Synthesis of Benzofulvenes via Cp?Co(III)-Catalyzed C-H Activation and Carbocyclization of Aromatic Ketones with Internal Alkynes

Article abstract of DOI:10.1021/acs.joc.9b00595

A highly efficient and practical synthesis of benzofulvenes was developed via ketone-directed Cp?Co(III)-catalyzed sequential C-H activation, addition, cyclization, and dehydration cascade processes between simple aromatic ketones and alkynes. The reactio

Full text of DOI:10.1021/acs.joc.9b00595

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Note
Synthesis of Benzofulvenes via Cp*Co(III)-Catalyzed C-H Activation
and Carbocyclization of Aromatic Ketones with Internal Alkynes
Yongqi Yu, Qianlong Wu, Da Liu, Liang Hu, Lin Yu, Ze Tan, and Gangguo Zhu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00595 • Publication Date (Web): 14 May 2019
Downloaded from http://pubs.acs.org on May 14, 2019
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Synthesis of Benzofulvenes via Cp*Co(III)-Catalyzed C−H Activation and Carbocyclization of
Aromatic Ketones with Internal Alkynes
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Yongqi Yu,† Qianlong Wu,† Da Liu,† Liang Hu,† Lin Yu,† Ze Tan,†,* and Gangguo Zhu‡
†State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and
Chemical Engineering, Hunan University, Changsha 410082, P. R. China
‡Department of Chemistry, Zhejiang Normal University, 688 Yingbin Road, Jinhua 321004, China
ztanze@gmail.com
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A highly efficient and practical synthesis of benzofulvenes was developed via ketone-directed
Cp*Co(III)-catalyzed sequential C−H activation, addition, cyclization and dehydration cascade
processes between simple aromatic ketones and alkynes. The reaction tolerates a variety of functional
groups, and various benzofulvenes were efficiently synthesized in 42-92% yields.
Benzofulvenes are an important class of structural scaffolds that are present in many
pharmaceutical molecules and they have found extensive applications in organic polymers,
metallocene catalysts, and functional materials.1 Consequently, the development of practical and
efficient approaches for the synthesis of benzofulvenes has continuously been an important
research topic. Traditionally, the synthesis of benzofulvenes has largely relied on the regular
functional group transformations of indenone derivatives.1b,c As a result, prefunctionalized
indenone derivatives must be prepared beforehand. In addition, benzofulvenes can also be
obtained via radical based or metal-catalyzed annulation reactions starting from the corresponding
mono or acyclic precursors.2 Although these methods do provide promising access to
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benzofulvenes, they generally suffer from problems such as harsh reaction conditions, expensive
catalysts or requiring multi-step prefunctionalized starting materials. Over the past several years,
transition metal-catalyzed C–H activation has emerged as an efficient and powerful tool in organic
synthesis.3 A variety of directing groups have been utilized to direct the activation of C−H bonds,
among which ketones were less reported due to their relatively weak coordination capability. It is
worth noting that ketone is one of the most common functional groups in organic chemistry due to
the ease of introduction through various methods. In addition, they are also widely present in
various functional materials and bioactive molecules.4 Hence, developing efficient and practical
strategies for the synthesis of benzofulvenes via ketone-directed C–H activation can be of high
synthetic value.
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Indeed, the formation of benzofulvenes through ketone-directed C−H bond functionalization
has been studied and expensive noble metals have been utilized as catalysts (Scheme 1a).5 In 2010,
Shibata reported the first C−H activation and carbocyclization reaction of aryl ketones and internal
alkynes catalyzed by a cationic iridium catalyst to give benzofulvenes. Later in 2011, Glorius
reported that benzofulvenes can be efficiently synthesized via Rh-catalyzed coupling of aromatic
ketones with alkynes. It should be noted that stoichiometric amounts of Cu(OAc)2 were
indispensable for the reaction. Subsequently, Jeganmohan achieved a similar transformation by
using [RuCl2(p-cymene)]2 as the catalyst, AgSbF6 and Cu(OAc)2·H2O as additives. However, due
to the relatively low abundance and high cost associated with noble metal catalysts such as Rh, Ru
and Ir complexes, their use in industry is not practical. In addition, to our knowledge, although
many examples of ketone-directed C–H activations catalyzed by expensive noble metal complexes
have been reported,6 the number of ketone-directed C−H functionalizations catalyzed by cheaper,
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more earth-abundant, less toxic first-row transition metals is still very few.7 Inspired by the
pioneering reports of Kanai and Matsunaga,8 a number of groups have showed that Cp*Co(III)
catalyst can provide analogous reactivity to its Cp*Rh(III) counterpart. Since then, great progress
in this area has been made by the groups of Kanai,9 Matsunaga,10 Ackermann,11 Sundararaju,7c,12
Chang,13 Glorius,14 Cheng,15 Shi,16 Li,17 and others.18 It should be mentioned that Li17a and
Zhang18b independently reported the synthesis of indenones via Cp*Co(III)-catalyzed C−H
activation and carboannulation of benzoates with internal alkynes. Inspired by these results as well
as continuing our effort in C–H bond functionalizations,19 we wondered whether Cp*Co(III) can
participate in the C–H activation reaction of aromatic ketones with alkynes. Herein, we report that
benzofulvenes can be efficiently synthesized via Cp*Co(III) catalyzed C−H activation and
carbocyclization reaction of aryl ketones with internal alkynes (Scheme 1b).
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Scheme 1. Synthesis of benzofulvenes from aromatic ketones via C-H activation.
We initiated our studies by choosing acetophenone (1a) and diphenylacetylene (2a) as the
model substrates (Table S1 in Supporting Information). When 1a was treated with 1.5 equivalents
of 2a in the presence of 10 mol % of Cp*Co(CO)I2, 25 mol % of AgSbF6, and 20 mol % of
o
NaOAc in DCE under N2 at 120 C for 24 h, much to our delight, the desired benzofulvene
product 3aa was isolated in 53% yield (Table S1, entry 1). Then several different additives were
examined, and KOAc was found to be the optimal one, giving 3aa in 72% yield (Table S1, entries
2-4). In sharp contrast, when the reaction was carried out in the absence of additive, a sharp
decrease of the product yield was observed (Table S1, entry 5). In addition, when AgOTf was
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employed in place of AgSbF6, no desired product was detected (Table S1, entry 6). A similar loss
of catalyst activity via anion change was also observed in Cp*Co(III)-catalyzed C−H activations
before.18b It also seems that only Cp*Co(CO)I2 is capable of effecting the transformation whereas
other cobalt catalysts such as Co(acac)3 and CoCl2 did not afford the desired product (Table S1,
entries 7 and 8). Subsequent screening of other solvents proved DCE to be the best choice, while
reactions employing solvents such as TFE, HFIP, and CH3CN all failed completely (Table S1,
entries 9-11). Test result also showed that performing the reaction under air was actually
detrimental to the yield (Table S1, entry 12). Finally it was observed that raising the reaction
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temperature to 130 C could improve the yield further to 81% (Table S1, entry 13). On the other
hand, the product yield actually dropped when the reaction temperature was raised further to 140
oC (Table S1, entry 14). This may be due to product decomposition at higher temperature. It
should be noted that no product was observed in the absence of the cobalt catalyst or silver salt
additive (Table S1, entries 15 and 16).
