Studies on the synthesis of bitungolides A-E: Synthesis of the C(1-C(12) fragment

Article abstract of DOI:10.1055/s-2008-1078486

Synthesis of the core segment of bitungolides A-E has been achieved in 17 steps and 4.7% overall yield. Six stereogenic centers of bitungolides A-E were established via allylation, dihydroxylation, Myers alkylation, and Evans aldol reaction Thieme Stuttgart.

Full text of DOI:10.1055/s-2008-1078486

LETTER
1665
Studies on the Synthesis of Bitungolides A–E: Synthesis of the C(1)–C(12)
Fragment
S
tudies on the Syn
a
thesis of Bi
n
tungolides
A
f
–E en Xu,a Xing Huo,a Xinyun Li,a Huaiji Zheng,a Xuegong She,*a,b Xinfu Pana
a
Department of Chemistry, State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P. R. of China
Fax +86(931)8912582; E-mail: shexg@lzu.edu.cn
b
State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences,
Lanzhou 730000, P. R. of China
Received 11 March 2008
R1
Abstract: Synthesis of the core segment of bitungolides A–E has
been achieved in 17 steps and 4.7% overall yield. Six stereogenic
centers of bitungolides A–E were established via allylation, dihy-
droxylation, Myers alkylation, and Evans aldol reaction
14
12
5
9
R3
R2
OH OH
O
1
Key words: bitungolide, allylation, dihydroxylation, Myers alkyla-
O
tion, Evans aldol reaction
bitungolide A (1): 12Z,14Z, R1 = Me, R2 = Cl, R3 = OH
bitungolide B (2): 12E,14E, R1 = Me, R2 = Cl, R3 = OH
bitungolide C (3): 12Z,14E, R1 = Me, R2 = Cl, R3 = OH
bitungolide D (4): 12E,14Z, R1 = Me, R2 = Cl, R3 = OH
bitungolide E (5): 12E,14E, R1 = Me, R2 = R3 = OH
bitungolide F (6): 12E,14E, R1 = R2 = R3 = H
Bitungolides A–F (1–6) were isolated in 2002 by Tanaka
and co-workers from Theonella cf Swinhoei, a specimen
of sponge collected in North Sulawesi Indonesia.1 The
bitungolides are also a new class of Theonella metabolites
that weakly inhibit dual-specificity phosphatase VHR.
The activity is of interest since protein phophatases are
considered to be a new class of potential targets for drug
development, and natural products that are able to inhibit
these enzymes might serve as biologically validated start-
ing points for the development of new and selective phos-
phatase inhibitors.2 Structurally, bitungolides consist of a
5,6-dihydropyran-2-one, an anti-1,3-diol and two conju-
gated double bonds attached to a substituted arene. Such
compounds offer a wide range of applications, such as
plant growth inhibitors, pheromones, antifeedal, antifun-
gal, antibacterial, and antitumor agents.3 Up to date, the
total synthesis of bitungolides A–E has not been report-
ed.4 The unique biological activity of bitungolides and
their challenging molecular architecture stimulated our
synthetic interest. Herein, we present an enantioselective
synthesis of the C(1)–C(12) fragment of bitungolides
A–E (Figure 1).
Figure 1 The structure of bitungolides
stereogenic center with a high level of enantio- and dia-
stereoselectivity.
The synthesis of aldehyde 10 began with the known alky-
lation reaction of chloromethylbenzyl ether and the titani-
um enolate of propionyl oxazolidinone 12.5 After
reductive removal of the chiral auxiliary,6 alcohol 11 was
obtained in 85% yield (Scheme 2). Then the primary alco-
hol was oxidized to aldehyde under Swern conditions.7
The resultant aldehyde was exposed to a chelation-con-
trolled, Lewis acid mediated addition of allylsilanes8 to
provide the anti alcohol 13 as the major diastereomer
(dr = 8:1, based on 1H NMR). Homoallylic alcohol 13 was
dihydroxylated9 to furnish diols 14a and 14b (8a/
8b = 2.5:1). Selective protections of the primary hydroxyl
group as it tert-butyldimethyl silyl ether and the second-
ary hydroxyl groups as an acetonide, respectively, yielded
15a and 15b. The acetal carbon in 15a appeared at d =
100.2 ppm in its 13C NMR spectrum. According to litera-
ture precedent,10 compound 15a should be the anti-1,3-
diol which was the desired motif in our synthesis. Where-
as the acetal carbon in compound 15b appeared at d = 98.3
ppm, and compound 15b should be the syn-1,3-diol.
