Facile conversion of cyclopropanols into linear conjugate enones

Article abstract of DOI:10.1002/ejoc.201402175

A practical method for the conversion of 1,2-disubstituted cyclopropanols derived from Kulinkovich cyclopropanation into linear enones was developed. The approach features regioselective cleavage of the cyclopropane rings in EtOH at ambient temperature with inexpensive and readily available Co(acac)₂ as the catalyst and air as the reagent. The crude intermediate peroxides were directly reduced with Ph₃P to afford the corresponding -hydroxy ketones, which, on mesylation and -elimination performed in a one-pot manner, furnished the end products in good to excellent yields after only one chromatography step at the end of the whole sequence. Although the reaction of esters with alkenes to afford cyclopropanols is well known, the potential of this reaction as a general coupling tool for connecting two multifunctional fragments into a larger linear entity as often required in total synthesis is probably not so clear to many investigators. The present procedure may help to change this perception. Copyright

Full text of DOI:10.1002/ejoc.201402175

FULL PAPER
DOI: 10.1002/ejoc.201402175
Facile Conversion of Cyclopropanols into Linear Conjugate Enones
Wei-Bo Han,[a] Shao-Gang Li,[a] Xiao-Wei Lu,[a] and Yikang Wu*[a]
Keywords: Synthetic methods / C–C coupling / Enones / Alkenes / Esters / Alcohols
A practical method for the conversion of 1,2-disubstituted cy-
clopropanols derived from Kulinkovich cyclopropanation into
linear enones was developed. The approach features re-
gioselective cleavage of the cyclopropane rings in EtOH at
ambient temperature with inexpensive and readily available
Co(acac)2 as the catalyst and air as the reagent. The crude
intermediate peroxides were directly reduced with Ph3P to
afford the corresponding β-hydroxy ketones, which, on mes-
ylation and β-elimination performed in a one-pot manner,
furnished the end products in good to excellent yields after
only one chromatography step at the end of the whole se-
quence.
atoms onto the substrates rather than to connect two major
fragments. Examples using substituted ethylenes are
scant,[3,4] presumably because of the regioselectivity prob-
lem at the required ring-opening step.[3,5] It thus seems that
the lack of mild and effective means for cleaving the three-
membered ring with satisfactory regioselectivity is a bottle-
neck for broader employment of the Kulinkovich reaction
as a practical tool for connecting complex multifunctional
fragments into longer linear structures. The limited number
of available choices, along with needs that arose from our
own synthetic endeavours, prompted us to seek new meth-
ods that were suitable for cleaving Kulinkovich cycloprop-
anols into their corresponding linear structures, especially
those with multiple functionalities in the substituents on the
three-membered rings.[6] Our efforts along these lines led to
some pleasing results with the system Co(acac)2 {cobalt(II)
acetylacetonate}/O2 (air)/EtOH, which are detailed here.
Introduction
The Kulinkovich cyclopropanation[1] is a reaction that
can be conducted under mild relatively conditions that has
found numerous applications in organic synthesis in recent
years. The functional groups to be coupled, in many cases
an ester and a terminal alkene, can be carried unmasked
through several transformation steps before the eventual ex-
ecution of the cross coupling. These features make the Kul-
inkovich reaction, in combination with a suitable ring-open-
ing transformation if the cyclopropane ring is not part of
the target structures (see below), a tool with distinct poten-
tial for connecting two multifunctional fragments (Figure 1)
to provide longer linear structures.
Results and Discussion
The combination of Co(acac)2, O2, and Et3SiH was first
introduced in 1989 by Isayama and Mukaiyama as a novel
way to install a silylperoxyl group onto alkenes.[7] Since
then, it has been successfully applied in many syntheses of
organic peroxides.[8,9] A range of natural and synthetic or-
ganic peroxy compounds, often with antimalarial activity,
were prepared by using this reaction to introduce the per-
oxy bonds.
Figure 1. A schematic illustration showing the potential of the Kul-
inkovich cyclopropanation as a tool for coupling two major frag-
ments into a longer linear structure, an operation often encoun-
tered in multistep syntheses.
However, it should also be noted that until now a large
fraction of synthetically significant reactions that are fol-
lowed by a ring-opening step involve only unsubstituted
ethylene (often formed in situ from EtMgBr),[2] and the Ku-
linkovich reaction was employed to append two carbon
According to the mechanisms[9] postulated in the early
2000’s by Nojima et al. and O’Neill et al. (Figure 2), the
triplet O2 is installed onto the alkene by coupling with a
carbon-centred radical generated through the addition of
HCoIII followed by homolysis of the Co–C bond. Because
Et3SiH plays a critical role in the generation of HCoIII, it
appears indispensable for the successful realization of the
whole reaction. Indeed, until now Et3SiH has been included
in all the literature precedents.
[a] State Key Laboratory of Bioorganic and Natural Products
Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences,
345 Lingling Road, Shanghai 200032, China
E-mail: yikangwu@sioc.ac.cn
www.sioc.ac.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402175.
Eur. J. Org. Chem. 2014, 3841–3846
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W.-B. Han, S.-G. Li, X.-W. Lu, Y. Wu
FULL PAPER
Table 1. Initial exploration of the cleavage of 1a with Co(acac)2/O2
followed by Ph3P reduction of the peroxy bond (cf. Scheme 1).
