Rhodium(I)-Catalyzed [4 + 2] Cycloaddition Reactions of 2-Alkylenecyclo-butanols with Alkynes and (E)-2-Nitroethenylbenzene through C(sp2)—C(sp3) Bond Cleavage

Article abstract of DOI:10.1002/cjoc.201900082

An intermolecular [4 + 2] cycloaddition was realized through C—C bond cleavage in the presence of Rh(I) catalyst. The selective ring opening of 2-alkylenecyclobutanols enables the generation of active alkenylrhodium species, which underwent smooth cross addition over alkynes and (E)-2-nitroethenylbenzene, leading to highly substituted all-carbon six-membered rings in a single step and in a complete atom economy.

Full text of DOI:10.1002/cjoc.201900082

Accepted Article
Title: Rhodium(I)-Catalyzed [4+2] Cycloaddition Reactions of 2-
Alkylenecyclobutanols with Alkyne and (E)-2-Nitroethenylbenzene through C(sp2)-
C(sp3) Bond Cleavage
Authors: Xinxin Zheng, Guozhu Zhang* and Dayong Zhang*
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This work may now be cited as: Chin. J. Chem. 2019, 37, 10.1002/cjoc.201900082.
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Rhodium(I)-Catalyzed [4+2] Cycloaddition Reactions of 2-Alkylenecyclobutanols with
Alkyne and (E)-2-Nitroethenylbenzene through C(sp2)-C(sp3) Bond Cleavage
Xinxin Zhengb, Guozhu Zhang*a and Dayong Zhang*b
a State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute
of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. China.
b Institute of Pharmaceutical Science, China Pharmaceutical University, Nanjing, P. R. China.
Cite this paper: Zheng, X.; Zhang, G.; Zhang, D. Chin. J. Chem. 2019, 37, XXX—XXX. DOI: 10.1002/cjoc.201900XXX
Summary of main observation and conclusion An intermolecular [4+2] cycloaddition was realized through C-C bond cleavage in the presence of Rh(I)
catalyst. The selective ring opening of 2-alkylenecyclobutanols enables the generation of active alkenylrhodium species, which underwent smooth cross
addition over alkynes and (E)-2-nitroethenylbenzene, leading to highly substituted all-carbon six-membered rings in a single step and in a complete atom
economy.
alkenylrhodium
species.
Compared
to
well-studied
Background and Originality Content
benzocyclobutanol counterparts, 2-alkylenecyclobutanol host the
potential utility as a versatile synthetic building block given its
readily availability; 2-alkyledenecyclobutanols could be prepared
from commercially available cyclobutanone via a 2-step procedure;
an aldol condensation followed by 1,2-addition. Encouraged by
the initial success, we envisioned that other two-carbon synthons
could serve as coupling partners as well, leading to diverse
molecular scaffolds through C(sp2)−C(sp3) bond cleavage and
cycloaddition of 2-alkylenecyclobutanol.
Organic motifs with all-carbon six-membered rings exist in
numerous natural and unnatural products that exhibit important
biological activities.[1] Intermolecular [4+2] cycloaddition has the
high synthetic potential for the synthesis of structurally diverse
and complex six-membered cyclic systems.[2] Despite the fact that
many methods of [4+2] cycloaddition including Diels-Alder (DA)
reaction[3] have been well-established, the synthesis of quaternary
centers which are often present as the structural core in natural
products of interesting biological activities remains a significant
challenge for synthetic chemists.[4] As a result, the development
of new and atom-economical approaches for the synthesis of
all-carbon six-membered rings containing quaternary centers in a
stereoselective manner are still highly desired.
Scheme
1
[4+2] cycloaddition of 2-alkylenecyclobutanol with
2-nitroethenylbenzene and alkyne
Carbon–carbon bonds constitute the major framework of
organic molecules. Such nonpolar σ-bonds are thermodynamically
stable and kinetically inert in general. Over the past two decades,
the difficulties associated with selective transformation of such
nonpolar σ-bonds have motivated and inspired chemists to seek
ways to activate these bonds. In such a way, organic skeletons
could be constructed and/or functionalized in
a more
straightforward while efficient manner.[5] From an atom economic
synthetic point of view, it would significantly streamline a unique
atom-efficient method if a C-C single bond is cleaved and an
unsaturated functionality is inserted therein to directly extend the
carbon skeleton with two C-C single bonds newly formed.
Cyclobutenols and cyclobutanols are privileged building blocks in
this field.[6] Murakami pioneered in a series of studies on
rhodium-catalyzed carbon–carbon bond cleavage/cycloaddition
reactions of benzocyclobutenols with various functionalities
including alkynes,[6d,6p] vinyl ketones,[6j] carbene precursors,[6l] and
allenes.[6e] We have been interested in this field and recently
reported a rhodium-catalyzed stereoselective [4+2] cycloaddition
of oxetanols with alkynes[6b]; and asymmetric [4+2] cycloaddition
of 2- alkylenecyclobutanols[7] with α,β-unsaturated cyclic ketones,
leading to synthetically valuable trans-bicyclic molecules.[8] In the
latter case, ring opening of 2- alkylenecyclobutanol, a rarely
exploited strained 4-carbon ring, selectively takes place on the
C(sp3)-C(sp2) side. Notably, the following cross addition over C-C
double bond represent the first example of utilization of internal
Herein, we report the successful expansion of this strategy to
(E)-2-nitroethenylbenzene and alkynes, those reactions provide a
rapid access to six-membered cyclic molecules with quaternary
center and valuable functionalities including nitro, exo-alkene for
facile derivatizations. Notably, (E)-2-nitroethenylbenzene has
attracted much less attention in C-C bond cleavage field (Scheme
1).
Results and Discussion
We
(E)-2-benzylidene-1-phenylcyclobutanol
(E)-2-nitroethenylbenzene
commenced
our
study
by
1a
employing
and
as the model substrates. The
reaction conditions were adopted from our previous study, Rh(I)
catalyst, in toluene at 70 ℃. As expected, screening of Rh(I)
*E-mail: cpuzdy@163.com;
guozhuzhang@sioc.ac.cn.
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First author et al.
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catalysts revealed that [Rh(OH)(COD)]2 gave the best results,
cyclic product (2a) was isolated in 38% yield as a single
diastereomer (Table 1, entry 1). Examination of different additives
did not provide better results. Switch of the solvent from toluene
to THF improved the product yield. Reaction in 1,4-dioxane
performed slightly better than that in THF. Interestingly, the
reaction proceeded equally well at room temperature whereas
raising the temperature to 110℃ resulted in decomposition of
the starting material. To our delighted, 85% yield was attained
when iPrOH was used instead of 1,4-dioxane as the solvent (entry
10).9
aReaction conditions: 2-alkylenecyclobutanol (0.2 mmol),
(E)-2-nitroethenylbenzene (1.1 equiv), [Rh(OH)(COD)]2 (2.5 mol%),
2-PrOH (0.2M), rt , 12 h. bIsolated yield.
Motivated by the success with (E)-2-nitroethenylbenzene, our
attention was then focused on alkyne counterpart. The
cycloaddition of 2-alkylenecyclobutanol with alkynes would allow
expedient access to alkylenecyclohexenols,[10] which represent an
interesting molecular scaffold and would be difficult to be
prepared by other means. We tested the reaction using
1,2-diphenylethyne with (E)-2-benzylidene-1-phenylcyclobutanol
1a. Benefit from previous investigations, it did not take long to
identify the optimal conditions. Simple heating of 1a with
diphenylethyne in toluene at 80 °C in the presence of
[Rh(OH)(COD)]2 provided the desired cycloadduct 3a in almost
quantitative yield.
Table
1
Optimization of the reaction conditions for the rhodium
(I)-catalyzed tandem ring-opening and cyclization.
Table 3 Scope studies: cycloaddition of alkyne.a, b
Entrya Additives
solvent
Temp (°C)
Yield (2a)[%]b
1
2
3
4
5
6
7
8
9
10
-
toluene
toluene
toluene
THF
70
70
70
70
70
70
110
r.t
38
-
K2CO3
10% iPrOH
34
58
34
60
-
-
-
-
-
-
-
-
xylene
1,4-dioxane
1,4-dioxane
1,4-dioxane
t-BuOH
50
50
85
r.t
iPrOH
r.t
aReaction
conditions:
2-alkylenecyclobutanol
(0.2
mmol),
(E)-2-nitroethenylbenzene (1.1 equiv), [Rh(OH)(COD)]2 (2.5 mol%), solvent
(0.2M), 12 h. b Isolated yield.
Efforts were then devoted to exploring the substrate scope
with regard to diversity of 2-alkylenecyclobutanols (Table 2). The
reaction seemed not sensitive to the electronic and steric
properties of the substitutions at either the R1 or R2 positions.
Both aryl and alkyl groups were compatible under current
reaction conditions. A chloro and fluoro group on the phenyl ring
remained intact. Those highly functionalized cyclic products were
obtained in generally over 80% yield.