With the optimized conditions in hand, the substrate scope of aromatic ketones was explored.
As shown in Table 1, the reaction worked very well for a variety of substituted aromatic ketones,
giving the desired benzofulvenes in yields ranging from 49-92%. Functional groups such as
methyl, methoxy, fluoro, chloro, bromo, iodo, phenyl, nitro as well as ester groups were well
tolerated on the phenyl ring of aromatic ketones. We were pleased to see that substrates bearing
methyl or methoxy group at the ortho-position could be used as viable substrates to give the
desired products 3ba and 3ca in 88% and 92% yields, respectively, showing that the reaction is
not sensitive to steric hindrance. It is worth noting that chloro, bromo and iodo substituted
acetophenones are also viable substrates in the reaction since these halogens can be used for
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further synthetic transformations (Table 1, 3ea, 3fa, 3ia-3ka, 3oa). Importantly, acetophenone
with a para-substituted CO2Me group also responded well to provide the desired product 3na in
58% yield. As for the meta-substituted substrates, the C–H activation tends to occur on the less
hindered site because of steric effect (Table 1, 3da-3fa, 3oa). However, in the case of 3pa, the
C–H activation actually took place on the crowded side, which is most likely due to the
extra-chelation from the ethereal oxygen atom which could help stabilize the metallacycle
intermediate once C–H activation takes place. On the other hand, it is interesting to note that
3'-methoxyacetophenone led to a mixture of regioisomers (3qa and 3qa′). Gratifyingly,
2-acetonaphthalene (1r) could participate in the reaction as well, affording the desired product 3ra
in 63% yield. We were also delighted to find that propiophenone (1s) and butanophenone (1t) also
reacted efficiently with 2a to deliver 3sa and 3ta in yields of 76% and 72% with E/Z ratios of
5.6:1 and 4.3:1, respectively. It is worth mentioning that the reaction of 1,2-diphenylethanone (1u)
with 2a also proceeded smoothly and gave product 3ua in 49% yield with high stereoselectivity
(E/Z > 20：1). We were disappointed to find that 4-acetylpyridine was not applicable for the
system.
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Table 1. Substrate scope of the aromatic ketonesa
aReaction conditions: 1 (0.2 mmol), 2a (0.3 mmol), Cp*Co(CO)I2 (10 mol %), AgSbF6 (25 mol %),
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KOAc (20 mol %), DCE (1 mL), 130 oC, N2, 24 h. Isolated yield. bE and Z stereochemistry were
determined by the known data of reference 5c. cE/Z ratio was determined by 1H NMR.
The scope of the alkynes was also examined under the optimized conditions (Table 2). It was
observed that both electron-donating (methyl and tert-butyl) and electron-withdrawing (chloro and
trifluoromethyl) groups on the phenyl rings of the diphenylacetylenes were well tolerated,
providing the corresponding benzofulvenes in moderate to good yields. In general, substrates
bearing electron-withdrawing substituents on the diphenylacetylenes led to slightly higher yields
(such as 3ad and 3ae). We were pleased to find that 1,2-di(2-naphthyl)ethyne (2g) reacted well
with 1a under the standard reaction conditions to give the desired product 3ag in 55% yield. In
addition, the unsymmetrical internal alkyne 1-phenyl-1-propyne (2h) could participate in the
reaction as well, giving the desired products 3ah and 3ah′ in a 42% combined yield with a
regioselectivity of 2.1:1. Moreover, unsymmetrical diarylacetylene 2i also reacted smoothly,
giving a mixture of two isomers (3ai and 3ai′). Unfortunately, alkynes 2j-2l were found to be
incompatible for the reaction. At least one aryl group is required for the internal alkyne in the
reaction and this may be due to the fact the aryl group could help stabilize the cobaltacycle
intermediate formed after the migratory insertion of alkyne. As for 2j and 2l, they may react with
Ag+ to form alkynyl silver, which may cause them to fail to react. Furthermore, we have also
conducted an experiment with aryl alkoxycarbonyl alkyne. However, the reaction was rather
messy.
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Table 2. Substrate scope of the alkynesa
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aReaction conditions: 1a (0.2 mmol), 2 (0.3 mmol), Cp*Co(CO)I2 (10 mol %), AgSbF6 (25 mol %),
KOAc (20 mol %), DCE (1 mL), 130 oC, N2, 24 h. Isolated yield.
To demonstrate the synthetic applicability of the procedure, a larger-scale reaction was
successfully conducted to give 3aa in 72% yield (Scheme 2a). Moreover, the usefulness of
benzofulvene 3aa was evaluated. When 3aa was treated with K2OsO2(OH)4 in the presence of 3.0
equiv NMO, the terminal alkene was selectively dihydroxylated to give 4 in 71% yield (Scheme
2b).
Scheme 2. Larger-scale synthesis and derivatization of 3aa
It is worthwhile to point out that we also successfully developed a straightforward one-pot
approach to benzofulvene 3ua through cyclodimerization of diphenylacetylene (Scheme 3).
Importantly, no reaction occurred in the absence of trifluoroethanol. When the TFE was replaced
by H2O (0.2 mL), no reaction was observed, suggesting that a large amount of water is detrimental
to the reaction. We reasoned that 1,2-diphenylethanone was generated in situ which subsequently
reacted with another molecule of diphenylacetylene to form the final product 3ua. GC-MS
analysis of the reaction mixture did show the presence of 1,2-diphenylethanone. It should be
mentioned that Hua20 and Chuang21 have also reported the synthesis of benzofulvenes from two
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arylacetylenes via Pd-catalysis.
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Scheme 3. Synthesis of benzofulvene derivative via direct cyclodimerization of
diarylacetylene
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In order to gain some insight on the reaction mechanism, a series of control experiments were
conducted (Scheme 4). At first, H/D exchange experiment between acetophenone (1a) and
CD3OD was performed to investigate the reversibility of the C−H activation step (Scheme 4a). A
significant amount of deuterium was incorporated at each ortho position of 1a after its recovery,
indicating that the C−H activation is reversible. Interestingly, performing the reaction in the
presence of 2a led to no deuterium incorporation at the C7-position of 3aa, suggesting that the
migratory insertion of alkyne may be faster than protonolysis of cobaltacycle species (Scheme 4b).
Then, competition experiment between electronically different acetophenones 1g and 1l revealed
that more electron-rich substrate 1g was favored for the reaction (Scheme 4c). This result is
consistent with the assumption that the electron-rich aromatic ring should bind with the
electrophilic metal center more easily, which in term suggests that a base (acetate)-assisted
intermolecular electrophilic substitution-type (BIES) mechanism is likely to be operative for the
C−H activation step.22 Furthermore, a reaction using a mixture of electron-rich and -deficient
alkynes 2e and 2f as the alkyne starting material was examined and the result revealed that the
electron-deficient alkyne to be more reactive (Scheme 4d). In addition, the kinetic-isotope effect
(KIE) was investigated in competitive and parallel experiments (Scheme 4e). The competitive and
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parallel KIE value were determined to be around 2.45 and 2.85, respectively, suggesting that C−H
activation may be involved in the turnover-limiting step of the reaction.