Entry Conditions[a]
Yield
(%)
Ratio
2/3[b]
1
2
3
4
5
6
Co(acac)2 (1 mol-%)/O2/EtOH/12 h[c] 81
19:1
19:1
19:1
20:1
23:1
Co(acac)2 (1 mol-%)/air/EtOH/7 h
Co(acac)2 (5 mol-%)/air/EtOH/5 h
81
83
Co(acac)2 (5 mol-%)/air/EtOH/1.5 h 87
Co(acac)2 (5 mol-%)/air/EtOH/1.5 h 87[d]
Co(acac)2 (5 mol-%)/air/CH2Cl2/1 h complex mixture
[a] All runs (except entry 1) were performed in an open flask at
ambient temperature with the reduction performed in CH2Cl2 after
removal of EtOH. [b] Measured by 1H NMR spectroscopic analysis
of the crude product mixture. [c] O2 balloon. [d] Reduction of the
peroxides was performed in EtOH/CH2Cl2 (1:4).
Figure 2. The O2/Co(acac)2/Et3SiH mediated silylperoxidation.[9b]
For clarity, the ligands on the CoII and CoIII species are not shown.
Use of air (i.e., conducting the reaction in an open flask)
instead of O2 did not cause any discernible difference
(Table 1, entry 2). Therefore, all subsequent runs were car-
ried out in an open flask. Increasing the amount of added
catalyst from 1 to 5 mol-% significantly shortened the reac-
tion time, while the yield and the product ratio remained
essentially unchanged (Table 1, entries 3 and 4).
Because concentrating the crude mixture (removal of the
EtOH) before reduction with Ph3P was potentially danger-
ous because of the presence of peroxides, we then tried to
skip this operation. To our satisfaction, addition of CH2Cl2,
which was required for dissolving Ph3P, to the reaction mix-
ture followed by treatment with Ph3P worked equally well
(Table 1, entry 5). The potential risk of explosion during
concentration was thus eliminated. However, it was also
noted that the use of CH2Cl2 instead of EtOH as the reac-
tion solvent from the beginning was not rewarding (despite
the fact that most previous alkene silylperoxidations were
performed in CH2Cl2), because a rather complex product
mixture resulted (Table 1, entry 6) under otherwise identical
conditions. The conditions employed in Table 1, entry 5 ap-
peared to be the most satisfactory, and these were employed
in all subsequent experiments.
Nevertheless, it still seems to us that interaction of Co-
(acac)2 with O2 and cyclopropanol may result in oxygen-
centred radical species (see below), with or without added
Et3SiH, and thus may initiate subsequent reactions in a
manner similar to those in Kulinkovich’s[10] conversion of
cyclopropanols into linear epoxy ketones mediated by MnII
abietate (in which the hydroperoxy intermediate reacted
with the carbanion generated at the carbon α to the ketone
carbonyl group by treatment with KOH).
Our initial explorations were performed on a readily ac-
cessible 1,2-disubstituted cyclopropanol 1a (Scheme 1). As
summarized in Table 1, treatment of 1a with 1 mol-% Co-
(acac)2 in EtOH under O2 (balloon) at ambient temperature
for 12 h led to complete disappearance of 1a. The product
mixture apparently contained several components, presum-
ably because of the coexistence of the two reaction paths
and ketone–hemiketal interconversion. Reduction of the
peroxy bonds in the crude products (after removal of EtOH
by rotary evaporation) with Ph3P in CH2Cl2 indeed af-
forded a simplified mixture that contained 2 and 3 in a 19:1
ratio (Table 1, entry 1) as measured by 1H NMR spec-
troscopy.[11]
A plausible mechanism for the observed facile conversion
of cyclopropanols into hydroperoxides is shown in Figure 3.
Scheme 1. Reagents and conditions: (a) Co(acac)2, O2, EtOH, room
temp.; (b) Ph3P, CH2Cl2, r.t.; (c) MsCl, DMAP, Et3N, r.t., cf. text;
Co(acac)2 = cobalt(II) acetylaceonate, MsCl = methanesulfonyl
chloride, DMAP = 4-(dimethylamino)pyridine.
Figure 3. A possible mechanism for the Co(acac)2-induced cleavage
of the Kulinkovich cyclopropanols. For clarity, only one of the two
possible ring-opening intermediate carbon-centred radicals (Path A
in Scheme 1) is shown; SET = single electron transfer.
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Eur. J. Org. Chem. 2014, 3841–3846

Facile Conversion of Cyclopropanols into Linear Conjugate Enones
The added Co(acac)2 was first oxidized by O2 (or air) to more stable carbon-centred radical, which readily trapped
afford a CoIII species. Subsequent single electron transfer a molecule of O2 to give a hydroperoxy radical. Finally, the
from the starting cyclopropanol to CoIII generated the tran- hydroperoxy radical was converted into product hydroper-
sient oxy radical of the cyclopropanol and a proton. The oxide either by SET followed by protonation or simply
highly reactive oxygen-centred radical then rearranged with through hydrogen abstraction.
opening of the strained three-membered ring to afford a
To facilitate the isolation and characterisation of the
products, and also to make it easier to find broader applica-
tions in multistep syntheses, we next elaborated the crude
β-hydroxy ketones (which are liable to β-eliminations) into
the corresponding enones by direct treatment with MsCl
and Et3N. The resulting mixture of enones was readily sepa-
rated on silica gel to afford pure 4a in 86% yield over three
steps from 1a (Table 2, entry 1).
Table 2.[a] The results of cleavage of cyclopropanols with Co-
(acac)2/air at room temp. followed by reduction of the peroxy bond
and β-elimination.