Table 2 Scope studies: cycloadditions of nitrostyrene a,b
a
Reaction conditions: 2-alkylenecyclobutanol (0.2 mmol), alkyne (1.1
equiv), [Rh(OH)(COD)]2 (2.5 mol%), Toluene (0.2M), 80 oC , 6 h. b Isolated
yield.
The six-membered ring forming reaction proceeded
successfully with various combinations of 2-alkylenecyclobutanols
1 and alkynes, demonstrating the generality of the unique
site-selective and efficient insertion of triple bond to the
C(sp2)-C(sp3) bond of four-membered ring (Table 3). With R1 as a
phenyl, the alkyl groups (R2) showed the same site-selectivity to
give cyclic products in satisfactory yields (3c - 3d). Notably, a
carbon-carbon double bond remained intact (3e). The presence of
electron-donating and withdrawing groups on the benzene ring
scarcely affected the reaction (3b, 3f - 3l). The effects of
variations of substitutions on the alkylene (R1) were then
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2
Chin. J. Chem. 2019, 37, XXX－XXX

Running title
Chin. J. Chem.
examined. To our delight, arenes bearing electron-donating
methyl and methoxy at the either para, or ortho positions with
various combinations of benzene substitutions (R1) are
compatible with the reaction conditions (3f - 3l). Even the alkyl
-substituted derivative 1m reacted well to afford 3M in 84% yield.
Chemicals were purchased from commercial suppliers. Unless
stated otherwise, all the substrates and solvents were purified
and dried according to standard methods prior to use. Reactions
requiring inert conditions were carried out in glove box.
Furthermore, the variations of diaryl alkynes were then briefly Generation procedure for cyclic products 2
investigated, alkynes with electron-donating methyl and methoxy
at the para position serve as the suitable substrates (3n - 3o). To
our delight, with R2 as a phenyl, a cyclohexyl of the R1 was well
tolerated, giving the corresponding product 3m in 84% yield. The
reaction of an unsymmetric alkyne bearing methyl and phenyl
substitution groups (3q) gave two separable regioisomers at a
ratio of 2 : 1 indicating that the steric properties of the alkyne
substitution groups has less effect on the site-selectivity of
insertion.
To an oven-dried sealed tube equipped with a stirrer bar was
added [Rh(OH)(COD)]2 (2.3 mg, 5.0 umol, 2.5 mol% ),
2-alkylenecyclobutanol (0.20 mmol, 1.0 equiv),
(E)-2-nitroethenylbenzene (0.40 mmol, 2.0 equiv) in glove box.
Then dry isopropanol (1.0 ml) was added. After the mixture was
stirred at room temperature for 12h , The resulting mixture was
passed through a pad of silica gel and eluted with ethyl acetate.
The filtrate was concentrated under reduced pressure. The
residue was purified by silica gel flash chromatography
(hexane/EtOAc = 10:1) to afford the product 2 .
1
Scheme 2 Proposed catalytic cycle.
(1S,2S,3S,E)-4-benzylidene-2-nitro-1,3-diphenylcyclohexanol
(2a) was obtained as white solid (85.1 mg, 0.22 mmol, 85%). mp =
o
1
125 - 128 C. H NMR (400 MHz, CDCl3) δ 7.52 (d, J = 7.6 Hz, 2H),
7.42 – 7.26 (m, 10H), 7.20 (t, J = 7.3 Hz, 1H), 7.10 (d, J = 7.3 Hz,
2H), 5.87 (s, 1H), 5.48 (d, J = 12.1 Hz, 1H), 4.66 (d, J = 12.0 Hz, 1H),
4.13 (d, J = 2.4 Hz, 1H), 3.02 – 2.94 (m, 1H), 2.78 (dd, J = 13.7, 9.2
Hz, 1H), 2.08 – 2.14 (m, 1H), 1.93 (dd, J = 17.9, 8.3 Hz, 1H). 13C
NMR (101 MHz, CDCl3) δ 142.2, 139.6, 137.1, 135.1, 129.6, 128.8,
128.76, 128.7, 128.4, 128.13, 128.1, 126.7, 124.5, 95.6, 75.1, 51.1,
39.2, 24.6. IR (neat) cm-1 ṽ: 3475, 3024, 2918, 2856, 1704, 1600,
1493, 1447, 1306, 1058, 1036, 950, 752, 695, 658, 611, 532, 477.
HRMS (EI(+), 70 eV) : C25H23NO3 [M-HNO2]+: calcd. 338.1678,
found: 338.1663.
According to previous studies and our observations,[7f,j] The
mechanistic scenario for the synthesis of 2a is depicted in Scheme
2. At the beginning, a well-established rhodium(I) cyclobutanolate
formation and β-carbon elimination of the C(sp2)-C(sp3) bond
occur to afford the vinylrhodium species I. Next, a cis- migratory
insertion of C(sp2)-Rh(I) across the (E)-2-nitroethenylbenzene
occurs to give II.[9] The last ring closing takes place in a highly
stereoselective manner.
(1R,2S,3S,E)-4-benzylidene-1-methyl-2-nitro-3-phenylcyclohex
anol (2b) was obtained as white solid (71.9 mg, 0.22 mmol, 89%).
o
mp = 105 - 108 C. 1H NMR (400 MHz, CDCl3) δ 7.37 (t, J = 7.3 Hz,
2H), 7.32 – 7.25 (m, 5H), 7.19 (d, J = 7.2 Hz, 1H), 7.05 (d, J = 7.6 Hz,
2H), 5.75 (s, 1H), 4.94 (d, J = 12.3 Hz, 1H), 4.48 (d, J = 12.3 Hz, 1H),
3.04 (d, J = 2.3 Hz, 1H), 2.85 (s, 1H), 2.59 (dd, J = 16.4, 11.7 Hz, 1H),
2.09 – 2.01 (m, 1H), 1.56 (d, J = 6.4 Hz, 1H), 1.36 (s, 3H). 13C NMR
(101 MHz, CDCl3) δ 140.0, 137.2, 135.7, 129.4, 128.8, 128.7, 128.1,
128.0, 127.9, 126.6, 96.8, 70.1, 50.3, 37.7, 27.4, 24.1. IR (neat)
cm-1 ṽ: 3538, 2920, 2855, 1537, 1493, 1455, 1365, 1274, 1202,
1152, 1124, 1076, 1000, 943, 920, 886, 761, 734, 698, 602, 571,
542, 443. HRMS (EI(+), 70 eV) : C20H21NO3 [M]+: calcd. 323.1521,
found: 323.1528.
(1S,2S,3S,E)-1-(3-chlorophenyl)-4-(2-methylbenzylidene)-2-nit
ro-3-phenylcyclohexanol (2c) was obtained as white solid (81.7
mg, 0.19 mmol, 82%). mp = 115 - 118 oC. 1H NMR (400 MHz,
CDCl3) δ 7.53 (dd, J = 6.5, 1.8 Hz, 1H), 7.41 – 7.34 (m, 5H), 7.33 –
7.28 (m, 2H), 7.28 – 7.26 (m, 1H), 7.12 (t, J = 4.3 Hz, 3H), 7.04 (dd,
J = 6.2, 3.1 Hz, 1H), 5.81 (s, 1H), 5.44 (d, J = 12.1 Hz, 1H), 4.67 –
4.61 (m, 1H), 4.17 (d, J = 2.7 Hz, 1H), 2.72 (dd, J = 7.8, 3.0 Hz, 2H),
2.07 (d, J = 6.9 Hz, 3H), 2.05 – 2.02 (m, 1H), 1.71 – 1.82 (m, 1H).
13C NMR (101 MHz, CDCl3) δ 144.5, 138.6, 136.4, 136.2, 135.1,
134.8, 130.0, 129.8, 129.4, 128.8, 128.7, 128.4, 128.2, 127.1,
125.4, 125.1, 122.7, 95.3, 74.9, 50.9, 39.2, 24.6, 19.8. IR (neat)
cm-1 ṽ: 3574, 2922, 2854, 1574, 1539, 1453, 1418, 1356, 1294,
1260, 1081, 1064, 968, 938, 897, 786, 740, 722, 696, 597, 569,
535, 451. HRMS (EI(+), 70 eV) : C26H24ClNO3 [M-HNO2]+: calcd.
386.1445, found: 386.1447.
(1S,2S,3S,E)-4-(cyclohexylmethylene)-2-nitro-1,3-diphenylcycl
ohexanol (2d) was obtained as white solid (84.8 mg, 0.22 mmol,
88%). mp = 95 - 98 oC. 1H NMR (400 MHz, CDCl3) δ 7.50 (d, J = 7.6
Hz, 2H), 7.39 – 7.27 (m, 5H), 7.26 (s, 1H), 7.21 (d, J = 6.8 Hz, 2H),
5.32 (d, J = 12.1 Hz, 1H), 4.60 (d, J = 9.1 Hz, 1H), 4.42 (d, J = 11.8
Hz, 1H), 4.11 (d, J = 2.8 Hz, 1H), 2.69 (s, 2H), 2.35 (d, J = 4.5 Hz,
1H), 2.22 (d, J = 8.8 Hz, 1H), 2.10 (s, 1H), 1.86 (t, J = 12.9 Hz, 1H),
1.65 (d, J = 23.3 Hz, 2H), 1.46 (d, J = 13.2 Hz, 1H), 1.33 – 1.18 (m,
3H), 1.07 (d, J = 12.3 Hz, 1H), 1.00 (s, 1H), 0.84 (dd, J = 24.1, 12.1
Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 142.5, 135.4, 134.6, 129.5,
Conclusions
In conclusion, two types of highly functionalized all-carbon
six-membered ring have been synthesised by an stepwise
[4+2]cycloaddition of 2-alkylenecyclobutanols with nitrostyrene
and alkynes using rhodium(I) complexes as catalyst. The excellent
site-selectivity and diastereoselectivity are remarkable. The
synthetic application of the methodology established in this work
to material and pharmaceutical science is positively expected.
