[3+2] Photooxygenation of aryl cyclopropanes via visible light photocatalysis

Article abstract of DOI:10.1016/j.tet.2014.02.045

We report that Ru(bpz)₃²⁺ is an excellent sensitizer for the photooxygenation of aryl cyclopropanes upon irradiation with visible light. The effectiveness of this photocatalyst enables the synthesis of a range of five-membered endoperoxides in excellent yield with quite low (0.5 mol %) catalyst loadings even when standard household light sources are utilized.

Full text of DOI:10.1016/j.tet.2014.02.045

Tetrahedron 70 (2014) 4270e4278
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[3þ2] Photooxygenation of aryl cyclopropanes via visible light
photocatalysis
*
Zhan Lu, Jonathan D. Parrish, Tehshik P. Yoon
Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706, USA
a r t i c l e i n f o
a b s t r a c t
2þ
Article history:
We report that RuðbpzÞ3 is an excellent sensitizer for the photooxygenation of aryl cyclopropanes upon
irradiation with visible light. The effectiveness of this photocatalyst enables the synthesis of a range of
five-membered endoperoxides in excellent yield with quite low (0.5 mol %) catalyst loadings even when
standard household light sources are utilized.
Received 12 January 2014
Received in revised form 16 February 2014
Accepted 18 February 2014
Available online 26 February 2014
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Cyclopropanes
Endoperoxide
Photocatalysis
Photooxygenation
Radical cation
1. Introduction
a variety of synthetically useful radical ion processes.6,7 We have
found that electron-deficient bipyrazyl and bipyrimidyl complex of
Cyclic peroxides are the characteristic pharmacophores of
a class of biologically active compounds that exhibit a range of
potent antibacterial, anticancer, and antimalarial activities.1 Five-
membered endoperoxides, in particular, have also been valued as
synthetic intermediates because of the ease with which their OeO
bonds can be reductively cleaved to afford 1,3-diols.2 Many
methods for the preparation of five-membered endoperoxides
involve sequences that require pre-installation of the reactive
peroxide moiety,3 which often limits the scope and yield of the
reaction. An attractive alternative strategy involves the ring-
expanding reaction of cyclopropanes with molecular oxygen.
Vinylcyclopropanes can be induced to undergo this transformation
upon reaction with phenylthiyl or phenylselenyl radicals,4 although
the requirement for a vinyl substituent represents a significant
limitation on the generality of this process. An arguably more
general method is the photooxygenation of aryl cyclopropanes,
originally developed by Mizuno and Otsuji,5 which is commonly
catalyzed by organic PET sensitizers such as 9,10-
dicyanoanthracene (DCA, 2).
Ru(II) in particular are excellent catalysts for the photochemical
one-electron oxidation of electron-rich styrenes (Eq. 1), which has
enabled us to develop a suite of synthetically useful reactions of the
resulting radical cations.8,9 Recognizing that the chemistry of
cyclopropanes can often offer homologous reactivity to that of
olefins, we have become interested in exploring radical cation
reactions of electron-rich cyclopropanes (Eq. 2). Zheng recently
2þ
demonstrated that RuðbpzÞ3
(1) is an effective visible light
photocatalyst for the [3þ2] cycloaddition of amine-substituted
cyclopropanes with a variety of alkenes.10 In this manuscript, we
2þ
demonstrate that RuðbpzÞ3
also catalyzes aerobic photo-
oxygenation of electron-rich aryl cyclopropanes upon irradiation
with visible light and is a markedly more effective catalyst for this
transformation than DCA (Scheme 1).
For the past several years, our research group has been
developing methods that exploit the remarkable photoredox
properties of transition metal polypyridyl complexes to perform
* Corresponding author. Tel.: þ1 608 262 2268; fax: þ1 608 265 4534; e-mail
Scheme 1.
addresses: tyoon@chem.wisc.edu, tyoon@wisc.edu (T.P. Yoon).
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.02.045

Z. Lu et al. / Tetrahedron 70 (2014) 4270e4278
4271
2. Results and discussion
DCA-sensitized photooxygenation of cyclopropanes5 suggests that
this reaction is initiated by one-electron oxidation of the substrate
to afford the corresponding radical cation. In line with this ex-
pectation, no endoperoxide is formed from unsubstituted 1,2-
diphenylcyclopropane (entry 2), even after long reaction times.
We similarly observed no reaction using a cyclopropane substrate
bearing one 3-methoxyphenyl substituent (entry 3). The analo-
gous 2-methoxy-substituted substrate underwent photo-
We began our initial investigations by examining the reaction of
1-(p-methoxyphenyl)-2-phenylcyclopropane (3a) under condi-
tions based upon those we had developed for the synthesis of
six-membered endoperoxides by aerobic [2þ2þ2] cycloaddition.11
Thus, irradiation of a solution of 3a in MeNO2 with a 23 W compact
fluorescent light bulb (CFL) in the presence of 0.5 mol
%
Ru(bpz)3(PF6)2 under an atmosphere of O2 afforded 16% yield of the
expected endoperoxide 4a (Table 1, entry 1); this compound was
isolated as a 3:1 mixture of syn to anti diastereomers. While the
reaction was much less efficient under an atmosphere of air in place
of oxygen (entry 2), the yield could be easily improved to syn-
thetically useful levels by conducting the reaction under 2 atm of
oxygen (entry 3). We attempted the same reaction using 10 mol % of
DCA as a sensitizer and observed no formation of 4a (entry 4),
oxygenation, but at a significantly slower rate than the
Table 2
Scope of the photooxygenation reactiona
Entry substrate
Product
Time Yieldb syn/antic
(h)
(%)
2þ
indicating that RuðbpzÞ3 is indeed a more effective visible light
photocatalyst for this transformation. Nitromethane proved to be
essential in this reaction; other solvents resulted in dramatically
diminished reactivity (entries 5e8). However, a 1:1 mixture of
MeNO2 and toluene allowed us to conduct the reaction at ꢀ30 ꢁC,
which resulted in a modest improvement of both the syn/anti ratio
1
2
3a R¼4-OMe
4a
4b
4c
4d
4e
4f
4g
4h
4i
3
48
48
48
1
3
1
3
1
99
0
0
47
78
95
70
93
99
77
5:1
d
3b R¼H
3
3c R¼3-OMe
3d R¼2-OMe
3e R¼4-OH
d
4d
5
5:1
>10:1
4:1
>10:1
5:1
10:1
5:1
Table 1
6
7
8
3f R¼4-OTIPS
3g R¼4-NH2
3h R¼4-NHBoc
3i R¼2,4-OMe
3j R¼3,4-OMe
Optimization of photooxygenation of 1
9
10d
4j
24
11
12
13
14
15
16
17
18
19
3k R¼2,4-OMe
3l R¼4-OMe
3m R¼4-Me
3n R¼4-Br
3o R¼4-Cl
4k
4l
1
1
1
1
1
1
1
1
1
98
99
98
99
98
97
99
98
94
6:1
9:1
10:1
9:1
10:1
>10:1
10:1
10:1
>10:1
4m
4n
4o
4p
4q
4r
3p R¼3-Cl
3q R¼2-Cl
3r R¼4-CF3
3s R¼2-CF3
4s
T (ꢁC)
Yielda (%)
syn/antib
20
1
75
6:1
Entry
O2
Solvent
1
2
15 psi
Air
MeNO2
MeNO2
MeNO2
MeNO2
MeCN
Acetone
Toluene
DMSO
23
23
23
23
23
23
23
23
ꢀ30
ꢀ30
ꢀ30
16
3
90
0
36
2
0
0
99
0
3:1
3:1
4:1
d
3
30 psi
30 psi
30 psi
30 psi
30 psi
30 psi
30 psi
30 psi
30 psi
4c
5
21
22
24
1
98
96
1:1
4:1
d
6
7
8
d
d
9d
10d,e
11d,f
1:1 MeNO2/toluene
1:1 MeNO2/toluene
1:1 MeNO2/toluene
5:1
d
10:1
0
d
a
Yields determined by 1H NMR spectroscopy using an internal standard unless
otherwise noted.
b
Diastereomer ratios determined by 1H NMR analysis of the unpurified reaction
23
24
1
99
94
6:1
mixture.
c
Using 10 mol % of 9,10-dicyanoanthracene (DCA) as photosensitizer in place of
Ru(bpz)3(PF6)2.
d
12
d
Reaction time: 3 h.
Reaction conducted in the dark.
Reaction conducted without RuðbpzÞ3
e
2þ
f
.
a
and the yield of the reaction (entry 9). Control experiments under
these conditions showed that no reaction occurred in the absence
of light or of RuðbpzÞ32þ, confirming the necessity of photoexcited
Ru(II) in order for this transformation to occur.
Experiments probing the scope of this reaction are summarized
in Table 2. Mizuno and Otsuji’s proposal for the mechanism of the
Unless otherwise noted, reactions were conducted in 1:1 MeNO2/toluene using
0.5 mol % RuðbpzÞ32þ, 30 psi O2, and a 23 W CFL bulb.
b
Values represent the averaged isolated yields from two reproducible
experiments.
c
Diastereomer ratios determined by 1H NMR analysis of the unpurified reaction
mixture.
d
Reaction conducted using 5 mol % Ru(bpz)3(PF6)2.

4272
Z. Lu et al. / Tetrahedron 70 (2014) 4270e4278
4-substituted isomer; only modest yields were obtained using
a higher loading (5 mol %) of the photocatalyst (entry 4). However,
a variety of aryl cyclopropanes bearing electron-donating 4-
substituents react smoothly and provide the corresponding en-
doperoxides in good yield (entries 5e8). Aryl cyclopropanes
bearing multiple electron-donating substituents are also easily
converted in high yields (entries 9 and 10).
3. Conclusion
In summary, a wide range of electron-rich aryl cyclopropanes
participate in aerobic [3þ2] photooxygenation reactions upon ir-
radiation with visible light in the presence of RuðbpzÞ32þ. In line
with our previous investigations involving photogenerated alkene
radical cations, we find that this photooxygenation reaction is
markedly more efficient using this Ru(II) chromophore in place of
DCA and enables the use of readily accessible household lighting
sources in place of conventional photochemical instrumentation.
The 1,2-dioxolane products are formed cleanly in high yield and can
be easily isolated by filtration through silica gel. We anticipate that
this method could be applied to the synthesis and discovery of
novel endoperoxide compounds with potent bioactivity profiles.
Provided that one of the aryl groups on the cyclopropane sub-
strate bears an electron-donating 2- or 4-substituent, we found the
scope of cyclopropanes that successfully undergo photo-
oxygenation to be quite broad. Substrates bearing a second phenyl
group with either electron-donating (entries 11e13) or electron-
withdrawing (entries 14e19) substitution patterns are easily
tolerated. The cyclopropane could also be substituted with
a heteroaryl group (entry 20) or an alkyne (entry 21), although the
latter reaction required much longer reaction times to proceed
to completion. We also examined photooxygenations of 1,2-
diarylcyclopropanes bearing additional alkyl substituents on the
central ring (entries 22 and 23), and in all cases, the bond linking
the two benzylic carbons exclusively undergoes photooxygenation,
consistent with the expectation that the weakest bond in the
cyclopropane be the most likely to fragment and undergo the
reaction. Finally, while we were able to obtain good yields of en-
doperoxide from a substrate bearing geminal methyl substituents
on the cyclopropane (entry 24), other less-substituted monoaryl
cyclopropanes failed to give appreciable yields of the photo-
oxygenation product.