A range of other 1,2-disubstituted cyclopropanols (pre-
pared by the Kulinkovich reaction) could also be cleaved,
reduced and elaborated into the corresponding enones in
good to excellent yields by using the same procedure. Re-
placement of the tert-butyldimethylsilyl (TBS) group in 1a
with a benzyl (Bn) group and/or extending the methyl
group in 1a into a phenylethyl group did not cause any dis-
cernible difference (Table 2, entries 2 and 4).
The methoxymethyl (MOM) protecting group was well
tolerated (Table 2, entry 3), and other commonly encoun-
tered ketal-type protecting groups, such as acetonide or 1,2-
dioxolane (the ketal of ethylene glycol) or thioketal, were
also compatible (Table 2, entries 5–7 and 10).
Several substrates with enantiopure stereogenic centres at
different positions in the carbon chains were then examined
to further demonstrate the potential applicability of this
procedure in natural product synthesis (Table 2, entries 8–
14). Again, rather good yields were obtained. Substitution
in the side chains at positions immediately next to the ring
(Table 2, entry 13–14) was also tolerated, although the
yields were slightly lower than those obtained with less ste-
rically hindered substrates.
Conclusions
In efforts to facilitate broader employment of the Kulin-
kovich cyclopropanation as a tool for coupling two complex
multifunctional fragments into longer linear structures,
cleavage of 1,2-disubstituted cyclopropanols derived from a
variety of different fragments carrying multiple stereogenic
centres and different protection groups was studied in a sys-
tematic way. By using readily available Co(acac)2 as cata-
lyst, the three-membered rings in the substrates were re-
gioselectively cleaved in EtOH at ambient temperature with
air as the reagent. The crude ring-cleavage products were
then reduced with Ph3P to afford the corresponding β-hy-
droxy ketones, which, on mesylation and β-elimination per-
formed in a one-pot manner, delivered linear conjugate en-
ones in high yields after a single chromatographic separa-
tion at the end of the whole sequence. Apart from the effi-
ciency and mild conditions, the low cost and operational
convenience of the newly developed protocol are also note-
worthy. Protocols of this type are expected to make it much
easier to realize the thus-far largely overlooked potential for
[a] All runs were performed by using the general procedure given
in the Experimental Section. [b] For the yields for 1a–n (obtained
by the Kulinkovich cyclopropanation), see the Supporting Infor-
mation. [c] Calculated from the pure products isolated by
chromatography.
Eur. J. Org. Chem. 2014, 3841–3846
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W.-B. Han, S.-G. Li, X.-W. Lu, Y. Wu
FULL PAPER
[M + Na]+. HRMS (ESI): m/z calcd. for C15H20O3Na [M + Na]+
271.1305; found 271.1315.
the Kulinkovich reaction as a coupling tool in multistep
synthesis.[12]
Compound 4d: Colourless oil. 1H NMR (400 MHz, CDCl3): δ =
7.30–7.16 (m, 5 H), 6.83 (dt, J = 16.0, 7.1 Hz, 1 H), 6.14 (d, J =
16.0 Hz, 1 H), 3.72 (t, J = 6.4 Hz, 2 H), 2.98–2.84 (m, 4 H), 2.41
(q, J = 6.3 Hz, 2 H), 0.88 (s, 9 H), 0.05 (s, 6 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 199.4, 144.3, 141.2, 131.8, 128.4, 128.3,
Experimental Section
General Methods: NMR spectra were recorded with a Bruker Av-
ance NMR spectrometer operating at 400 MHz for 1H unless
otherwise stated. IR spectra were measured with a Nicolet 380 In-
frared spectrophotometer. ESI-MS data were acquired with a Shi-
madzu LCMS-2010EV mass spectrometer. ESI-HRMS data were
obtained with a Bruker APEXIII 7.0 Tesla FT-MS spectrometer.
EI-MS were recorded with an Agilent Technologies 5973N spec-
trometer. HRMS (EI) were acquired with a Waters Micromass
GCT Premier instrument. Optical rotations were measured with a
Jasco P-1030 polarimeter. All reagents were of reagent grade and
used as purchased. Column chromatography was performed on sil-
ica gel (300–400 mesh) under slightly positive pressure. Petroleum
ether (PE) for chromatography had a boiling range 60–90 °C.
126.0, 61.5, 41.5, 35.9, 30.0, 25.8, 18.2, –5.4 ppm. FTIR (film): ν =
˜
3085, 3062, 3028, 2955, 2929, 2857, 2738, 1698, 1676, 1632, 1604,
1496, 1471, 1462, 1454, 1362, 1256, 1178, 1102, 1006, 978, 938,
836, 777, 699 cm–1. MS (ESI): m/z = 341.2 [M + Na]+. HRMS
(ESI): m/z calcd. for C19H30O2SiNa [M + Na]+ 341.1907; found
341.1910.
Compound 4e: Colourless oil. 1H NMR (400 MHz, CDCl3): δ =
7.30–7.16 (m, 5 H), 6.80 (dt, J = 15.9, 7.0 Hz, 1 H), 6.10 (d, J =
16.1 Hz, 1 H), 4.10–4.01 (m, 2 H), 3.50 (t, J = 7.1 Hz, 1 H), 2.96–
2.83 (m, 4 H), 2.24 (q, J = 6.6 Hz, 2 H), 1.46–1.06 (m, 4 H), 1.40
(s, 3 H), 1.34 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
199.3, 146.7, 141.1, 130.5, 128.4, 128.3, 126.0, 108.8, 75.6, 69.3,
General Procedure for the Co(acac)2-Catalyzed Oxidative Cleavage
of Cyclopropanols under Air: Cyclopropanol 1 (0.2 mmol) and Co-
(acac)2 (2.6 mg, 0.01 mmol) were added to a 25-mL round-bot-
tomed flask. Anhydrous EtOH (1.0 mL) was then introduced and
the mixture was stirred at ambient temperature for 1.5 h, when
TLC showed complete disappearance of the starting material.
