Studies related to the total synthesis of the sesquiterpene core of the pyrrolobenzoxazine natural products CJ-12662 and CJ-12663

Article abstract of DOI:10.1016/j.tetlet.2009.02.105

A highly effective procedure is reported to synthesize a substituted bicyclo[4.2.0]octenol derivative by regioselective cycloaddition of phenyl-1-propynyl sulfide with cyclohexenone followed by selective reduction of the ketone group and reductive elimina

Full text of DOI:10.1016/j.tetlet.2009.02.105

Tetrahedron Letters 50 (2009) 3359–3362
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Studies related to the total synthesis of the sesquiterpene core
of the pyrrolobenzoxazine natural products CJ-12662 and CJ-12663
Małgorzata Commandeur a, Claude Commandeur a, Michael De Paolis a,
Andrew J. F. Edmunds b, Peter Maienfisch b, Léon Ghosez a,
*
a Institut Européen de Chimie et Biologie, UMR 5248-CNRS, 2, rue Robert Escarpit, 33607 Pessac, France
b Syngenta Crop Protection, Muenchwilen AG WST-820.1.15, Schaffhauserstrasse, CH-4332 Stein, Switzerland
a r t i c l e i n f o
a b s t r a c t
Article history:
A highly effective procedure is reported to synthesize a substituted bicyclo[4.2.0]octenol derivative by
regioselective cycloaddition of phenyl-1-propynyl sulfide with cyclohexenone followed by selective
reduction of the ketone group and reductive elimination of phenylsulfonyl group. The strained
cyclobutene ring was then engaged in a ring-opening/cross metathesis sequence in the presence of
Hoveyda–Grubbs 2nd generation catalyst. The synthesis serves as a model study toward the synthesis
of the sesquiterpene diol portion of the terpenoid pyrrolobenzoxazine alkaloids, CJ-12662 and CJ-12663.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 10 February 2009
Accepted 13 February 2009
Available online 21 February 2009
Keywords:
[2+2] Cycloaddition
Ring-opening metathesis/cross metathesis
Phenyl-1-propynyl sulfide
Cyclohexenone
Stereoselectivity
TMSNTf2
Terpenoid pyrrolobenzoxazine alkaloid
CJ-12662
CJ-12663
Natural product alkaloids of the general formula A (Fig. 1) have
been isolated from the fermentation broth of Aspergillus fischeri var.
thermomutatus ATCC 18618.1 They belong to a unique class of
terpenoid pyrrolobenzoxazine alkaloids which display broad anti-
parasitic and antibiotic properties. A single-crystal structure deter-
OH
O
R
HO
N
N
O
AcO
A
O
H
H
H
mination established that CJ-12662 and CJ-12663 contain
a
pyrrolobenzoxazine carboxylic acid esterified with a sesquiterpene
Alkaloid core
Terpenoid core
diol (Fig. 1).2
R = Cl, CJ-12662
R = H, CJ-12663
The alkaloid cores of CJ-12662 and CJ-12663 have been synthe-
sized by the groups of Barrett and Baldwin, respectively.2,3 There
are currently no reports on the total synthesis of the sesquiterpene
core of these natural products. This challenging terpenoid structure
is a cis-decalin containing no less than six stereocenters and three
contiguous oxygenated functional groups. The general strategy we
have envisioned for the total synthesis of this terpene is depicted in
Scheme 1. We had planned to construct ring A and the cis-diol by a
stereodirected pinacol coupling (disconnection a).
The most challenging part of the synthesis is the stereoselective
construction of the two vicinal olefinic side chains with simulta-
neous control of the configuration of the double bond of the allylic
acetate. The cis-relationship between the two vicinal carbon chains
Figure 1. Structure of terpenoid pyrrolobenzoxazine alkaloids CJ-12662 and
CJ-12663.
could be established by a regio- and stereoselective cycloaddition
reaction (step d) of an activated acetylene to the less hindered face
of (R)- 6-methylcyclohexenone. A ring opening metathesis of the
cyclobutene ring coupled with a cross metathesis (step c) with
an allylic acetate derived (step e) from (R)-glyceraldehyde would
generate an advanced intermediate for the pinacol coupling. This
Letter reports some model studies on the cycloaddition and
ROM/CM reactions performed on cyclohexenone.