Our retrosynthetic analysis of bitungolides is illustrated in
Scheme 1. Disconnection of C(12)–C(13) bond and lac-
tone C–O ester bond gives commercially available cin-
namic alcohol derivative 7 and the C(1) –C(12) fragment
8, which contains all six stereogenic centers of bitun-
golides. Segment 8 was anticipated to be assembled via
Evans aldol reaction of 10 and followed by Wittig–Hor-
ner–Emmons reaction. Myers alkylation reaction was
adapted to establish the 1,3-anti methyl groups of 10 be-
cause this approach could ensure the construction of the
Deprotection of the benzyl group of 15a with Raney Ni
and H2 afforded alcohol 16 in 90% yield (Scheme 3).
Treatment of 16 with triphenylphosphine, iodine, and im-
idazole produced iodide 17 in 92% yield.11 This set the
stage to install the second chiral methyl group (C6 stereo-
genic center). To this end, alkylation of the enolate of
(–)-pseudoephedrine propionamide 18 with iodide 17
afforded the 1,3-anti-alkylated substrate 19.18 The alde-
hyde 10 was obtained in one step by partial reduction 19
with LiAlH(OEt)3. However, in this transformation, an in-
separable byproduct 20 was also obtained.12 Therefore we
SYNLETT 2008, No. 11, pp 1665–1668
Advanced online publication: 11.06.2008
DOI: 10.1055/s-2008-1078486; Art ID: W04308ST
© Georg Thieme Verlag Stuttgart · New York
x
x
.x
x
.2
0
0
8

1666
Y. Xu et al.
LETTER
R1
OH
R3
14
12
9
5
R2
R3
7
R2
OH OH
O
1
O
O
OMOM
O
bitungolides A–E
HO
CO2Et
8
O
O
O
O
O
TBSO
N
HO
OBn
O
H
Bn
11
10
9
Scheme 1 Retrosynthetic analysis of bitungolides
O
O
turned to a two-step process involving reduction of 19 to
the corresponding alcohol with in situ generated lithium
amidotrihydroborate, followed by IBX oxidation. This se-
quence provided the aldehyde 10 in 85% yield.13,18
OH
c
a, b
N
O
HO
OBn
OBn
Bn
13
12
11
With the aldehyde 10 in hand, the synthesis of key inter-
mediate 21 was achieved by an aldol addition14–16 be-
tween the enolate of oxazolidineone 9 and 10 in the
presence of sparteine. This progress gave only the Evans
syn-adduct 21in 90% yield (Scheme 4).18 Protection of the
resulting secondary alcohol and reductive removal of the
chiral auxiliary gave primary alcohol 23. Oxidation of 23
with IBX provided the corresponding aldehyde 24, which
underwent Wittig–Horner–Emmons reaction to give 26
OH OH
OH OH
d
HO
HO
+
OBn
OBn
14a
14b
e, f
e, f
δ = 98.3 ppm
δ = 100.2 ppm
O
O
O
O
1
TBSO
(Z/E ratio = 8:1, based on H NMR).17 Treatment of 26
TBSO
OBn
OBn
with tetrabutylammonium fluoride (TBAF) furnished the
15a
15b
core segment alcohol 8 of bitungolides A–E.18
Scheme 2 Reagents and conditions: (a) TiCl4, BnOCH2Cl, CH2Cl2,
0 °C, 90%; (b) NaBH4, THF–H2O (2.5:1), 90%; (c) 1. (COCl)2,
DMSO, Et3N, CH2Cl2, –78 °C, 85%; 2. allyltrimethylsilane, SnCl4,
CH2Cl2, –78 °C, 86%; (d) AD-mix-a, t-BuOH–H2O, 99%, 8a/8b
(2.5:1); (e) TBSCl, imidazole, CH2Cl2, 91%; (f) 2,2-dimethoxypro-
pane, PPTS, CH2Cl2, 90%.