CH2Cl2 (4.0 mL) was added, followed by Ph3P (58 mg, 0.22 mmol)
and the mixture was stirred at ambient temperature for 1 h before
the solvents were removed by rotary evaporation. The residue was
dissolved in CH2Cl2 (2.0 mL) and to the resulting solution were
added in turn DMAP (2 mg, 0.02 mmol), Et3N (0.23 mL,
1.6 mmol) and MsCl (46 μL, 0.6 mmol). The mixture was stirred
at ambient temperature for 3–4 h. When TLC showed completion
of the reaction, water (5 mL) was added and the mixture was ex-
tracted with Et2O (3ϫ 10 mL). The combined organic layers were
washed with water (5 mL) and brine (5 mL) before being dried with
anhydrous Na2SO4. The drying agent was filtered off and the fil-
trate was concentrated on a rotary evaporator to leave an oily resi-
due, which was purified by chromatography on silica gel (PE/
EtOAc) to furnish the end product enone 4 in the yield listed in
Table 2.
41.6, 32.9, 32.2, 30.0, 26.9, 25.6, 24.2 ppm. FTIR (film): ν = 3061,
˜
3027, 2985, 2933, 2865, 1697, 1673, 1629, 1604, 1497, 1454, 1409,
1378, 1369, 1248, 1214, 1156, 1060, 979, 856, 749, 700 cm–1. MS
(ESI): m/z = 325.1 [M + Na]+. HRMS (ESI): m/z calcd. for
C19H26O3Na [M + Na]+ 325.1774; found 325.1764.
Compound 4f: Colourless oil. 1H NMR (400 MHz, CDCl3): δ =
6.83 (dt, J = 15.8, 7.4 Hz, 1 H), 6.23 (d, J = 15.8 Hz, 1 H), 3.98–
3.88 (m, 4 H), 3.71 (t, J = 6.3 Hz, 2 H), 2.86 (s, 2 H), 2.41 (q, J =
5.5 Hz, 2 H), 1.40 (s, 3 H), 0.86 (s, 9 H), 0.02 (s, 6 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 196.7, 144.8, 132.3, 108.1, 64.6, 61.5,
49.4, 35.9, 25.8, 24.6, 18.2, –5.4 ppm. FTIR (film): ν = 2954, 2930,
˜
2885, 2858, 1692, 1666, 1626, 1472, 1380, 1255, 1213, 1099, 1048,
979, 949, 836, 777 cm–1. MS (ESI): m/z = 337.2 [M + Na]+. HRMS
(ESI): m/z calcd. for C16H30O4SiNa [M + Na]+ 337.1806; found
337.1821.
Compound 4g: Colourless oil. 1H NMR (400 MHz, CDCl3): δ =
7.38–7.25 (m, 5 H), 6.86 (dt, J = 15.8, 6.8 Hz, 1 H), 6.27 (d, J =
16.0 Hz, 1 H), 4.51 (s, 2 H), 3.98–3.88 (m, 4 H), 3.60 (t, J = 6.4 Hz,
2 H), 2.88 (s, 2 H), 2.53 (q, J = 6.5 Hz, 2 H), 1.43 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 196.7, 144.5, 138.0, 132.1, 128.3,
1
Compound 4a:[13] Colourless oil. H NMR (400 MHz, CDCl3): δ =
127.6, 108.1, 73.0, 68.2, 64.6, 49.5, 32.8, 24.7 ppm. FTIR (film): ν
˜
= 3041, 2980, 2938, 2865, 1718, 1689, 1662, 1624, 1495, 1454, 1349,
1278, 1204, 1174, 1101, 1044, 949, 902, 738, 698 cm–1. MS (EI):
m/z (%) = 91 (100), 105 (54), 43 (26), 77 (26), 199 (0.74) [M –
Bn]+. HRMS (EI): m/z calcd. for C10H15O4 [M – Bn]+ 199.0970;
found 199.0964.
6.79 (dt, J = 16.0, 7.0 Hz, 1 H), 6.08 (d, J = 6.0 Hz, 1 H), 3.72 (t,
J = 7.2 Hz, 2 H), 2.41 (q, J = 6.3 Hz, 2 H), 2.22 (s, 3 H), 0.87 (s,
9 H), 0.03 (s, 6 H) ppm.
Compound 4b: Colourless oil. 1H NMR (400 MHz, CDCl3): δ =
7.36–7.16 (m, 10 H), 6.83 (dt, J = 15.8, 6.8 Hz, 1 H), 6.15 (d, J =
16.1 Hz, 1 H), 4.50 (s, 2 H), 3.57 (t, J = 6.2 Hz, 2 H), 2.96–2.82
(m, 4 H), 2.50 (q, J = 6.5 Hz, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 199.3, 143.9, 141.2, 138.0, 131.6, 128.41, 128.38, 128.3,
127.68, 127.65, 126.0, 73.0, 68.2, 41.6, 32.8, 29.9 ppm. FTIR (film):
Compound 4h: Colourless oil; [α]2D7 = –12.4 (c = 1.0, CHCl3). 1H
NMR (400 MHz, CDCl3): δ = 7.36–7.26 (m, 5 H), 6.82 (dt, J =
15.8, 7.6 Hz, 1 H), 6.11 (d, J = 16.1 Hz, 1 H), 4.53 (d, J = 12.3 Hz,
1 H), 4.50 (d, J = 12.3 Hz, 1 H), 3.96 (quint, J = 5.5 Hz, 1 H), 3.42
(dd, J = 9.5, 5.3 Hz, 1 H), 3.34 (dd, J = 9.6, 6.3 Hz, 1 H), 2.54–
2.45 (m, 3 H), 2.42–2.34 (m, 1 H), 1.67–1.58 (m, 2 H), 0.92 (t, J =
7.3 Hz, 3 H), 0.87 (s, 9 H), 0.04 (s, 6 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 200.5, 143.4, 138.1, 132.6, 128.3, 127.6, 74.0, 73.3,
70.4, 41.7, 38.0, 25.7, 18.0, 17.6, 13.8, –4.5, –4.8 ppm. FTIR (film):
ν = 3062, 3028, 2924, 2857, 1697, 1672, 1630, 1603, 1496, 1454,
˜
1408, 1363, 1288, 1205, 1178, 1098, 1028, 977, 738, 698 cm–1. MS
(ESI): m/z = 317.1 [M + Na]+. HRMS (ESI): m/z calcd. for
C20H22O2Na [M + Na]+ 317.1512; found 317.1509.
