CDCl3, 400 MHz), d: 5.95 (m, 1H, olefinic-H), 5.59
(d, J = 10.0 Hz, 1H, olefinic-H), 4.0–3.8 (m, 4H, ketal ring-H), 3.6 (d, J = 6.0 Hz,
2H, –CH2OH), 2.2–2.1 (m, 2H, ring-H), 1.94 (m, 1H, ring-H), 1.7–1.5 (m, 3H,
ring-H).13C NMR (CDCl3, 100 MHz), d: 131.48 (CH@C), 127.38 (CH@C), 105.90
(–O–C–O), 66.76 (–CH2OH), 64.68 (–O–CH2–), 64.30 (–O–CH2–), 36.07 (CH2),
35.26 (CH), 27.93 (CH2).½a D28
ꢃ
ꢀ12.2 (c 1.0, MeOH).
1H NMR (CDCl3, 400 MHz), d: 7.0 (m, 1H), 6.15–6.0 (m, 3H), 5.68 (dt, J = 13.6,
7.2 Hz, 1H), 5.48 (dd, J = 14.8, 8.8 Hz, 1H), 3.9 (m, 1H, –CH2OH), 3.78 (m, 1H, –
CH2OH), 2.92 (m, 1H), 2.7 (br s, 1H, –OH), 2.5–2.35 (m, 3H), 2.0 (q, J = 7.2 Hz,
2H), 1.4 (q, J = 7.2 Hz, 2H), 0.9 (t, J = 7.2 Hz, 3H).13C NMR (CDCl3, 100 MHz), d:
202.36 (C@O), 149.95 (CH), 135.08 (CH), 132.73 (CH), 131.33 (CH), 129.57 (CH),
129.41 (CH), 60.92 (CH2), 52.85 (CH), 40.98 (CH), 34.70 (CH2), 33.06 (CH2),
12. Griffith, W. P.; Ley, S. V.; Whitcombe, G. P.; White, A. D. J. Chem. Soc., Chem.
Commun. 1987, 1625–1626.
13. (R)-1,4-Dioxa-spiro-[4.5]-dec-9-ene-7-carbaldehyde (11):
a
solution of
compound 10 (170 mg, 1 mol) in 10 mL of dichloromethane is treated with
TPAP (21 mg, 0.06 mmol), powdered molecular sieves (4 Å, 150 mg) and NMO
(175 mg, 1.5 mmol). The dark reaction mixture is stirred at room temperature
over 6 h and then filtered through a pad of silica and washed several times
with dichloromethane. Evaporation and purification through silica gel
chromatography (1:3; hexane/EtOAc) afforded the aldehyde 11 (160 mg,
88%).1H NMR (CDCl3, 400 MHz), d: 9.70 (s, 1H, –CHO), 6.0 (dt, J = 10.0, 3.6 Hz,
1H, olefinic-H), 5.65 (d, J = 10.0 Hz, 1H, olefinic-H), 4.0 (m, 4H, ketal ring-H), 2.8
(m, 1H, ring-H), 2.5–2.3 (m, 3H, ring-H), 1.8 (m, 1H, ring-H).13C NMR (CDCl3,
100 MHz), d: 202.47 (–CHO), 130.15 (CH@C), 128.10 (CH@C), 105.05 (–O–C–O),
64.88 (–O–CH2–), 64.51 (–O–CH2–), 45.48 (CH), 33.01 (CH2), 24.07 (CH2).
14. Johnstone, C.; Kerr, W. J.; Scott, J. S. Chem. Commun. 1996, 341–342.
15. Blakemore, P. R.; Cole, W. J.; Kocienski, P. J.; Morley, A. Synlett 1998, 26–28.
22.39 (CH2), 13.73 (CH3).½a D28
ꢀ39.4 (c 0.5, MeOH).HRMS (ESIMS) calcd for
ꢃ
C14H20O2Na (M+Na)+ 243.1355, found 243.1361.
24. (5S,6S)-5-((1E,3E)-Hepta-1,3-dienyl)-6-hydroxymethyl-cyclohex-2-enone(epi-
penienone):
1H NMR (CDCl3, 400 MHz), d: 6.93 (m, 1H), 6.07–5.88 (m, 3H), 5.66 (dt, J = 13.6,
7.2 Hz, 1H), 5.52 (dd, J = 14.6, 9.2 Hz, 1H), 3.96 (m, 1H, –CH2OH), 3.48 (m, 1H, –
CH2OH), 2.94 (m, 1H), 2.87–2.75 (m, 2H), 2.67 (br s, 1H, –OH), 2.44 (m, 1H),
2.06 (q, J = 7.2 Hz, 2H), 1.4 (q, J = 7.2 Hz, 2H), 0.92 (t, J = 7.2 Hz, 3H).
13C NMR (CDCl3, 100 MHz), d: 202.30 (C@O), 148.85 (CH), 135.18 (CH), 133.43
(CH), 129.83 (CH), 129.67 (CH), 128.41 (CH), 62.62 (CH2), 52.65 (CH), 40.82
(CH), 34.86 (CH2), 32.60 (CH2), 22.59 (CH2), 13.93 (CH3).