Experimental
Generally information
NMR spectra were recorded at room temperature on the
following spectrometers: Agilent (400 MHz) and VARIAN (400
MHz). Chemical shifts are given in ppm and coupling constants in
Hz. 1H spectra were calibrated in relation to the reference
measurement of TMS (0.00 ppm). 13C spectra were calibrated in
relation to deuterated solvents, namely CDCl3 (77.16 ppm). The
following abbreviations were used for 1H NMR spectra to indicate
the signal multiplicity: s (singlet), d (doublet), t (triplet), q
(quartet) and m (multiplet) as well as combinations of them.
When combinations of multiplicities are given the first character
noted refers to the largest coupling constant. High performance
liquid chromatography (HPLC) was carried out with Agilent 1260
Infinity on a UV spectrophotometric detector (210 nm, Agilent).
For ESI+-spectra and EI-HR (GC-TOF) spectrometer was applied.
Infrared Spectroscopy (IR) was processed on an FT-IR
spectrometer named Nicolet 380. The method is denoted in
brackets. For the most significant bands the wave number ṽ (cm-1)
is given.
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www.cjc.wiley-vch.de
3

First author et al.
Report
128.6, 128.5, 128.0, 127.7, 124.5, 96.0, 75.1, 50.8, 39.4, 36.8, 33.5,
(E)-6'-benzylidene-3'-ethyl-3',4',5',6'-tetrahydro-[1,1':2',1''-ter
32.7, 25.82, 25.8, 24.1. IR (neat) cm-1 ṽ: 3523, 2921, 2850, 1667,
phenyl]-3'-ol (3d) was obtained as yellow oil (36.0 mg, 0.098
1
1540, 1444 1364, 1268, 1204, 1110, 1063, 983, 900, 886, 742, 697, mmol, 64%). H NMR (400 MHz, CDCl3) δ 7.28 (t, J = 7.2 Hz, 2H),
603, 550, 532, 453.HRMS (EI(+), 70 eV) : C25H29NO3 [M-HNO2]+:
calcd. 344.2147, found: 344.2126.
7.18 (dd, J = 17.3, 7.8 Hz, 3H), 7.11 – 6.92 (m, 10H), 6.01 (s, 1H),
3.06 – 2.94 (m, 1H), 2.84 (t, J = 10.7 Hz, 1H), 2.11 (dd, J = 12.5, 5.8
Hz, 1H), 2.00 – 1.90 (m, 1H), 1.84 – 1.75 (m, 1H), 1.62 – 1.54 (m,
(1S,2S,3S,E)-1-(4-fluorophenyl)-4-(4-methylbenzylidene)-2-nitr
o-3-phenylcyclohexanol (2e) was obtained as white solid (86.8 mg, 2H), 0.93 (t, J = 7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 144.5,
o
1
0.21 mmol, 80%). mp = 100 - 105 C. H NMR (400 MHz, CDCl3) δ
7.51 – 7.47 (m, 2H), 7.40 – 7.35 (m, 2H), 7.34 – 7.30 (m, 3H), 7.13
– 7.08 (m, 2H), 7.07 – 7.02 (m, 2H), 6.99 (d, J = 8.0 Hz, 2H), 5.84 (s,
1H), 5.43 (d, J = 12.1 Hz, 1H), 4.62 (d, J = 12.2 Hz, 1H), 4.12 (t, J =
4.9 Hz, 1H), 3.02 – 2.92 (m, 1H), 2.75 (d, J = 4.9 Hz, 1H), 2.32 (d, J =
5.7 Hz, 3H), 2.13 – 2.03 (m, 1H), 1.91 – 1.82 (m, 1H). 13C NMR (101
MHz, CDCl3) δ 162.4 (d, JC-F= 248.5 Hz), 138.7, 138.2, 136.5, 135.1,
140.0, 139.7, 138.4, 138.3, 137.8, 130.7, 130.6, 129.8, 129.1,
128.0, 127.24, 127.2, 126.4, 126.2, 125.9, 72.8, 32.5, 32.0, 24.4,
7.7. IR (neat) cm-1 ṽ: 3564, 2936, 1597, 1571, 1488, 1440, 1369,
1330, 1271, 1116, 1073, 982, 913, 878, 759, 739, 695. HRMS (EI(+),
70 eV) : C27H26O [M]+: calcd. 366.1984, found: 366.1977.
(E)-6'-benzylidene-3'-(but-3-en-1-yl)-3',4',5',6'-tetrahydro-[1,1
':2',1''-terphenyl]-3'-ol (3e) was obtained as yellow oil (36.0 mg,
0.092 mmol, 76%). 1H NMR (400 MHz, CDCl3) δ 7.28 (d, J = 7.3 Hz,
3H), 7.23 – 7.15 (m, 3H), 7.13 – 6.93 (m, 9H), 6.01 (s, 1H), 5.77 (dd,
134.1, 129.5, 128.83, 128.8, 128.6, 128.4, 128.1, 126.4 (d, JC-F
=
8.1 Hz), 115.6 (d, JC-F = 21.2 Hz ), 95.6, 74.9, 51.1, 39.4, 24.6, 21.1.
IR (neat) cm-1 ṽ: 3537, 2923, 1602, 1539, 1509, 1451, 1350, 1304, J = 17.0, 6.7 Hz, 1H), 4.96 (dd, J = 31.0, 13.5 Hz, 2H), 2.99 (s, 1H),
1229, 1160, 1067, 970, 894, 836, 746, 701, 556, 521, 505.
HRMS (EI(+), 70 eV) : C26H24NO3 [M-HNO2]+: calcd. 370.1740,
found: 370.1727.
2.86 (d, J = 10.6 Hz, 1H), 2.17 (s, 3H), 2.00 (d, J = 10.5 Hz, 1H), 1.89
(d, J = 10.1 Hz, 1H), 1.64 (d, J = 14.5 Hz, 2H). 13C NMR (101 MHz,
CDCl3) δ 144.3, 140.0, 139.6 138.6, 138.2, 138.1, 137.7, 130.7,
130.6, 130.0, 129.1, 128.0, 127.3, 127.27, 126.4, 126.3, 126.0,
114.6, 72.6, 38.5, 33.2, 27.8, 24.5. IR (neat) cm-1 ṽ: 2924, 1640,
1599, 1573, 1488, 1440, 1368, 1330, 1266, 1072, 1029, 908, 870,
761, 731, 696. HRMS (EI(+), 70 eV) : C29H28O [M]+: calcd. 392.2140,
found: 392.2128.
(E)-4-butyl-4'-(2-methylbenzylidene)-3'-phenyl-1',4',5',6'-tetra
hydro-[1,1':2',1''-terphenyl]-1'-ol (3f) was obtained as yellow oil
(30.0 mg, 0.062 mmol, 80%). 1H NMR (400 MHz, CDCl3) δ 7.62 (d, J
= 8.0 Hz, 2H), 7.23 (d, J = 7.8 Hz, 2H), 7.15 (s, 4H), 7.08 (dd, J = 8.0,
4.0 Hz, 4H), 6.94 (d, J = 1.6 Hz, 3H), 6.83 (d, J = 3.4 Hz, 2H), 6.15 (s,
1H), 2.77 – 2.62 (m, 3H), 2.47 (s, 1H), 2.30 (d, J = 3.7 Hz, 1H), 2.09
(s, 3H), 2.03 (s, 1H), 1.64 (dd, J = 15.2, 7.8 Hz, 2H), 1.39 (dd, J =
14.8, 7.4 Hz, 2H), 0.96 (t, J = 7.3 Hz, 3H). 13C NMR (101 MHz,
CDCl3) δ 142.9, 141.9, 141.8, 141.1, 139.6, 138.0, 137.6, 136.9,
136.6, 130.7, 130.5, 129.7, 129.6, 128.6, 128.1, 127.4, 126.7,
126.45, 126.4, 126.2, 125.1, 76.3, 39.2, 35.2, 33.5, 24.0, 22.4, 19.9,
14.0. IR (neat) cm-1 ṽ: 2924, 2854, 1600, 1484, 1439, 1409, 1326,
1258, 1182, 1104, 1054, 938, 888, 834, 788, 748, 698. HRMS
(ESI(+), 70 eV) : C36H36O [M+Na]+: calcd. 507.2766, found:
507.2662.