4. Experimental section
4.1. General information
THF and CH2Cl2 were purified by elution through alumina as
described by Grubbs.12 MeNO2 was purified by distillation from
MgSO4 prior to use. A 23 W compact fluorescent light bulb was
used for all photochemical reactions depicted in Tables 1 and 2.
Flash column chromatography was performed with Silicycle
40e63 A silica (230e400 mesh). Ru(bpz)3(PF6)213 was prepared as
ꢀ
previously described. Diastereomer ratios for all compounds were
determined by 1H NMR analysis of the unpurified reaction mixture.
1H and 13C NMR data for all previously uncharacterized compounds
were obtained using Varian Inova-500 and Varian Unity-500
spectrometers and are referenced to TMS (0.0 ppm) and CDCl3
(77.0 ppm), respectively. IR spectral data were obtained using
a Bruker Vector 22 spectrometer (thin film on NaCl). Melting points
were obtained using a Mel-Temp II (Laboratory Devices, Inc., USA)
melting point apparatus. Mass spectrometry was performed with
a Waters (Micromass) AutoSpec (electrospray ionization, time-of-
flight analyzer).
Our working model for the mechanism of this process is sum-
2þ
marized in Scheme 2. Photoexcitation of the RuðbpzÞ3 chromo-
phore affords a strongly oxidizing (þ1.4 V vs SCE) excited state that
we propose can be reductively quenched by the aryl cyclopropane
substrate. The resulting aryl cyclopropane radical cation undergoes
stepwise reaction with ground-state triplet oxygen to afford en-
doperoxide radical cation 4aꢂD, which would lose an electron to
produce the final product, presumably by chain-propagating oxi-
dation of another equivalent of substrate cylcopropane 3a. Re-
generation of the Ru(II) photocatalyst requires a one-electron
oxidation, which could be accomplished either by chain-
D
terminating reaction with radical cation 4aꢂ or by reaction with
4.2. Synthesis of cyclopropane substrates
molecular oxygen.
Cyclopropane substrates 3a,14 3b,14 3c,15 3g,16 3i17 were pre-
pared as previously reported.
4.2.1. General procedure for synthesis of cyclopropane sub-
strates. Cyclopropane substrates were prepared using the method
of Beech et al.,18 as follows. A 100 mL round-bottomed flask was
charged with the appropriate benzaldehyde (1 equiv) and aceto-
phenone (1 equiv) in 12.5 mL EtOH. Added 12.5 mL of 6 M NaOH
and stirred the reaction mixture at room temperature for 12e24 h.
The reaction mixture was cooled to 0 ꢁC and neutralized with 6 M
HCl. The solids were isolated by filtration, washed with water, and
placed in a second 100 mL round-bottomed flask along with 25 mL
EtOH. Hydrazine monohydrate (3.0 mL, 62 mmol) was added
slowly to the resulting solution. The flask was fitted with a reflux
condenser, and the solution was heated to reflux for 2 h. The
reaction mixture was then treated with 500 mg KOH (8.9 mmol).
Upon consumption of the starting material, the flask was cooled to
ambient temperature, and the residue was loaded directly onto
a silica gel column and eluted with a gradient of 16:1 to 3:1 hex-
anes/EtOAc to obtain the desired cyclopropane.
The diastereomeric purity of the product could be upgraded
photocatalytically. A solution of the cyclopropane (1.0 g, 1 equiv) in
MeNO2 was placed in a 20 mL vial. The solution was sparged with
N2 gas before adding Ru(bpz)3(PF6)2 (0.1 mol %) and sealing the vial
with a Teflon cap. The reaction mixture was irradiated in front of
a 23 W CFL light bulb for 1e3 h, and the pure product was isolated
Scheme 2.

Z. Lu et al. / Tetrahedron 70 (2014) 4270e4278
4273
by passing the solution through a pad of silica gel and removing the
solvent by rotary evaporation to afford pure trans cyclopropane.
(ddd, J¼8.4, 6.5, 4.6 Hz, 1H), 2.09 (ddd, J¼8.4, 6.2, 4.6 Hz, 1H),
1.43e1.37 (m, 2H); 13C NMR: (125.7 MHz, CDCl3)
148.9, 147.3,
d
142.6, 135.0, 128.3, 125.6, 117.5, 111.3, 109.8, 55.9, 55.8, 27.7, 27.5,
17.7. HRMS (EI) calculated for [C17H18O2]þ (Mþ) requires m/z
254.1302, found m/z 254.1309.
4.2.2. trans-1-(20-Methoxyphenyl)-2-phenylcyclopropane(3d).
Prepared from 13.6 g (100 mmol) of benzaldehyde and 12.0 g
(100 mmol) of 20-methoxyacetophenone using the general pro-
cedure to afford 15.7 g (70% yield) of cyclopropane. The cyclopro-
pane was isomerized using 3.9 mg (0.004 mmol) of Ru(bpz)3(PF6)2
in 7.4 mL of MeNO2 to obtain 999 mg (100% yield) of the pure trans
diastereomer. All analytical data were consistent with previously
reported values.19
4.2.7. trans-1,2-Bis(20,40-dimethoxyphenyl)cyclopropane
(3k).
Prepared from 4.15 g (25 mmol) of 2,4-dimethoxybenzaldehyde
and 4.5 g (25 mmol) of 20,40-dimethoxyacetophenone using the
general procedure to afford 7.3 g (93% yield) of cyclopropane. The
cyclopropane was isomerized using 2.8 mg (0.0032 mmol) of
Ru(bpz)3(PF6)2 in 5.3 mL of MeNO2 to obtain 842 mg (84% yield) of
the pure trans diastereomer as a crystalline solid. Mp: 78e80 ꢁC
(hexane/EtOAc). IR (neat) 2999, 2937, 2835, 1615, 1585, 1506, 1290,
4.2.3. trans-1-(40-Hydroxyphenyl)-2-phenylcyclopropane
(3e).
Prepared from 2.5 mL (25 mmol) of benzaldehyde and 3.4 g
(25 mmol) of 20-hydroxyacetophenone using the general procedure
to afford 2.6 g (49% yield) of diastereomerically pure cyclopropane
as a crystalline solid. Mp: 72e73 ꢁC (hexane/EtOAc). IR (neat) 3396,
1208, 1037 cmꢀ1. 1H NMR: (499.9 MHz, CDCl3)
d
6.96 (d, J¼8.2 Hz,
2H), 6.45e6.41 (m, 4H), 3.79 (s, 6H), 3.77 (s, 6H), 2.26 (t, J¼7.3 Hz,
2H), 1.19 (t, J¼7.3 Hz, 2H); 13C NMR: (125.7 MHz, CDCl3)
d 159.1,
3029, 1615, 1600, 1516, 1449, 1225 cmꢀ1
CDCl3)
.
1H NMR: (499.9 MHz,
158.7, 126.0, 123.7, 103.9, 98.4, 55.4, 55.2, 19.2, 15.5. HRMS (ESI)
calculated for [C19H22O4]þ (Mþ) requires m/z 314.1513, found m/z
314.1505.
d
7.28 (t, J¼7.8 Hz, 2H), 7.17 (t, J¼7.4 Hz, 1H), 7.14e7.11
(m, 2H), 7.02 (d, J¼8.6 Hz, 2H), 6.76 (d, J¼8.6 Hz, 2H), 5.22 (br s, 1H),
2.14e2.05 (m, 2H), 1.41e1.34 (m, 2H); 13C NMR: (125.7 MHz, CDCl3)
d
153.4, 142.6, 134.7, 128.3, 127.1, 125.7, 125.6, 115.3, 27.4, 27.2, 17.8.
4.2.8. trans-1-(20,40-Dimethoxyphenyl)-2-(40-methoxyphenyl)cyclo-
HRMS (EI) calculated for [C15H14O]þ (Mþ) requires m/z 210.1040,
found m/z 210.1033.
propane (3l). Prepared from 4.15
g
(25 mmol) 2,4-
dimethoxybenzaldehyde and 3.75 g (25 mmol) of 40-methox-
yacetophenone using the general procedure to afford 4.79 g (67%
yield) of cyclopropane. The cyclopropane was isomerized using
3 mg (0.0035 mmol) of Ru(bpz)3(PF6)2 in 8.9 mL of MeNO2 to obtain
954 mg (95% yield) of the pure trans diastereomer as a crystalline
solid. Mp: 103e106 ꢁC (hexane/ethyl acetate). IR (neat) 2988, 2926,
4.2.4. trans-1-Phenyl-2-(40-triisopropylsilyloxyphenyl)cyclopropane
(3f). A 25 mL round-bottomed flask was charged with 500 mg
(2.38 mmol) 3e and 5.9 mL DMF. To this solution were added
324 mg (4.76 mmol) imidazole and 0.76 mL (3.57 mmol) TIPSCl.
After 24 h the flask was placed in a water bath, and the reaction was
quenched by slow addition of water. The mixture was extracted
three times with hexanes, and the combined organic phases were
dried over MgSO4 and concentrated by rotary evaporation. Purifi-
cation on SiO2 afforded 377 mg (43% yield) of a clear oil. IR (neat)
.
2835, 1613, 1586, 1508, 1157, 1034 cmꢀ1 1H NMR: (499.9 MHz,
CDCl3)
d
7.13 (d, J¼8.3 Hz, 2H), 6.88 (d, J¼7.9 Hz, 1H), 6.83
(d, J¼8.3 Hz, 2H), 6.46e6.41 (m, 2H), 3.80 (s, 3H), 3.79 (s, 3H), 3.78
(s, 3H), 2.25 (dt, J¼8.7, 5.5 Hz, 1H), 2.00 (dt, J¼8.7, 5.5 Hz, 1H),
1.29e1.22 (m, 2H); 13C NMR: (125.7 MHz, CDCl3)
d 159.1, 158.9,
2945, 2867, 1607, 1513, 1463, 1265 cmꢀ1
CDCl3)
.
1H NMR: (499.9 MHz,
157.7, 135.2, 127.3, 125.9, 123.4, 113.7, 103.9, 98.4, 55.5, 55.4, 55.3,
25.2, 20.8, 15.9. HRMS (ESI) calculated for [C18H20O3]þ (Mþ)
requires m/z 284.1407, found m/z 284.1408.
d
7.27 (t, J¼7.5 Hz, 2H), 7.16 (t, J¼7.5 Hz, 1H), 7.14e7.10
(m, 2H), 6.98 (d, J¼8.6 Hz, 2H), 6.80 (d, J¼8.6 Hz, 2H), 2.13e2.05
(m, 2H), 1.36 (ddd, J¼7.9, 6.6, 0.9 Hz, 2H), 1.28e1.20 (m, 3H), 1.10
(d, J¼7.2 Hz, 18H); 13C NMR: (125.7 MHz, CDCl3)
d
154.2, 142.8,
4.2.9. trans-1-(20,40-Dimethoxyphenyl)-2-(40-methylphenyl)cyclo-
134.7, 128.3, 126.7, 125.7, 125.6, 119.7, 27.5, 27.4, 18.0, 17.9, 12.7.