Scheme 4. Control experiments
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Based on the control experiments and precedent literatures,5,7b,c,7e,17a,18b,23 a plausible reaction
mechanism is proposed in Scheme 5. First, the active cationic Cp*Co(III) species A is generated
from Cp*Co(CO)I2 in the presence of AgSbF6 and KOAc. Then coordination of the carbonyl
oxygen of aromatic ketone to A followed by C−H activation forms a five-membered cobaltacycle
B. Next a seven-membered cobaltacyclic intermediate C is produced via coordination and
subsequent migratory insertion of alkyne with intermediate B. After intramolecular migratory
insertion of the C-Co bond into the C=O group, intermediate C is transformed into a Co(III)
alkoxide species D. Finally protonolysis of D by HOAc regenerates the active Co(III) catalyst and
releases the tertiary alcohol intermediate E, which undergoes dehydration with the assistance of
Ag+ to deliver the product 3.5c
Scheme 5. Possible mechanism
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In summary, we have developed a highly efficient and practical synthesis of benzofulvenes via
Cp*Co(III)-catalyzed sequential C−H activation, addition, cyclization and dehydration cascade
reactions between simple aromatic ketones and internal alkynes, and H2O is the only by-product in
the reaction. Air-stable and cost-effective Cp*Co(III) was used as the catalyst and weak
coordinating ketone carbonyl was utilized as the directing group. To the best of our knowledge,
this is the first example of a first-row transition metal catalyzed C−H activation and
carbocyclization of aromatic ketones with internal alkynes. The reaction tolerates a variety of
functional groups, and various benzofulvenes were efficiently synthesized in moderate to excellent
yields. In addition, we also successfully developed a straightforward one-pot approach to
benzofulvenes through cyclodimerization of readily available aryl alkynes. Further investigations
on expanding the reaction scope are currently underway in our laboratory, and the results will be
reported in due course.
EXPERIMENTAL SECTION
General. Unless otherwise noted, all reagents were obtained from commercial suppliers and used
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without further purification. The Cp*Co(CO)I2 and d5-acetophenone25 were prepared according
the previous reports. Products were purified by column chromatography on 200-300 mesh silica
1
gel, SiO2. H and 13C NMR spectra were measured on a 400 MHz NMR spectrometer using
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CDCl3 as the solvent. The chemical shifts are given in δ relative to TMS, and the coupling
constants are given in Hertz. The peak patterns are indicated as follows: s, singlet; d, doublet; t,
triplet; q, quartet; m, multiplet; qui, quintet; sxt, sextet. The high-resolution mass spectra (HRMS)
analyses were conducted using a TOF MS instrument with an ESI or APCI source. Melting points
were measured by a melting point instrument and were uncorrected.
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General procedure for Cp*Co(III)-catalyzed C−H functionalization to form benzofulvenes.
Acetophenone 1 (0.2 mmol, 1.0 equiv), diphenylacetylene 2 (0.3 mmol, 1.5 equiv), Cp*Co(CO)I2
(9.5 mg, 0.02 mmol, 10 mol %), AgSbF6 (17.1 mg, 0.05 mmol, 25 mol %), KOAc (3.9 mg, 0.04
mmol, 20 mol %) and DCE (1.0 mL) were added to a 35 mL Schlenk flask equipped with a
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high-vacuum PTFE valve-to-glass seal. Then the flask was sealed under N2 and stirred at 130 C
for 24 h. It was then cooled to room temperature, the solvent was removed in vacuum and the
product was isolated through column chromatography to afford the desired product 3.
1-methylene-2,3-diphenyl-1H-indene (3aa). Purification by column chromatography on silica gel
(eluent: petroleum ether) afforded 3aa as a yellow oil (45.4 mg, 81% yield); 1H NMR (400 MHz,
CDCl3): δ 7.74 (d, J = 6.8 Hz, 1H), 7.39-7.35 (m, 2H), 7.33-7.27 (m, 9H), 7.22 (d, J = 7.2 Hz, 2H),
6.28 (s, 1H), 5.75 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 147.6, 142.7, 141.9, 137.5, 136.2,
134.6, 134.5, 130.7, 129.4, 128.2, 128.0, 127.4, 126.9, 125.6, 120.1, 119.8, 114.1. The spectral
data were in accordance with the literature.5c
7-methyl-1-methylene-2,3-diphenyl-1H-indene (3ba). Purification by column chromatography on
silica gel (eluent: petroleum ether) afforded 3ba as a yellow solid (51.8 mg, 88% yield); mp
126-128 oC; 1H NMR (400 MHz, CDCl3): δ 7.26-7.17 (m, 12H), 7.06 (d, J = 6.8 Hz, 1H), 6.25 (s,
1H), 5.80 (s, 1H), 2.62 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 149.0, 143.4, 141.1, 138.5,
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134.7, 134.6, 133.7, 132.5, 131.0, 129.6, 129.0, 128.1, 127.9, 127.7, 127.2, 126.8, 118.6, 118.4,
21.0; HRMS (ESI, m/z) calcd for C23H18Na [M + Na]+ 317.1301, found 317.1305.
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7-methoxy-1-methylene-2,3-diphenyl-1H-indene (3ca). Purification by column chromatography on
silica gel (eluent: petroleum ether) afforded 3ca as a yellow solid (57.1 mg, 92% yield); mp
110-112 oC; 1H NMR (400 MHz, CDCl3): δ 7.31-7.28 (m, 9H), 7.22 (d, J = 7.2 Hz, 2H), 7.04 (d, J
= 7.6 Hz, 1H), 6.90 (d, J = 8.0 Hz, 1H), 6.77 (s, 1H), 5.87 (s, 1H), 4.03 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3): δ 156.3, 146.6, 144.7, 140.8, 138.2, 134.8, 134.6, 130.9, 129.6, 129.0, 128.1,
127.9, 127.2, 126.8, 121.6, 119.8, 113.5, 109.0, 55.3. The spectral data were in accordance with
the literature.5a
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6-fluoro-1-methylene-2,3-diphenyl-1H-indene (3da). Purification by column chromatography on
silica gel (eluent: petroleum ether) afforded 3da as a yellow solid (36.4 mg, 61% yield); mp
169-171 oC; 1H NMR (400 MHz, CDCl3): δ 7.51 (d, J = 7.2 Hz, 1H), 7.28-7.19 (m, 9H), 7.14 (d, J
= 6.4 Hz, 2H), 6.98 (t, J = 9.4 Hz, 1H), 6.28 (s, 1H), 5.76 (s, 1H); 13C{1H} NMR (100 MHz,
CDCl3): δ 156.4 (d, J = 250.0 Hz), 147.4 (d, J = 1.4 Hz), 140.0 (d, J = 3.5 Hz), 139.2 (d, J = 5.5
Hz), 138.3, 134.9 (d, J = 1.1 Hz), 134.1, 130.7, 129.7 (d, J = 2.5 Hz), 128.0, 127.5, 127.4, 127.1,
127.0, 126.9, 116.2 (d, J = 21.7 Hz), 115.8; 19F NMR (376 MHz, CDCl3): δ -117.9; LRMS (EI, 70
ev) m/z (%):298 (M+, 100), 276 (17), 220 (38), 138 (17).