In summary, synthesis of key fragment 8, comprising the
C(1)–C(12) backbone of bitungolides have been achieved
in 17 steps in 4.7% overall yield. The cornerstone of syn-
thetic strategy for 8 entailed dihydroxylation, Myers alky-
lation, Evans aldol reaction and Wittig–Horner–Emmons
O
O
O
O
a
TBSO
15a
TBSO
O
b
I
OH
17
16
O
O
O
O
O
c
d
TBSO
Ph
TBSO
N
18
or e
H
OH
19
10
Ph
O
O
O
O
Ph
TBSO
N
N
OH
18
20
Scheme 3 Reagents and conditions: (a) Raney Ni, H2, MeOH, 90%; (b) PPh3, I2, imidazole, CH2Cl2, 92%; (c) LDA, LiCl, 18, THF, –78 °C
to 0 °C, 88%; (d) LiAlH(OEt)3, THF–hexane, 40%; (e) 1. LDA, NH3·BH3, THF, 0 °C; 2. IBX, DMSO, r.t., 85% yield for two steps.
Synlett 2008, No. 11, 1665–1668 © Thieme Stuttgart · New York

LETTER
Studies on the Synthesis of Bitungolides A–E
1667
O
O
N
O
O
O
HO
O
O
O
O
O
O
Bn
9
TBSO
TBSO
N
O
H
a
10
21
Bn
O
O
MOMO
O
O
O
OMOM
b
c
TBSO
N
O
TBSO
TBSO
OH
22
23
Bn
O
O
OMOM
O
O
OMOM
CHO
d
e
TBSO
CO2Et
24
26
O
O
OMOM
f
HO
CO2Et
8
Scheme 4 Reagents and conditions: (a) TiCl4, sparteine, CH2Cl2, 0 °C, 90%; (b) MOMCl, i-Pr2NEt, CH2Cl2, 92%; (c) NaBH4, THF–H2O
(2.5:1), 90%; (d) IBX, DMSO, r.t., 85%; (e) NaH, THF, (PhO)2P(O)CH2CO2Et (25), 70%; (f) TBAF, THF, 90%.
(8) (a) Heathcock, C. H.; Kiyooka, S.; Blumenkopf, T. A.
J. Org. Chem. 1984, 49, 4214. (b) Trost, B. M.; Kondo, Y.
Tetrahedron Lett. 1991, 32, 1613.
(9) Kolb, H. C.; Van Nieuwenhze, M. S.; Sharpless, K. B.
Chem. Rev. 1994, 94, 2483.
(10) (a) Rychnovsky, S. D.; Skalitzky, D. J. Tetrahedron Lett.
1990, 31, 945. (b) Rychnovsky, S. D.; Rogers, B.; Yang, G.
J. Org. Chem. 1993, 58, 3511. (c)Rychnovsky, S. D.; Yang,
G.; Powers, J. P. J. Org. Chem. 1993, 58, 5251.
(d) Rychnovsky, S. D.; Rogers, B. N.; Richardson, T. I. Acc.
Chem. Res. 1998, 31, 9. (e) Evans, D. A.; Rieger, D. L.;
Gage, J. R. Tetrahedron Lett. 1990, 31, 7099.
reaction. We are currently optimizing this synthetic route
to allow diversity of the total synthesis of this type of nat-
ural products and its derivatives, further study of the struc-
ture–activity relationships of the bitungolides will be
reported in due course.
Acknowledgment
We are grateful for the generous financial support by NSFC (QT
program, No. 20572037), NCET-05-0879, and Gansu Science
Foundation (3ZS051-A25-004).
(11) Garegg, P. J.; Samuelson, B. J. Chem. Soc., Perkin Trans. 1
1978, 43, 2866.
References and Notes
(12) (a) Myers, A. G.; Yang, B. H.; Chen, H.; Mckinstry, L.;
Kopecky, D. J.; Gleason, J. L. J. Am. Chem. Soc. 1997, 117,
6496. (b) Myers, A. G.; Yang, B. H.; Chen, H.; Kopeckym,
D. J. Synlett 1997, 457.
(1) Sirirath, S.; Tanaka, J.; Ohtani, I. I.; Ichiba, T.; Rachmat, R.;
Ueda, K.; Usui, T.; Osada, H.; Higa, T. J. Nat. Prod. 2002,
65, 1820.
(2) Brohm, D.; Metzger, S.; Bhargwa, A.; Müller, O.; Lieb, F.;
Waldman, H. Angew. Chem. Int. Ed. 2002, 41, 307.