Compound 4c: Colourless oil. 1H NMR (400 MHz, CDCl3): δ =
7.30–7.17 (m, 5 H), 6.84 (dt, J = 16.0, 6.8 Hz, 1 H), 6.18 (d, J =
16.1 Hz, 1 H), 4.61 (s, 2 H), 3.64 (t, J = 6.3 Hz, 2 H), 3.34 (s, 3 H),
2.97–2.85 (m, 4 H), 2.50 (qd, J = 6.5, 1.2 Hz, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 199.2, 143.8, 141.2, 131.7, 128.4, 128.3,
ν = 3031, 2957, 2929, 2890, 2857, 1697, 1676, 1632, 1496, 1462,
˜
1362, 1254, 1203, 1104, 983, 835, 776, 736, 698 cm–1. MS (ESI):
m/z = 399.2 [M + Na]+. HRMS (ESI): m/z calcd. for C22H36O3SiNa
[M + Na]+ 399.2326; found 399.2306.
126.0, 96.4, 65.8, 55.3, 41.7, 32.8, 29.9 ppm. FTIR (film): ν = 2930,
Compound 4i: Colourless oil; [α]2D7 = –7.5 (c = 1.0, CHCl3). 1H
NMR (400 MHz, CDCl3): δ = 7.34–7.16 (m, 10 H), 6.82 (dt, J =
16.0, 7.3 Hz, 1 H), 6.12 (d, J = 16.1 Hz, 1 H), 4.50 (s, 2 H), 3.94
˜
2887, 1697, 1673, 1631, 1602, 1497, 1454, 1366, 1290, 1211, 1178,
1149, 1110, 1039, 975, 918, 750, 700 cm–1. MS (ESI): m/z = 271.1
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Facile Conversion of Cyclopropanols into Linear Conjugate Enones
(quint, J = 5.6 Hz, 1 H), 3.40 (dd, J = 9.4, 5.2 Hz, 1 H), 3.32 (dd,
J = 9.5, 6.2 Hz, 1 H), 2.94–2.89 (m, 2 H), 2.85–2.80 (m, 2 H), 2.54–
2.34 (m, 2 H), 0.92 (t, J = 7.9 Hz, 9 H), 0.57 (q, J = 7.8 Hz, 6
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 199.2, 143.7, 141.3,
138.0, 132.5, 128.4, 128.3, 127.7, 126.0, 73.8, 73.3, 70.2, 41.4, 38.0,
+ Na]+. HRMS (ESI): m/z calcd. for C29H52O3Si2Na [M + Na]+
527.3347; found 527.3323.
Compound 4n: Colourless oil; [α]2D5 = –37.9 (c = 1.0, CHCl3). 1H
NMR (400 MHz, CDCl3): δ = 7.37–7.26 (m, 5 H), 6.88 (dt, J =
15.8, 7.5 Hz, 1 H), 6.25 (d, J = 15.6 Hz, 1 H), 4.53 (d, J = 12.3 Hz,
1 H), 4.49 (d, J = 12.5 Hz, 1 H), 3.95 (quint, J = 5.7 Hz, 1 H),
3.72–3.57 (m, 3 H), 3.42 (dd, J = 9.5, 5.5 Hz, 1 H), 3.37–3.33 (m,
4 H), 2.95–2.88 (m, 1 H), 2.54–2.34 (m, 2 H), 1.70–1.55 (m, 2 H),
1.10 (d, J = 7.1 Hz, 3 H), 0.89 (s, 9 H), 0.87 (s, 9 H), 0.04 (s, 6 H),
0.03 (s, 6 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 201.7, 143.4,
138.2, 131.6, 128.4, 127.61, 127.59, 79.4, 74.1, 73.4, 70.6, 59.5, 58.2,
47.8, 38.0, 35.6, 25.9, 25.8, 18.2, 18.1, 12.1, –4.5, –4.8, –5.3,
30.0, 6.8, 4.8 ppm. FTIR (film): ν = 3393, 3064, 3027, 2953, 2911,
˜
2875, 1601, 1496, 1455, 1413, 1365, 1237, 1096, 1006, 739,
697 cm–1. MS (ESI): m/z = 461.3 [M + Na]+. HRMS (ESI): m/z
calcd. for C27H38O3SiNa [M + Na]+ 461.2482; found 461.2484.