6-chloro-1-methylene-2,3-diphenyl-1H-indene (3ea). Purification by column chromatography on
silica gel (eluent: petroleum ether) afforded 3ea as a yellow solid (40.3 mg, 64% yield); mp
116-118 oC; 1H NMR (400 MHz, CDCl3): δ 7.66 (s, 1H), 7.29-7.26 (m, 10H), 7.18 (d, J = 6.4 Hz,
2H), 6.24 (s, 1H), 5.77 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 146.7, 141.3, 141.0, 137.9,
137.7, 134.2, 134.1, 131.6, 130.6, 129.3, 128.3, 128.1, 128.0, 127.6, 127.1, 120.9, 120.3, 115.3;
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LRMS (EI, 70 ev) m/z (%):314 (M+, 90), 279 (100), 138 (19).
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6-bromo-1-methylene-2,3-diphenyl-1H-indene (3fa). Purification by column chromatography on
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silica gel (eluent: petroleum ether) afforded 3fa as a yellow oil (51.7 mg, 72% yield); H NMR
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(400 MHz, CDCl3): δ 7.85 (s, 1H), 7.46 (d, J = 8.4 Hz, 1H), 7.35-7.29 (m, 9H), 7.23 (d, J = 8.0 Hz,
2H), 6.28 (s, 1H), 5.82 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 146.7, 141.5, 141.3, 138.1,
137.6, 134.1, 134.0, 130.8, 130.6, 129.3, 128.3, 128.1, 127.6, 127.1, 123.2, 121.3, 119.5, 115.4;
HRMS (APCI, m/z) calcd for C22H16Br [M + H]+ 359.0430, found 359.0459.
5-methyl-1-methylene-2,3-diphenyl-1H-indene (3ga). Purification by column chromatography on
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silica gel (eluent: petroleum ether) afforded 3ga as a yellow oil (44.2 mg, 75% yield); H NMR
(400 MHz, CDCl3): δ 7.62 (d, J = 7.6 Hz, 1H), 7.36-7.29 (m, 8H), 7.21 (d, J = 7.6 Hz, 2H), 7.17 (s,
1H), 7.11 (d, J = 6.8 Hz, 1H), 6.21 (s, 1H), 5.69 (s, 1H), 2.41 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3): δ 147.5, 142.9, 141.8, 138.2, 137.8, 134.7, 134.6, 133.6, 130.7, 129.5, 128.2, 127.9, 127.3,
126.8, 126.3, 120.8, 119.6, 113.3, 21.8. The spectral data were in accordance with the literature.5c
5-fluoro-1-methylene-2,3-diphenyl-1H-indene (3ha). Purification by column chromatography on
silica gel (eluent: petroleum ether) afforded 3ha as a yellow solid (40.0 mg, 67% yield); mp
105-107 oC; 1H NMR (400 MHz, CDCl3): δ 7.69-7.63 (m, 1H), 7.32-7.30 (m, 8H), 7.22 (d, J = 6.4
Hz, 2H), 7.07 (d, J = 9.2 Hz, 1H), 6.97 (t, J = 8.8 Hz, 1H), 6.21 (s, 1H), 5.74 (s, 1H); 13C{1H}
NMR (100 MHz, CDCl3): δ 163.5 (d, J = 243.4 Hz), 146.6, 144.8 (d, J = 8.9 Hz), 140.9 (d, J = 2.5
Hz), 139.1, 134.2, 134.0, 131.9 (d, J = 2.4 Hz), 130.6, 129.3, 128.4, 128.1, 127.6, 127.2, 120.8 (d,
J = 9.2 Hz), 114.4, 112.0 (d, J = 23.3 Hz), 107.6 (d, J = 24.1 Hz); 19F NMR (376 MHz, CDCl3): δ
-113.3. The spectral data were in accordance with the literature.5c
5-chloro-1-methylene-2,3-diphenyl-1H-indene (3ia). Purification by column chromatography on
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silica gel (eluent: petroleum ether) afforded 3ia as a yellow solid (44.7 mg, 71% yield); mp
122-124 oC; 1H NMR (400 MHz, CDCl3): δ 7.64 (d, J = 7.6 Hz, 1H), 7.35-7.28 (m, 10H), 7.22 (d,
J = 6.4 Hz, 2H), 6.26 (s, 1H), 5.79 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 146.6, 144.3,
141.0, 138.8, 134.4, 134.1, 134.0, 133.9, 130.6, 129.3, 128.4, 128.1, 127.7, 127.2, 125.4, 120.7,
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120.3, 115.1; HRMS (APCI, m/z) calcd for C22H16Cl [M + H]+ 315.0935, found 315.0979.
5-bromo-1-methylene-2,3-diphenyl-1H-indene (3ja). Purification by column chromatography on
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silica gel (eluent: petroleum ether) afforded 3ja as a yellow oil (47.4 mg, 66% yield); H NMR
(400 MHz, CDCl3):δ 7.55 (d, J = 8.0 Hz, 1H), 7.46 (s, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.32-7.24 (m,
8H), 7.18 (d, J = 6.8 Hz, 2H), 6.24 (s, 1H), 5.77 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ
146.7, 144.6, 141.0, 138.6, 134.9, 134.1, 133.8, 130.6, 129.3, 128.4, 128.3, 128.1, 127.7, 127.2,
123.2, 122.2, 121.1, 115.2. The spectral data were in accordance with the literature.5c
5-iodo-1-methylene-2,3-diphenyl-1H-indene (3ka). Purification by column chromatography on
silica gel (eluent: petroleum ether) afforded 3ka as a yellow solid (50.4 mg, 62% yield); mp
119-121 oC; 1H NMR (400 MHz, CDCl3): δ 7.68 (s, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.46 (d, J = 7.6
Hz, 1H), 7.36-7.28 (m, 8H), 7.20 (d, J = 7.6 Hz, 2H), 6.28 (s, 1H), 5.80 (s, 1H); 13C{1H} NMR
(100 MHz, CDCl3): δ 146.8, 144.7, 141.0, 138.3, 135.6, 134.3, 134.0, 133.9, 130.6, 129.3, 129.0,
128.4, 128.1, 127.7, 127.2, 121.4, 115.3, 93.8. The spectral data were in accordance with the
literature.5c
1-methylene-5-nitro-2,3-diphenyl-1H-indene (3la). Purification by column chromatography on
silica gel (eluent: petroleum ether:ethyl acetate=100:1, v/v) afforded 3la as a yellow solid (33.8
o
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mg, 52% yield); mp 191-193 C; H NMR (400 MHz, CDCl3): δ 8.21-8.19 (m, 2H), 7.81 (d, J =
8.0 Hz, 1H), 7.37-7.29 (m, 8H), 7.21 (d, J = 6.0 Hz, 2H), 6.44 (s, 1H), 5.97 (s, 1H); 13C{1H} NMR
(100 MHz, CDCl3): δ 148.3, 146.1, 143.7, 141.9, 140.8, 139.8, 133.5, 133.2, 130.5, 129.2, 128.6,
128.3, 128.1, 127.6, 121.3, 120.0, 118.6, 115.1; HRMS (APCI, m/z) calcd for C22H16NO2 [M +
H]+ 326.1176, found 326.1199.