Procedure for cyclic products 3
To an oven-dried sealed tube equipped with a stirrer bar was
added [Rh(OH)(COD)]2 (2.3 mg, 5.0 umol, 2.5 mol% ),
2-alkylenecyclobutanol 1 (0.20 mmol, 1.0 equiv) and alkyne (0.40
mmol, 2.0 equiv) in glove box. Then dry toluene (1.0 ml) was
o
added. After the mixture was stirred at 80 C for 6h, the resulting
mixture was cooled to room temperature. The resulting mixture
was passed through a pad of silica gel and eluted with ethyl
acetate. The filtrate was concentrated under reduced pressure.
The residue was purified by silica gel flash chromatography
(hexane/EtOAc = 10:1) to afford 3.
(E)-4'-benzylidene-3'-phenyl-1',4',5',6'-tetrahydro-[1,1':2',1''-t
erphenyl]-1'-ol (3a) was obtained as yellow oil (52.2 mg, 0.13
1
mmol, 98%). H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 7.6 Hz, 2H),
7.41 (t, J = 7.5 Hz, 2H), 7.34 – 7.29 (m, 1H), 7.27 – 7.17 (m, 5H),
7.16 – 7.07 (m, 5H), 6.93 (d, J = 4.8 Hz, 3H), 6.84 – 6.79 (m, 2H),
6.17 (s, 1H), 2.96 (d, J = 16.2 Hz, 1H), 2.62 (t, J = 14.4 Hz, 1H), 2.39
– 2.32 (m, 1H), 2.19 – 2.04 (m, 2H). 13C NMR (101 MHz, CDCl3) δ
145.5, 142.1, 141.5, 139.4, 137.9, 137.6, 130.8, 130.62, 130.6,
130.4, 129.1, 128.1, 128.0,127.45, 127.4, 127.2, 126.5, 126.4,
126.2, 76.2, 39.0, 24.4. HRMS (ESI(+), 70 eV) : C31H26O [M-Na]+:
calcd. 437.1984, found: 437.1876.
(E)-3-chloro-4'-(4-methylbenzylidene)-3'-phenyl-1',4',5',6'-tetr
ahydro-[1,1':2',1''-terphenyl]-1'-ol (3g) was obtainedas yellow oil
1
(53.0 mg, 0.11 mmol, 82%). H NMR (400 MHz, CDCl3) δ 7.72 (s,
(E)-4'-benzylidene-4-fluoro-3'-phenyl-1',4',5',6'-tetrahydro-[1,
1':2',1''-terphenyl]-1'-ol (3b) was obtained as yellow oil (82.0 mg,
0.19 mmol, 84%). 1H NMR (400 MHz, CDCl3) δ 7.69 (dd, J = 8.7, 5.4
Hz, 2H), 7.29 – 7.04 (m, 12H), 6.98 – 6.90 (m, 3H), 6.84 – 6.76 (m,
2H), 6.18 (s, 1H), 2.97 (dd, J = 12.3, 3.9 Hz, 1H), 2.60 (s, 1H), 2.38 –
2.30 (m, 1H), 2.11 (dd, J = 10.7, 6.0 Hz, 2H). 13C NMR (101 MHz,
CDCl3) δ 162.2 (d, JC-F = 246.4 Hz), 141.9, 141.7, 141.4 (d, JC-F = 3.0
Hz), 139.3, 137.8, 137.6, 137.5, 131.0, 130.8, 130.5, 129.2, 128.3
(d, JC-F = 8.1 Hz), 128.1, 127.6, 127.5, 126.7, 126.6, 126.4, 116.0 (d,
JC-F = 21.2 Hz), 75.9, 39.1, 24.4. IR (neat) cm-1 ṽ: 2926, 1599, 1501,
1440, 1328, 1223, 1156, 1057, 1031, 1010, 907, 837, 759, 731,
696. HRMS (ESI(+), 70 eV) : C31H25FO [M+Na]+: calcd. 455.1889,
found: 455.1778.
1H), 7.60 (d, J = 7.5 Hz, 1H), 7.36 – 7.27 (m, 2H), 7.06 – 7.15 (m,
9H), 7.00 – 6.91 (m, 3H), 6.84 – 6.74 (m, 2H), 6.16 (s, 1H), 2.98 (d,
J = 16.0 Hz, 1H), 2.61 (s, 1H), 2.35 (dd, J = 12.6, 4.3 Hz, 1H), 2.30 (s,
3H), 2.12 (d, J = 12.5 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 148.1,
142.1, 140.1, 139.3, 137.6, 136.8, 136.5, 134.6, 134.4, 131.1,
130.7, 130.5, 129.2, 129.1, 128.7, 127.5, 127.48, 127.4, 126.8,
126.6, 126.3, 124.9, 75.9, 38.9, 24.3, 21.2. IR (neat) cm-1 ṽ: 3610,
3528, 3174, 2342, 2166, 2107, 1588, 1485, 1440, 1322, 1097,
1056, 997, 895, 808, 788, 755, 729, 698, 633. HRMS (ESI(+), 70
eV) : C32H27ClO [M+Na]+: calcd. 485.1750, found: 485.1643.
(E)-2-fluoro-4'-(4-methylbenzylidene)-3'-phenyl-1',4',5',6'-tetr
ahydro-[1,1':2',1''-terphenyl]-1'-ol (3h) was obtained as yellow oil
1
(88.0 mg, 0.20 mmol, 70%). H NMR (400 MHz, CDCl3) δ 7.58 (t, J
(E)-6'-benzylidene-3'-methyl-3',4',5',6'-tetrahydro-[1,1':2',1''-t
erphenyl]-3'-ol (3c) was obtained as yellow oil (54.1 mg, 0.15
= 7.9 Hz, 1H), 7.22 – 7.16 (m, 1H), 7.13 – 6.97 (m, 11H), 6.87 (s,
5H), 6.14 (s, 1H), 2.97 (d, J = 10.3 Hz, 1H), 2.92 – 2.81 (m, 1H),
1
mmol, 90%). H NMR (400 MHz, CDCl3) δ 7.27 (t, J = 7.5 Hz, 2H),
2.50 (dd, J = 19.4, 7.1 Hz, 2H), 2.30 (s, 3H), 2.22 – 2.13 (m, 1H). 13
C
7.17 (dd, J = 17.5, 7.4 Hz, 3H), 7.11 – 6.95 (m, 10H), 6.01 (s, 1H),
3.09 – 3.00 (m, 1H), 2.92 – 2.82 (m, 1H), 2.12 – 1.98 (m, 2H), 1.36
(s, 3H). 13C NMR (101 MHz, CDCl3) δ 143.9, 139.5, 139.4, 138.6,
138.3, 137.7, 130.52, 130.5, 129.9, 129.0, 127.9, 127.2, 126.4,
126.2, 126.0, 70.6, 37.7, 28.2, 24.8. IR (neat) cm-1 ṽ: 2920, 1508,
1488, 1439, 1327, 1183, 1155, 1110, 1054, 908, 876, 818, 758,
732, 698. HRMS (EI(+), 70 eV) : C26H24O [M]+: calcd. 352.1827,
found: 352.1821.
NMR (101 MHz, CDCl3) δ 159.7 (d, JC-F = 247.5 Hz), 141.50, 140.2,
139.7, 138.4, 137.4, 136.3, 134.7, 133.2 (d, JC-F = 10.1 Hz), 130.7,
130.3, 129.1, 128.9, 128.8, 128.7, 128.5 (d, JC-F = 3.0 Hz), 127.3,
127.0, 126.1, 123.8, 123.7, 115.9(d, JC-F = 23.2 Hz), 74.18, 37.2,
24.0, 21.1. IR (neat) cm-1 ṽ: 2930, 1605, 1506, 1442, 1286, 1242,
1176, 1107, 1032, 908, 824, 757, 732, 697, 622. HRMS (ESI(+), 70
eV) : C32H27FO [M+Na]+: calcd. 469.2046, found: 469.1935.
This article is protected by copyright. All rights reserved.
www.cjc.wiley-vch.de © 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
4
Chin. J. Chem. 2019, 37, XXX－XXX

Running title
Chin. J. Chem.