HRMS (EI) calculated for [C24H34OSi]þ (Mþ) requires m/z 366.2374,
found m/z 366.2387.
propane (3m). Prepared from 2.95
g
(25 mmol) 4-
methylbenzaldehyde and 4.5 g (25 mmol) of 20,40-dimethox-
yacetophenone using the general procedure to afford 5.57 g (83%
yield) of cyclopropane. The cyclopropane was isomerized using
3.2 mg (0.0037 mmol) of Ru(bpz)3(PF6)2 in 9.2 mL of MeNO2 to
obtain 993 mg (99% yield) of the pure trans diastereomer as
a crystalline solid. Mp: 67e68 ꢁC (hexane/ethyl acetate). IR (neat)
3001, 2957, 2939, 2835, 1613, 1586, 1507, 1464, 1207, 1157 cmꢀ1. 1H
4.2.5. trans-tert-Butyl
4-(2-phenylcyclopropyl)phenylcarbamate
(3h). A 100 mL round-bottomed flask was charged with 1.05 g
(5 mmol) 3g and 30 mL 1,4-dioxane. To this solution were added
0.84 mL (6 mmol) of Et3N and 1.31 g (6 mmol) Boc2O. After 24 h, the
solvent was removed by rotary evaporation, and the residue was
purified by flash column chromatography (gradient, 8:1 to 3:1
hexanes/EtOAc) to afford 1.41 g (91% yield) of a yellow oil. IR (neat)
3394, 2981, 2934, 1808, 1727, 1593, 1525, 1162, 1110, 1072 cmꢀ1. 1H
NMR: (499.9 MHz, CDCl3)
d
7.08 (s, 4H), 6.87 (d, J¼8.2 Hz, 1H),
6.45e6.40 (m, 2H), 3.772 (s, 3H), 3.767 (s, 3H), 2.32e2.27 (m, 4H),
2.01 (ddd, J¼8.1, 6.2, 4.8 Hz, 1H), 1.31e1.25 (m, 2H); 13C NMR:
(125.7 MHz, CDCl3)
d 159.1, 158.9, 140.1, 134.9, 128.9, 126.0, 125.9,
NMR: (500.2 MHz, CDCl3)
d
7.30e7.25 (m, 4H), 7.14e7.11 (m, 2H),
123.3, 103.9, 98.4, 55.4, 55.3, 25.6, 21.2, 20.9, 16.3. HRMS (EI) cal-
culated for [C18H20O2]þ (Mþ) requires m/z 268.1458, found m/z
268.1470.
7.09e7.05 (m, 3H), 6.41 (br s, 1H), 2.15e2.07 (m, 2H), 1.51 (s, 9H),
1.42e1.38 (m, 2H). HRMS (EI) calculated for [C20H23NO2]þ (Mþ)
requires m/z 309.1724, found m/z 309.1716.
4.2.10. trans-1-(40-Bromophenyl)-2-(20,40-dimethoxyphenyl)cyclo-
4.2.6. trans-1-(30,40-Dimethoxyphenyl)-2-phenylcyclopropane (3j).
Prepared from 8.3 g (50 mmol) of benzaldehyde and 6.0 g
(50 mmol) of 20-methoxyacetophenone using the general pro-
cedure to afford 10.0 g (79% yield) of cyclopropane. The cyclopro-
pane was isomerized using 3.4 mg (0.004 mmol) of Ru(bpz)3(PF6)2
in 6.6 mL of MeNO2 to obtain 987 mg (99% yield) of the pure trans
diastereomer. IR (neat) 3000, 2934, 2834, 1604, 1589, 1518, 1254,
propane
(3n). Prepared from 4.6
g
(25 mmol) 4-
bromobenzaldehyde and 4.5 g (25 mmol) of 20,40-dimethox-
yacetophenone using the general procedure to afford 5.06 g (61%
yield) of cyclopropane. The cyclopropane was isomerized using
2.6 mg (0.003 mmol) of Ru(bpz)3(PF6)2 in 5 mL of MeNO2 to obtain
961 mg (96% yield) of the pure trans diastereomer as a crystalline
solid. Mp: 84e85 ꢁC (hexane/ethyl acetate). IR (neat) 3003, 2958,
1236, 1140, 1028 cmꢀ1
.
1H NMR: (499.9 MHz, CDCl3)
d
7.28
2936, 2836, 1612, 1586, 1507, 1489, 1207 cmꢀ1
(499.9 MHz, CDCl3)
7.39 (d, J¼8.4 Hz, 2H), 7.05 (d, J¼8.4 Hz, 2H),
6.88 (d, J¼8.3 Hz, 1H), 6.45 (d, J¼2.5 Hz, 1H), 6.43 (dd, J¼8.3, 2.5 Hz,
.
1H NMR:
(t, J¼7.27 Hz, 2H), 7.17 (t, J¼7.4 Hz, 1H), 7.15e7.11 (m, 2H), 6.80
d
(d, J¼7.9 Hz, 1H), 6.71e6.67 (m, 2H), 3.87 (s, 3H), 3.85 (s, 3H), 2.13

4274
Z. Lu et al. / Tetrahedron 70 (2014) 4270e4278
1H), 3.80 (s, 3H), 3.80 (s, 3H), 2.27 (ddd, J¼8.9, 6.2, 5.1 Hz, 1H), 1.98
(dt, J¼8.7, 5.1 Hz, 1H), 1.35 (ddd, J¼8.7, 6.2, 5.1 Hz, 1H), 1.27
isomerized using 2.7 mg (0.0031 mmol) of Ru(bpz)3(PF6)2 in 8.2 mL
of MeNO2 to obtain 997 mg (100% yield) of the pure trans di-
astereomer as a crystalline solid. Mp: 93e95 ꢁC (hexane/ethyl ac-
etate). IR (neat) 2998, 2967, 1616, 1584, 1508, 1324, 1120 cmꢀ1. 1H
(dd, J¼8.9, 5.1 Hz, 1H); 13C NMR: (125.7 MHz, CDCl3)
d 159.2, 159.1,
142.3, 131.2, 127.9, 126.0, 122.8, 119.0, 103.9, 98.5, 55.5, 55.4, 25.5,
21.8, 16.2. HRMS (EI) calculated for [C17H17BrO2]þ (Mþ) requires m/z
332.0407, found m/z 332.0417.
NMR: (499.9 MHz, CDCl3)
d
7.52 (d, J¼8.1 Hz, 2H), 7.25 (d, J¼8.1 Hz,
2H), 6.89 (d, J¼8.1 Hz, 1H), 6.47e6.42 (m, 2H), 3.792 (s, 3H), 3.789
(s, 3H), 2.34 (ddd, J¼8.9, 6.2, 5.0 Hz, 1H), 2.06 (dt, J¼8.7, 5.2 Hz, 1H),
1.42 (ddd, J¼8.7, 6.2, 5.2 Hz, 1H), 1.35 (dt, J¼8.9, 5.5 Hz, 1H); 13C
4.2.11. trans-1-(40-Chlorophenyl)-2-(20,40-dimethoxyphenyl)cyclo-
propane (3o). Prepared from 4.15 g (25 mmol) 20,40-dimethox-
ybenzaldehyde and 3.24 g (25 mmol) of 40-chloroacetophenone
using the general procedure to afford 6.31 g (87% yield) of cy-
NMR: (125.7 MHz, CDCl3)
d 159.2, 159.2, 147.6, 126.1, 126.1, 125.2
(q, J¼3.8 Hz),122.4,103.9, 98.5, 55.4, 55.4, 25.9, 22.4,16.7. HRMS (EI)
calculated for [C18H17F3O2]þ (Mþ) requires m/z 322.1176, found m/z
322.1171.
clopropane. The cyclopropane was isomerized using
3 mg
(0.0035 mmol) of Ru(bpz)3(PF6)2 in 8.8 mL of MeNO2 to obtain
995 mg (99% yield) of the pure trans diastereomer as a crystalline
solid. Mp: 76e78 ꢁC (hexane/ethyl acetate). IR (neat) 3001, 2956,
4 . 2 .15 . t r a n s - 1 - ( 2 0, 4 0- D i m e t h o x y p h e n y l ) - 2 - ( 2 0- t r i -
fluoromethylphenyl)cyclopropane (3s). Prepared from 3.3 mL
(25 mmol) 2-(trifluoromethyl)benzaldehyde and 4.5 g (25 mmol) of
20,40-dimethoxyacetophenone using the general procedure to
afford 67.3 g (91% yield) of cyclopropane. The cyclopropane was
isomerized using 2.7 mg (0.0031 mmol) of Ru(bpz)3(PF6)2 in 5.2 mL
of MeNO2 to obtain 980 mg (98% yield) of the pure trans di-
astereomer as a colorless oil. IR (neat) 3004, 3939, 2837, 1614, 1587,
2835, 1614, 1586, 1509, 1208, 1037 cmꢀ1 1H NMR: (499.9 MHz,
.
CDCl3)
d
7.23 (d, J¼8.2 Hz, 2H), 7.10 (d, J¼8.2 Hz, 2H), 6.88
(d, J¼8.2 Hz, 1H), 6.46e6.41 (m, 2H), 3.788 (s, 3H), 3.786 (s, 3H),
2.27 (dt, J¼8.9, 5.5 Hz, 1H), 1.98 (dt, J¼8.9, 5.3 Hz, 1H), 1.34
(dt, J¼8.8, 5.5 Hz, 1H), 1.27 (dt, J¼8.8, 5.5 Hz, 1H); 13C NMR:
(125.7 MHz, CDCl3)
d 159.15, 159.09, 141.7, 131.0, 128.3, 127.4,
126.0, 122.8, 103.9, 98.4, 55.4, 55.3, 25.4, 21.7, 16.2. HRMS (EI)
calculated for [C17H17ClO2]þ (Mþ) requires m/z 288.0912, found
m/z 288.0907.
.
1510, 1316, 1209, 1158, 1125, 1036 cmꢀ1 1H NMR: (499.9 MHz,
CDCl3)
d
7.60 (d, J¼7.7 Hz, 1H), 7.45 (t, J¼7.7 Hz, 1H), 7.28e7.20 (m,
2H), 6.94 (d, J¼8.1 Hz, 1H), 6.47e6.42 (m, 2H), 3.79 (s, 3H), 3.78 (s,
3H), 2.44 (dt, J¼8.9, 5.5 Hz, 1H), 2.41e2.35 (m, 1H), 1.38 (ddd, J¼8.9,
6.1, 5.1 Hz, 1H), 1.33 (dt, J¼8.9, 5.5 Hz, 1H); 13C NMR: (125.7 MHz,
4.2.12. trans-1-(30-Chlorophenyl)-2-(20,40-dimethoxyphenyl)cyclo-
propane (3p). Prepared from 2.83
g
(25 mmol) 3-
CDCl3)
d
159.2, 159.2, 141.6, 131.8, 126.3, 126.2, 125.7 (q, J¼5.8 Hz),
chlorobenzaldehyde and 4.5 g (25 mmol) of 20,40-dimethox-
yacetophenone using the general procedure to afford 5.38 g (75%
yield) of cyclopropane. The cyclopropane was isomerized using
3 mg (0.0035 mmol) of Ru(bpz)3(PF6)2 in 5.8 mL of MeNO2 to
obtain 999 mg (100% yield) of the pure trans diastereomer as
a crystalline solid. Mp: 55e56 ꢁC (hexane/ethyl acetate). IR (neat)
125.4, 122.4, 103.9, 98.4, 55.4, 55.3, 21.9, 21.9, 21.2, 16.8. HRMS (EI)
calculated for [C18H17F3O2]þ (Mþ) requires m/z 322.1176, found m/z
322.1187.
