Synthesis of Selectively Substituted or Deuterated Indenes via Sequential Pd and Ru Catalysis

Article abstract of DOI:10.1021/acs.joc.7b00200

A strategy for the synthesis of functionalized indenes is presented. The readily available substituted phenols are used as starting materials in the reaction sequence composed of Pd-catalyzed Suzuki coupling and Ru-catalyzed ring-closing metathesis, thus representing a practical method for the controlled construction of functionalized indene derivatives. The methodology has been successfully applied to a broad range of substrates, producing substituted indenes in excellent yields. This approach is also utilized for the synthesis of substituted indenes selectively deuterated in position 3, which are rare in literature.

Full text of DOI:10.1021/acs.joc.7b00200

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Article
Synthesis of Selectively Substituted or Deuterated
Indenes via Sequential Pd and Ru Catalysis
Anupam Jana, Kasjan Misztal, Anna Zak, and Karol Grela
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 23 Mar 2017
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The Journal of Organic Chemistry
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Synthesis of Selectively Substituted or Deuterated Indenes
via
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Sequential Pd and Ru Catalysis
Anupam Jana,a,§ Kasjan Misztal,b,§ Anna Żakb and Karol Grelaa,b*
aFaculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Żwirki i Wigury 101, 02ꢀ089 Warꢀ
saw, Poland
bInstitute of Organic Chemistry Polish Academy of Sciences, Kasprzaka 44/52, 01ꢀ224, Warsaw, Poland
Supporting Information Placeholder
ABSTRACT: A strategy for the synthesis of functionalised indenes is presented. The readily available substituted phenols are used
as starting materials in the reaction sequence composed of Pdꢀcatalysed Suzuki coupling and Ruꢀcatalysed ringꢀclosing metathesis,
thus representing a practical method for the controlled construction of functionalized indene derivatives. The methodology has been
successfully applied to a broad range of substrates, producing substituted indenes in excellent yields. This approach is also utilized
for the synthesis of substituted indenes selectivity deuterated in position 3, which are rare in literature.
commonly exploited in photovoltaics, but expensive, phenylꢀ
C61ꢀbutyric acid methyl ester (PCBM).19
INTRODUCTION
The indene moiety, an important building block in organic1
and organometallic chemistry2 is present in a large number of
drug candidates possessing interesting biological activities
including antitumor, antiꢀhypercholesterolemic, anticonvulꢀ
sant, antiallergic, herbicidal, fungicidal, and antimicrobial
activities (Fig. 1).3 Access to indene systems has gained growꢀ
ing interest among the synthetic community owing to the conꢀ
tinuing identification of the indeneꢀringꢀcontaining natural
products with the appealing pharmacological activities.4
Therefore, a number of considerable efforts for the controlled
construction of indene ring systems including the reduction or
dehydration of indanone,5 the cyclization of substituted 1,3ꢀ
butadienes in the presence of Lewis acids,6 or the ring expanꢀ
sion of suitably substituted cyclopropenes7 have been develꢀ
oped. A variety transition metal complex e.g. Pd,8 Ni,9 Pt,10
Co,11 Au,12 and Fe13 have been used to synthesize indenes.
However, the introduction of a wide range of different substitꢀ
uents into the indene ring system often encountered difficulꢀ
ties, when multisubstituted indene derivatives were concerned.
For example, functionalisation of a preformed indene ring via
electrophilic aromatic substitution (eg. nitration or acylaꢀ
tion)14,15 or alkylation of the indene carboanion,16 seems to be
rather problematic in the case of polysubstituted indenes.17
Thus, development of novel, more efficient, selective, lowꢀ
cost, scalable and atom economy synthetic methodologies for
the accessing of multisubstituted indenes would be warmly
welcomed. Recently special interest was shown in case of 3ꢀ
indenepropionic acid esters which can be coupled with fullerꢀ
enes in oneꢀstep DielsꢀAlder type of reaction.18 Products of
this reaction were shown to exhibit better properties than
Figure 1. Selected examples of natural and synthetic products
bearing indene skeletons
RESULTS AND DISCUSSION
Herein, we describe an efficient and selective synthesis of
indene derivatives from substituted phenols as widely availaꢀ
ble starting materials, through Suzuki coupling20 and ringꢀ
closing metathesis21 (Scheme 1). Our initial goal was to develꢀ
op a very efficient route for the construction of the diene E
(Scheme 1). Synthesis of indenes22ꢀ26 and related compounds23
via RCM reaction from corresponding dienes was already
reported a number of times. Unfortunately often starting mateꢀ
rials are not easily accessible and need to be synthesised in
conditions not compatible with a number of functional groups,
e.g. with use of Grignard22 or organolithium23b reagents, often
multistep.24,25 The majority of the reports present synthesis of
1ꢀsubstitued indenes, whereas there are scarce examples of
products with substituents attach selectively to position 3.23b In
addition, relatively high loading of ruthenium catalysts (min.
5 mol %) was used in the RCM step. Two possible ways for
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the synthesis of diene E were envisioned by us (Scheme 1). (Scheme 3). Ringꢀclosing metathesis reaction of diene 5a with
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We deduced that the Suzukiꢀcoupling of either boronate A