(3) Davies-Coleman, M. T.; Rivett, D. E. A. Fortschr. Chem.
Org. Naturst. 1989, 55, 1.
(13) Frigerio, M.; Santagostino, M.; Sputore, S.; Palmisano, G.
J. Org. Chem. 1995, 60, 7272.
(14) Gage, J. R.; Evans, D. A. Org. Synth. 1989, 68, 83.
(15) Arya, P.; Qin, H. Tetrahedron 2000, 56, 917.
(16) (a) Crimmins, M. T.; King, B. W.; Tabet, E. A. J. Am. Chem.
Soc. 1997, 119, 7883. (b) Crimmins, M. T.; King, B. W.;
Tabet, E. A.; Chaudhary, K. J. Org. Chem. 2001, 66, 894.
(17) Kaori, A. J. Org. Chem. 1997, 62, 1934.
(4) Ghosh, S.; Kumar, S. U.; Shashidhar, J. J. Org. Chem. 2008,
73, 1582.
(5) (a) Evans, D. A.; Urpi, F.; Somers, T. C.; Clark, J. C.;
Bilodeau, M. T. J. Am. Chem. Soc. 1990, 112, 8215.
(b) Harried, S. S.; Lee, C. P.; Yang, G.; Lee, T. I. H.; Myles,
D. C. J. Org. Chem. 2003, 68, 6646. (c) Crimmins, M. T.;
Carroll, C. A.; King, B. W. Org. Lett. 2002, 2, 597.
(6) Prashad, M.; Har, D.; Kim, H. Y.; Repic, O. Tetrahedron
Lett. 1998, 39, 7067.
(18) Selected Experimental and Spectroscopic Data
Compound 19
A solution of n-BuLi in hexane (1.85 M, 15.8 mL, 29.23
mmol) was added via cannula to a suspension of LiCl (3.94
g, 92.73 mmol) and diisopropylamine (4.4 mL, 32.86 mmol)
in THF (50 mL) at –78 °C. The resulting suspension was
warmed to 0 °C briefly and then was cooled to –78 °C, an
ice-cooled solution of amide (–)-18 (3.39 g, 15.33 mmol) in
THF (50 mL, followed by a 4 mL rinse) was added via
cannula. The mixture was stirred at –78 °C for 1 h, at 0 °C
(7) Mancuso, A. J.; Huang, S. L.; Swern, D. J. Org. Chem. 1978,
43, 2480.
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Y. Xu et al.
LETTER
for 15 min and at 23 °C for 5 min. The mixture was cooled
to 0 °C, and iodide 17 (3.125 g, 7.33 mmol) was added neat
to the reaction via cannula. After being stirred for 18 h at 0
°C, the reaction mixture was treated with half-saturated aq
NH4Cl solution (40 mL) and the resulting mixture was
extracted with EtOAc (4 × 50 mL). The combined organic
extracts were dried over Na2SO4 and concentrated.
Purification of the residue by flash column chromatography
(hexane–EtOAc, 3:1) afforded amide 19 (3.35 g, 88%);
[a]D20 +34.2 (c 7.6, CH2Cl2). IR (KBr): 3385, 2931, 1620,
1465, 1377, 1106, 838 cm–1. 1H NMR (300 MHz, CDCL3):
d = 0.03 (s, 6 H), 0.77 (d, J = 5.7 Hz, 3 H), 0.86 (s, 9 H),
0.96–1.07 (m, 1 H), 0.99 (d, J = 7.2 Hz, 3 H), 1.11 (d, J = 6.9
Hz, 3 H), 1.27 (s, 3 H), 1.28 (s, 3 H), 1.33–1.52 (m, 4 H),
2.71–2.86 (m, 1 H), 2.82 (s, 3 H), 3.42 (dd, J = 15.3, 7.5 Hz,
1 H), 3.51 (dd, J = 10.5, 5.1 Hz, 1 H), 3.59 (dd, J = 10.5, 6.3
Hz, 1 H), 3.73–3.81 (m, 1 H), 4.38 (br s, 1 H), 4.58 (app t,
J = 6.9 Hz, 1 H), 4.70 (br s, 1 H), 7.18–7.31 (m, 5 H).