4.2.16. trans-1-(20,40-Dimethoxyphenyl)-2-(20-furyl)cyclopropane
(3t). Prepared from 2.07 mL (25 mmol) of 2-furaldehyde and 4.5 g
(25 mmol) of 20,40-dimethoxyacetophenone using the general
procedure to afford 5.04 g (83% yield) of cyclopropane. The cyclo-
propane was isomerized using 3.5 mg (0.004 mmol) of
Ru(bpz)3(PF6)2 in 6.8 mL of MeNO2 to obtain 918 mg (92% yield) of
the pure trans diastereomer as a colorless oil. IR (neat) 2938, 2836,
3001, 2956, 2835, 1615, 1598, 1509, 1290, 1208, 1037 cmꢀ1
.
1H
NMR: (499.9 MHz, CDCl3) 7.19e7.15 (m, 2H), 7.13e7.10 (m, 1H),
d
7.06e7.02 (dt, 1H), 6.86 (d, J¼8.3 Hz, 1H), 3.78 (s, 3H), 3.77 (s, 3H),
2.29 (ddd, J¼8.9, 6.2, 4.9 Hz, 1H), 1.98 (dt, J¼8.9, 5.3 Hz, 1H), 1.34
(ddd, J¼8.7, 6.3, 5.2 Hz, 1H), 1.28 (dt, J¼8.8, 5.3 Hz, 1H); 13C NMR:
(125.7 MHz, CDCl3)
d
159.1, 145.4, 134.1, 129.4, 126.2, 126.1, 125.5,
1611, 1507, 1208, 1120, 1036 cmꢀ1 1H NMR: (500.2 MHz, CDCl3)
.
124.3, 122.6, 103.8, 98.4, 55.4, 55.3, 25.6, 21.8, 16.3. HRMS (EI)
calculated for [C17H17ClO2]þ (Mþ) requires m/z 288.0912, found m/
z 288.0917.
d
7.27 (dd, J¼2.0,1.0 Hz,1H), 6.87 (d, J¼8.4 Hz,1H), 6.45 (d, J¼2.4 Hz,
1H), 6.42 (dd, J¼8.4, 2.4 Hz, 1H), 6.29 (dd, J¼3.2, 1.8 Hz, 1H), 6.03
(d, J¼3.2 Hz, 1H), 3.82 (s, 3H), 3.79 (s, 3H), 2.44e2.39 (m, 1H), 2.07
(dt, J¼8.8, 5.2 Hz, 1H), 1.36 (ddd, J¼8.8, 5.6, 4.6 Hz, 1H), 1.24
4.2.13. trans-1-(20-Chlorophenyl)-2-(20,40-dimethoxyphenyl)cyclo-
(ddd, J¼8.8, 6.2, 4.6 Hz, 1H); 13C NMR: (125.8 MHz, CDCl3)
d 159.2,
propane (3q). Prepared from 2.82
g
(25 mmol) 2-
159.1, 156.7, 140.4, 126.1, 122.3, 110.3, 103.9, 103.6, 98.5, 55.5, 55.4,
19.3, 18.7, 14.5. HRMS (EI) calculated for [C15H16O3]þ (Mþ) requires
m/z 244.1094, found m/z 244.1104.
chlorobenzaldehyde and 4.5 g (25 mmol) of 20,40-dimethox-
yacetophenone using the general procedure to afford 6.22 g (86%
yield) of cyclopropane. The cyclopropane was isomerized using
3 mg (0.0035 mmol) of Ru(bpz)3(PF6)2 in 5.8 mL of MeNO2 to obtain
977 mg (98% yield) of the pure trans diastereomer as a colorless oil.
4.2.17. trans-2,4-Dimethoxy-1-(2-(phenylethynyl)cyclopropyl)ben-
zene (3u). Ethyl diethylphosphonoacetate (6.72 g, 30 mmol) was
added to a suspension of 60% NaH (1.20 g, 30 mmol) in 80 mL THF at
0 ꢁC. The reaction mixture was stirred at room temperature for 2 h.
IR (neat) 3001, 2956, 2835, 1615, 1598, 1509, 1290, 1208, 1037 cmꢀ1
.
1H NMR: (499.9 MHz, CDCl3)
d
7.34 (dd, J¼8.1, 1.2 Hz, 1H), 7.20e7.16
(m, 1H), 7.12 (dd, J¼7.8, 1.7 Hz, 1H), 7.09 (td, J¼7.6, 1.7 Hz, 1H), 6.99
(d, J¼8.1 Hz, 1H), 6.47e6.42 (m, 2H), 3.80 (s, 3H), 3.78 (s, 3H), 2.39
(dt, J¼8.8, 5.4 Hz, 1H), 2.32 (dt, J¼8.8, 5.4 Hz, 1H), 1.33 (ddd, J¼8.6,
6.2, 4.9 Hz, 1H), 1.28 (ddd, J¼8.8, 5.8, 4.9 Hz, 1H); 13C NMR:
The flask was again cooled to
0
ꢁC, and 2,4-
dimethoxybenzaldehyde (4.98 g, 30 mmol) was added. The re-
action mixture was warmed to 40 ꢁC for 4 h and quenched with
saturated NH4Cl (aq). The mixture was extracted twice with Et2O,
and the combined organic layers were washed with brine, dried
over MgSO4, and concentrated by rotary evaporation. The residue
was placed in a 250 mL round-bottomed flask and dissolved in
100 mL CH2Cl2. The flask was cooled to ꢀ78 ꢁC, and a 1.0 M solution
of DIBAL-H in hexanes (90 mL, 90 mmol) was added dropwise by
syringe. After 30 min at ꢀ78 ꢁC and 1 h at 0 ꢁC, the reaction was
quenched by adding a saturated aqueous solution of Rochelle’s salt
and stirred at room temperature for an additional 1 h. The mixture
was extracted twice with Et2O, and the combined organic layers
were washed with brine and dried over MgSO4. After concentration
(125.7 MHz, CDCl3)
d 159.2, 159.1, 140.3, 135.1, 129.0, 126.7, 126.5,
126.2, 122.7, 103.8, 98.4, 55.4, 55.3, 22.9, 20.6, 15.8. HRMS (EI) cal-
culated for [C17H17ClO2]þ (Mþ) requires m/z 288.0912, found m/z
288.0917.
4 . 2 .14 . t r a n s - 1 - ( 2 0, 4 0- D i m e t h o x y p h e n y l ) - 2 - ( 4 0- t r i -
fluoromethylphenyl)cyclopropane (3r). Prepared from 2.41 mL
(25 mmol) of 4-(trifluoromethyl)benzaldehyde and 4.5 g (25 mmol)
of 20,40-dimethoxyacetophenone using the general procedure to
afford 3.7 g (65% yield) of cyclopropane. The cyclopropane was

Z. Lu et al. / Tetrahedron 70 (2014) 4270e4278
4275
by rotary evaporation, the residue was used to next step without
further purification.
28.6, 19.0, 18.9. HRMS (EI) calculated for [C18H20O2]þ (Mþ) requires
m/z 268.1458, found m/z 268.1455.
The resulting cinnamyl alcohol was dissolved in CH2Cl2
(300 mL). A solution of ZnEt2 (35 mL, 35 mmol, 1.17 equiv, 1 M in
hexane) was added dropwise at 0 ꢁC. The suspension was stirred
for 30 min. In a second flask, ZnEt2 (35 mL, 35 mmol, 1.17 equiv,
1 M in hexane) was added to diiodomethane (4.8 mL, 60 mmol,
2 equiv) in dry CH2Cl2 (90 mL) and stirred for 30 min at 0 ꢁC. The
solution in the first flask was transferred into the second flask at
0 ꢁC and the mixture was stirred at room temperature for 1.5 h. A
saturated solution of NH4Cl (50 mL) was added, followed by
aq 10% HCl (100 mL). The mixture was extracted with DCM
(300 mL), then the organic layer was washed with saturated
solutions of Na2SO3, NaHCO3, and brine. After drying over
MgSO4 and concentrating by rotary evaporation, the
residue was purified with column chromatography (hexane/
EtOAc¼5:1) to afford the cyclopropylmethanol (5.2 g, 83% in
three steps).
4.2.19. 2,4-Dimethoxy-1-(1-methyl-2-phenylcyclopropyl)benzene
(3w). Sodium methoxide was freshly prepared by adding 660 mg
of Na to 20 mL of methanol in a flame-dried 50 mL round-bottomed
flask. Dimethyl 2-oxo-2-phenylethylphosphonate (2.75 g, 12 mmol)
was added to the solution. After 20 min, 1.8 g (10 mmol) 20,40-
dimethoxyacetophenone was added, and the flask was fitted with
a reflux condenser and heated to reflux for 24 h. After cooling to
room temperature, the reaction was quenched with water and
extracted five times with CH2Cl2. The organic phases were dried
over MgSO4 and concentrated by rotary evaporation. The residue
was purified by flash column chromatography to obtain 950 mg
(3.37 mmol, 34% yield) of 3-(2,4-dimethoxyphenyl)-1-phenylprop-
2-en-1-one as a yellow oil. This material was immediately placed in
a 100 mL round-bottomed flask and dissolved in 10 mL EtOH. Hy-
drazine monohydrate (0.5 mL, 10.3 mmol) was added, the flask was
fitted with a reflux condenser, and the reaction mixture was heated
to reflux for 2 h. Potassium hydroxide (0.1 g, 1.78 mmol) was added,
and after 15 min the reaction mixture was cooled to room tem-
perature. The reaction mixture was loaded directly onto a silica gel
column with dichloromethane. After flash column chromatography
(gradient, 8:1 to 4:1 hexanes/EtOAc), 232.2 mg (0.87 mmol, 26%
yield, 1:1 dr) of the title compound was obtained as a yellow oil. IR
To a stirred solution of above cyclopropyl alcohol (2.08 g,
10 mmol) in CH2Cl2 (20 mL) was added PCC (4.48 g, 20 mmol,
2.0 equiv) at room temperature. After 4 h, the mixture was filtered
though a plug of Celite and concentrated. The residue was purified
with column chromatography (hexane/EtOAc¼10:1) to afford the
aldehyde (1.62 g, 79%). To a stirred solution of PPh3 (1.60 g,
6 mmol) in CH2Cl2 (10 mL) was added CBr4 (2.0 g, 6 mmol) at 0 ꢁC.
After 1 h, the aldehyde (1.03 g, 5 mmol) was added into the re-
action mixture. After 2 h, the reaction mixture was filtered
through a plug of Celite and concentrated. The residue was puri-
fied with column chromatography (hexane/EtOAc¼10:1) to afford
the dibromoalkene (1.54 g, 86%). This material was dissolved in
THF (10 mL) and treated with n-BuLi (2 mL, 2.5 M in hexane) at
ꢀ78 ꢁC. The reaction mixture was warmed to room temperature
slowly over 3 h and then quenched with saturated NH4Cl (10 mL).