[2+2] Cycloadditions of acetylenes to electron-deficient olefins
have been studied by several groups.4 Best yields have been ob-
tained in the presence of a Lewis acid catalyst. We selected
* Corresponding author. Tel.: +33 5 4000 2217/2223; fax: +33 5 4000 2215.
E-mail address: l.ghosez@iecb.u-bordeaux.fr (L. Ghosez).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.02.105

3360
M. Commandeur et al. / Tetrahedron Letters 50 (2009) 3359–3362
O
O
SPh
O
ROM/CM
H
H
TMSNTf2
90%
O
PhS
HO
HO
O
B
O
AcO
O
AcO
A
H
a
b
AcO
1
2
O
O
Scheme 3. Cycloaddition step.
+
O
c
OAc
O
S
O
O
S
OR
O
Ph
Ph
d
e
H
H
H
H
H
H
PhS
a
b
X
C
O
O
O
O
H
+
O
C
O
2
3
4: R = H
Me
c
X = SPh
5: R = TES
Scheme 1. Retrosynthetic analysis of the terpenoid core of CJ-12662 and CJ-12663.
d,e
f
phenyl-1-propynyl sulfide (X = PhS) as acetylene partner to ensure
(a) the activation of the triple bond, (b) the control of the regiose-
lectivity of the cycloaddition, (c) an easy replacement of the X sub-
stituent by hydrogen. Phenyl-1-propynyl sulfide 1 was prepared in
two steps inspired by literature procedure (Scheme 2).5
OH
H
H
It was found that the cycloaddition of 1 with cyclohexenone
took place readily in the presence of 10 mol % of TMSNTf2 (Scheme
3). A single regio- and stereoisomer (2) was obtained in 90% yield
after one hour at À40 °C.6 Here again TMSNTf2 was found superior7
to TMSOTf and the corresponding Brönstedt acids HOTf and HNTf2.
These showed a much lower catalytic activity (reaction time >
1 day) and gave lower yields (45 to 65%).
6
Scheme 4. Reagents and conditions: (a) m-CPBA, CH2Cl2, 0 °C, 10 min; (b) NaBH4,
MeOH, À40 °C, 1 h; (c) TESCl, imidazole, CH2Cl2, 0 °C, rt, 12 h (87% for 3 steps); (d)
activated Mg, MeOH, 50 °C, 1 h; (e) TBAF, THF, 2 h (91% for 2 steps); (f) steps (a), (b)
and (d) sequentially performed without purification of any intermediate.
We then explored the ring-opening metathesis/cross metathe-
sis sequence by reacting adduct 2 with acrylonitrile,
a-methyl
acrylonitrile or 2-methylprop-2-enol in the presence of Grubbs
and Hoveyda–Grubbs 2nd generation catalysts.8,9 Compound 2
was recovered unaffected in each case (Scheme 3). Precedents for
metathesis reaction with substrates carrying sulfide had however
been reported.10 Thus, the poor reactivity of 2 probably resulted
from the high degree of substitution of the cyclobutene double
bond. Therefore, the phenylsulfide group has to be removed before
the ROM/CM reactions.
To this aim, oxidation of 2 with m-CPBA gave the corresponding
phenylsulfone 3 in 72% yield (Scheme 4, step a). Treatment of 3
with activated magnesium turnings resulted in a slow reductive
elimination of the phenylsulfone group with concomitant reduc-
tion of the ketone group to yield 6 (29%) as a mixture of epimeric
alcohols.11 A much better procedure consisted of a stereoselective
reduction of the ketone group of crude 3 with sodium borohydride
(step b) yielding a single alcohol 4 where the OH group is cis with
respect to the cyclobutene ring (86% for two steps). The relative
configuration of 4 has been confirmed by X-ray diffraction analysis
(Fig. 2).12
Figure 2. Ortep drawing of 4.
Subsequent removal of the phenyl sulfone with activated mag-
nesium turnings (step d) led to 6 but again only in poor yields.
However, it was found that protection of the alcohol function (step
c) followed by treatment of the resulting triethylsilyl ether 5 with
activated magnesium turnings in methanol at 50 °C (step d) gave
the target alcohol 6 after desilylation with tetrabutylammonium
fluoride (step e). Optimization of this reaction sequence (Scheme
4, step f) led to a 70% yield for the synthesis of diastereomerically
pure 6 from 2 without purification of any intermediate.
