Stereoselective synthesis of a mevinic acid analogue

Article abstract of DOI:10.1055/s-2007-965904

An efficient and versatile synthetic method for the stereoselective synthesis of a mevinic acid analogue is described. This approach uses a combination of a Cosford protocol with a catecholborane-mediated stereoselective reduction of acyclic P-hydroxy ket

Full text of DOI:10.1055/s-2007-965904

PAPER
705
Stereoselective Synthesis of a Mevinic Acid Analogue1
A
Stereoselective
Synthesis of
w
a
M
evinic
A
cid
A
n
alogue avaram Sabitha,* K. Sudhakar, Ch. Srinivas, J. S. Yadav
Organic Division I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Fax sabitha@iictnet.org; E-mail: +91(40)27160512
Received 24 October 2006; revised 15 November 2006
HO
O
HO
O
Abstract: An efficient and versatile synthetic method for the stere-
oselective synthesis of a mevinic acid analogue is described. This
approach uses a combination of a Cosford protocol with a cate-
cholborane-mediated stereoselective reduction of acyclic b-hy-
droxy ketones to syn-1,3-diols, as key steps.
O
O
O
O
O
O
H
H
Key words: mevinic acid analogue, Cosford protocol, b-hydroxy
ketones, catecholborane, syn-1,3-diols
R
R = Me; mevinolin
H; compactin
simvastatin
Mevinolin, a fungal metabolite isolated from the fungus
Aspergillus sp., is a potent anti-hypercholesterolemic
agent and a competitive inhibitor of 3-hydroxy-3-methyl-
glutaryl coenzyme A (HMGCoA).2 Mevinolin and its rel-
atives compactin, pravastatin and simvastatin, are useful
in helping to reduce cholesterol and other fat levels in the
blood. They also show promise in helping to slow the pro-
gression of coronary arthrosclerosis. Such drugs act by
blocking enzymes that synthesize cholesterol, while si-
multaneously increasing the level of high-density lipopro-
teins. Despite the relatively simple structure of these
compounds, the lactone moiety has proved to be essential
for the biological activity of such compounds.3 Thus, the
synthesis of many analogues of the lactone moiety have
been reported in literature.4
HO
COOH
O
O
O
O
O
H
OH
HO
pravastatin
mevinic acid analogue 1
Figure 1
OH
OH
I
An efficient protocol for the cross-coupling of alkynes
with aryl and heteroaryl substrates using a Pd/C-CuI-PPh3
catalytic system in aqueous media has been developed by
Cosford and coworkers,5 that has wide applicability to the
formation of C–C bonds in organic synthesis. Similarly
the stereoselective reduction of acyclic b-hydroxy ketones
to syn-1,3-diols can be achieved using catecholborane as
an effective reagent.6 We envisaged that by combining
these two methods, an effective synthetic strategy for the
preparation of mevinic acid analogues could be devel-
oped.
a
OTHP
+
OTHP
3
2
4
Scheme 1 Reagents and conditions: (a) 10% Pd/C (cat.), CuI (4
equiv), Ph3P (0.1 equiv), K2CO3, H2O–DME, 80 °C, 2 h, 90%.
bonate and catalytic amounts of Pd/C, CuI, and PPh3, to
afford the propargylic alcohol 4 in 90% yield (Scheme 1).
The triple bond of compound 4 was reduced using Pd/C in
ethanol to afford the saturated alcohol 5 in 90% yield. The
secondary hydroxy group of 5 was protected as the corre-
sponding silyl ether 6 and the deprotection of the tetrahy-
dropyran (THP) group was achieved using pyridinium p-
toluenesulfonate (PPTS) in methanol affording 7. The pri-
mary alcohol 7, upon oxidation, resulted in the corre-
sponding aldehyde 8 in 90% yield, which was converted
into b-keto ester 9 (80% yield) by the reaction with ethyl
diazoacetate in the presence of a catalytic amount of
tin(II)chloride. Desilylation of 9 was achieved using tet-
rabutylammonium fluoride (TBAF) to afford b-hydroxy-
b-keto ester 10 in 85% yield. The stereoselective reduc-
tion of 10 to the corresponding syn-1,3-diol 11, in 95%
yield with high diastereoselectivity, was achieved using
The synthesis of mevinic acid analogue 1 could be
achieved by combining the Cosford protocol with the ste-
reoselective reduction of acyclic b-hydroxy ketones to
syn-1,3-diols using catecholborane. Thus, the enantiose-
lective synthesis of mevinic acid analogue started from
the key intermediate 4. Coupling of iodobenzene 2 and
alkyne 37 was achieved by heating in 1,2-dimethoxy-
ethane/water solution in the presence of potassium car-
SYNTHESIS 2007, No. 5, pp 0705–0708
x
x
.