13C NMR (75 MHz, CDCl3): d = –5.3, –5.2, 14.3, 15.1, 17.1,
18.2, 24.4, 24.6, 25.8, 32.3, 34.6, 35.7, 37.7, 66.1, 67.8, 67.9,
71.2, 76.2, 100.0, 126.2, 126.8, 128.1, 142.5, 179.2. HRMS
[M + H]: m/z calcd for C29H52NO5Si: 522.3609; found:
522.3614.
(d, J = 7.2 Hz, 3 H), 1.29 (s, 3 H), 1.30 (s, 3 H), 1.39–1.65
(m, 5 H), 2.38–2.47 (m, 1 H), 3.44–3.64 (m, 3 H), 3.77–3.86
(m, 1 H), 9.61 (d, J = 1.8 Hz, 1 H). 13C NMR (75 MHz,
CDCl3): d = –5.3, –5.2, 13.1, 14.5, 18.3, 24.5. 24.7, 25.8,
32.5, 33.3, 35.4, 44.1, 66.2, 67.8, 70.8, 100.2, 205.2.
Compound 21
To a cooled (0 °C) solution of the oxazolidinone 9 (364 mg,
1.47 mmol) in CH2Cl2 (10 mL) was added dropwise TiCl4
(0.18 mL, 1.54 mmol) and the mixture allowed to stir for 5
min. Subsequently, (–)-sparteine (0.862 g, 3.68 mmol) was
added to the yellow slurry. The dark red enolate solution was
stirred for 20 min at 0 °C before aldehyde 10 (632 mg, 1.76
mmol) was added dropwise and the mixture stirred for 1 h at
0 °C The reaction was quenched with half-saturated NH4Cl
solution (6 mL). After separation of the layers, the organic
layer was dried (Na2SO4), filtered, and concentrated in
vacuo. Purification of the residue by flash chromatography
(hexane–EtOAc, 8:1) afforded (0.82 g, 90%) of 21, colorless
oil; [a]D20 +28 (c 2.30, CH2Cl2). IR (KBr): 3448, 2932, 1465,
1110, 1036, 704 cm–1. 1H NMR (400 MHz, CDCl3): d = 0.04
(s, 6 H), 0.79 (d, J = 6.8 Hz, 3 H), 0.88 (s, 9 H), 0.90 (d,
J = 6.4 Hz, 3 H), 0.98 (t, J = 7.2 Hz, 3 H), 1.31 (s, 6 H),
1.35–1.44 (m, 2H), 1.52–1.77 (m, 5 H), 1.89–1.97 (m, 1 H),
2.66 (br, 1 H), 2.70 (dd, J = 13.2, 10.4 Hz, 1 H), 3.37 (dd,
J = 13.2, 3.2 Hz, 1 H), 3.47 (dd, J = 15.6, 6.4 Hz, 1 H), 3.54
(dd, J = 10.4, 4.8 Hz, 1 H), 3.61 (dd, J = 10.4, 6.4 Hz, 1 H),
3.78–3.83 (m, 1 H), 4.10–4.15 (m, 1 H), 4.15 (d, J = 4.8 Hz,
2 H), 4.66–4.72 (m, 1 H), 7.22–7.34 (m, 5 H). 13C NMR (100
MHz, CDCl3): d = –5.3, –5.2, 11.8, 14.7, 15.8, 18.3, 19.3,
24.5. 24.7, 25.8, 32.3, 33.8, 34.8, 35.4, 37.9, 46.7, 55.6, 65.8,
66.2, 67.9, 71.2, 76.4,100.2, 127.3, 128.9, 129.3, 135.2,
153.0, 176.2. HRMS [M + Na]: m/z calcd for
Aldehyde 10
n-Butyllithium (1.72 M in hexanes, 19.95 mmol) was added
to diisopropylamine (3.2 mL, 21.95 mmol) in THF (30 mL)
at –78 °C. After stirring the mixture at –78 °C for 10 min and
at 0 °C for 10 min, BH3·NH3 (0.631 g, 20.44 mmol) was
added in one portion. After stirring the mixture at 0 °C for 15
min and then at r.t. for 15 min, (–)-19 (2.597 g, 4.98 mmol)
in THF (10 mL) was added via cannula at 0 °C and the
mixture was stirred at r.t. for 3 h. The reaction was quenched
by slow addition of sat. NH4Cl (20 mL) at 0 °C (gas
evolution!). The aqueous phase was extracted with Et2O
(4 × 50 mL), and the combined organic layers were washed
with brine (25 mL), and dried over Na2SO4. After
concentration in vacuo, purification by flash chromato-
graphy (hexane–EtOAc, 10:1) provided the alcohol (2.00 g,
92% yield) as a colorless liquid; [a]D20 –7.7 (c 5.3, CH2Cl2).