The mixture was extracted with ether (3ꢃ20 mL), then the com-
bined organic layers were washed with brine, dried over MgSO4,
and concentrated by rotary evaporation. The residue was placed in
a 25 mL round-bottomed with PhI (1.22 g, 6 mmol), Pd(PPh3)2Cl2
(70 mg, 2 mol %), CuI (38 mg, 4 mol %), CH3CN (5 mL), and Et3N
(1 mL). After stirring 9 h, the reaction mixture was treated with
10 mL of water and extracted with ether (3ꢃ20 mL). The combined
organic layers were washed with brine, dried over Na2SO4, and
concentrated. The crude product were purified by column chro-
matography (hexane/EtOAc¼10:1) to afford the desired product
(0.83 g, 60% in two steps) as a crystalline solid. Mp: 46e48 ꢁC
(hexane/ethyl acetate). IR (neat) 3003, 2956, 2936, 2835, 2226,
(neat) 2999, 2955, 2835, 1615, 1583, 1506, 1208 cmꢀ1
.
1H NMR:
(499.9 MHz, CDCl3)
d
7.38 (d, J¼7.4 Hz, 1H), 7.31 (t, J¼7.7 Hz, 1H),
7.23 (d, J¼8.3 Hz, 0.5H), 7.20 (t, J¼7.4 Hz, 0.5H), 7.09 (d, J¼8.3 Hz,
0.5H), 6.99 (t, J¼7.4 Hz, 1H), 6.93 (t, J¼7.4 Hz, 0.5H), 6.72e6.69
(m, 1H), 6.47 (d, J¼2.4 Hz, 0.5H), 6.43 (dd, J¼8.4, 2.6 Hz, 0.5H), 6.34
(dd, J¼8.4, 2.6 Hz, 0.5H), 6.12 (d, J¼2.4 Hz, 0.5H), 3.89 (s, 1.5H), 3.78
(s, 1.5H), 3.70 (s, 1.5H), 3.28 (s, 1.5H), 2.23 (dd, J¼8.6, 6.5 Hz, 0.5H),
2.13 (dd, J¼8.5, 6.0 Hz, 0.5H), 1.44 (s, 1.5H), 1.32 (t, J¼5.6 Hz, 0.5H),
1.25 (dd, J¼8.6, 4.9 Hz, 0.5H), 1.17 (dd, J¼8.6, 5.2 Hz, 0.5H), 1.09 (dd,
J¼6.1, 4.9 Hz, 0.5H), 0.98 (s, 1.5H). HRMS (EI) calculated for
[C18H20O2]þ (Mþ) requires m/z 268.1458, found m/z 268.1458.
4.2.20. 1-(2,2-Dimethylcyclopropyl)-2,4-dimethoxybenzene (3x). A
solution of isopropyltriphenylphosphonium iodide (6.48 g,
15 mmol) in THF (25 mL) at 0 ꢁC was treated with n-BuLi (2 mL,
2.5 M in hexane). After 1 h, 2,4-dimethoxybenzaldehyde (1.98 g,
12 mmol) was added, and the mixture was stirred at room tem-
perature for 1.5 h. The reaction mixture was then filtered through
a plug of Celite with ether/hexane (1:1) and concentrated by rotary
evaporation. The residue was purified with column chromatogra-
phy (hexane/EtOAc¼20:1) to afford 1.94 g (84%) of pure Wittig
adduct. The styrene thus obtained was dissolved in CHCl3 (15 mL)
and treated with NaOH (50% aq) and 0.1 mL of BnMe3NCl (40% in
MeOH). After 16 h, the reaction mixture was partitioned between
DCM (50 mL) and water (10 mL), and the aqueous layer was
extracted with DCM (2ꢃ10 mL). The combined organic layers were
washed with brine, dried over MgSO4, and concentrated by rotary
evaporation. The residue was purified with column chromatogra-
phy (hexane/EtOAc¼50:1) to afford the corresponding dichlor-
ocyclopropane (2.24 g, 82% yield). A stirred solution of the
dichlorocyclopropane (0.825 g, 3 mmol) in EtOH (10 mL) was
warmed to 80 ꢁC and treated with five portions of solid sodium
metal over 6 h. After 10 h more, the reaction mixture was cooled to
room temperature and quenched by slow addition of 10 mL water.
The reaction mixture was concentrated and extracted with ether
(3ꢃ20 mL). The combined organic layers were washed with brine,
dried over MgSO4, and purified by column chromatography (hex-
ane/DCM¼4:1) to afford the desired product (0.329 g, 53%) as an oil.
IR (neat) 2996, 2941, 2866, 1616, 1585, 1508, 1208 cmꢀ1. 1H NMR:
1615, 1586, 1509, 1209 cmꢀ1 1H NMR: (499.9 MHz, CDCl3)
.
d
7.42e7.38 (m, 2H), 7.30e7.24 (m, 3H), 6.81 (d, J¼8.3 Hz, 1H), 6.45
(d, J¼2.4 Hz, 1H), 6.40 (dd, J¼8.3, 2.4 Hz, 1H), 3.85 (s, 3H), 3.79 (s,
3H), 2.48 (ddd, J¼8.9, 6.4, 4.8 Hz, 1H), 1.62 (dt, J¼8.6, 4.8 Hz, 1H),
1.32 (dt, J¼8.9, 4.6 Hz, 1H), 1.24 (ddd, J¼8.6, 6.4, 4.6 Hz, 1H); 13C
NMR: (125.7 MHz, CDCl3)
d 159.3, 159.3, 131.6, 128.1, 127.4, 126.3,
124.0, 121.4, 103.8, 98.5, 92.7, 55.5, 55.4, 21.0, 16.6, 10.0. HRMS (EI)
calculated for [C19H18O2]þ (Mþ) requires m/z 278.1302, found m/z
278.1308.
4.2.18. 2,4-Dimethoxy-1-(2-methyl-3-phenylcyclopropyl)benzene
(3v). Prepared
from
4.15
g
(25
mmol)
2,4-
dimethyloxybenzaldehyde and 3.35 g (25 mmol) ethyl phenyl ke-
tone using the general procedure to afford 0.74 g (11% yield) of
diastereomerically pure cyclopropane as a colorless oil. IR (neat)
3000, 2953, 2835, 1614, 1507, 1465, 1208 cmꢀ1 1H NMR:
.
(499.9 MHz, CDCl3)
d 7.05e7.00 (m, 2H), 6.99e6.95 (m, 1H),
6.85e6.81 (m, 2H), 6.27 (dd, J¼8.4, 2.4 Hz, 1H), 6.23 (d, J¼2.4 Hz,
1H), 3.71 (s, 3H), 3.56 (s, 3H), 2.15e2.11 (m, 2H), 1.67e1.60 (m, 1H),
1.37 (d, J¼5.9 Hz, 3H); 13C NMR: (125.7 MHz, CDCl3)
d
159.6, 159.0,
(500.2 MHz, CDCl3)
6.38 (dd, J¼8.0, 2.3 Hz, 1H), 3.80 (s, 3H), 3.78 (s, 3H), 1.72 (dd, J¼8.0,
d
6.89 (d, J¼8.0 Hz, 1H), 6.44 (d, J¼2.3 Hz, 1H),
139.7, 130.0, 127.8, 127.2, 124.9, 119.2, 103.4, 98.2, 55.3, 55.2, 31.9,

4276
Z. Lu et al. / Tetrahedron 70 (2014) 4270e4278
6.1 Hz, 1H), 1.22 (s, 3H), 0.72e0.63 (m, 5H); 13C NMR: (125.7 MHz,
13C NMR: (125.7 MHz, CDCl3)
d 155.9,139.0,129.4,128.7,128.5,128.2,
CDCl3)
d
160.4, 157.6, 126.9, 120.4, 104.2, 98.4, 83.7, 77.8, 55.4, 55.3,
126.4, 115.6, 83.4, 83.4, 51.2. HRMS (EI) calculated for [C24H34O3Si]þ
53.7, 26.3, 26.0. HRMS (EI) calculated for [C13H18O2]þ (Mþ) requires
(Mþ) requires m/z 398.2272, found m/z 398.2278.
m/z 206.1302, found m/z 206.1306.
4.3.6. cis-4-(5-Phenyl-1,2-dioxolan-3-yl)benzenamine
(4g). Prepared according to the general procedure using 104.3 mg
(0.5 mmol) of 3g, 2.2 mg (0.0025 mmol) of Ru(bpz)3(PF6)2, 5 mL of
toluene, 5 mL of nitromethane, and an irradiation time of 1 h to
afford a colorless oil; 85.1 mg (71% yield) in experiment 1 and
82.5 mg (68% yield) in experiment 2 with a >10:1 dr. IR (neat) 3463,
4.3. Synthesis of endoperoxides
4.3.1. General procedure for photooxygenation of aryl cyclo-
propanes. A 0.05 M solution of the cyclopropane substrate (1 equiv)
in 1:1 toluene/MeNO2 was placed in a 35 mL pressure vessel along
with Ru(bpz)3(PF6)2 (0.005 or 0.05 equiv). A pressure regulator
gauge was attached, and the solution was pressurized to 30 psi with
O2. The vessel was placed cooled to ꢀ30 ꢁC and irradiated with
a 23 W CFL bulb. Following irradiation, the vessel was depressur-
ized and the solution was filtered through a pad of silica with
CH2Cl2. The solvent was then removed by rotary evaporation to
obtain analytically pure endoperoxide.
3375, 3222, 3032, 2916, 1623, 1520, 1286 cmꢀ1
.
1H NMR:
(499.9 MHz, CDCl3)
d
7.43 (d, J¼7.3 Hz, 2H), 7.37 (t, J¼7.3 Hz, 2H),
7.31 (t, J¼7.3 Hz, 1H), 7.17 (d, J¼8.2 Hz, 2H), 6.64 (d, J¼8.2 Hz, 2H),
5.44 (t, J¼7.3 Hz,1H), 5.32 (dd, J¼8.2, 7.2 Hz,1H), 3.70 (br s, 2H), 3.37
(dt, J¼12.4, 7.3 Hz, 1H), 2.70 (ddd, J¼12.4, 8.2, 7.3 Hz, 1H); 13C NMR:
(125.7 MHz, CDCl3)
d 146.8, 139.8, 128.6, 128.4, 128.0, 126.6, 126.3,
115.0, 83.6, 83.2, 51.1. HRMS (EI) calculated for [C15H15NO2]þ (Mþ)
requires m/z 241.1098, found m/z 241.1100.
4.3.2. cis-3-(40-Methoxyphenyl)-5-phenyl-1,2-dioxolane
(4a).