x
x
.2
0
0
7
Advanced online publication: 25.01.2007
DOI: 10.1055/s-2007-965904; Art ID: Z21706SS
© Georg Thieme Verlag Stuttgart · New York

706
G. Sabitha et al.
PAPER
OTBDPS
OH
b
a
OR
OTHP
4
5
6, R = THP
7, R = H
c
OTBDPS
CHO
O
O
OR
d
e
OEt
8
9, R = TBDPS
10, R = H
f
O
O
OH
OH
O
i
g
OEt
OH
11
h
O
O
O
OEt
12
Scheme 2 Reagents and conditions: (a) Pd/C, EtOH, 2 h, 90%; (b) TBDPSCl, imidazole, CH2Cl2, DMAP, 2 h, 95%; (c) PPTS, MeOH, 12 h,
90%; (d) 2-iodoxybenzoic acid, DMSO, CH2Cl2, 0 °C to r.t., 2 h, 90%; (e) anhyd SnCl2 (cat.), N2CHCOOEt, CH2Cl2, 0 °C to r.t., 40 min, 80%;
(f) TBAF, THF, 2 h, 85%; (g) catecholborane, THF, –10 °C, 4 h, 95%; (h) 2,2-dimethoxypropane, PPTS, 87%; (i) PTSA, CH2Cl2, 3 h, 84%.
NMR spectra were recorded on Varian FT-200MHz (Gemini) or a
Bruker UXNMR FT-300MHz (Avance) in CDCl3. Chemical shift
values are reported in parts per million (d) relative to TMS (d = 0.0)
as an internal standard. Mass spectra were recorded under EI at
70eV on an LC-MSD (Agilent technologies). Column chromatog-
raphy was performed on silica gel (60–120 mesh) supplied by Acme
Chemical Co., India. Optical rotations were measured with a
JASCO DIP-370 Polarimeter at 20 °C.
catecholborane (2.2 equiv). The stereochemistry of syn-
diol 11 was confirmed by analyzing the 13C NMR spectral
data of the corresponding acetonide 12. Characteristic
peaks at d = 19.8, 30.1 and 99.0 ppm in the 13C NMR spec-
tra of 1,3-diol8 12, confirmed the syn-geometry of the diol.
Compound 11, on treatment with p-toluenesulfonic acid
(PTSA) in dichloromethane, furnished the target lactone 1
1
in 84% yield (Scheme 2). The lactone 1 showed H and
(3S)-1-Phenyl-5-(tetrahydro-2H-2-pyranyloxy)pent-1-yn-3-ol
(4)
13C NMR spectral data and optical rotation {[a]D25 +47.2
(c 0.3, CHCl3)} in good agreement with the previously re-
ported compound.9
To a solution of 2 (3 g, 14.7 mmol) in DME (60 mL) was added H2O
(25 mL), K2CO3 (5 g, 36.75 mmol), CuI (0.11 g, 0.58 mmol), Ph3P
(0.29 g, 1.17 mmol) and a catalytic amount of10% Pd/C. The result-
ing mixture was stirred at r.t. for 30 min, then compound 3 (4.3 g,
22.0 mmol) was added and the reaction was warmed to 80 °C for 2
h. The mixture was cooled to r.t., filtered through a celite pad and
washed with EtOAc (100 mL). The solution was diluted with H2O
(100 mL) and extracted with EtOAc (2 × 300 mL). The organic
phase was washed with brine (100 mL), dried (Na2SO4) and concen-
trated under reduced pressure. The residue was purified by column
chromatography (n-hexane–EtOAc, 70:30) to afford 4.
In summary, we have applied a Cosford cross-coupling
protocol for the reaction of iodobenzene with an acetylen-
ic alcohol, along with a stereoselective reduction of an
acyclic b-hydroxy ketone to the syn-1,3-diol using cate-
cholborane, as key steps in the synthesis of a mevinic acid
analogue. This strategy provides rapid access to a range of
analogues of the lactone moiety of mevinolin.