Compound 4j: Colourless oil; [α]2D7 = –7.4 (c = 1.0, CHCl3). 1H
NMR (400 MHz, CDCl3): δ = 7.38–7.26 (m, 5 H), 6.88 (dt, J =
15.8, 7.3 Hz, 1 H), 6.12 (d, J = 15.8 Hz, 1 H), 4.54 (d, J = 12.8 Hz,
1 H), 4.50 (d, J = 12.8 Hz, 1 H), 3.96 (quint, J = 5.5 Hz, 1 H), 3.42
(dd, J = 9.3, 5.3 Hz, 1 H), 3.38–3.26 (m, 5 H), 2.82 (t, J = 7.6 Hz,
2 H), 2.55–2.47 (m, 1 H), 2.43–2.35 (m, 1 H), 2.21 (t, J = 7.6 Hz,
2 H), 1.78 (s, 3 H), 0.88 (s, 9 H), 0.05 (s, 6 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 199.4, 143.7, 138.1, 132.5, 128.4, 127.63,
127.60, 74.0, 73.3, 70.4, 66.3, 40.1, 38.6, 38.0, 37.5, 32.9, 25.8, 18.1,
–5.4 ppm. FTIR (film): ν = 2954, 29219, 2896, 2856, 1693, 1667,
˜
1628, 1471, 1462, 1362, 1255, 1097, 1005, 836, 776, 734, 697 cm–1.
MS (ESI): m/z = 587.5 [M + Na]+. HRMS (ESI): m/z calcd. for
C31H56O5Si2Na [M + Na]+ 587.3559; found 587.3553.
Supporting Information (see footnote on the first page of this arti-
1
cle): Synthesis of the substrates, and copies of H, 13C NMR and
–4.5, –4.8 ppm. FTIR (film): ν = 3033, 2953, 2927, 2856, 1697,
˜
FTIR spectra for new compounds.
1672, 1632, 1453, 1362, 1254, 1099, 982, 836, 776, 736, 698 cm–1.
MS (ESI): m/z = 503.3 [M + Na]+. HRMS (ESI): m/z calcd. for
C25H40O3S2SiNa [M + Na]+ 503.2080; found 503.2103.
Acknowledgments
Compound 4k: Colourless oil; [α]2D8 = –35.4 (c = 1.0, CHCl3). 1H
NMR (400 MHz, CDCl3): δ = 6.95 (dd, J = 16.0, 6.8 Hz, 1 H),
6.16 (dd, J = 16.0, 1.2 Hz, 1 H), 3.98–3.91 (m, 4 H), 3.83 (quint, J
= 4.0 Hz, 1 H), 3.69–3.58 (m, 2 H), 2.91 (d, J = 13.8 Hz, 1 H), 2.87
(d, J = 13.6 Hz, 1 H), 2.56–2.48 (m, 1 H), 1.68–1.58 (m, 2 H), 1.55–
1.47 (m, 1 H), 1.43 (s, 3 H), 1.02 (d, J = 6.8 Hz, 3 H), 0.89 (s, 9
This work was supported by the National Basic Research Program
of China (973 Program, grant number 2010CB833200), the
National Natural Science Foundation of China (NSFC) (grant
numbers 21372248, 21172247, 21032002, and 20921091) and the
Chinese Academy of Sciences
H), 0.87 (s, 9 H), 0.05 (s, 3 H), 0.04 (s, 3 H), 0.03 (s, 6 H) ppm. 13
C
NMR (100 MHz, CDCl3): δ = 197.0, 150.6, 130.6, 108.2, 72.2, 64.6,
59.6, 49.2, 42.2, 36.5, 25.9, 25.8, 24.7, 18.2, 18.0, 14.1, –4.5, –4.6,
[1] For reviews, see: a) O. G. Kulinkovich, A. de Meijere, Chem.
Rev. 2000, 100, 2789–2834; b) I. Haym, M. A. Brimble, Org.
Biomol. Chem. 2012, 10, 7649–7665; c) A. Wolan, Y. Six, Tetra-
hedron 2010, 66, 15–61.
–5.3, –5.4 ppm. FTIR (film): ν = 2955, 2930, 2885, 2857, 1692,
˜
1663, 1623, 1472, 1463, 1380, 1361, 1255, 1095, 1047, 939, 836,
775 cm–1. MS (ESI): m/z = 509.4 [M + Na]+. HRMS (ESI): m/z
calcd. for C25H50O5Si2Na [M + Na]+ 509.3089; found 509.3103.
[2] See, for example: a) O. Kulinkovich, N. Masalov, V. Tyvorskii,
Tetrahedron Lett. 1996, 37, 1095–1096; b) A. L. Hurski, O. G.
Kulinkovich, Russ. J. Org. Chem. 2011, 47, 1653–1674; c) K.
Kim, J. K. Cha, Angew. Chem. Int. Ed. 2009, 48, 5334–5336;
Angew. Chem. 2009, 121, 5438; d) J. S. Kingsbury, E. J. Corey,
J. Am. Chem. Soc. 2005, 127, 13813–13815; e) A. Gollner, J.
Mulzer, Org. Lett. 2008, 10, 4701–4704; f) A. Gollner, K.-H.
Altmann, J. Gertsch, J. Mulzer, Chem. Eur. J. 2009, 15, 5979–
5997; g) H. Vnekatesan, M. C. Davic, Y. Altas, J. P. Snyder,
D. C. Liotta, J. Org. Chem. 2001, 66, 3653–3661; h) A. V. Brek-
ish, K. N. Prokhorevich, O. G. Kulinkovich, Eur. J. Org. Chem.
2006, 5069–5075; i) Z. Ye, T. Gao, G. Zhao, Tetrahedron 2011,
67, 5979–5989; j) D. Shklyaruck, E. Matiushenkov, Tetrahe-
dron: Asymmetry 2011, 22, 1448–1454; k) S. Baktharaman, S.