1-methylene-2,3,5-triphenyl-1H-indene (3ma). Purification by column chromatography on silica
gel (eluent: petroleum ether) afforded 3ma as a yellow solid (59.2 mg, 83% yield); mp 122-124 oC;
1H NMR (400 MHz, CDCl3): δ 7.77 (d, J = 7.6 Hz, 1H), 7.60-7.56 (m, 3H), 7.50 (d, J = 7.2 Hz,
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1H), 7.41 (t, J = 7.2 Hz, 2H), 7.32-7.28 (m, 9H), 7.21 (d, J = 7.6 Hz, 2H), 6.27 (s, 1H), 5.75 (s,
1H); 13C{1H} NMR (100 MHz, CDCl3): δ 147.3, 143.3, 141.8, 141.6, 141.5, 138.2, 135.3, 134.5,
134.4, 130.7, 129.5, 128.7, 128.3, 128.0, 127.5, 127.3, 127.2, 127.0, 124.7, 120.1, 119.0, 114.3;
HRMS (ESI, m/z) calcd for C28H21 [M + H]+ 357.1638, found 357.1664.
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methyl 1-methylene-2,3-diphenyl-1H-indene-5-carboxylate (3na). Purification by column
chromatography on silica gel (eluent: petroleum ether:ethyl acetate=100:1, v/v) afforded 3na as a
yellow solid (39.2 mg, 58% yield); mp 148-150 oC; 1H NMR (400 MHz, CDCl3): δ 8.04-8.02 (m,
2H), 7.77 (d, J = 8.0 Hz, 1H), 7.35-7.29 (m, 8H), 7.23-7.20 (m, 2H), 6.36 (s, 1H), 5.86 (s, 1H),
3.92 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 167.3, 146.9, 142.8, 141.5, 140.5, 138.3, 134.1,
133.9, 130.6, 129.9, 129.4, 128.4, 128.1, 127.7, 127.5, 127.2, 121.0, 119.6, 116.4, 52.1; HRMS
(ESI, m/z) calcd for C24H19O2 [M + H]+ 339.1380, found 339.1382.
5,6-dichloro-1-methylene-2,3-diphenyl-1H-indene (3oa). Purification by column chromatography
on silica gel (eluent: petroleum ether) afforded 3oa as a yellow solid (39.1 mg, 56% yield); mp
o
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137-139 C; H NMR (400 MHz, CDCl3): δ 7.75 (s, 1H), 7.41 (s, 1H), 7.34-7.29 (m, 7H),
7.26-7.24 (m, 1H), 7.20-7.17 (m, 2H), 6.24 (s, 1H), 5.81 (s, 1H); 13C{1H} NMR (100 MHz,
CDCl3): δ 146.0, 142.4, 140.6, 138.9, 135.9, 133.8, 133.6, 131.9, 130.5, 129.3, 129.2, 128.5, 128.2,
127.9, 127.4, 121.7, 121.6, 116.0; HRMS (ESI, m/z) calcd for C22H15Cl2 [M + H]+ 349.0545 ,
found 349.0553.
6-methylene-7,8-diphenyl-6H-indeno[4,5-d][1,3]dioxole (3pa). Purification by column
chromatography on silica gel (eluent: petroleum ether:ethyl acetate=100:1, v/v) afforded 3pa as a
yellow solid (39.6 mg, 61% yield); mp 157-159 oC; 1H NMR (400 MHz, CDCl3): δ 7.32-7.30 (m,
2H), 7.28-7.23 (m, 7H), 7.16-7.14 (m, 2H), 6.74 (d, J = 8.0 Hz, 1H), 6.08 (s, 1H), 5.90 (s, 2H),
5.56 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 149.0, 147.4, 140.2, 139.1, 139.0, 134.5, 134.3,
131.5, 130.7, 129.9, 128.0, 127.5, 127.4, 127.0, 123.8, 113.4, 112.6, 105.1, 101.0; HRMS (ESI,
m/z) calcd for C23H17O2 [M + H]+ 325.1223, found 325.1228.
The mixture of 3qa and 3qa′. Purification by column chromatography on silica gel (eluent:
petroleum ether:ethyl acetate=100:1, v/v) afforded the mixture of 3qa and 3qa′ as a yellow oil
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(44.0 mg, 71% yield); H NMR (400 MHz, CDCl3): δ 7.39 (d, J = 7.2 Hz, 1.22H), 7.30-7.29 (m,
6.62H), 7.26-7.23 (m, 10.32H), 7.21-7.19 (m, 5.91H), 7.12-7.10 (m, 2.57H), 6.87-6.83 (m, 2.36H),
6.24 (s, 1.22H), 6.20 (s, 1H), 5.70 (s, 2.22H), 3.88 (s, 3H), 3.59 (s, 3.65H); 13C{1H} NMR (100
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MHz, CDCl3): δ 158.8, 154.0, 147.8, 147.5, 141.7, 138.2, 138.1, 137.0, 136.3, 135.9, 135.8, 134.8,
134.7, 130.9, 130.7, 130.1, 129.5, 129.3, 129.0, 128.9, 128.4, 128.3, 128.2, 128.0, 127.9, 127.8,
127.7, 127.4, 126.9, 126.8, 126.7, 126.6, 126.5, 120.6, 114.6, 113.5, 113.0, 112.9, 112.5, 106.7,
55.7, 55.6; HRMS (ESI, m/z) calcd for C23H19O [M + H]+ 311.1430, found 311.1433.
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1-methylene-2,3-diphenyl-1H-cyclopenta[b]naphthalene (3ra). Purification by column
chromatography on silica gel (eluent: petroleum ether) afforded 3ra as a yellow solid (41.6 mg, 63%
yield); mp 116-118 oC; 1H NMR (400 MHz, CDCl3): δ 8.12 (s, 1H), 7.88-7.87 (m, 1H), 7.79-7.77
(m, 1H), 7.69-7.65 (m, 1H), 7.43-7.41 (m, 2H), 7.35-7.34 (m, 4H), 7.32-7.28 (m, 4H), 7.24-7.23
(m, 2H), 6.25 (s, 1H), 5.64 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ 146.9, 142.1, 141.1,
140.8, 135.3, 134.5, 134.4, 134.0, 132.4, 130.6, 129.5, 128.5, 128.4, 128.3, 128.0, 127.6, 127.1,
125.9, 125.4, 118.8, 118.3, 111.0; HRMS (ESI, m/z) calcd for C26H19 [M + H]+ 331.1481, found
331.1472.