Yield: 5 g (90%); colorless liquid; [a]D25 +12.5 (c 1.00, CHCl3).
Reactions were conducted under nitrogen atmosphere using anhy-
drous solvents. All reactions were monitored by thin layer chroma-
tography (TLC) using Merck 60 F-254 silica gel plates with UV
visualization. Light petroleum had a distillation range 60–80 °C.
Yields refer to chromatographically and spectroscopically (1H, 13C)
homogeneous material. Air sensitive reagents were transferred by
syringe or with a double-ended needle. Evaporation of solvents was
performed at reduced pressure, using a Büchi rotary evaporator. 1H
IR (neat): 2943, 1618, 1490, 1353, 1200, 1073, 1034, 757, 692 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.46–1.88 (m, 6 H), 1.93–2.22 (m,
2 H), 2.85 (br s, 1 H), 3.42–4.24 (m, 4 H), 4.59–4.82 (m, 1 H), 4.79
(dd, J = 4.6, 7.0 Hz, 1 H), 7.23–7.31 (m, 3 H), 7.35–7.43 (m, 2 H).
13C NMR (100 MHz, CDCl3): d = 131.5, 128.1, 122.5, 98.8, 89.4,
84.7, 64.6, 62.1, 61.4, 36.8, 30.3, 25.1, 19.2.
Synthesis 2007, No. 5, 705–708 © Thieme Stuttgart · New York

PAPER
Stereoselective Synthesis of a Mevinic Acid Analogue
707
LC-MS: m/z = 283 [M + Na]+.
in vacuo. The crude product was purified by column chromatogra-
phy (n-hexane–EtOAc, 80:20) to afford aldehyde 8.
(3R)-1-Phenyl-5-(tetrahydro-2H-2-pyranyloxy)pentan-3-ol (5)
To a solution of 4 (3 g, 11.5 mmol) in anhyd EtOAc (10 mL) was
added a catalytic amount of 10% Pd/C and the mixture was stirred
at r.t. under a H2 atmosphere for 6 h. The catalyst was filtered off
and washed with EtOAc (100 mL) and the filtrate was concentrated
under reduced pressure. Purification by column chromatography (n-
hexane–EtOAc, 75:25) afforded pure 5.
25
Yield: 2.6 g (90%); viscous colorless liquid; [a]D –14.4 (c 0.7,
CHCl3).
IR (neat): 3068, 2929, 2855, 1721, 1590, 1426, 1363, 1188, 1003,
820 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.06 (s, 9 H), 1.76–1.88 (m, 2 H),
2.46–2.58 (m, 4 H), 4.19–4.28 (m, 1 H), 6.88–6.96 (m, 2 H), 7.03–
7.21 (m, 3 H), 7.27–7.49 (m, 5 H), 7.58–7.73 (m, 5 H), 9.65 (t,
J = 2.45 Hz, 1 H).
Yield: 2.7 g (90%); colorless liquid; [a]D25 +40.3 (c 0.5, CHCl3).
IR (neat): 3451, 2925, 2364, 1639, 1454, 1354, 1209, 1027, 981
cm–1.
LC-MS: m/z = 439 [M + Na]+.
1H NMR (300 MHz, CDCl3): d = 1.45–1.92 (m, 10 H), 2.56–2.87
(m, 2 H), 2.86–2.99 (br s, 1 H, OH), 3.43–3.66 (m, 2 H), 3.74–4.03
(m, 3 H), 4.52–4.63 (m, 1 H) 7.08-7.37 (m, 5H).
Ethyl (5R)-5-[1-(tert-Butyl)-1,1-diphenylsilyl]oxy-3-oxo-7-phe-
nylheptanoate (9)
To anhyd tin(II) chloride (0.1 g, 0.48 mmol) was added CH2Cl2 (15
mL) followed by ethyl diazoacetate (0.6 g, 5.2 mmol) at r.t. while
stirring. A few drops of 8 (2 g, 4.8 mmol) in dry CH2Cl2 (5 mL)
were slowly added and, after nitrogen evolution had begun, the re-
mainder of the solution was added dropwise over 10 min. After ni-
trogen evolution had stopped (~30 min) the reaction was transferred
to a separating funnel with saturated brine (20 mL) and extracted
into Et2O (50 mL). The organic layers were combined, dried
(Na2SO4) and the solvent was removed in vacuo to give a residue
that was purified by silica gel column chromatography (n-hexane–
EtOAc, 90:10) to afford 9.