Selvakumar, V. K. Singh, Tetrahedron Lett. 2005, 46, 7527–
7529; l) S. E. Denmark, L. R. Marcin, J. Org. Chem. 1997, 62,
1675–1686; m) V. N. Odinokov, E. R. Shakurova, L. M. Khali-
lov, U. M. Dzhemilev, Russ. J. Org. Chem. 2009, 45, 1464–1467;
n) B. Achmatowicz, P. Jankowski, J. Wicha, Tetrahedron Lett.
1996, 37, 5589–5592; o) A. L. Hurski, N. A. Sokolov, O. G. Ku-
linkovich, Tetrahedron 2009, 65, 3518–3524; p) I. L. Lysenko,
A. V. Bekish, O. G. Kulinkovich, Russ. J. Org. Chem. 2002, 38,
875–879; q) V. N. Kovalenko, N. V. Masalov, O. G. Kulinkov-
ich, Russ. J. Org. Chem. 2009, 45, 1318–1324; r) A. V. Bekish,
K. N. Prokhorevich, O. G. Kulinkovich, Tetrahedron Lett.
2004, 45, 5253–5255; s) A. V. Bekish, V. E. Isakov, O. G. Kulin-
kovich, Tetrahedron Lett. 2005, 46, 6979–6981; t) I. L. Lysenko,
O. G. Kulinkovich, Russ. J. Org. Chem. 2005, 41, 70–74; u) I. V.
Mineyeva, O. G. Kulinkovich, Tetrahedron Lett. 2010, 51,
1836–1839.
Compound 4l: Colourless oil; [α]2D8 = –9.9 (c = 0.5, CHCl3). 1H
NMR (400 MHz, CDCl3): δ = 7.39–7.25 (m, 5 H), 6.95 (dd, J =
16.0, 7.4 Hz, 1 H), 6.16 (dd, J = 16.1, 1.0 Hz, 1 H), 3.72 (t, J =
5.2 Hz, 1 H), 3.72 (dd, J = 10.1, 5.6 Hz, 1 H), 3.69 (dd, J = 10.0,
7.0 Hz, 1 H), 3.05–3.00 (m, 2 H), 2.97–2.91 (m, 2 H), 2.67–2.58 (m,
1 H), 1.89 (quint, J = 6.3 Hz, 1 H), 1.12 (d, J = 6.8 Hz, 3 H), 0.98
(d, J = 6.8 Hz, 3 H), 0.97 (s, 9 H), 0.96 (s, 9 H), 0.13 (s, 3 H), 0.11
(s, 3 H), 0.10 (s, 3 H), 0.08 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 199.4, 151.4, 141.3, 129.2, 128.46, 128.35, 126.0, 76.5,
64.9, 41.7, 40.5, 40.4, 30.0, 26.0, 25.9, 18.31, 18.26, 14.4, 14.1, –4.0,
–4.1, –5.3, –5.4 ppm. FTIR (film): ν = 2956, 2929, 2881, 2857,
˜
1694, 1678, 1627, 1472, 1361, 1254, 1086, 1025, 836, 774, 698 cm–1.
MS (ESI): m/z = 527.4 [M + Na]+. HRMS (ESI): m/z calcd. for
C29H52O3Si2Na [M + Na]+ 527.3347; found 527.3328.
1
Compound 4m: Colourless oil; [α]2D7 = +28.3 (c = 0.5, CHCl3). H
NMR (400 MHz, CDCl3): δ = 7.30–7.16 (m, 5 H), 6.91 (dd, J =
16.2, 7.4 Hz, 1 H), 6.05 (d, J = 16.1 Hz, 1 H), 3.82 (dd, J = 6.3,
1.8 Hz, 1 H), 3.41 (t, J = 9.5 Hz, 1 H), 3.34 (dd, J = 9.8, 6.0 Hz, 1
H), 2.97–2.83 (m, 4 H), 2.58–2.49 (m, 1 H), 1.71–1.64 (m, 1 H),
1.04 (d, J = 6.8 Hz, 3 H), 0.91 (s, 9 H), 0.88 (s, 9 H), 0.75 (d, J =
6.8 Hz, 3 H), 0.06 (s, 3 H), 0.05 (s, 3 H), 0.03 (s, 3 H), 0.02 (s, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 199.6, 150.6, 141.3,
129.2, 128.5, 128.3, 126.0, 74.3, 65.6, 42.0, 41.4, 38.9, 30.1, 26.0,
25.9, 18.4, 18.2, 15.8, 10.8, –3.9, –4.3, –5.32, –5.36 ppm. FTIR
[3] a) K. A. Keaton, A. J. Phillips, Org. Lett. 2007, 9, 2717–2719;
b) K. A. Keaton, A. J. Phillips, Org. Lett. 2008, 10, 1083–1086;
c) J. McCabe, A. J. Phillips, Tetrahedron 2013, 69, 5710–5714.
(film): ν = 2956, 2928, 2856, 1698, 1679, 1627, 1471, 1361, 1252,
˜
1093, 1051, 836, 774, 698, 669 cm–1. MS (ESI): m/z = 527.4 [M
Eur. J. Org. Chem. 2014, 3841–3846
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3845

W.-B. Han, S.-G. Li, X.-W. Lu, Y. Wu
FULL PAPER
For the coupling of smaller/less functionalized fragments, see
also: d) O. G. Kulinkovich, O. L. Epstein, Tetrahedron Lett.