(E)- and (Z)-1-ethylidene-2,3-diphenyl-1H-indene (3sa). Purification by column chromatography
on silica gel (eluent: petroleum ether) afforded 3sa as a yellow solid (44.7 mg, 76% yield); mp
130-132 oC; 1H NMR (400 MHz, CDCl3): δ 7.88 (d, J = 5.6 Hz, 1H), 7.63 (d, J = 4.8 Hz, 0.18H),
7.40 (d, J = 5.6 Hz, 1H), 7.33-7.22 (m, 12.34 H), 7.16 (d, J = 7.2 Hz, 2H), 6.89 (q, J = 7.6 Hz,
0.18 H), 6.36 (q, J = 7.6 Hz, 1H), 2.38 (d, J = 7.6 Hz, 3H), 1.66 (d, J = 7.6 Hz, 0.54H); 13C{1H}
NMR (100 MHz, CDCl3): δ 143.5, 141.6, 139.4, 138.6, 135.3, 135.2, 134.9, 132.8, 131.1, 130.3,
129.6, 129.4, 129.3, 128.1, 128.0, 127.9, 127.8, 127.2, 127.0, 126.9, 126.8, 126.7, 125.2, 123.8,
120.2, 119.9, 15.9, 15.4. The spectral data were in accordance with the literature.5c
(E)- and (Z)-2,3-diphenyl-1-propylidene-1H-indene (3ta). Purification by column chromatography
on silica gel (eluent: petroleum ether) afforded 3ta as a yellow solid (44.4 mg, 72% yield); mp
112-114 oC; 1H NMR (400 MHz, CDCl3): δ 7.85 (d, J = 6.4 Hz, 1H), 7.66 (d, J = 3.9 Hz, 0.23H),
7.39 (d, J = 6.4 Hz, 1H), 7.28-7.24 (m, 12.99H), 7.17 (d, J = 6.8 Hz, 2H), 6.76 (t, J = 7.8 Hz,
0.23H), 6.25 (t, J = 7.4 Hz, 1H), 2.88 (m, 2H), 2.01 (m, 0.46H), 1.22 (t, J = 7.4 Hz, 3H), 0.94 (t, J
= 7.4 Hz, 0.68H); 13C{1H} NMR (100 MHz, CDCl3): δ 143.5, 140.4, 140.1, 139.5, 138.8, 137.8,
137.7, 137.0, 136.6, 135.2, 135.1, 134.9, 134.7, 131.1, 130.2, 129.6, 129.4, 128.1, 127.9, 127.8,
127.2, 127.0, 126.9, 126.8, 126.7, 125.3, 125.2, 123.7, 120.1, 119.9, 118.3, 23.3, 22.3, 14.1, 13.9;
HRMS (ESI, m/z) calcd for C24H21 [M + H]+ 309.1638, found 309.1659.
(E)- and (Z)-1-benzylidene-2,3-diphenyl-1H-indene (3ua). Purification by column
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chromatography on silica gel (eluent: petroleum ether) afforded 3ua as a yellow solid (34.9 mg,
49% yield); mp 175-177 oC; 1H NMR (400 MHz, CDCl3): δ 7.60 (t, J = 6.6 Hz, 3H), 7.47 (t, J =
7.2 Hz, 2H), 7.42 (t, J = 7.4 Hz, 2H), 7.37-7.28 (m, 11H), 7.22 (s, 1H), 7.07 (t, J = 7.4 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3): δ 143.8, 141.4, 140.4, 139.7, 137.0, 135.0, 134.7, 134.5, 134.4,
131.2, 129.5, 129.3, 128.4, 128.1, 128.0, 127.9, 127.2, 127.0, 125.2, 123.3, 120.1. The spectral
data were in accordance with the literature.5c
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1-methylene-2,3-di-m-tolyl-1H-indene (3ab). Purification by column chromatography on silica gel
(eluent: petroleum ether) afforded 3ab as a yellow oil (34.5 mg, 56% yield); 1H NMR (400 MHz,
CDCl3): δ 7.72 (d, J = 7.2 Hz, 1H), 7.37 (d, J = 7.2 Hz, 1H), 7.34-7.28 (m, 2H), 7.21-7.16 (m, 3H),
7.10-7.08 (m, 4H), 6.99 (d, J = 7.2 Hz, 1H), 6.25 (s, 1H), 5.74 (s, 1H), 2.32 (s, 6H); 13C{1H} NMR
(100 MHz, CDCl3): δ 147.8, 142.9, 141.8, 137.6, 137.4, 137.3, 136.2, 134.6, 134.5, 131.3, 129.9,
128.1, 128.0, 127.8, 127.7, 127.6, 126.6, 125.5, 120.1, 119.7, 113.9, 21.5, 21.4. The spectral data
were in accordance with the literature.2f
1-methylene-2,3-di-p-tolyl-1H-indene (3ac). Purification by column chromatography on silica gel
(eluent: petroleum ether) afforded 3ac as a yellow oil (38.9 mg, 63% yield); 1H NMR (400 MHz,
CDCl3): δ 7.69 (d, J = 6.8 Hz, 1H), 7.34 (d, J = 6.8 Hz, 1H), 7.29 (d, J = 6,8 Hz, 1H), 7.24 (d, J =
3.2 Hz, 1H), 7.19 (d, J = 7.2 Hz, 2H), 7.12-7.09 (m, 6H), 6.21 (s, 1H), 5.70 (s, 1H), 2.34 (s, 6H);
13C{1H} NMR (100 MHz, CDCl3): δ 147.7, 142.9, 141.5, 137.0, 136.5, 136.3, 131.7, 131.6, 130.6,
129.3, 128.9, 128.7, 128.1, 125.4, 120.0, 119.7, 113.7, 21.3, 21.2. The spectral data were in
accordance with the literature.2f
2,3-bis(4-chlorophenyl)-1-methylene-1H-indene (3ad). Purification by column chromatography on
silica gel (eluent: petroleum ether) afforded 3ad as a yellow solid (57.3 mg, 82% yield); mp
139-141 oC; 1H NMR (400 MHz, CDCl3): δ 7.73 (d, J = 6.0 Hz, 1H), 7.32-7.29 (m, 7H), 7.23 (d, J
= 8.0 Hz, 2H), 7.13 (d, J = 8.0 Hz, 2H), 6.28 (s, 1H), 5.71 (s, 1H); 13C{1H} NMR (100 MHz,
CDCl3): δ 147.2, 142.0, 141.1, 136.5, 136.0, 133.5, 133.2, 132.7, 132.6, 131.9, 130.7, 128.7, 128.5,
128.4, 126.0, 120.0, 119.9, 114.5; HRMS (APCI, m/z) calcd for C22H15Cl2 [M + H]+ 349.0545,
found 349.0557.
1-methylene-2,3-bis(4-(trifluoromethyl)phenyl)-1H-indene (3ae). Purification by column
chromatography on silica gel (eluent: petroleum ether) afforded 3ae as a yellow solid (65.0 mg, 78%
yield); mp 120-122 oC; 1H NMR (400 MHz, CDCl3): δ 7.77 (d, J = 6.0 Hz, 1H), 7.62-7.58 (m, 4H),
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7.41 (d, J = 8.0 Hz, 2H), 7.37-7.30 (m, 5H), 6.35 (s, 1H), 5.74 (s, 1H); 13C{1H} NMR (100 MHz,
CDCl3): δ 147.1, 141.7, 141.6, 137.9, 137.8, 137.0, 136.0, 130.9, 130.1 (q, J = 32.0 Hz), 129.7,
129.4 (q, J = 32.3 Hz), 128.6, 126.5, 125.5 (q, J = 3.7 Hz), 125.2 (q, J = 3.7 Hz), 124.1 (q, J =
270.4 Hz), 124.0 (q, J = 270.5 Hz), 120.2, 120.1, 115.3; 19F NMR (376 MHz, CDCl3): δ -62.5,
-62.6; HRMS (ESI, m/z) calcd for C24H15F6 [M + H]+ 417.1072, found 417.1085.