SH
S
S
a)
b)
The ring opening metathesis of unsubstituted and monosubsti-
tuted double bonds of cyclobutenes followed by cross-metathesis
with unsubstituted terminal olefins has been extensively studied
by Snapper et al.13 The factors effecting regioselectivity of the ring
opening and the stereoselectivity of the formation of the new dou-
ble bond have been studied in detail, and have shown to be depen-
1
Scheme 2. Reagents and conditions: (a) NaOH (1.7 equiv), propargyl bromide
(1 equiv), TBAB (10 mol %), H2O, 0 °C, 4 h; (b) t-BuOK (1.5 equiv), t-BuOH, 50 °C,
10 min (86%, 2 steps).

M. Commandeur et al. / Tetrahedron Letters 50 (2009) 3359–3362
3361
OH
n
n
OH
5 equiv.
RO
Hoveyda-Grubbs
2nd gen. (10 mol%)
+
Solvent [0.2M]
OR
sealed tube, 22h
8: R = H, n = 1
9: R = TES, n = 1
1 equiv.
10: R = H, n = 2
11: R = TES, n = 2
6: R = H
7: R = TES
Scheme 5. Tandem ring opening metathesis/cross metathesis reactions.
dant on the nature and degree of substitution of the cyclobutene
double bond as well as that of the olefin partner. Further examples
of the ROM/CM sequences have been reported by the groups of
Harrity14 and Szeimies.15 To the best of our knowledge the tandem
ROM/CM of a monosubstituted cyclobutene double bond with a
1,1-disubstituted olefin has not been described.16
Fivefold excesses of 2-methyl-2-propenol were reacted with
compound 6 or the corresponding triethylsilyl ether 7 in the pres-
ence of 10 mol % of Hoveyda–Grubbs 2nd generation catalyst
(Scheme 5, Table 1).17 In all cases the reactions were totally regio-
selective but, the stereoselectivity was poor in all but one case.
Stereoisomers Z-8 (the required isomer for pinacol coupling) and
E-8 were separated by chromatography over silica gel and were
recrystallized from chloroform.12 The structure and configuration
of both isomers were confirmed by a single-crystal X-ray diffrac-
tion analysis (Figs. 3 and 4).
Figure 3. Ortep drawing of Z-8.
Examination of Table 1 shows that both free alcohol 6 and the
corresponding TES ether 7 gave similar results (entries a and b).
Increasing the temperature led to a lower yield but a slightly better
stereoselectivity in favour of the undesired isomer E-8 (entry c).
The best yields were obtained when the reaction was conducted
at room temperature but the stereoselectivity was not improved
(entry d). Interestingly 3-methyl-3-butenol didn’t react at room
temperature, extended reaction time led to partial decomposition
of cyclobutene 6 (entry g). At 60 °C a mixture of isomers was ob-
tained in moderate yield (entry f). Surprisingly, E-stereoselectivity
was observed for the ROM/CM of 7 with 3-methyl-3-butenol, but
yields dramatically dropped (entry e).
The above results are very promising in terms of implementing
steps c and d of our retrosynthetic scheme (Scheme 1). In sum-
mary, we have developed a simple synthetic protocol for the
attachment of the two cis-related carbon chains using a [2+2]
cycloaddition to an enone. This should be applicable to a wide
diversity of cyclic enones. The ROM/CM step is regiospecific but
suffers from a poor stereoselectivity. However, in our model exper-
iments, yields were high and after chromatographic separation, the
desired (Z) isomer could be obtained in 42% yield.
Figure 4. Ortep drawing of E-8.
Acknowledgments
This work was generously supported by Syngenta Crop Protec-
tion. We also thank IECB for the technical facilities. We would also
like to acknowledge the contribution of K. Bathany (mass spectra)
and B. Kauffmann (X-ray diffraction analyses).