LC-MS: m/z = 287 [M + Na]+.
tert-Butyl[(1R)-1-phenethyl-3-(tetrahydro-2H-2-pyranyl-
oxy)propyl]oxydiphenylsilane (6)
To a stirred solution of alcohol 5 (2.5 g, 9.4 mmol) and imidazole
(1.2 g, 18.8 mmol) in anhyd CH2Cl2 (15 mL) was added TBDPS-Cl
(3.1 g, 11.3 mmol), portion-wise, at 0 °C. The reaction mixture was
stirred at the same temperature for 2 h and then quenched with H2O.
The organic layer was separated and the aqueous layer was extract-
ed with CH2Cl2 (2 × 20 mL). The combined organic layers were
washed with H2O (40 mL), brine (20 mL) and dried (Na2SO4). The
solvent was removed in vacuo and the residue was purified by col-
umn chromatography (n-hexane–EtOAc, 95:5) to afford 6.
25
Yield: 1.9 g (80%); viscous colorless liquid; [a]D –16.2 (c 0.5,
CHCl3).
IR (neat): 3448, 2926, 2855, 2361, 1717, 1636, 1461, 1231, 1108,
820 cm–1.
Yield: 4.5 g (95%); colorless liquid; [a]D25 –15.8 (c 0.5, CHCl3).
IR (neat): 2929, 2856, 2356, 1558, 1427, 1260, 1067, 857 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.05 (s, 9 H), 1.28 (t, J = 7.03 Hz,
3 H), 2.67 (d, J = 5.46 Hz, 2 H), 3.18 (s, 2 H), 4.12 (q, J = 7.03 Hz,
2 H), 4.18–4.31 (m, 1 H), 6.87–7.24 (m, 5 H), 7.27–7.48 (m, 5 H),
7.58–7.76 (m, 5 H).
1H NMR (300 MHz, CDCl3): d = 1.06 (s, 9 H), 1.36–1.61 (m, 6 H),
1.63–1.90 (m, 4 H), 2.55 (t, J = 8.30 Hz, 2 H), 3.27–3.45 (m, 2 H),
3.61–3.77 (m, 2 H) 3.87–4.02 (m, 1 H) 4.43 (t, J = 3.02 Hz, 1 H),
6.89–6.97 (m, 2 H), 7.02–7.20 (m, 3 H), 7.28–7.43 (m, 5 H), 7.61–
7.71 (m, 5 H).
LC-MS: m/z = 525 [M + Na]+.
LC-MS: m/z = 525 [M + Na]+.
Ethyl (5R)-5-Hydroxy-3-oxo-7-phenylheptanoate (10)
To compound 9 (2 g, 3.9 mmol) in anhyd THF (10 mL) was added
TBAF (1 M in THF, 3.9 mL, 3.9 mmol), dropwise at 0 °C, and the
mixture was stirred for 30 min. H2O (2 mL) was added and the mix-
ture was extracted with EtOAc (50 mL). The organic extracts were
washed with brine (20 mL), dried (Na2SO4), and the solvent was
evaporated to give a residue that was purified by column chroma-
tography (n-hexane–EtOAc, 60:40) to afford the product 10.
(3R)-3-[1-(tert-Butyl)-1,1-diphenylsilyl]oxy-5-phenylpentan-1-
ol (7)
To a stirred solution of compound 6 (4.5 g, 8.9 mmol) in MeOH (20
mL) was added a catalytic amount of PPTS (0.2 g, 0.89 mmol). The
reaction mixture was stirred at r.t. for 2 h then the MeOH was re-
moved under reduced pressure. The crude residue was purified by
column chromatography (n-hexane–EtOAc, 80:20) to afford 7.
Yield: 0.89 g (85%); colorless liquid; [a]D25 –12.5 (c 1.0, CH2Cl2).
25
Yield: 3.3 g (90%); viscous colorless liquid; [a]D –32.6 (c 0.5,
CHCl3).
IR (film): 3442, 3027, 2931, 1741, 1712, 1496, 1455, 1409, 1368,
1318, 1155, 1029, 750, 701 cm–1.
IR (neat): 3067, 2931, 2857, 1592, 1426, 1364, 1106, 1058, 820
cm–1.