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2,3-bis(4-(tert-butyl)phenyl)-1-methylene-1H-indene
(3af).
Purification
by
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chromatography on silica gel (eluent: petroleum ether) afforded 3af as a yellow solid (40.0 mg, 51%
yield); mp 63-65 oC; 1H NMR (400 MHz, CDCl3): δ 7.70 (d, J = 6.8 Hz, 1H), 7.38 (d, J = 7.2 Hz,
1H), 7.33-7.24 (m, 8H), 7.14 (d, J = 8.0 Hz, 2H), 6.22 (s, 1H), 5.72 (s, 1H), 1.32 (s, 18H); 13C{1H}
NMR (100 MHz, CDCl3): δ 150.1, 149.6, 147.8, 143.0, 141.4, 137.0, 136.3, 131.6, 131.5, 130.3,
129.1, 128.1, 125.4, 125.0, 124.8, 120.2, 119.6, 113.8, 34.6, 34.5, 31.4, 31.3. The spectral data
were in accordance with the literature.2f
2,2'-(1-methylene-1H-indene-2,3-diyl)dinaphthalene
(3ag).
Purification
by
column
chromatography on silica gel (eluent: petroleum ether) afforded 3ag as a yellow solid (41.9 mg, 55%
yield); mp 109-111 oC; 1H NMR (400 MHz, CDCl3): δ 7.99 (s, 1H), 7.82-7.80 (m, 6H), 7.69 (d, J
= 8.8 Hz, 2H), 7.51-7.46 (m, 5H), 7.40-7.28 (m, 4H), 6.36 (s, 1H), 5.87 (s, 1H); 13C{1H} NMR
(100 MHz, CDCl3): δ 147.7, 142.7, 142.0, 137.5, 136.4, 133.3, 133.2, 132.7, 132.4, 132.2, 132.1,
129.8, 128.8, 128.4, 128.3, 128.1, 128.0, 127.8, 127.7, 127.6, 127.5, 126.1, 126.0, 125.9, 125.8,
120.2, 119.9, 114.4; HRMS (APCI, m/z) calcd for C30H21 [M + H]+ 381.1638, found 381.1651.
The mixture of 3ah and 3ah′. Purification by column chromatography on silica gel (eluent:
1
petroleum ether) afforded the mixture of 3ah and 3ah′ as a yellow oil (18.3 mg, 42% yield); H
NMR (400 MHz, CDCl3): δ 7.65 (d, J = 7.2 Hz, 2.10H), 7.61 (d, J = 6.8 Hz, 1H), 7.47-7.42 (m,
8.68H), 7.36-7.28 (m, 11.84H), 7.24-7.18 (m, 4.85H), 6.09 (s, 3.10H), 5.78 (s, 1H), 5.58 (s,
2.10H), 2.20 (s, 6.30H), 2.18 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 148.6, 147.4, 143.8,
143.5, 141.4, 138.4, 137.1, 136.1, 136.0, 135.0, 134.9, 133.0, 130.3, 129.0, 128.4, 128.2, 128.1,
128.0, 127.4, 126.9, 125.4, 124.9, 119.4, 119.3, 119.1, 118.6, 111.7, 110.6, 11.4, 10.5. The spectral
data were in accordance with the literature.5b,26
The mixture of 3ai and 3ai′. Purification by column chromatography on silica gel (eluent:
1
petroleum ether) afforded the mixture of 3ai and 3ai′ as a yellow oil (33.5 mg, 54% yield); H
NMR (400 MHz, CDCl3): δ 7.71-7.69 (m, 2.20H), 7.38-7.34 (m, 2.09H), 7.32-7.28 (m, 9.24H),
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7.26-7.24 (m, 5.13H), 7.22-7.20 (m, 4.33H), 7.13-7.11 (m, 2.19H), 6.84-6.81 (m, 4.57H), 6.23 (s,
1H), 6.21 (s, 1.2H), 5.72 (s, 1H), 5.69 (s, 1.2H), 3.78 (s, 6.66H); 13C{1H} NMR (100 MHz,
CDCl3): δ 158.9, 158.6, 147.8, 147.6, 142.8, 141.4, 141.3, 137.1, 136.7, 136.3, 136.1, 134.9, 134.7,
131.8, 130.7, 130.6, 129.4, 128.2, 128.2, 128.1, 128.0, 127.3, 126.8, 126.7, 125.6, 125.5, 120.0,
119.9, 119.7, 114.0, 113.7, 113.5, 55.1; HRMS (ESI, m/z) calcd for C23H19O [M + H]+ 311.1430,
found 311.1429.
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Procedure for the larger-scale synthesis of 3aa. Acetophenone 1a (2.0 mmol, 1.0 equiv),
diphenylacetylene 2a (3.0 mmol, 1.5 equiv), Cp*Co(CO)I2 (95.0 mg, 0.2 mmol, 10 mol %),
AgSbF6 (171.8 mg, 0.5 mmol, 25 mol %), KOAc (39.2 mg, 0.4 mmol, 20 mol %) and DCE (10
mL) were added to a 50 mL Schlenk flask equipped with a high-vacuum PTFE valve-to-glass seal.
o
Then the flask was sealed under N2 and stirred at 130 C for 24 h. It was then cooled to room
temperature, the solvent was removed in vacuum. Purification by column chromatography on
silica gel (eluent: petroleum ether) afforded the product 3aa (403.1 mg, 72% yield).
o
Procedure for the dihydroxylation of 3aa. To a cooled (0 C) solution of 3aa (0.2 mmol, 1.0
equiv) in t-BuOH/H2O/PhMe (2.1 mL, v/v/v = 15/5/1) was added N-methyl morpholine N-oxide
(0.6mmol, 3.0 equiv) and potassium osmate (VI) dihydrate (0.02 mmol, 10 mol%). After being
o
stirred for 24h at 0 C, the reaction mixture was quenched with a saturated aqueous solution of
NaHSO3 and stirred for another 1 h. The mixture was extracted with EtOAc and the combined
organic extracts were washed with brine. Dried, filtrated and concentrated, the residue was
purified by column chromatography on silica gel (eluent: petroleum ether:ethyl acetate=4:1, v/v)
to afford 4 as a white solid (44.6 mg, 71% yield); mp 146-148 oC; 1H NMR (400 MHz, CDCl3): δ
7.60 (d, J = 7.6 Hz, 1H), 7.40-7.37 (m, 2H), 7.31-7.26 (m, 7H), 7.24-7.20 (m, 4H), 3.91 (d, J =
11.6 Hz, 1H), 3.61 (d, J = 11.6 Hz, 1H), 2.83 (s, 1H), 2.02 (s, 1H); 13C{1H} NMR (100 MHz,
CDCl3): δ 146.2, 143.8, 142.9, 141.2, 134.7, 134.3, 129.3, 129.2, 128.8, 128.5, 128.1, 127.7, 127.5,
126.6, 123.1, 121.0, 85.3, 67.4; HRMS (ESI, m/z) calcd for C22H18NaO2 [M + Na]+ 337.1199,
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found 337.1201.