Table 1
ROM/CM of compound 6 and 7
Entry
R
n
Solvent
Temp (°C)b
Yield (%)
Z/E (NMR)
a
b
c
d
ea
f
TES
H
H
H
TES
H
1
1
1
1
2
2
2
DCM
DCM
DCE
DCM
DCM
DCM
DCM
60
60
90
rt
60
60
rt
60 (9)
47 (8)
40 (8)
85 (8)
15(11)
31(10)
no reaction
1/1
1/1
1/2
1/1
<1/20
1/3
References and notes
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M. J. Org. Chem. 2004, 69, 7875–7879.
g
H
3. Schwaebisch, D.; Tchabanenko, K.; Adlington, R. M.; Cowley, A. M.; Baldwin, J.
E. Chem. Commun. 2004, 2552–2553. See also: Kamenecka, T. M.; Danishefsky,
S. J. Chem. Eur. J. 2001, 7, 41–63.
a
15 mol % HG2nd were used.
Reaction performed in sealed tube.
b

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M. Commandeur et al. / Tetrahedron Letters 50 (2009) 3359–3362
4. Reactions with alkynyl amines: (a) Ficini, J.; Touzin, A. M. Tetrahedron Lett.
1972, 13, 2093–2096; Ficini, J. Tetrahedron 1976, 32, 1449–1485; reactions with
alkynyl sulfides (b) Hayashi, Y.; Narasaka, K. Chem. Lett. 1990, 1295–1298;
Narasaka, K.; Hayashi, Y.; Shimadzu, H.; Niihata, S. J. Am. Chem. Soc. 1992, 114,
8869–8885; Takenaka, Y.; Ito, H.; Hasegawa, M.; Iguchi, K. Tetrahedron 2006,
62, 3380–3388; reactions with silyloxy alkynes (c) Sweis, R. F.; Schramm, M. P.;
Kozmin, S. A. J. Am. Chem. Soc. 2004, 126, 7442–7443; reactions with alkynyl
selenoate (d) Koketsu, M.; Mizutani, K.; Ogawa, T.; Takahashi, A.; Ishihara, H. J.
Org. Chem. 2004, 69, 8938–8941.
5. (a) Lindén, A. A.; Krüger, L.; Bäckvall, J.-E. J. Org. Chem. 2003, 68, 5890–5896; (b)
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1996, 52, 7391–7420; (c) Guillerm, G.; Guillerm, D.; Vandenplas-Witkowki, D.;
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Med. Chem. 2001, 44, 2743–2752.
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9611; (d) Snapper, M. L.; Tallarico, J. A.; Randall, M. L. J. Am. Chem. Soc. 1997,
119, 1478–1479; (e) Tallarico, J. A.; Bonitatebus, P. J., Jr.; Snapper, M. L. J. Am.
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Lett. 2000, 41, 9685–9689; (g) Snapper, M. L.; Schrader, T. O. J. Am. Chem. Soc.
2002, 124, 10998–11000; (h) Snapper, M. L.; Pandya, B. A. J. Org. Chem. 2008,
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8072; (j) White, B. H.; Snapper, M. L. J. Am. Chem. Soc. 2003, 125, 14901–14904.
14. Bassindale, M. J.; Hamley, P.; Harrity, J. P. A. Tetrahedron Lett. 2001, 42, 9055–
9057.
15. Feng, J.; Szeimies, G. Eur. J. Org. Chem. 2002, 2942–2947.
16. (a) Schrader, T. O.; Snapper, M. L.. In Handbook of Metathesis; Grubbs, R.
H., Ed.; Wiley-VCH: Weinheim, 2003; Vol. 2, pp 205–237; (b) Nicolaou, K.
C.; Bulger, P. G.; Sarlah, D. Angew. Chem. Int. Ed. 2005, 44, 4490–4527; (c)
Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413–4450; (d) Fürstner, A.
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Angew. Chem. Int. Ed. 2003, 42, 1900–1923; (f) Grela, K. Angew. Chem. Int.
Ed. 2008, 47, 5504–5507.
6. Procedure for [2+2] cycloaddition for the synthesis of 2: Allyltrimethylsilane
(37
lL, 0.23 mmol, 0.12 equiv) was added at room temperature to a 0.5 M
solution of HNTf2 in CH2Cl2 (390
lL, 0.194 mmol, 0.1 equiv) (Aldrich, cat. no.