(E)-4-fluoro-4'-(4-methylbenzylidene)-3'-phenyl-1',4',5',6'-tetr
yellow oil (50.0 mg, 0.11 mmol, 80%). 1H NMR (400 MHz, CDCl3) δ
7.72 (d, J = 7.6 Hz, 2H), 7.41 (t, J = 7.3 Hz, 2H), 7.33 (d, J = 7.1 Hz,
1H), 7.22 (dd, J = 15.5, 7.0 Hz, 4H), 7.15 (d, J = 6.6 Hz, 1H), 7.04 (d,
J = 6.3 Hz, 2H), 6.72 (d, J = 7.5 Hz, 4H), 6.49 (d, J = 8.5 Hz, 2H), 6.20
(s, 1H), 3.73 (s, 3H), 3.61 (s, 3H), 2.94 (d, J = 16.2 Hz, 1H), 2.66 –
2.56 (m, 1H), 2.36 – 2.28 (m, 1H), 2.12 (d, J = 11.7 Hz, 2H). 13C
ahydro-[1,1':2',1''-terphenyl]-1'-ol (3i) was obtained as yellow oil
1
(42.0 mg, 0.094 mmol, 78%). H NMR (400 MHz, CDCl3) δ 7.74 –
7.64 (m, 2H), 7.21 – 7.03 (m, 11H), 6.94 (s, 3H), 6.79 (d, J = 3.6 Hz,
2H), 6.14 (s, 1H), 2.98 (d, J = 16.3 Hz, 1H), 2.58 (t, J = 14.7 Hz, 1H),
2.40 – 2.25 (m, 4H), 2.13 – 2.03 (m, 2H). 13C NMR (101 MHz,
CDCl3) δ 162.0 (d, JC-F= 246.4 Hz), 141.8, 141.4, 139.4, 137.7, 136.9, NMR (101 MHz, CDCl3) δ 157.8, 157.7, 145.8 141.8, 141.1, 138.4,
136.5, 134.6, 130.9, 130.8, 130.4, 129.1, 128.7, 128.3 (d, JC-F= 8.1
Hz), 127.5, 126.5, 126.2, 114.90 (d, JC-F = 21.2 Hz), 75.8, 39.1, 24.4,
21.1. IR (neat) cm-1 ṽ: 2733, 1599, 1503,, 1440, 1327, 1222, 1156,
1057, 836, 759, 739, 697, 618. HRMS (ESI(+), 70 eV) : C32H27FO
[M+Na]+: calcd. 469.2046, found: 469.1936.
137.7, 131.9, 131.6, 130.1, 130.0, 129.1, 128.1, 127.9, 127.1,
126.5, 126.4, 113.0, 112.9, 76.2 55.0, 54.8, 39.0, 24.4. IR (neat)
cm-1 ṽ: 2931, 2834, 1605, 1505, 1442, 1329, 1285, 1241, 1175,
1106, 1083, 1032, 907, 823, 791, 764, 729, 698, 645. HRMS (ESI(+),
70 eV) : C33H30O3 [M+Na]+: calcd. 497.2195, found: 497.2081.
Product 3q, 3q’ was obtained as yellow oil (29.5 mg, 0.083
(E)-4-methyl-4'-(4-methylbenzylidene)-3'-phenyl-1',4',5',6'-tet
rahydro-[1,1':2',1''-terphenyl]-1'-ol (3j) was obtained as yellow oil
(81.0 mg, 0.18 mmol, 78%). 1H NMR (400 MHz, CDCl3) δ 7.61 (d, J
= 8.1 Hz, 2H), 7.22 (d, J = 7.9 Hz, 2H), 7.18 – 7.01 (m, 9H), 6.96 –
6.89 (m, 3H), 6.86 – 6.79 (m, 2H), 6.13 (s, 1H), 2.95 (d, J = 16.3 Hz,
1H), 2.60 (t, J = 14.0 Hz, 1H), 2.38 (s, 3H), 2.32 (dd, J = 12.8, 3.8 Hz,
1H), 2.28 (s, 3H), 2.11 (dd, J = 8.1, 4.2 Hz, 1H), 2.02 (s, 1H). 13C
NMR (101 MHz, CDCl3) δ 142.6, 141.9, 141.4, 139.6, 138.0, 137.2,
136.8, 136.3, 134.7, 130.8, 130.5, 130.4, 129.1, 128.8, 128.7 127.4,
127.3, 126.5, 126.3, 126.1, 76.1, 39.0, 24.6, 21.1, 21.0. IR (neat)
cm-1 ṽ: 2920, 1601, 1574, 1509, 1439, 1411, 1328, 1182, 1057,
1006, 907, 815, 759, 731, 698. HRMS (ESI(+), 70 eV) : C33H30O
[M+Na]+: calcd. 465.2297, found: 465.2185.
mmol, 78%, 2:1).
(E)-4'-benzylidene-4''-methyl-3'-(p-tolyl)-1',4',5',6'-tetrahydro-
[1,1':2',1''-terphenyl]-1'-ol (3o) was obtained as yellow oil (52.0
1
mg, 0.12 mmol, 91%). H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 6.3
Hz, 2H), 7.41 (t, J = 6.7 Hz, 2H), 7.32 (d, J = 7.3 Hz, 1H), 7.25 – 7.18
(m, 4H), 7.13 (d, J = 7.2 Hz, 1H), 6.99 (d, J = 16.0 Hz, 4H), 6.72 (dd,
J = 19.4, 7.0 Hz, 4H), 6.16 (s, 1H), 2.94 (d, J = 15.9 Hz, 1H), 2.64 –
2.56 (m, 1H), 2.38 – 2.28 (m, 2H), 2.23 (s, 3H), 2.10 (s, 4H). 13C
NMR (101 MHz, CDCl3) δ 145.8, 141.8, 141.2 138.2, 137.7, 136.5,
135.8, 135.5, 134.8, 130.6, 130.2, 129.2, 128.2, 128.1, 127.9,
127.1, 126.6, 126.4, 76.2, 39.0, 24.4, 21.1, 20.97. IR (neat) cm-1 ṽ:
3022, 2921, 1598, 1489, 1443, 1328, 1181, 1108, 1082, 1049, 907,
815, 760, 730, 698, 641. HRMS (ESI(+), 70 eV) : C33H30O [M+Na]+:
calcd. 465.2297, found: 465.2188.
(E)-4-benzylidene-5,6-diethyl-1,2,3,4-tetrahydro-[1,1'-bipheny
l]-1-ol (3p) was obtained as yellow oil (30.0 mg, 0.094 mmol, 85%).
1H NMR (400 MHz, CDCl3) δ 7.45 (d, J = 7.1 Hz, 2H), 7.37 – 7.25 (m,
7H), 7.19 (d, J = 6.8 Hz, 1H), 6.67 (s, 1H), 2.66 (d, J = 15.2 Hz, 1H),
2.55 (dd, J = 14.6, 7.2 Hz, 2H), 2.40 – 2.23 (m, 3H), 2.02 – 1.90 (m,
4H), 1.23 (t, J = 7.4 Hz, 3H), 1.07 (t, J = 7.5 Hz, 3H). 13C NMR (101
MHz, CDCl3) δ 146.0, 141.0, 138.3, 138.1, 136.1, 129.2, 128.0,
126.9, 126.2, 126.15, 123.4, 76.7, 40.8, 24.6, 23.3, 21.2, 15.5, 14.3.
IR (neat) cm-1 ṽ: 2962, 1599, 1490, 1444, 1373, 1320, 1154, 1017,
983, 911, 851, 763, 732, 697, 622. HRMS (EI(+), 70 eV) : C23H26O
[M]+: calcd. 318.1984, found: 318.1990.
(E)-4'-benzylidene-3'-methyl-1',4',5',6'-tetrahydro-[1,1':2',1''-t
erphenyl]-1'-ol (3q). 1H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 7.8 Hz,
2H), 7.40 – 7.27 (m, 7H), 7.23 (dd, J = 17.3, 5.3 Hz, 4H), 7.00 (s,
2H), 6.76 (s, 1H), 2.85 (d, J = 16.0 Hz, 1H), 2.50 (t, J = 14.4 Hz, 1H),
2.21 – 2.14 (m, 1H), 2.08 – 1.98 (m, 1H), 1.89 (s, 4H). 13C NMR
(101 MHz, CDCl3) δ 145.6, 141.6, 138.8, 137.9, 137.5, 132.7, 129.3,
128.1, 128.0, 127.1, 127.0, 126.6, 126.5, 125.8, 77.4, 39.4, 24.3,
17.3. IR (neat) cm-1 ṽ: 3564, 3055, 2924,, 2860, 2245, 1601, 1488,
1442, 1328, 1261, 1102, 1064, 1018, 986, 907, 860, 799, 760, 730,
699, 645. HRMS (ESI(+), 70 eV) : C26H24O [M-H2O]+: calcd.
335.1827, found: 335.1792.
(E)-4'-(4-methoxybenzylidene)-3'-phenyl-1',4',5',6'-tetrahydro
-[1,1':2',1''-terphenyl]-1'-ol(3k) was obtained as yellow oil (90.0
1
mg, 0.20 mmol, 82%). H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 7.5
Hz, 2H), 7.41 (t, J = 7.6 Hz, 2H), 7.31 (t, J = 7.3 Hz, 1H), 7.20 – 7.02
(m, 7H), 6.92 (dd, J = 6.9, 3.4 Hz, 3H), 6.85 – 6.75 (m, 4H), 6.11 (s,
1H), 3.74 (s, 3H), 2.95 (dd, J = 12.0, 8.0 Hz, 1H), 2.60 (d, J = 2.4 Hz,
1H), 2.40– 2.32 (m, 1H), 2.18 – 2.06 (m, 2H). 13C NMR (101 MHz,
CDCl3) δ 158.2, 145.6, 141.6, 141.3, 139.6, 138.0, 136.3, 130.8,
130.5, 130.2, 128.1, 127.4, 127.35, 127.2, 126.6, 126.3, 126.2,
113.4, 76.2, 55.2, 39.0, 24.5. IR (neat) cm-1 ṽ: 2896, 2049, 1973,
1601, 1506, 1441, 1327, 1247, 1175, 1082, 1030, 888, 830, 764,
741, 697, 624. HRMS (ESI(+), 70 eV) : C32H28O2 [M+Na]+: calcd.