Prepared according to the general procedure using 112.2 mg
(0.5 mmol) of 3a, 2.2 mg (0.0025 mmol) of Ru(bpz)3(PF6)2, 5 mL of
toluene, 5 mL of nitromethane, and an irradiation time of 3 h to
afford a colorless oil; 126.5 mg (99% yield) in experiment 1 and
126.3 mg (99% yield) in experiment 2 with a 5:1 dr. All analytical
data were consistent with previously reported values.5b
4.3.7. cis-tert-Butyl 4-(5-phenyl-1,2-dioxolan-3-yl)phenylcarbamate
(4h). Prepared according to the general procedure using 150.2 mg
(0.5 mmol) of 3h, 2.2 mg (0.0025 mmol) of Ru(bpz)3(PF6)2, 5 mL of
toluene, 5 mL of nitromethane, and an irradiation time of 3 h to
afford a colorless oil; 156.2 mg (94% yield) as an oil in experiment 1
and 151.4 mg (91% yield) in experiment 2 with a 5:1 dr. IR (neat)
3347, 3033, 2980, 2932, 1807, 1729, 1616, 1597, 1525, 1159 cmꢀ1. 1H
4.3.3. cis-3-(20-Methoxyphenyl)-5-phenyl-1,2-dioxolane
(4d).
NMR: (499.9 MHz, CDCl3) d 7.41e7.33 (m, 6H), 7.32e7.28 (m, 3H),
Prepared according to the general procedure using 112.2 mg
(0.5 mmol) of 3d, 21.6 mg (0.025 mmol) of Ru(bpz)3(PF6)2, 5 mL of
toluene, 5 mL of nitromethane, and an irradiation time of 48 h to
afford a colorless oil; 61.5 mg (48% yield) in experiment 1 and
57.6 mg (45% yield) in experiment 2 with a 5:1 dr. IR (neat) 2960,
6.59 (br s, 1H), 5.43 (t, J¼7.4 Hz, 1H), 5.38 (t, J¼7.4 Hz, 1H), 3.42 (dt,
J¼12.5, 7.4 Hz, 1H), 2.67 (dt, J¼12.5, 7.4 Hz, 1H), 1.51 (s, 9H); 13C
NMR: (125.7 MHz, CDCl3)
d 152.6, 138.9, 138.4, 132.6, 128.6, 128.2,
127.4, 126.5, 118.6, 83.3, 83.0, 51.4, 28.3, 27.3. HRMS (EI) calculated
for [C20H23NO4]þ (Mþ) requires m/z 341.1622, found m/z 341.1612.
2903, 2838, 1687, 1602, 1495, 1244, 1028 cmꢀ1
.
1H NMR:
(499.9 MHz, CDCl3)
d
7.59 (d, J¼7.3 Hz, 1H), 7.47e7.22 (m, 6H),
4.3.8. cis-3-(20,40-Dimethoxyphenyl)-5-phenyl-1,2-dioxolane
(4i). Prepared according to the general procedure using 127.2 mg
(0.5 mmol) of 3i, 2.2 mg (0.0025 mmol) of Ru(bpz)3(PF6)2, 5 mL of
toluene, 5 mL of nitromethane, and an irradiation time of 1 h to
afford a colorless oil; 140.0 mg (99% yield) in experiment 1 and
139.2 mg (98% yield) in experiment 2 with a 10:1 dr. IR (neat) 2960,
7.02e6.96 (m, 1H), 6.90e6.84 (m, 1H), 5.73 (t, J¼7.3 Hz, 1H), 5.37 (t,
J¼7.8 Hz, 1H), 3.79 (s, 3H), 3.52 (dt, J¼12.5, 7.6 Hz, 1H), 2.55 (ddd,
J¼12.4, 8.1, 6.6 Hz,1H); 13C NMR: (125.7 MHz, CDCl3)
d 156.2,138.0,
128.6, 128.5, 128.2, 126.9, 126.6, 125.8, 120.6, 110.2, 83.4, 78.4, 55.2,
50.7. HRMS (EI) calculated for [C16H15O]þ([MꢀOOH]þ) requires m/z
223.1118, found m/z 223.1113.
2939, 2837, 1613, 1589, 1507, 1287, 1209, 1035 cmꢀ1
.
1H NMR:
(499.9 MHz, CDCl3)
d
7.43 (d, J¼8.4 Hz, 1H), 7.37e7.25 (m, 5H), 6.49
4.3.4. cis-3-(40-Hydroxyphenyl)-5-phenyl-1,2-dioxolane
(4e). Prepared according to the general procedure using 105.1 mg
(0.5 mmol) of 3e, 2.2 mg (0.0025 mmol) of Ru(bpz)3(PF6)2, 5 mL of
toluene, 5 mL of nitromethane, and an irradiation time of 1 h to
afford a colorless oil; 92.1 mg (76% yield) experiment 1 and 97.1 mg
(80% yield) in experiment 2 with a >10:1 dr. IR (neat) 3385, 3064,
3031, 2903, 1654, 1600, 1517, 1449, 1219 cmꢀ1. 1H NMR: (499.9 MHz,
(dd, J¼8.4, 2.3 Hz, 1H), 6.44 (d, J¼2.3 Hz, 1H), 5.68 (t, J¼7.2 Hz, 1H),
5.38 (t, J¼7.7 Hz, 1H), 3.78 (s, 3H), 3.76 (s, 3H), 3.44 (dt, J¼12.4,
7.7 Hz, 1H), 2.58 (ddd, J¼12.4, 7.7, 7.2 Hz, 1H); 13C NMR: (125.7 MHz,
CDCl3)
d 160.5, 157.6, 138.6, 128.5, 128.1, 127.0, 126.7, 120.0, 104.2,
98.4, 83.3, 78.3, 55.3, 55.2, 50.4. HRMS (EI) calculated for
[C17H18O4]þ (Mþ) requires m/z 286.1200, found m/z 286.1187.
CDCl3)
d
7.42e7.39 (m, 2H), 7.38e7.34 (m, 2H), 7.33e7.28 (m, 1H),
4.3.9. cis-3-(30,40-Dimethoxyphenyl)-5-(40-methoxyphenyl)-1,2-
dioxolane (4j). Prepared according to the general procedure using
127.2 mg (0.5 mmol) of 3i, 21.6 mg (0.025 mmol) of Ru(bpz)3(PF6)2,
5 mL of toluene, 5 mL of nitromethane, and an irradiation time of
24 h to afford a colorless oil; 107.4 mg (75% yield) in experiment 1
and 112.3 mg (78% yield) in experiment 2 with a 5:1 dr. IR (neat)
2958, 2936, 2836, 1606, 1594, 1518, 1464, 1263, 1140 cmꢀ1. 1H NMR:
7.23 (d, J¼8.5 Hz, 2H), 6.79 (d, J¼8.5 Hz, 2H), 5.60 (br s, 1H), 5.44 (t,
J¼7.3 Hz, 1H), 5.36 (t, J¼7.6 Hz, 1H), 3.39 (dt, J¼12.5, 7.3 Hz, 1H), 7.0
(dt, J¼12.5, 7.6 Hz, 1H); 13C NMR: (125.7 MHz, CDCl3)
d 155.9, 139.0,
129.4, 128.7, 128.5, 128.2, 126.4, 115.6, 83.4, 83.4, 51.2. HRMS (EI)
calculated for [C15H14O3]þ (Mþ) requires m/z 242.0938, found m/z
242.0932.
(499.9 MHz, CDCl3)
d
7.42 (d, J¼7.7 Hz, 2H), 7.36 (dd, J¼7.7, 7.6 Hz,
4.3.5. cis-Triisopropyl(4-(5-phenyl-1,2-dioxolan-3-yl)phenoxy)silane
(4f). Prepared according to the general procedure using 183.3 mg
(0.5 mmol) of 3f, 2.2 mg (0.0025 mmol) of Ru(bpz)3(PF6)2, 5 mL of
toluene, 5 mL of nitromethane, and an irradiation time of 3 h to
afford a colorless oil; 189.7 mg (95% yield) in experiment 1 and
187.4 mg (94% yield) in experiment 2 with a 4:1 dr. IR (neat) 2945,
2H), 7.30 (t, J¼7.6 Hz, 1H), 6.90 (dd, J¼8.3, 1.8 Hz, 1H), 6.84 (d,
J¼1.8 Hz, 1H), 6.81 (d, J¼8.3 Hz, 1H), 5.46 (t, J¼7.1 Hz, 1H), 5.37 (t,
J¼7.4 Hz, 1H), 3.85 (s, 3H), 3.77 (s, 3H), 3.45 (dt, J¼12.3, 7.4 Hz, 1H),
2.72 (dt, J¼12.3, 7.1 Hz, 1H); 13C NMR: (125.7 MHz, CDCl3)
d 149.0,
139.3, 130.5, 128.6, 128.0, 126.6, 126.3, 119.4, 110.9, 109.6, 83.1, 83.0,
55.8, 55.6, 51.3. HRMS (EI) calculated for [C17H18O4]þ (Mþ) requires
m/z 286.1200, found m/z 286.1209.
2867, 1608, 1512, 1463, 1268 cmꢀ1 1H NMR: (499.9 MHz, CDCl3)
.
d
7.42e7.28 (m, 5H), 7.24 (d, J¼8.6 Hz, 2H), 6.85 (d, J¼8.6 Hz, 2H), 5.44
(t, J¼7.5 Hz, 1H), 5.37 (t, J¼7.5 Hz, 1H), 3.41 (dt, J¼12.3, 7.4 Hz, 1H),
2.70 (dt, J¼12.3, 7.6 Hz,1H),1.30e1.20 (m, 3H),1.09 (d, J¼7.3 Hz,18H);
4.3.10. cis-3,5-Bis(20,40-dimethoxyphenyl)-1,2-dioxolane
(4k). Prepared according to the general procedure using 157.1 mg

Z. Lu et al. / Tetrahedron 70 (2014) 4270e4278
4277
(0.5 mmol) of 3k, 2.2 mg (0.0025 mmol) of Ru(bpz)3(PF6)2, 5 mL of
toluene, 5 mL of nitromethane, and an irradiation time of 1 h to
afford a colorless oil; 168.4 mg (97% yield) as an oil in experiment 1
and 171.2 mg (99% yield) in experiment 2 with a 6:1 dr. IR (neat)
a 10:1 dr. IR (neat) 3001, 2960, 2837, 1615, 1589, 1507, 1209 cmꢀ1. 1H
NMR: (499.9 MHz, CDCl3)
d
7.36 (d, J¼8.4 Hz, 1H), 7.27 (s, 4H), 6.47
(dd, J¼8.6, 2.5 Hz, 1H), 6.43 (d, J¼2.5 Hz, 1H), 5.65 (t, J¼7.4 Hz, 1H),
5.34 (t, J¼7.6 Hz, 1H), 3.77 (s, 3H), 3.75 (s, 3H), 3.43 (dt, J¼12.3,
7.6 Hz, 1H), 2.52 (dt, J¼12.3, 7.4 Hz, 1H); 13C NMR: (125.7 MHz,
3001, 2940, 2838, 1613, 1507, 1210 cmꢀ1
.
1H NMR: (499.9 MHz,
CDCl3)
d
7.37 (d, J¼8.6 Hz, 2H), 6.46 (dd, J¼8.6, 2.3 Hz, 2H), 6.42 (d,
CDCl3) d 160.6, 157.7, 137.7, 133.7, 128.6, 128.0, 127.0, 119.2, 104.2,
J¼2.3 Hz, 2H), 5.66 (t, J¼7.4 Hz, 2H), 3.77 (s, 6H), 3.76 (s, 6H), 3.40
98.4, 82.4, 78.3, 55.2, 55.2, 50.2. HRMS (EI) calculated for
(dt, J¼12.3, 7.6 Hz, 1H), 2.45 (dt, J¼12.3, 7.3 Hz, 1H); 13C NMR:
[C17H17ClO4]þ (Mþ) requires m/z 320.0810, found m/z 320.0822.