15199) placed in a dried Schlenk tube under argon atmosphere. After 20 min,
the mixture was diluted with 9.7 mL of anhydrous CH2Cl2 (0.2 M) and cooled
17. Procedure for the synthesis of 8: To a dried, sealed tube under argon atmosphere
cyclobutene 6 (397 mg, 2.87 mmol, 1 equiv), anhydrous CH2Cl2 (14.35 mL,
0.2 M) and 2-methyl-2-propenol (1.21 mL, 14.35 mmol, 5 equiv) were
introduced and the reaction mixture was degassed by bubbling a moderate
stream of argon. Subsequently, Hoveyda–Grubbs 2nd generation catalyst
(180 mg, 0.28 mmol, 0.1 equiv) as a CH2Cl2 solution was added and reaction
mixture was stirred at room temperature for 22 h. After completion of the
reaction, monitored by TLC, ethyl vinyl ether (2.14 mL, 22.4 mmol, 80 equiv/
catalyst) was added and stirring was continued at room temperature for
30 min. Then mixture was concentrated under vacuum and dissolved again in
CH2Cl2 (100 mL, 0.03 M) followed by addition of methanol solution of
isocyanide potassium salt18 (152 mg, 1.23 mmol, 4.4 equiv/catalyst, in 6 mL
of methanol). After stirring at room temperature for 30 min. mixture was
concentrated under vacuum, triturated three times with methanol and
filtrated. The methanol extracts were combined, concentrated and finally
purified by chromatography over silica gel using CH2Cl2/acetone = 8/1; 5:1
then 1:1 as eluent. The two stereoisomers E-8 and Z-8 were isolated
respectively with 43% and 42% yield. A side-product, resulting from ROM/CM
reaction between the cyclobutene 6 and the aromatic ligand of catalyst, was
isolated with 10% yield. Z-8: 1H NMR (CDCl3, 300 MHz): d 5.28 (d, J = 10.8 Hz,
1H, @CH), 4.72 (s, 1H, part of @CH2), 4.61 (s, 1H, part of @CH2), 4.24 (d,
J = 11.7 Hz, 1H, part of CH2OH), 3.78–3.70 (overlapped d, J = 11.4 Hz, part of
down to À40 °C. Subsequently, cyclohex-2-en-1-one (188
lL, 1.94 mmol,
1 equiv) was added dropwise and was followed after 10 min by phenyl-1-
propynyl sulfide 1 (0.575 g, 3.88 mmol, 2 equiv), and reaction was continued
1 h at À40 °C. After completion, monitored by TLC, the reaction mixture was
diluted with CH2Cl2 (10 mL), quenched with saturated solution of NaHCO3
(25 mL) at À40 °C, and next moved to room temperature and stirred for 30 min.
The two layers were separated, and aqueous phase was extracted three times
with CH2Cl2 (15 mL). The combined organic layers were dried over Na2SO4,
then filtrated and concentrated under vacuum. The crude compound was
purified by flash chromatography using PE/EE: 20/1, 15/1, 10/1, 5/1 then 1/1 as
eluent to give 0.429 g of the desired cycloadduct 2 as a pale yellow oil (90%
yield). Pure 1-propynyl-phenylsulfide 1 (161 mg, 28%) was recovered. 1H NMR
(400 MHz, (CD3)2CO): d 7.39 (d, J = 7.2 Hz, 2H, HAr-ortho), 7.33 (t, J = 7.2 Hz, 2H,
HAr-meta), 7.26 (d, J = 7.2 Hz, 1H, HAr-para), 3.38 (br s, 1H, CHC@O), 3.28 (br s, 1H,
CHCMe), 2.34 (m, 1H, part of CH2C@O), 2.14–1.96 (m, 3H, part of CH2C@O and
CH2CHCMe), 1.82–1.69 (m, 5H, CH2CH2C@O and CH3); 13C NMR (100 MHz,
(CD3)2CO): d 208.9 (C@O), 158.2 (@CMe), 135.7 (@CS), 132.0 (CAr-ipso), 130.8
(CAr-meta), 128.5 (CAr-ortho), 127.5 (CAr-para), 56.5 (CHC@O), 44.8 (CHCMe), 41.2
(CH2C@O), 25.5 (CH2CHCMe), 19.4 (CH2CH2C@O), 13.6 (CH3); full assignment
based on 2D NMR experiments (HMQC, HMBC); HRMS (MS ES+, Na) Calcd, for
C15H17OS: 245.1000, found: 245.1010,
D = 4 ppm.