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Procedure for synthesis of benzofulvene derivative through direct cyclodimerization of
diarylacetylene. Diphenylacetylene 2a (0.4 mmol, 1.0 equiv), Cp*Co(CO)I2 (9.5 mg, 0.02 mmol,
5 mol %), AgSbF6 (27.4 mg, 0.08 mmol, 20 mol %), KOAc (3.9 mg, 0.04 mmol, 10 mol %), TFE
(0.2 mL) and DCE (1.8 mL) were added to a 35 mL Schlenk flask equipped with a high-vacuum
PTFE valve-to-glass seal. Then the flask was sealed under N2 and stirred at 130 oC for 24 h. It was
then cooled to room temperature, the solvent was removed in vacuum and the product was isolated
through column chromatography (eluent: petroleum ether) to afford 3ua, and
1,2-diphenylethanone was detected by GC-MS (please see Supporting Information)
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H/D exchange experiment in the absence of 2a. Acetophenone 1a (24.1 mg, 0.2 mmol, 1.0
equiv), Cp*Co(CO)I2 (9.5 mg, 0.02 mmol, 10 mol %), AgSbF6 (17.1 mg, 0.05 mmol, 25 mol %),
KOAc (3.9 mg, 0.04 mmol, 20 mol %), CD3OD (72.1 mg, 2.0 mmol, 10.0 equiv) and DCE (1.0
mL) were added to a 35 mL Schlenk flask equipped with a high-vacuum PTFE valve-to-glass seal.
o
Then the flask was sealed under N2 and stirred at 130 C for 5 h. It was then cooled to room
temperature, the solvent was removed in vacuum and then the reaction mixture was passed
1
through a short pad of silica gel (eluent: petroleum ether:ethyl acetate = 50:1, v/v). The H NMR
of the isolated product shows deuterium incorporation of about 25% in ortho position with respect
to carbonyl of 1a.
H/D exchange experiment in the prensence of 2a. Acetophenone 1a (24.1 mg, 0.2 mmol, 1.0
equiv), diphenylacetylene 2a (53.5 mg, 0.3 mmol, 1.5 equiv), Cp*Co(CO)I2 (9.5 mg, 0.02 mmol,
10 mol %), AgSbF6 (17.1 mg, 0.05 mmol, 25 mol %), KOAc (3.9 mg, 0.04 mmol, 20 mol %),
CD3OD (72.1 mg, 2.0 mmol, 10.0 equiv) and DCE (1.0 mL) were added to a 35 mL Schlenk flask
equipped with a high-vacuum PTFE valve-to-glass seal. Then the flask was sealed under N2 and
o
stirred at 130 C for 24 h. It was then cooled to room temperature, the solvent was removed in
vacuum and the product was isolated through column chromatography (eluent: petroleum ether) to
1
afford 3aa. The H NMR spectra of 3aa shows no deuterium incorporation at the C7-position of
3aa.
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Intermolecular competition experiment between different acetophenones with 2a.
1-(p-tolyl)ethan-1-one 1g (26.8 mg, 0.2 mmol, 1.0 equiv), 1-(4-nitrophenyl)ethan-1-one 1l (33.0
mg, 0.2 mmol, 1.0 equiv), diphenylacetylene 2a (35.7 mg, 0.2 mmol, 1.0 equiv), Cp*Co(CO)I2
(9.5 mg, 0.02 mmol, 10 mol %), AgSbF6 (17.1 mg, 0.05 mmol, 25 mol %), KOAc (3.9 mg, 0.04
mmol, 20 mol %) and DCE (1.0 mL) were added to a 35 mL Schlenk flask equipped with a
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high-vacuum PTFE valve-to-glass seal. Then the flask was sealed under N2 and stirred at 130 C
for 24 h. It was then cooled to room temperature, the solvent was removed in vacuum and then the
crude mixture was purified by column chromatography (eluent: pure petroleum ether) on silica gel.
Only product 3ga was obtained (25.3 mg, 43% yield), and no 3la was detected.
Intermolecular competition experiment between different alkynes with 1a. Acetophenone 1a
(24.1 mg, 0.2 mmol, 1.0 equiv), 1,2-bis(4-(trifluoromethyl)phenyl)ethyne 2e (62.8 mg, 0.2 mmol,
1.0 equiv), 1,2-bis(4-(tert-butyl)phenyl)ethyne 2f (58.0 mg, 0.2 mmol, 1.0 equiv), Cp*Co(CO)I2
(9.5 mg, 0.02 mmol, 10 mol %), AgSbF6 (17.1 mg, 0.05 mmol, 25 mol %), KOAc (3.9 mg, 0.04
mmol, 20 mol %) and DCE (1.0 mL) were added to a 35 mL Schlenk flask equipped with a
o
high-vacuum PTFE valve-to-glass seal. Then the flask was sealed under N2 and stirred at 130 C
for 24 h. It was then cooled to room temperature, the solvent was removed in vacuum and then the
crude mixture was purified by column chromatography (eluent: pure petroleum ether) on silica gel
afforded mixture of 3ae and 3af. The ratio of 3ae and 3af (3ae:3af = 9.09:1.00) was calculated by
1H NMR analysis.
Intermolecular competition KIE experiment. Acetophenone 1a (24.1 mg, 0.2 mmol), [D5]-1a
(25.0 mg, 0.2 mmol), diphenylacetylene 2a (107.0 mg, 0.6 mmol,), Cp*Co(CO)I2 (19.0 mg, 0.04
mmol), AgSbF6 (34.2 mg, 0.10 mmol), KOAc (7.8 mg, 0.08 mmol) and DCE (2.0 mL)were added
to a 35 mL Schlenk flask equipped with a high-vacuum PTFE valve-to-glass seal. Then the flask
was sealed under N2 and stirred at 130 oC for 10 min. It was then cooled to room temperature, the
solvent was removed in vacuum and the product was isolated through column chromatography
(eluent: pure petroleum ether) to afford the desired product less than 21 % yield. The KIE value
was calculated as kH:kD = 2.45.
Intermolecular parallel KIE experiment. Acetophenone 1a (24.1 mg, 0.2 mmol) or [D5]-1a
(25.0 mg, 0.2 mmol), diphenylacetylene 2a (53.5 mg, 0.3 mmol,), Cp*Co(CO)I2 (9.5 mg, 0.02
mmol), AgSbF6 (17.1 mg, 0.05 mmol), KOAc (3.9 mg, 0.04 mmol) and DCE (1.0 mL)were added
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to a 35 mL Schlenk flask equipped with a high-vacuum PTFE valve-to-glass seal. Then the flask
was sealed under N2 and stirred at 130 oC for 10 min. It was then cooled to room temperature, mix
the two reaction mixtures together, the solvent was removed in vacuum and the product was
isolated through column chromatography (eluent: pure petroleum ether) to afford the desired
product less than 19 % yield. The KIE value was calculated as kH:kD = 2.85.
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Supporting Information: Table S1, Copies of H, 13C and 19F NMR Spectrum. This material is
available free of charge via the Internet at http://pubs.acs.org.
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