467.2089, found: 467.1981.
(E)-3-chloro-4'-(4-methoxybenzylidene)-3'-phenyl-1',4',5',6'-te
trahydro-[1,1':2',1''-terphenyl]-1'-ol (3l) was obtained as yellow
1
oil (45.0 mg, 0.097 mmol, 80%). H NMR (400 MHz, CDCl3) δ 7.72
(s, 1H), 7.60 (d, J = 7.4 Hz, 1H), 7.36 – 7.27 (m, 2H), 7.18 – 7.03 (m,
7H), 6.94 (s, 3H), 6.80 (d, J = 7.5 Hz, 4H), 6.12 (s, 1H), 3.76 (s, 3H),
2.97 (d, J = 16.2 Hz, 1H), 2.60 (t, J = 14.1 Hz, 1H), 2.38 – 2.31 (m,
1H), 2.12 (d, J = 11.8 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 158.3,
148.1, 142.1, 140.6, 139.4, 137.6, 135.9, 134.4, 130.7, 130.5,
130.46, 130.1, 129.2, 127.5, 127.46, 127.4 , 126.8, 126.6, 126.3,
124.9, 113.5, 75.8, 55.2, 38.9, 24.3. IR (neat) cm-1 ṽ: 2927, 1599,
1506, 1465, 1439, 1414, 1301, 1247, 1175, 1097, 1031, 888, 830,
787, 754, 733, 697, 627. HRMS (ESI(+), 70 eV) : C32H27ClO2
[M+Na]+: calcd. 501.1700, found: 501.1591.
(E)-4'-benzylidene-2'-methyl-1',4',5',6'-tetrahydro-[1,1':3',1''-t
1
erphenyl]-1'-ol (3q’). H NMR (400 MHz, CDCl3) δ 7.55 (d, J = 7.2
(E)-4'-(cyclohexylmethylene)-3'-phenyl-1',4',5',6'-tetrahydro-[
1,1':2',1''-terphenyl]-1'-ol (3m) was obtained from as yellow oil
(35.0 mg, 0.083 mmol, 84%). 1H NMR (400 MHz, CDCl3) δ 7.67 (d, J
= 7.7 Hz, 2H), 7.38 (t, J = 7.2 Hz, 2H), 7.30 (d, J = 7.0 Hz, 1H), 7.13 –
6.97 (m, 5H), 6.91 (s, 3H), 6.75 (s, 2H), 4.99 (d, J = 9.2 Hz, 1H), 2.70
(d, J = 14.9 Hz, 1H), 2.28 (t, J = 11.3 Hz, 3H), 2.11 (s, 1H), 2.04 (s,
1H), 1.56 (dd, J = 39.4, 13.4 Hz, 5H), 1.27 – 1.17 (m, 2H), 1.07 (d, J
= 11.5 Hz, 1H), 0.98 – 0.87 (m, 2H). 13C NMR (101 MHz, CDCl3) δ
146.1, 141.1, 139.8, 139.6, 138.2, 133.7, 130.8, 130.5, 128.0,
127.4, 127.2, 127.0, 126.5, 126.2, 125.9, 76.7, 76.2, 39.0, 37.2,
32.8, 32.3, 26.0, 25.9, 25.8, 22.2. IR (neat) cm-1 ṽ: 2921, 2848,
1598, 1488, 1442, 1328, 1256, 1178, 1050, 1004, 906, 761, 734,
697, 630. HRMS (ESI(+), 70 eV) : C31H32O [M+Na]+: calcd.
443.2453, found: 443.2344.
Hz, 2H), 7.41 (q, J = 7.5 Hz, 4H), 7.34 – 7.28 (m, 2H), 7.27 – 7.21
(m, 4H), 7.14 (d, J = 6.7 Hz, 3H), 5.90 (s, 1H), 2.82 (dd, J = 13.5, 7.1
Hz, 1H), 2.60 – 2.50 (m, 1H), 2.18 – 2.08 (m, 3H), 1.44 (s, 3H). 13C
NMR (101 MHz, CDCl3) δ 145.6, 140.7, 140.3, 138.6, 137.8, 136.7,
129.9, 129.0, 128.6, 128.3, 128.2, 127.9, 127.1, 126.7, 126.3,
126.0, 76.4, 40.2, 24.3, 17.0. IR (neat) cm-1 ṽ: 3384, 3056, 3023,
2923, 2855, 1599, 1491, 1444, 1328, 1179, 1046, 1028, 918, 876,
764, 736, 700. HRMS (ESI(+), 70 eV) : C26H24O [M-H2O]+: calcd.
335.1827, found: 335.1794.
Supporting Information
The supporting information for this article is available on the
WWW under https://doi.org/10.1002/cjoc.2018xxxxx.
(E)-4'-benzylidene-4''-methoxy-3'-(4-methoxyphenyl)-1',4',5',6
'-tetrahydro-[1,1':2',1''-terphenyl]-1'-ol (3n) was obtained as
This article is protected by copyright. All rights reserved.
Chin. J. Chem. 2019, 37, XXX－XXX © 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
5

First author et al.
Report
Alder cycloadducts by whole cells of Penicillium brasilianum. Mol.
Divers. 2016, 20, 877; (c) Schubert, M.; Metz, P. Enantioselective
Total Synthesis of the Diterpenes Kempene‐2, Kempene‐1, and 3‐
epi‐Kempene‐1 from the Defense Secretion of Higher Termites.
Angew. Chem., Int. Ed. 2011, 50, 2954; (d) Brocksom, T. J.; Donatoni,
M. C. The Diels-Alder reaction at the beginning of the Twenty-First
century. Quim. Nova. 2010, 33, 2211; (e) Shing, T. K. M.; Lee, C. M.;
Lo, H. Y. A synthetic approach toward taxol analogs: studies on the
construction of the CD ring. Tetrahedron 2004, 60, 9179. (f) Feng,
M.; Jiang, X. Stereoselective Construction of a Key Hydroindole
precursor of Epidithiodiketopiperazine (ETP) Natural Products.
Chem. Commun. 2014, 50, 9690.
Acknowledgement
We are grateful to NSFC-21772218, 21421091, XDB20000000,
the “Thousand Plan” Youth program, State Key Laboratory of
Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, and the Chinese Academy of Sciences.
References
[1] (a) Kreuger, M. R. O.; Grootjans, S.; Biavatti, M. W.; Vandenabeele, P.;
D’Herde, K. Sesquiterpene lactones as drugs with multiple targets in
cancer treatment: focus on parthenolide. Anti-Cancer Drugs. 2012,
23, 883; (b) Kusari, G.; Li, S.; Spiteller, M. Natural products containing
‘decalin’ motif in microorganisms. Nat. Prod. Rep. 2014, 31, 1175; (c)
Hernandez-Guerrero, C. J.; Zubía, E.; Ortega, M. J.; Carballo, J. L.
Sesterterpene metabolites from the sponge Hyatella intestinalis.
Tetrahedron 2006, 62, 5392; (d) Xu, G.; Hou, A.-J.; Zheng, Y.-T.; Zhao,
Y.; Li, X.-L.; Peng, L.-Y.; Zhao, Q.-S. Przewalskin B, a Novel Diterpenoid
with an Unprecedented Skeleton from Salvia przewalskii Maxim. Org.
Lett. 2007, 9, 291; (e) Wang, Y.-S.; Huang, R.; Li, Y.; Shang, W.-B.; Chen,
F.; Zhang, H.-B.; Yang, J.-H. Panamonon A and B, a pair of novel
tetrahydrobenzofuran derivatives from Litsea panamonja (Nees)
Hook. f. Phytochem. Lett. 2013, 6, 26; (f) Isaka, M.; Yangchum, A.;
Supothina, S.; Chanthaket, R.; Srikitikulchai, P. Isopimaranes and
eremophilanes from the wood-decay fungus Xylaria allantoidea BCC
23163. Phytochem. Lett. 2014, 8, 59.
[2] For selected reviews and examples on [4+2] cycloaddition, see: (a) Bai,
Z.; Tong, H.; Wang, H.; Chen, G.; He, G.; Copper Catalyzed
Asymmetric [4＋2] Annulations of D-A Cyclobutanes with Aldehydes.
Chin. J. Chem. 2019, 37, 119. (b) Jiang-Lin Hu, Li Zhou, Lijia Wang,
Zuowei Xie, Yong Tang, [4＋2] reactions via ring-expansion: Copper
Catalyzed Asymmetric [4＋2] Annulations of D-A Cyclobutanes with
Aldehydes. Chin. J. Chem. 2018, 36, 47. (c) Liu, X.; Zheng, H.; Xia, Y.;
Lin, L.; Feng, X. Asymmetric Cycloaddition and Cyclization Reactions
Catalyzed by Chiral N,N′-Dioxide–Metal Complexes. Acc. Chem. Res.