1H NMR (200 MHz, CDCl3): d = 1.29 (t, J = 7.70 Hz, 3 H), 1.56–
1.88 (m, 2 H), 2.60–2.88 (m, 4 H), 3.39 (s, 2 H), 3.96–4.11 (m,
1 H), 4.18 (q, J = 14.4 Hz, 2 H), 7.05–7.43 (m, 5 H).
1H NMR (300 MHz, CDCl3): d = 1.07 (s, 9 H), 1.58 (br s, OH),
1.62–1.92 (m, 4 H), 2.37–2.53 (m, 2 H), 3.56–3.79 (m, 2 H), 3.92–
4.02 (m, 1 H), 6.84–6.91 (m, 2 H), 7.03–7.19 (m, 3 H), 7.30–7.46
(m, 3 H), 7.62–7.72 (m, 5 H).
13C NMR (75 MHz, CDCl3): d = 203.5, 166.8, 141.6, 128.3 (2 × C),
125.8, 66.7, 61.4, 49.8, 49.6, 38.0, 31.6, 14.0.
LC-MS: m/z = 287 [M + Na]+.
LC-MS: m/z = 441 [M + Na]+.
Ethyl (3R,5R)-3,5-Dihydroxy-7-phenylheptanoate (11)
(3R)-3-[1-(tert-Butyl)-1,1-diphenylsilyl]oxy-5-phenylpentanal
(8)
A solution of 10 (0.5 g, 1.89 mmol) in anhyd THF (10 mL) was
chilled in a MeOH–ice bath (–10 °C) and freshly distilled cate-
cholborane (0.56 g, 4.72 mmol) was added. After 5 h, the reaction
mixture was quenched by the addition of anhyd MeOH (1 mL) and
sat. aq sodium potassium tartrate (2 mL). The mixture was allowed
to stir at r.t. for 1 h, and the desired product was purified by column
chromatography (n-hexane–EtOAc, 40:60) to afford the diol 11.
To an ice-cold solution of 2-iodoxybenzoic acid (2.4 g, 8.6 mmol)
in DMSO (3 mL, 42.6 mmol) was added a solution of alcohol 7 (3
g, 7.1 mmol) in anhyd CH2Cl2 (10 mL). The mixture was stirred at
r.t. for 2 h and then filtered through a celite pad and washed with
Et2O (100 mL). The combined organic filtrates were washed with
H2O (100 mL) and brine (50 mL), dried (Na2SO4) and concentrated
Yield: 0.47 g (95%); colorless liquid; [a]D25 –4.8 (c 1.0, CHCl3).
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708
G. Sabitha et al.
PAPER
IR (KBr): 3444, 2923, 2853, 2361, 1729, 1456, 1376, 1159, 1028
cm–1.
13C NMR (75 MHz, CDCl3): d = 32.0, 36.0, 37.5, 38.6, 75.0, 77.0,
126.0, 128.3, 128.5, 141.1, 170.5.
1H NMR (300 MHz, CDCl3): d = 1.28 (t, J = 7.1 Hz, 3 H), 1.51–
1.89 (m, 4 H), 2.43 (t, J = 7.5 Hz, 2 H), 2.62–2.84 (m, 2 H), 3.79–
3.94 (m, 1 H), 4.20–4.26 (m, 1 H), 4.16 (q, J = 14.1 Hz, 2 H), 7.09–
7.27 (m, 5 H).
LC-MS: m/z = 243 [M + Na]+.
Acknowledgements
LC-MS: m/z = 289 [M + Na]+.
K.S. and Ch.S. thank UGC, New Delhi for the award of a fel-
lowship.
Ethyl 2-[(4R,6R)-2,2-Dimethyl-6-phenethyl-1,3-dioxan-
4-yl]acetate (12)
References
To a solution of diol 11 (0.1 g, 3.7 mmol) in anhyd acetone (5 mL),
2,2-dimethoxy propane (0.07 mL, 0.55 mmol) and PPTS (0.009 g,
0.37 mmol) were added. The mixture was stirred at r.t. for 12 h, then
NaHCO3 was added to neutralize the PPTS, and filtered. Removal
of the solvent under reduced pressure gave a residue that was puri-
fied by silica gel column chromatography (n-hexane–EtOAc,
90:10) to afford the acetonide 12.
(1) IICT Communication No: 060910.