IR (KBr): 3368, 2931, 1465, 1225, 839 cm–1. 1H NMR (400
MHz, CDCl3): d = 0.03 (s, 6 H), 0.80–0.92 (m, 15 H), 1.05–
1.12 (m, 1 H), 1.30 (s, 3 H), 1.31 (s, 3 H), 1.34–1.40 (m, 1
H), 1.52–1.63 (m, 3 H), 1.70–1.75 (m, 1 H), 2.15 (br, 1 H),
3.39–3.50 (m, 3 H), 3.51–3.54 (m, 1 H), 3.58–3.62 (m, 1 H),
3.79–3.83 (m, 1 H). 13C NMR (75 MHz, CDCl3): d = –5.3, –
5.2, 15.0, 15.9, 18.3, 24.5. 24.7, 25.8, 32.2, 33.1, 34.5, 36.0,
66.2, 67.9, 68.6, 71.2, 100.2.
C33H55NO7SiNa: 628.3640; found: 628.3652.
Compound 8
To a stirred solution of (Z)-26 (51 mg, 0.094 mmol) in anhyd
THF (5 mL) at r.t. was added TBAF (59 mg, 0.188 mmol) in
THF (59 mg, 0.188 mmol), and the mixture was stirred for
12 h. Then, H2O (10 mL) was added, the layers were
separated, and the aqueous layer was extracted with EtOAc
(3 × 20 mL). The combined organic layers were dried
(Na2SO4) and concentrated in vacuo. The residue was
purified by column chromatography (hexane–EtOAc, 4:1) to
give 8 (36 mg, 90%) as a colorless oil; [a]D20 –9 (c 1.00,
CH2Cl2). IR (KBr): 3421, 2926, 1718, 1642, 1458, 1378,
1035cm–1. 1H NMR (300 MHz, CDCl3): d = 0.70 (d, J = 7.2
Hz, 3 H), 0.75 (t, J = 7.2 Hz, 3 H), 0.89 (d, J = 6.9 Hz, 3 H),
1.24 (t, J = 7.2 Hz, 3 H), 1.30 (s, 3 H), 1.31 (s, 3 H), 1.29–
1.39 (m, 2 H), 1.48–1.64 (m, 4 H), 1.71–1.81 (m, 1 H), 2.24–
2.28 (m, 1 H), 3.15–3.18 (m, 1 H), 3.36 (s, 3 H), 3.42–3.49
(m, 2 H), 3.52–3.56 (m, 1 H), 3.62–3.72 (m, 1 H), 3.80–3.86
(m, 1 H), 4.11 (q, J = 7.2 Hz, 2 H), 4.60 (s, 2 H), 5.80 (d,
J = 11.7 Hz, 1 H), 5.96 (m, 1 H). 13C NMR (100 MHz,
CDCl3): d = 11.5, 13.3, 14.2, 16.4, 22.8, 24.3. 24.8, 30.7,
33.4, 33.5, 34.7, 42.2, 56.0, 59.8, 65.4, 67.8, 70.9, 87.9, 98.5,
100.3, 120.5, 151.4, 166.2. HRMS: [M + Na]: m/z calcd for
C23H42O7Na: 453.2823; found: 453.2823.
IBX (1.46g, 5.22 mmol) was added to a solution of alcohol
(1.253 g, 3.48 mmol) in DMSO. After 5 h, the reaction
mixture was diluted with H2O, filtered, and extracted with
Et2O, and the organic layers were dried (Na2SO4) and
evaporated. The crude product was purified by flash
chromatography (hexane–EtOAc, 20:1) to give 10 (1.15 g,
92%); [a]D20 –20.7 (c 8.8, CH2Cl2). IR (KBr): 2931, 1728,
1462, 1224, 1138, 839 cm–1. 1H NMR (300 MHz, CDCl3):
d = 0.04 (s, 6 H), 0.83 (d, J = 7.2 Hz, 3 H), 0.87 (s, 9 H), 1.05
Synlett 2008, No. 11, 1665–1668 © Thieme Stuttgart · New York