2017, 50, 2621; (d) Jeon, B.; Wang, S.; Ruszczycky, M. W.; Liu, H.
Natural [4 + 2]-Cyclases. Chem. Rev. 2017, 117, 5367; (c) Hall, D. G.;
[4] (a) Prusov, E. V. Construction of Quaternary Stereogenic Centers in the
Total Synthesis of Natural Products. Angew. Chem. Int. Ed. 2017, 56,
14356; (b) Chuang, K. V.; Xu, C.; Reisman, S. E. A 15-step synthesis of
(+)-ryanodol. Science 2016, 353, 912; (c) Zhu, L.; Lu, J.; Li, T.; Zhu, G.;
Han, Q.; Hsiao, W.; Liu, L.; Jiang, Z. J. Immunosuppressive Decalin
Derivatives from Red Yeast Rice. Nat. Prod. 2012, 75, 567.
[5] (a) Zhao, B.; Tan, H.; Chen, C.; Jiao, N.; Shi, Z. Photoinduced C—C
Bond Cleavage and Oxidation of Cycloketoxime Esters, Chin. J. Chem.,
2018, 36, 995; (b) Tao Shen, T.; Zhu, B.; Lin, F.; Pan, J.; Wei, J.; Luo, X.;
Liu, J.; Jiao, N. Direct Synthesis of Structurally Divergent Indole
Alkaloids from Simple Chemicals, Chin. J. Chem., 2018, 36, 815; (c)
Souillart, L.; Cramer, N. Catalytic C–C Bond Activations via Oxidative
Addition to Transition Metals. Chem. Rev. 2015, 115, 9410; (b) Marek,
I.; Masarwa, A.; Delaye, P. O.; Leibeling, M. Selective Carbon–Carbon
Bond Cleavage for the Stereoselective Synthesis of Acyclic Systems.
Angew. Chem., Int. Ed. 2015, 54, 414; (d) Kong, D.-L.; Huang, Y.; Ren,
L.-Y.; Feng ， W.-H.
A highly efficient way to recycle inactive
stereoisomers of Bedaquiline into two previous intermediates via
base-catalyzed Csp3–Csp3 bond cleavage. Chin. Chem. Lett. 2015, 26,
790–792 (e) Dermenci, A.; Coe, J. W.; Dong, G. Direct activation of
relatively unstrained carbon–carbon bonds in homogeneous systems.
Org. Chem. Front. 2014, 1, 567; (f) Zhou, X.; Ji, H. Highly Efficient
Oxidative Cleavage of Carbon‐Carbon Double Bond over meso‐
Tetraphenyl Cobalt Porphyrin Catalyst in the Presence of Molecular
Oxygen. Chin. J. Chem. 2012, 11, 2103; (g) Chen, F.; Wang, T.; Jiao, N.
Recent Advances in Transition-Metal-Catalyzed Functionalization of
Unstrained Carbon–Carbon Bonds. Chem. Rev. 2014, 114, 8613; (h)
Wu, X.; Zhou, C. Recent Advances in Radical‐Mediated C—C Bond
Fragmentation of Non‐Strained Molecules. Chin. J. Chem. 2018, 36,
587; (i) Aïssa, C. Transition-Metal-Catalyzed Rearrangements of Small
Cycloalkanes: Regioselectivity Trends in β-Carbon Elimination
Reactions. Synthesis 2011, 21, 3389; (j) Murakami, M.; Matsuda, T.
Metal-catalysed cleavage of carbon–carbon bonds. Chem. Commun.
2011, 47, 1100; (k) Seiser, T.; Cramer, N. Org. Enantioselective
metal-catalyzed activation of strained rings. Biomol. Chem. 2009, 7,
2835; (l) Yorimitsu, H.; Oshima, K. Metal-Mediated Retro-Allylation of
Homoallyl Alcohols for Highly Selective Organic Synthesis. Bull. Chem.
Soc. Jpn. 2009, 82, 778; (m) Park, Y. J.; Park, J. W.; Junn, C. H.
Metal−Organic Cooperative Catalysis in C−H and C−C Bond Activation
and Its Concurrent Recovery. Acc. Chem. Res. 2008, 41, 222; (n)
Murakami, M.; Makino, M.; Ashida, S.; Matsuda, T. Construction of
Carbon Frameworks through β-Carbon Elimination Mediated by
Transition Metals. Bull. Chem. Soc. Jpn. 2006, 79, 1315; (o) Tunge, J.
A.; Burger, E. C. Transition metal catalyzed decarboxylative additions
of enolates. Eur. J. Org. Chem., 2005, 1715; (p) Jun, C. H. Transition
metal-catalyzed carbon–carbon bond activation. Chem. Soc. Rev.
2004, 33, 610; (q) Perthuisot, C.; Edelbach, B. L.; Zubris, D. L.; Simhai,
N.; Iverson, C. N.; Muller, C.; Satoh, T.; Jones, W. D. Cleavage of the
carbon–carbon bond in biphenylene using transition metals. J. Mol.
Catal. 2002, 189, 157; (r) Murakami, M.; Ito, Y. Cleavage of
Carbon—Carbon Single Bonds by Transition Metals. Topics in
Organomet. Chem., 1999, 3, 97; (s) Beauchamps, J. L. Transition
metal-hydrogen and metal-carbon bond strengths: the keys to
catalysis. Chem. Rev. 1990, 90, 629.
Rybak, T.; Verdelet, T. Multicomponent Hetero-[4
+
2]
Cycloaddition/Allylboration Reaction: From Natural Product Synthesis
to Drug Discovery. Acc. Chem. Res. 2016, 49, 2489; (e) Bittner, B.;
Koppe, K.; Bilir, V.; Frank, W.; Willner, H.; Ignat’ev, N.
Difluorotris(pentafluoroethyl)phosphorane—A highly active catalyst
for Diels–Alder reaction. J. Fluorine. Chem. 2015, 169, 50; (f) Terada, T.
Diastereoselective Construction of Trans-Fused Octalone Framework
via Ruthenium-Porphyrin-Catalyzed Cycloaddition. Org. Lett. 2014, 16,
2594; (g) Schmidt, R. K.; Mꢀther, K.; Lichtenfeld, C.; Grimme, S.
Oestreich, M. Silylium Ion-Catalyzed Challenging Diels–Alder
Reactions: The Danger of Hidden Proton Catalysis with Strong Lewis
Acids. J. Am. Chem. Soc. 2012, 134, 4421; (h) Lee, J.; Zhang, Y.;
Danishefsky, S. J.
A Straightforward Route to Functionalized
trans-Diels−Alder Motifs. J. Am. Chem. Soc. 2010, 132, 14330; (i)
Klare, H. F. T.; Bergander, K.; Oestreich, M. Taming the Silylium Ion for
Low‐Temperature Diels–Alder Reactions. Angew. Chem., Int. Ed. 2009,
48, 9077; (j) Todo, H.; Terao, J.; Watanabe, H.; Kuniyasu, H.; Kambe, N.
Cu-catalyzed regioselective carbomagnesiation of dienes and enynes
with sec-and tert-alkyl Grignard reagents. Chem. Commun. 2008,
1332; (k) Ryu, D. H.; Corey, E. J. Triflimide Activation of a Chiral
Oxazaborolidine Leads to a More General Catalytic System for
Enantioselective Diels−Alder Addition. J. Am. Chem. Soc. 2003, 125,
6388; (l) Fringuelli, F.; Pizzo, F.; Taticchi, A.; Wenkert, E. Diels-Alder
reactions of cycloalkenones. 3. Effects of specific reaction parameters.
J. Org. Chem. 1983, 48, 2802.
[3] For selected reviews and examples on Diels-Alder reaction, see: (a)
Oikawa, H.; Tokiwano, T. Enzymatic catalysis of the Diels–Alder
reaction in the biosynthesis of natural products. Nat. Prod. Rep.
2004, 21, 321; (b) Din, Z. U.; Fill, T. P.; Donatoni, M. C.; Dos. Santos,
C. A.; Brocksom, T. J.; Filho, E. R. Microbial diversification of Diels–
[6] (a)Zhang, J.-J.; Cheng, Y.-B.; Duan, X.-H. Metal-Free Oxidative
This article is protected by copyright. All rights reserved.
www.cjc.wiley-vch.de © 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
6
Chin. J. Chem. 2019, 37, XXX－XXX

Running title
Chin. J. Chem.