(2) Alberts, A. W.; Chen, J.; Kuron, G.; Hunt, V.; Huff, J.;
Hoffman, C.; Rothrock, J.; Lopez, M.; Joshua, H.; Harris, E.;
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Schonberg, G.; Hensens, O.; Hirshfield, J.; Hoogsteen, K.;
Liesch, J.; Springer, J. Proc. Natl. Acad. Sci. USA 1980, 77,
3957.
Yield: 0.1 g (87%); colorless liquid; [a]D25 –8.6 (c 1.0, CHCl3).
(3) Stokker, G. E.; Hoffman, W. F.; Alberta, W.; Cragon, E. J.
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IR (KBr): 3451, 2989, 2936, 1737, 1636, 1454, 1379, 1263, 1165,
1026, 950 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.26 (t, J = 7.1 Hz, 3 H,), 1.36 (s,
3 H), 1.41 (s, 3 H), 1.48–1.86 (m, 4 H), 2.25–2.53 (m, 2 H), 2.55–
2.79 (m, 2 H) 3.69–3.82 (m, 1 H), 4.12 (q, J = 7.1 Hz, 2 H), 4.14–
4.26 (m, 1 H), 7.1–7.24 (m, 5 H).
(4) For some examples of total synthesis, see: (a) Clive, D. L.
J.; Murthy, K. S. K.; Wee, A. G. H.; Prasad, J. S.; da Silva,
G. V. J.; Majewski, M.; Anderson, P. C.; Evans, C. F.;
Haugen, R. D.; Heerze, L. D.; Barrie, J. R. J. Am. Chem. Soc.
1990, 112, 3018. (b) Hagiwara, H.; Nakano, T.; Kon-no, M.;
Uda, H. J. Chem. Soc., Perkin Trans. 1 1995, 777.
(c) Ghosh, A. K.; Lei, H. J. Org. Chem. 2000, 65, 4779.
(d) Bouzbouz, S.; Cossy, J. Tetrahedron Lett. 2000, 41,
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Chem. 2002, 67, 1034. (f) Solladie, G.; Bauder, C.; Rossi, L.
J. Org. Chem. 1995, 60, 7774. (g) Aggarwal, V. K.; Bae, I.;
Lee, H.-Y. Tetrahedron 2004, 60, 9725.
(5) Bleicher, L.; Cosford, N. D. P. Synlett 1995, 1115.
(6) Evans, D. A.; Hoveyda, A. H. J. Org. Chem. 1990, 55, 5190.
(7) Yadav, J. S.; Deshpande, P. K.; Sharma, G. V. M.
Tetrahedron 1990, 46, 7033.
(8) Evans, D. A.; Rieger, D. L.; Gage, J. R. Tetrahedron Lett.
1990, 31, 7099.
13C NMR (75 MHz, CDCl3): d = 14.2, 19.8, 30.1, 31.0, 37.0, 38.0,
41.5, 60.5, 66.0, 67.7, 99.0, 126.0, 128.4, 128.5, 142.0, 171.0.
LC-MS: m/z = 329 [M + Na]+.
(4R,6R)-4-Hydroxy-6-phenethyltetrahydro-2H-2-pyranone (1)
To a stirred solution of 11 (0.3 g, 1.12 mmol) in anhyd CH2Cl2 (5
mL) was added a catalytic amount of PTSA under an N2 atmo-
sphere. The mixture was stirred at r.t. for 6 h, then the reaction was
quenched by the addition of solid NaHCO3 (0.004 g, 0.05 mmol).
The mixture was filtered and the solvent was removed from the fil-
trate under reduced pressure. The residue was purified by column
chromatography (n-hexane–EtOAc, 40:60) to afford 1.
Yield: 0.2 g (84%); colorless solid; [a]D25 +47.2 (c 0.3, CHCl3).
IR (KBr): 3442, 2980, 1730, 1650, 1435, 1370, 1135, 1036 cm–1.
(9) Johnson, C. R.; Senanayake, C. H. J. Org. Chem. 1989, 54,
735.
1H NMR (300 MHz, CDCl3): d = 1.0–1.5 (br s, 1 H), 2.09–1.71 (m,
4 H), 2.59–2.96 (m, 4 H), 4.32–4.39 (m, 1 H), 4.60–4.71 (m, 1 H),
7.11–7.30 (m, 5 H).
Synthesis 2007, No. 5, 705–708 © Thieme Stuttgart · New York