(125.7 MHz, CDCl3) d 160.4, 157.7, 127.1, 119.9, 104.2, 98.2, 77.9, 55.2,
49.0. HRMS (EI) calculated for [C19H22O6]þ (Mþ) requires m/z
346.1411, found m/z 346.1400.
4.3.15. cis-3-(30-Chlorophenyl)-5-(20,40-dimethoxyphenyl)-1,2-
dioxolane (4p). Prepared according to the general procedure using
144.4 mg (0.5 mmol) of 3p, 2.2 mg (0.0025 mmol) of
Ru(bpz)3(PF6)2, 5 mL of toluene, 5 mL of nitromethane, and an
irradiation time of 1 h to afford a colorless oil; 157.2 mg (98% yield)
as an oil in experiment 1 and 154.3 mg (96% yield) in experiment 2
with a >10:1 dr. IR (neat) 3001, 2960, 2837, 1614, 1589, 1507,
4.3.11. cis-3-(20,40-Dimethoxyphenyl)-5-(40-methoxyphenyl)-1,2-
dioxolane (4l). Prepared according to the general procedure using
142.2 mg (0.5 mmol) of 3l, 2.2 mg (0.0025 mmol) of Ru(bpz)3(PF6)2,
5 mL of toluene, 5 mL of nitromethane, and an irradiation time of
1 h to afford a colorless oil; 156.6 mg (99% yield) as an oil in ex-
periment 1 and 155.1 mg (98% yield) in experiment 2 with a 9:1 dr.
1209 cmꢀ1 1H NMR: (499.9 MHz, CDCl3)
. d 7.37 (s, 1H), 7.35
(d, J¼8.0 Hz, 1H), 7.25e7.21 (m, 3H), 6.48 (dd, J¼8.5, 2.4 Hz, 1H),
6.43 (d, J¼2.4 Hz, 1H), 5.64 (t, J¼7.4 Hz, 1H), 5.35 (t, J¼7.4 Hz, 1H),
3.78 (s, 3H), 3.75 (s, 3H), 3.43 (dt, J¼12.4, 7.4 Hz, 1H), 2.56
IR (neat) 3001, 2959, 2937, 1676, 1613, 1515, 1251, 1034 cmꢀ1
.
1H
NMR: (499.9 MHz, CDCl3)
d
7.47 (d, J¼8.4 Hz, 1H), 7.26 (d, J¼8.7 Hz,
2H), 6.84 (d, J¼8.7 Hz, 2H), 6.50 (dd, J¼8.4, 2.5 Hz, 1H), 6.44 (d,
J¼2.5 Hz, 1H), 5.67 (t, J¼7.1 Hz, 1H), 5.32 (t, J¼7.6 Hz, 1H), 3.79 (s,
3H), 3.77 (s, 3H), 3.76 (s, 3H), 3.39 (dt, J¼12.5, 7.6 Hz, 1H), 2.58e2.52
(dt, J¼12.4, 7.4 Hz, 1H); 13C NMR: (125.7 MHz, CDCl3)
d 160.7, 157.8,
141.7, 134.3, 129.8, 128.0, 127.2, 126.6, 124.6, 118.7, 104.2, 98.5, 82.4,
78.5, 55.3, 55.2, 50.0. HRMS (EI) calculated for [C17H17ClO4]þ (Mþ)
requires m/z 320.0810, found m/z 320.0819.
(m, 1H); 13C NMR: (125.7 MHz, CDCl3)
d 160.4, 159.6, 157.5, 129.7,
128.4, 126.8, 120.6, 113.9, 104.2, 98.3, 83.2, 78.3, 55.3, 55.2, 55.1,
50.2. HRMS (EI) calculated for [C18H20O5]þ (Mþ) requires m/z
316.1306, found m/z 316.1292.
4.3.16. cis-3-(20-Chlorophenyl)-5-(20,40-dimethoxyphenyl)-1,2-
dioxolane (4q). Prepared according to the general procedure using
144.4 mg (0.5 mmol) of 3q, 2.2 mg (0.0025 mmol) of
Ru(bpz)3(PF6)2, 5 mL of toluene, 5 mL of nitromethane, and an ir-
radiation time of 1 h to afford a colorless oil; 158.9 mg (99% yield) in
experiment 1 and 159.2 mg (99% yield) in experiment 2 with a 10:1
dr. IR (neat) 3000, 2960, 2837, 1615, 1589, 1508, 1288, 1209,
4.3.12. cis-3-(20,40-Dimethoxyphenyl)-5-(40-methylphenyl)-1,2-
dioxolane (4m). Prepared according to the general procedure using
134.2 mg (0.5 mmol) of 3m, 2.2 mg (0.0025 mmol) of
Ru(bpz)3(PF6)2, 5 mL of toluene, 5 mL of nitromethane, and an
irradiation time of 1 h to afford a colorless oil; 147.2 mg (98% yield)
in experiment 1 and 146.5 mg (98% yield) in experiment 2 with
a 9:1 dr. IR (neat) 3000, 2958, 2837, 1614, 1589, 1507, 1209,
1035 cmꢀ1. 1H NMR: (499.9 MHz, CDCl3)
d
7.70 (dd, J¼8.0, 1.5 Hz,
1H), 7.31 (dd, J¼8.0, 0.9 Hz, 1H), 7.27 (td, J¼7.3, 0.9 Hz, 1H), 7.22
(d, J¼8.2 Hz, 1H), 7.18 (td, J¼7.7, 1.5 Hz, 1H), 6.44e6.39 (m, 2H), 5.73
(dd, J¼8.0, 6.0 Hz,1H), 5.65 (t, J¼7.7 Hz,1H), 3.75 (s,1H), 3.71 (s,1H),
1035 cmꢀ1
.
1H NMR: (499.9 MHz, CDCl3)
d
7.46 (d, J¼8.6 Hz, 1H),
7.23 (d, J¼7.9 Hz, 2H), 7.12 (d, J¼7.9 Hz, 2H), 6.50 (dd, J¼8.6, 2.4 Hz,
1H), 6.44 (d, J¼2.4 Hz, 1H), 5.67 (t, J¼7.1 Hz, 1H), 5.34 (t, J¼7.7 Hz,
1H), 3.79 (s, 3H), 3.77 (s, 3H), 3.41 (dt, J¼12.4, 7.5 Hz, 1H), 2.56 (ddd,
J¼12.4, 7.7, 7.1 Hz, 1H), 2.31 (s, 3H); 13C NMR: (125.7 MHz, CDCl3)
3.60 (dt, J¼12.4, 8.0 Hz, 1H), 2.46 (ddd, J¼12.4, 8.0, 6.0 Hz, 1H); 13
C
NMR: (125.7 MHz, CDCl3)
d 160.8, 158.2, 139.2, 131.5, 129.2, 128.4,
127.6, 126.9, 126.5, 117.5, 104.3, 98.4, 80.0, 78.3, 55.2, 55.2, 49.1.
HRMS (EI) calculated for [C17H17ClO4]þ (Mþ) requires m/z 320.0810,
found m/z 320.0809.
d
160.4, 157.6, 137.9, 135.2, 129.2, 126.9, 126.9, 120.3, 104.2, 98.3,
83.3, 78.2, 55.3, 55.3, 50.4, 21.1. HRMS (EI) calculated for
[C18H20O4]þ (Mþ) requires m/z 300.1357, found m/z 300.1351.
4.3.17. cis-3-(20,40-Dimethoxyphenyl)-5-(40-trifluoromethylphenyl)-
1,2-dioxolane (4r). Prepared according to the general procedure
using 161.2 mg (0.5 mmol) of 3r, 2.2 mg (0.0025 mmol) of
Ru(bpz)3(PF6)2, 5 mL of toluene, 5 mL of nitromethane, and an
irradiation time of 1 h to afford a colorless oil; 171.7 mg (97% yield)
as an oil in experiment 1 and 174.4 mg (98% yield) in experiment 2
with a 10:1 dr. IR (neat) 2962, 2942, 2840, 1616, 1589, 1508, 1326,
4.3.13. cis-3-(40-Bromophenyl)-5-(20,40-dimethoxyphenyl)-1,2-
dioxolane (4n). Prepared according to the general procedure using
166.6 mg (0.5 mmol) of 3n, 2.2 mg (0.0025 mmol) of
Ru(bpz)3(PF6)2, 5 mL of toluene, 5 mL of nitromethane, and an ir-
radiation time of 1 h as a colorless oil; 180.7 mg (99% yield) in
experiment 1 and 180.2 mg (99% yield) in experiment 2 with a 9:1
dr. IR (neat) 3000, 2960, 2937, 1616, 1589, 1507, 1209 cmꢀ1. 1H NMR:
1124 cmꢀ1
.
1H NMR: (499.9 MHz, CDCl3)
d
7.59 (d, J¼7.8 Hz, 2H),
7.48 (d, J¼8.2 Hz, 2H), 7.33 (d, J¼8.2 Hz, 1H), 6.48 (dd, J¼8.4, 2.5 Hz,
1H), 6.44 (d, J¼2.5 Hz, 1H), 5.66 (t, J¼7.4 Hz, 1H), 5.45 (t, J¼7.4 Hz,
1H), 3.79 (s, 3H), 3.75 (s, 3H), 3.49 (dt, J¼12.2, 7.6 Hz, 1H), 2.57
(499.9 MHz, CDCl3)
d
7.43 (d, J¼8.2 Hz, 2H), 7.36 (d, J¼8.4 Hz, 1H),
7.22 (d, J¼8.2 Hz, 2H), 6.47 (dd, J¼8.4, 2.4 Hz, 1H), 6.43 (d, J¼2.4 Hz,
1H), 5.64 (t, J¼7.4 Hz, 1H), 5.33 (t, J¼7.5 Hz, 1H), 3.78 (s, 3H), 3.75
(dt, J¼12.2, 7.2 Hz, 1H); 13C NMR: (125.7 MHz, CDCl3)
d 160.8, 157.9,
(s, 3H), 3.43 (dt, J¼12.2, 7.5 Hz, 1H), 2.52 (dt, J¼12.2, 7.4 Hz, 1H); 13
C
144.0, 127.2, 126.7, 125.5 (q, J¼3.9 Hz), 118.6, 104.3, 98.5, 82.3, 78.5,
55.3, 55.2, 50.2. HRMS (EI) calculated for [C18H17F3O4]þ (Mþ)
requires m/z 354.1074, found m/z 354.1086.
NMR: (125.7 MHz, CDCl3)
d 160.6, 157.7, 138.3, 131.6, 128.3, 127.0,
121.8, 119.1, 104.2, 98.4, 82.5, 78.3, 55.3, 55.2, 50.2. HRMS (EI) cal-
culated for [C17H17BrO4]þ (Mþ) requires m/z 364.0305, found m/z
364.0321.