Decarboxylative Acylation/Ring Expansion of Vinylcyclobutanols with
Complementary to Thermal Ring Opening. J. Am. Chem. Soc, 2012,
134, 17502; (r) Seiser, T.; Cramer, N. Rhodium-Catalyzed Ring
Opening of Benzocyclobutenols with Site-Selectivity Complementary
to Thermal Ring Opening. J. Am. Chem. Soc, 2010, 132, 5340; (s)
Shigeno, M.; Yamamoto, T.; Murakami, M. Stereoselective
Restructuring of 3‐Arylcyclobutanols into 1‐Indanols by Sequential
Breaking and Formation of Carbon–Carbon Bonds. Chem. Eur. J. 2009,
15, 12929; (t) Seiser, T.; Roth, O. A.; Cramer, N. Enantioselective
Synthesis of Indanols from tert‐Cyclobutanols Using a Rhodium‐
Catalyzed C-C/C-H Activation Sequence. Angew. Chem., Int. Ed. 2009,
48, 6320; (u) Seiser, T.; Cramer, N. Enantioselective C-C Bond
Activation of Allenyl Cyclobutanes: Access to Cyclohexenones with
Quaternary Stereogenic Centers. Angew. Chem., Int. Ed. 2008, 47,
9294; (v) Matsuda, T.; Makino, M.; Murakami, M. Rhodium-Catalyzed
Addition/Ring-Opening Reaction of Arylboronic Acids with
Cyclobutanones Org. Lett. 2004, 6, 1257; (w) Nishimura, T.; Ohe, K.;
Uemura, S. Palladium(II)-Catalyzed Oxidative Ring Cleavage of
tert-Cyclobutanols under Oxygen Atmosphere. J. Am. Chem. Soc.
1999, 121, 2645.
α-Keto Acids by Visible Light Photoredox Catalysis, Chin. J.
Chem.,2017, 35, 311. (b) Guo, R.; Zhang, G. Expedient Synthesis of
1,5-Diketones by Rhodium-Catalyzed Hydroacylation Enabled by C–C
Bond Cleavage. J. Am. Chem. Soc. 2017, 139, 12891; (c) Yu, J.; Yan, H.;
Zhu, C. Synthesis of Multiply Substituted Polycyclic Aromatic
Hydrocarbons by Iridium‐Catalyzed Annulation of Ring‐Fused
Benzocyclobutenol with Alkyne through C−C Bond Cleavage. Angew.
Chem., Int. Ed. 2016, 55, 1143; (d) Ren, R.; Wu, Z.; Xu, Y.; Zhu, C. C−C
Bond‐Forming Strategy by Manganese‐Catalyzed Oxidative Ring‐
Opening Cyanation and Ethynylation of Cyclobutanol Derivatives.
Angew. Chem., Int. Ed. 2016, 55, 2866; (e) Tian, Q.; Chen, B.; Zhang,
G. Silver-initiated radical ring expansion/fluorination of ethynyl
cyclobutanols:
efficient
synthesis
of
monofluoroethenyl
cyclopentanones. Green. Chem. 2016, 18, 6236; (f) Zhao, C.; Liu, L. C.;
Wang, J.; Jiang, C.; Zhang, Q. W.; He, W. Rh(I)-Catalyzed Insertion of
Allenes into C–C Bonds of Benzocyclobutenols. Org. Lett. 2016, 18,
328; (g) Ren, R.; Zhao, H.; Huan, L.; Zhu, C. Manganese‐Catalyzed
Oxidative Azidation of Cyclobutanols: Regiospecific Synthesis of Alkyl
Azides by C C Bond Cleavage. Angew. Chem., Int. Ed. 2015, 54, 12692;
(h) Zhao, H.; Fan, X.; Yu, J.; Zhu, C. Silver-Catalyzed Ring-Opening
Strategy for the Synthesis of β- and γ-Fluorinated Ketones. J. Am.
Chem. Soc. 2015, 137, 3490; (i) Ishida, N.; Nečas, D.; Masuda, Y.;
Murakami, M. Enantioselective Construction of 3‐Hydroxypiperidine
Scaffolds by Sequential Action of Light and Rhodium upon N‐
Allylglyoxylamides. Angew. Chem., Int. Ed. 2015, 54, 7418; (i) Ishida,
N.; Ishikawa, N.; Sawano, S.; Masuda, Y.; Murakami, M. Construction
of tetralin skeletons based on rhodium-catalysed site-selective ring
opening of benzocyclobutenols. Chem. Commun. 2015, 51, 1882; (k)
Souillart, L.; Cramer, N. Exploitation of Rh(I)–Rh(III) cycles in
enantioselective C–C bond cleavages: access to β-tetralones and
benzobicyclo[2.2.2]octanones. Chem. Sci. 2014, 5, 837; (l) Xia, Y.; Liu,
Z.; Liu, Z.; Ge, R.; Ye, F.; Hossain, M.; Zhang, Y.; Wang, J. Formal
Carbene Insertion into C–C Bond: Rh(I)-Catalyzed Reaction of
Benzocyclobutenols with Diazoesters. J. Am. Chem. Soc. 2014, 136,
3013; (m) Yada, A.; Fujita, S.; Murakami, M. Enantioselective
[7] (a) Zhou, Y.; Rao, C.; Song, Q. Divergent reactivities in fluoronation of
allylic alcohols: synthesis of Z-fluoroalkenes via carbon–carbon bond
cleavage. Org. Lett. 2016, 18, 4000; (b) Liu, T.; Wu, J.; Zhao, Y.
Z-Selective Synthesis of γ,δ-Unsaturated Ketones via Pd-Catalyzed
Ring Opening of 2-Alkylenecyclobutanones with Arylboronic Acids.
Chem. Sci. 2017, 8, 3885.
[8] Zheng, X.; Guo, R.; Zhang, G.; Zhang, D. Rhodium(I)-catalyzed
asymmetric
[4
+
2]
cycloaddition
reactions
of
2-alkylenecyclobutanols with cyclic enones through C–C bond
cleavage: efficient access to trans-bicyclic compounds. Chem. Sci.
2018, 9, 1873.
[9] Shi, D.; Xie, Y.; Zhou, H.; Xia, C.; Huang, H. A Highly Diastereo‐ and
Enantioselective Reaction for Constructing Functionalized
Cyclohexanes: Six Contiguous Stereocenters in One Step. Angew.
Chem. Int. Ed. 2012, 51, 1248.
[10] (a) Komori, A.; Okabe, S.; Suganuma, M.; Kerr, M. A.; Busch-Petersen,
J.; Oh, L. M.; Zhuo, J.; Kannangara, G. S. K.; Zou, X.; Tius, M. A.; Fujiki,
H. Jpn. Anti‐tumor Promoting Activity of Canventol and Its Synthetic
Analogs through Inhibition of Protein Isoprenylation. J. Cancer Res.
1996, 87, 875; (b) Biswas D K, Mhashilkar A M, Ewaniuk D S.
Inhibition of HIV-1 replication by combination of a novel inhibitor of
TNF-alpha with AZT. J Acquir Immune Defic Syndr Hum Retrovirol,
1998, 18:426-434.
Insertion of
a Carbenoid Carbon into a C–C Bond To Expand
Cyclobutanols to Cyclopentanols. J. Am. Chem. Soc. 2014, 136, 7217;
(n) Ishida, N.; Nakanishi, Y.; Murakami, M. Reactivity Change of
Cyclobutanols towards Isocyanates: Rhodium Favors C‐
Carbamoylation over O‐Carbamoylation. Angew. Chem., Int. Ed. 2013,
52, 11875; (o) Ishida, N.; Shimamoto, Y.; Yano, T.; Murakami, M.
1,5-Rhodium Shift in Rearrangement of N-Arenesulfonylazetidin-3-ols
into Benzosultams. J. Am. Chem. Soc, 2013, 135, 19103; (p) Matsuda,
T.; Miura, N. Synthesis of tetrasubstituted benzenes
(The following will be filled in by the editorial staff)
Manuscript received: XXXX, 2019
Manuscript revised: XXXX, 2019
Manuscript accepted: XXXX, 2019
Accepted manuscript online: XXXX, 2019
Version of record online: XXXX, 2019
viarhodium(I)-catalysed
ring-opening
benzannulation
of
cyclobutenols with alkynes. Org. Biomol. Chem, 2013, 11, 3424; (q)
Ishida, N.; Sawano, S.; Masuda, Y.; Murakami, M. Rhodium-Catalyzed
Ring Opening of Benzocyclobutenols with Site-Selectivity
This article is protected by copyright. All rights reserved.
Chin. J. Chem. 2019, 37, XXX－XXX © 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Running title
Chin. J. Chem.
Entry for the Table of Contents
XXX
Rhodium(I)-Catalyzed [4+2] Cycloaddition
Reactions of 2-Alkylenecyclobutanols with
Alkynes and (E)-2-Nitroethenylbenzene through
C(sp2)-C(sp3) Bond Cleavage
An intermolecular [4+2] cycloaddition was realized through C-C bond cleavage in the
presence of Rh(I) catalyst. The selective ring opening of 2-alkylenecyclobutanols
enables the generation of active alkenylrhodium species, which underwent smooth
cross addition over alkynes and (E)-2-nitroethenylbenzene, leading to highly
substituted all-carbon six-membered rings in a single step.
Xinxin Zheng, Guozhu Zhang*, Dayong Zhang*
This article is protected by copyright. All rights reserved.
Chin. J. Chem. 2019, 37, XXX－XXX © 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
9