7. Mathieu, B.; de Fays, L.; Ghosez, L. Tetrahedron Lett. 2000, 41, 9561–9564;
Mathieu, B.; Ghosez, L. Tetrahedron 2002, 58, 8219–8226; Takasu, K.; Miyakawa,
Y.; Ihara, M.; Tokuyama, H. Chem. Pharm. Bull. 2008, 56, 1205–1206; Takasu, K.;
Hosokawa, N.; Inanaga, K.; Ihara, M. Tetrahedron Lett. 2006, 47, 6053–6056;
Takasu, K.; Ishii, T.; Inanaga, K.; Ihara, M. Org. Synth. 2006, 83, 193–199; Inanaga,
K.; Takasu, K.; Ihara, M. J. Am. Chem. Soc. 2005, 127, 3668–3669.
8. Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 953–956.
9. Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2000,
122, 8168–8179.
CH2OH and m, 1H, CHOH), 3.15–3.09 (m, 1H, CHCHOH), 2.73 (br s, 2H, 2 OH),
*
2.09 (m, 1H, CHC@CH2), 1.85 (s, 3H, CH3CCH2OH), 1.65 (s, 3H, CH3C@CH2),
1.54–1.24 (m, 6H, CH2CH2CH2CHOH); 13C NMR (CDCl3, 75 MHz):
d 147.3
(C@CH2), 140.1 (@CCH2OH), 122.6 (C@CH), 109.7 (C@CH2), 72.8 (CHOH), 61.4
(CH2OH), 46.1 (CHCHOH), 41.8 (CHC@CH2), 30.6 (CH2CHOH), 23.9
(CH2CHC@CH2), 23.8 (CH2CH2CHOH), 23.4 (CH3C@CH2), 22.1 (CH3C@CH); full
assignment based on 2D NMR experiments (HMQC, HMBC); HRMS (MS ES+,
Na) calcd, for C13H22O2Na: 233.1517, found: 233.1518,
D
= 0.2 ppm. E-8: 1H
NMR (CDCl3, 400 MHz): d 5.39 (d, J = 10.8 Hz, 1H, @CH), 4.69 (s, 1H, part of
@CH2), 4.57 (s, 1H, part of @CH2), 3.98 (s, 2H, CH2OH), 3.70 (m, 1H, CHOH), 3.09
(m, 1H, CHCHOH), 2.57 (br s, 1H, OH), 2.21 (br s, 1H, OH), 2.11 (br s, 1H,
CHC@CH2), 1.70 (s, 3H, CH3C@CH2), 1.66 (s, 3H, CH3C@CH), 1.51–1.33 (m, 6H,
10. Shon, Y.-S.; Lee, R. Tetrahedron Lett. 1997, 38, 1283–1286; Liu, Z.; Rainier, J. D.
Org. Lett. 2005, 7, 131.
11. Brown, A. C.; Carpino, L. A. J. Org. Chem. 1985, 50, 1749–1750.
12. Crystallographic data (excluding structure factors) for compounds 4, Z-8 and E-
8 have been deposited with the Cambridge Crystallographic Data Centre as
supplementary publication Nos. 719864, 719863 and 719862, respectively.
Copies of the data can be obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK, (fax: +44-(0)1223-336033 or e-mail:
deposit@ccdc.cam.ac.Uk).
CH2CH2CH2CHOH); 13C NMR (CDCl3, 100 MHz):
d 147.4 (C@CH2), 140.6
(@CCH2OH), 119.8 (C@CH), 109.5 (C@CH2), 73.6 (CHOH), 69.0 (CH2OH), 46.4
(CHCHOH), 42.1 (CHC@CH2), 30.5 (CH2CHOH), 24.1 (CH2CHC@CH2), 24.0
(CH2CH2CHOH), 22.2 (CH3C@CH2), 14.5 (CH3C@CH); full assignment based on
2D NMR experiments (HMQC, HMBC); HRMS (MS ES+, Na) calcd, for
C13H22O2Na: 233.1517, found: 233.1508,
D = 4.1 ppm.
13. (a) Tallarico, J. A.; Randall, M. L.; Snapper, M. L. Tetrahedron 1997, 53, 16511–
16520; (b) Randall, M. L.; Snapper, M. L. J. Mol. Catal. 1998, 133, 29–40; (c)
18. Galan, B. R.; Kalbarczyk, K. P.; Szczepankiewicz, S.; Keister, J. B.; Diver, S. T. Org.
Lett. 2007, 9, 1203–1206.