4.3.18. cis-3-(20,40-Dimethoxyphenyl)-5-(20-trifluoromethylphenyl)-
1,2-dioxolane (4s). Prepared according to the general procedure
using 161.2 mg (0.5 mmol) of 3s, 2.2 mg (0.0025 mmol) of
Ru(bpz)3(PF6)2, 5 mL of toluene, 5 mL of nitromethane, and an
irradiation time of 1 h to afford a colorless oil; 163.4 mg (92% yield)
as an oil in experiment 1 and 169.5 mg (96% yield) in experiment 2
with a >10:1 dr. IR (neat) 3003, 2962, 2941, 2839, 1616, 1589, 1507,
4.3.14. cis-3-(40-Chlorophenyl)-5-(20,40-dimethoxyphenyl)-1,2-
dioxolane (4o). Prepared according to the general procedure using
144.4 mg (0.5 mmol) of 3o, 2.2 mg (0.0025 mmol) of
Ru(bpz)3(PF6)2, 5 mL of toluene, 5 mL of nitromethane, and an
irradiation time of 1 h to afford a colorless oil; 158.8 mg (99% yield)
in experiment 1 and 153.5 mg (96% yield) in experiment 2 with
1314, 1121 cmꢀ1. 1H NMR: (499.9 MHz, CDCl3)
d
7.90 (d, J¼8.0 Hz,

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Z. Lu et al. / Tetrahedron 70 (2014) 4270e4278
1H), 7.60 (d, J¼8.0 Hz, 1H), 7.56 (t, J¼7.7 Hz, 1H), 7.38e7.32 (m, 2H),
6.48 (dd, J¼8.5, 2.3 Hz, 1H), 6.43 (d, J¼2.3 Hz, 1H), 5.81 (t, J¼7.6 Hz,
1H), 5.66 (t, J¼7.6 Hz, 1H), 3.79 (s, 3H), 3.75 (s, 3H), 3.52 (dt, J¼12.7,
7.6 Hz, 1H), 2.49 (dt, J¼12.7, 7.6 Hz, 1H); 13C NMR: (125.7 MHz,
(s, 3H), 3.16 (dd, J¼12.8, 8.1 Hz, 1H), 2.87 (dd, J¼12.8, 8.1 Hz, 1H),
1.66 (s, 3H); 13C NMR: (125.7 MHz, CDCl3)
159.9, 156.5, 137.7,
128.4, 128.2, 127.2, 126.5, 126.1, 103.6, 99.0, 86.5, 84.2, 55.6, 55.3,
55.1, 24.9. HRMS (EI) calculated for [C18H20O4]þ (Mþ) requires m/z
300.1357, found m/z 300.1346.
d
CDCl3)
d 160.9, 158.1, 140.0, 132.4, 127.5, 127.3, 127.1, 125.6
(q, J¼5.6 Hz), 117.7, 104.3, 98.5, 79.2 (q, J¼2.0 Hz), 78.6, 55.3, 55.3,
51.1. HRMS (EI) calculated for [C18H17F3O4]þ (Mþ) requires m/z
354.1074, found m/z 354.1079.
4.3.23. 5-(2,4-Dimethoxyphenyl)-3,3-dimethyl-1,2-dioxolane
(4x). Prepared according to the general procedure using 103 mg
(0.5 mmol) of 3x, 2.2 mg (0.0025 mmol) of Ru(bpz)3(PF6)2, 5 mL of
toluene, 5 mL of nitromethane, and an irradiation time of 12 h to
afford a colorless oil; 110.4 mg (93% yield) as an oil in experiment 1
and 112.1 mg (94% yield) in experiment 2. IR (neat) 2974, 2934,
4.3.19. cis-3-(20,40-Dimethoxyphenyl)-5-(20-furyl)-1,2-dioxolane
(4t). Prepared according to the general procedure using 122.2 mg
(0.5 mmol) of 3t, 2.2 mg (0.0025 mmol) of Ru(bpz)3(PF6)2, 5 mL of
toluene, 5 mL of nitromethane, and an irradiation time of 1 h to af-
ford a colorless oil; 101.9 mg (74% yield) as an oil in experiment 1 and
105.6 mg (76% yield) in experiment 2 with a 6:1 dr. IR (neat) 3001,
2838, 1615, 1589, 1507, 1209 cmꢀ1
.
1H NMR: (499.9 MHz, CDCl3)
d
7.41 (d, J¼8.6 Hz,1H), 6.49 (dd, J¼8.6, 2.4 Hz,1H), 6.43 (d, J¼2.4 Hz,
1H), 5.54 (t, J¼7.6 Hz, 1H), 3.80 (s, 3H), 3.79 (s, 3H), 2.80 (dd, J¼11.9,
2940, 2838, 1613, 1507, 1209, 1034 cmꢀ1
CDCl3)
.
1H NMR: (499.9 MHz,
8.0 Hz, 1H), 2.29 (dd, J¼11.9, 7.2 Hz, 1H), 1.42 (s, 3H), 1.40 (s, 3H); 13
C
d
7.46 (d, J¼8.7 Hz,1H), 7.41 (s,1H), 6.50 (dd, J¼8.2, 2.2 Hz,1H),
NMR: (125.7 MHz, CDCl3) d 160.4, 157.6, 126.9, 120.4, 104.2, 98.4,
6.45 (d, J¼2.2 Hz, 1H), 6.37 (d, J¼3.1 Hz, 1H), 6.34 (dd, J¼3.1, 1.8 Hz,
1H), 5.66 (t, J¼7.5 Hz, 1H), 5.41 (t, J¼7.5 Hz, 1H), 3.29 (dt, J¼12.2,
7.7 Hz,1H), 2.81 (dt, J¼12.2, 7.2 Hz,1H); 13C NMR: (125.7 MHz, CDCl3)
83.7, 77.8, 55.4, 55.3, 53.7, 26.3, 26.0. HRMS (EI) calculated for
[C13H18O4]þ (Mþ) requires m/z 238.1200, found m/z 238.1208.
d
160.6, 157.8, 151.0, 143.1, 127.1, 119.2, 110.4, 109.5, 104.3, 98.4, 77.7,
Acknowledgements
76.2, 55.4, 55.3, 45.5. HRMS (EI) calculated for [C15H16O5]þ (Mþ)
requires m/z 276.0993, found m/z 276.0984.
We thank the NIH (GM095666) and Sloan Foundation for
funding of this research.
4.3.20. 3-(2,4-Dimethoxyphenyl)-5-(phenylethynyl)-1,2-dioxolane
(4u). Prepared according to the general procedure using 139.2 mg
(0.5 mmol) of 3u, 2.2 mg (0.0025 mmol) of Ru(bpz)3(PF6)2, 5 mL of
toluene, 5 mL of nitromethane, and an irradiation time of 24 h as
a colorless oil; 151.9 mg (98% yield) in experiment 1 and 152.7 mg
(98% yield) in experiment 2 with approx. 1:1 dr. IR (neat) 3001,
References and notes
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D. A. Nat. Prod. Rep. 1992, 9, 289e312; (b) Casteel, D. A. Nat. Prod. Rep. 1999, 16,
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359e378.
2962, 2938, 2837, 2232, 1615, 1507, 1209, 1034 cmꢀ1
.
1H NMR:
(499.9 MHz, CDCl3)
d
7.54 (d, J¼8.5 Hz, cis, 1H), 7.48e7.45
(m, J¼trans Hz, 2H), 7.44e7.41 (m, J¼cis Hz, 2H), 7.36 (d, J¼8.5 Hz,
trans, 1H), 7.33e7.27 (m, J¼cis and trans Hz, 6H), 6.52e6.43
(m, J¼cis and trans Hz, 4H), 5.70 (dd, J¼7.7, 6.1 Hz, trans, 1H), 5.60
(t, J¼7.4 Hz, cis, 1H), 3.81e3.77 (m, J¼cis and trans Hz, 12H), 3.34
(dt, J¼12.2, 8.3 Hz, cis, 1H), 3.17 (ddd, J¼12.3, 8.0, 5.2 Hz, trans, 1H),
2.91 (ddd, J¼12.3, 8.0, 6.1 Hz, trans, 1H), 2.73 (ddd, J¼12.2, 6.8,
5.5 Hz, cis, 1H). HRMS (EI) calculated for [C19H18O4]þ (Mþ) requires
m/z 310.1200, found m/z 310.1197.
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4.3.21. 3-(2,4-Dimethoxyphenyl)-4-methyl-5-phenyl-1,2-dioxolane
(4v). Prepared according to the general procedure using 134.2 mg
(0.5 mmol) of 3v, 2.2 mg (0.0025 mmol) of Ru(bpz)3(PF6)2, 5 mL of
toluene, 5 mL of nitromethane, and an irradiation time of 3 h to
afford a colorless oil; 142.6 mg (95% yield) as an oil in experiment 1
and 145.7 mg (97% yield) in experiment 2 with a 10:1 dr. IR (neat)
2966, 2936, 2838, 1676, 1612, 1507, 1456, 1209 cmꢀ1
.
1H NMR:
(499.9 MHz, CDCl3)
d
7.47 (d, J¼8.5 Hz, 1H), 7.38e7.26 (m, 5H), 6.53
(dd, J¼8.5, 2.3 Hz, 1H), 6.47 (d, J¼2.3 Hz, 1H), 5.47 (d, J¼7.6 Hz, 1H),
5.28 (d, J¼6.2 Hz, 1H), 3.80 (s, 3H), 3.79 (s, 3H), 3.22e3.13 (m, 1H),
0.80 (d, J¼6.9 Hz, 3H); 13C NMR: (125.7 MHz, CDCl3)
d 160.8, 158.4,
136.7, 128.1, 128.0, 127.6, 126.8, 118.1, 104.4, 98.5, 85.4, 83.7, 55.4,
55.3, 53.8, 13.9. HRMS (EI) calculated for [C18H20O4]þ (Mþ) requires
m/z 300.1358, found m/z 300.1363.
9. Ischay, M. A.; Yoon, T. P. Eur. J. Org. Chem. 2012, 3359e3372.
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14, 1640e1643.
12. Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K.; Timmers, F. J.
4.3.22. 3-(2,4-Dimethoxyphenyl)-3-methyl-5-phenyl-1,2-dioxolane
(4w). Prepared according to the general procedure using 134.2 mg
(0.5 mmol) of 3w, 2.2 mg (0.0025 mmol) of Ru(bpz)3(PF6)2, 5 mL of
toluene, 5 mL of nitromethane, and an irradiation time of 1 h to
afford a colorless oil; 148.5 mg (99% yield) as a solid in experiment 1
and 146.9 mg (98% yield) in experiment 2 with a 9:1 dr. Mp:
99e100 ꢁC (hexane/EtOAc). IR (neat) 2960, 2934, 2837, 1615, 1586,
Organometallics 1996, 15, 1518e1520.
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4686e4690.
1505, 1208 cmꢀ1. 1H NMR: (499.9 MHz, CDCl3)
d
7.62 (d, J¼8.5 Hz,
1H), 7.24e7.20 (m, 3H), 7.15e7.11 (m, 2H), 6.52 (dd, J¼8.5, 2.5 Hz,
1H), 6.48 (d, J¼2.5 Hz, 1H), 5.36 (t, J¼8.1 Hz, 1H), 3.82 (s, 3H), 3.77
19. Theys, R. D.; Vargas, R. M.; Wang, Q.; Hossain, M. M. Organometallics 1998, 17,
1333e1339.