2001, 42, 3757–3758; e) I. Haym, M. A. Brimble, Synlett 2009,
2315–2319; f) O. G. Kulinkovich, O. L. Epstein, Tetrahedron
Lett. 1998, 39, 1823–1826; g) T. A. Chevtchouk, V. E. Isakov,
O. G. Kulinkovich, Tetrahedron 1999, 55, 13205–13210.
2009, 50, 5719–5722; f) P. M. O’Neill, M. Pugh, J. Davies, S. A.
Ward, B. K. Park, Tetrahedron Lett. 2001, 42, 4569–4571.
[9] a) T. Tokuyasu, S. Kunikawa, A. Masuyama, M. Nojima, Org.
Lett. 2002, 4, 3595–3598; b) P. M. O’Neill, S. Hindley, M. D.
Pugh, J. Davies, P. G. Bray, B. K. Park, D. S. Kapu, S. A. Ward,
P. A. Stocks, Tetrahedron Lett. 2003, 44, 8135–8138; c) J.-M.
Wu, S. Kunikawa, T. Tokuyasu, A. Masuyama, M. Nojima,
H.-S. Kim, Y. Wataya, Tetrahedron 2005, 61, 9961–9968.
[10] O. G. Kulinkovich, D. A. Astashko, V. I. Tyvoskii, N. A. Ilyina,
Synthesis 2001, 1453–1455.
[11] Reduction with Me2S was very slow; after 48 h, some peroxy
intermediates remained. Reduction with Mg/MeOH com-
pletely failed, see: A. Ahmed, P. H. Dussault, Org. Lett. 2004,
6, 3609–3611.
[12] For some of the previous conversions of cyclopropanols (not
necessarily related to the Kulinkovich reaction) into α,β-unsat-
urated ketones/esters see, for example: a) A. Oku, M. Abe, M.
Iwamoto, J. Org. Chem. 1994, 59, 7445–7452; b) see ref.[3b]
above; c) ref.[5a] above; d) see ref.[5d] above. See also those cases
where the resulting conjugated alkenes were 2,2-disubstituted
instead of 1,2-disubstituted as in this work: e) B. Achmatowicz,
P. Jankowski, J. Wicha, Tetrahedron Lett. 1996, 37, 5589–5592;
f) see ref.[2k] above; g) V. N. Kovalenko, N. V. Masalov, O. G.
Kulinkovich, Russ. J. Org. Chem. 2009, 45, 1318–1324; h) L.-
Z. Li, B. Xiao, Q.-X. Guo, S. Xue, Tetrahedron 2006, 62, 7762–
7771; i) V. I. Tyvorskii, D. A. Astashko, O. G. Kulinkovich, Tet-
rahedron 2004, 60, 1473–1479; j) S. Baktharaman, S. Selvaku-
mar, V. K. Singh, Tetrahedron Lett. 2005, 46, 1473–1479; k) Y.
Harada, T. Jinnai, H. Mishima, H. Okumoto, H. Shimizu, A.
Suzuki, Synlett 2000, 629–630.
[4]
[5]
S.-G. Li, Y.-K. Wu, Chem. Asian J. 2013, 8, 2792–2800.
For selected previous studies on the regioselectivity in the ring-
opening of the Kulinkovich reactions-related cyclopropanols,
see: a) P. P. Das, B. B. Parida, J. K. Cha, ARKIVOC (Gaines-
ville, FL, U.S.) 2012, 74–84; b) D. T. Ziegler, A. M. Steffens,
T. W. Funk, Tetrahedron Lett. 2010, 51, 6726–6729; c) D. G.
Kananovich, A. L. Hurski, O. G. Kulinkovich, Tetrahedron
Lett. 2007, 48, 8424–8429; d) S.-B. Park, J. K. Cha, Org. Lett.
2000, 2, 147–149; e) H. Okumoto, T. Jinnai, H. Shimizu, Y.
Harada, H. Mishima, A. Suzuki, Synlett 2000, 629–630; f) I. L.
Lysenko, H. G. Lee, J. K. Cha, Org. Lett. 2006, 8, 2671–2673;
g) L. G. Quan, H. G. Lee, J. K. Cha, Org. Lett. 2007, 9, 4439–
4442.
[6] The procedure disclosed herein was not incorporated into the
total synthesis of demethyl cezomycin because a better method,
which made use of the transient radical to achieve oxidation of
a remote silyl protected alcohol into an desired aldehyde, was
later developed for that particular endeavour; see ref.[4] above.
[7] S. Isayama, T. Mukaiyama, Chem. Lett. 1989, 573–576.
[8] For CoII-mediated syntheses of peroxides see, for example: a)
X.-X. Xu, H.-Q. Dong, J. Org. Chem. 1995, 60, 3039–3044; b)
B. Barnych, J.-M. Vatèle, Org. Lett. 2012, 14, 564–567; c) T.
Tokuyasu, A. Masuyama, M. Nojima, K. J. McCullough, H.-
S. Kim, Y. Wataya, Tetrahedron 2001, 57, 5979–5989; d) T. Ito,
T. Tokuyasu, A. Masuyama, M. Nojima, K. J. McCullough,
Tetrahedron 2003, 59, 525–536; e) S. Gemma, F. Marti, E. Gab-
ellieri, G. Campiani, E. Novellino, S. Butini, Tetrahedron Lett.
[13] I. Paterson, F. A. Muhlthau, C. J. Cordier, M. P. Housden,
P. M. Burton, O. Loiseleur, Org. Lett. 2009, 11, 353–356.
Received: March 2, 2014
Published Online: May 6, 2014
3846
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 3841–3846