with appropriate bromide B or the reaction of phenol triflate C
with boronate D would be the feasible route to our desired
ringꢀclosing metathesis precursor. Compound A and C can in
principle be derived from substituted phenols. Compound D
could easily be obtained from corresponding bromide B. The
resulting functionalised diene E in the presence of a Ru meꢀ
tathesis catalyst shall yield in RCM reaction functionalized
indene TM.
1 mol % of commercial nitroꢀHoveydaꢀGrubbs catalyst [Ru-2]
produced the substituted indene 6a in almost quantitative
yield. Therefore, comparing the both routes we ended with a
conclusion that Route II is apparently more efficient and userꢀ
friendly.
Scheme 2. Synthesis of Substituted Nitro-Indene 6a Utilis-
ing Route I and Self-Cleaning RCM
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Scheme 1. Routes Examined for the Controlled Synthesis
of Substituted Indenes
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Scheme 3. Synthesis of Substituted Nitro-Indene 6b Utilis-
ing Route II
First, we decided to experimentally test the feasibility of
both planed routes for accessing the diene E. To do so, we
chose paraꢀnitrophenol 1 as a prototypical starting material.
Allylation of phenol 1 followed by Claisen rearrangement
provided 2ꢀallylꢀ4ꢀnitrophenol,27 that was converted with triꢀ
flic anhydride and pyridine into triflate 2a (Scheme 2). Then,
Route I was tested. To this end, triflate 2a was converted into
a pinacol boronic ester derivative 3. This reagent was subjectꢀ
ed to Suzuki crossꢀcoupling reaction with bromide 4. During
the CꢀC coupling reaction, we observed formation of minor
impurity 5a’ along with the desired product 5a (ratio 5a/5a’ =
75:25). We assumed that formation of 5a’ is due to the isomerꢀ
isation of the allylic double bond in presence of Pdꢀcatalyst.
Unfortunately, despite all optimisation attempts, were not able
to stop formation of this impurity. These two products, 5a and
5a’, formed in overall 68% yield, were inseparable by chromaꢀ
tographic methods. Fortunately, we speculated that only the
major alkene 5a can undergo ringꢀclosing metathesis reaction,
while the impurity 5a’ cannot form the cyclised product (four
membered rings are not formed easily by RCM) but rather
undergo oligomerisation or other transformations. Therefore,
we pursued the indene synthesis using the inseparable mixture
of products 5a and 5a’, in the hope that during the reaction the
mixture will selfꢀclean. The RCM reaction was conducted
under typical conditions,28 in a presence of commercial
Grubbs IIꢀgeneration catalyst [Ru-1]. Inspection by TLC
showed a new spot and we separated this new compound by
column chromatography. As a result, nitroindeneꢀderivative 6a
was isolated in pure form in 62% yield. Despite the fact that
selfꢀcleaning RCM approach29 apparently worked well, taking
into account the low yield of borylation step and related techꢀ
nical problems we considered this route being not sufficiently
optimal.
Scheme 4. Suzuki-Coupling Leading to Dienes 5a-pa,b
Therefore, instead of spending efforts in further optimisaꢀ
tion of route I, we focussed on route II, in a hope that it will be
more selective and will give indene derivatives in better overꢀ
all yield. To this end triflate 2a was subjected to Suzukiꢀ
coupling with pinacol boronic ester 7a at 100 °C leading to
desired diene 5a in 75% yield without any isomerisation
°
aConditions: degassed dioxaneꢀwater (4:1), 120 C, Pd(PPh3)4 (12
b
mol %), K2CO3 (3 equiv). Isolated yields after flash chromatogꢀ
raphy
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After successfully demonstrating the effectiveness of route
5k, 5l, 5p) in very good yield. Furthermore, electron donating
groups presend in the triflate 2 ring are well tolerated, as the
corresponding dienes (5h, 5l) were obtained in good yield.
Naturally, also triflates substituted with electron withdrawing
groups can be used in the studied Suzuki coupling with excelꢀ
lent results (5a, 5g, 5iꢀk, 5mꢀn). Based on the results complied
in Scheme 4, one can state that practically all combinations of
FG and R1 substituents at the cross coupling partners lead to
good results. Finally, in order to extend our methodology to
benzannulated systems, we scheduled to carry out the reaction
with 2ꢀallylꢀ1ꢀnaphthol triflate. Coupling of this partner with
two vinyl boronic acid pinacol esters underwent efficiently to
form the expected products (5o, 5p) in 81% and 92% yield
respectively (Scheme 4).
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II for the construction of one arbitrary chosen disubstituted
indene (6a), we focussed on the synthesis of a small library of
indenes having various substituents at different positions. To
do so, we prepared a set of RCM precursors using Suzuki couꢀ
pling under previously elaborated conditions. All the reactions
were carried out in deoxygenated dioxaneꢀwater (4:1) mixture
at 120 oC in a sealed Schlenk tube in presence of
tetrakis(triphenylphosphine)palladium(0) and potassium carꢀ
bonate used as base.
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Scheme 5. Synthesis of Substituted Indenes via RCM Reac-
tiona,b
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With the dienes ready in hand, we performed ringꢀclosing
metathesis to afford the substituted indenes as shown in
Scheme 5, using 1.0 mol % or 1.7 mol % (as indicated) nitroꢀ
HoveydaꢀGrubbs catalyst [Ru-2] in refluxing dichloromethane
(Scheme 5). At first, we attempted cyclisation of orthoꢀ
substituted diene 5b and observed that 4ꢀmethylindene 6b was
formed in 90% yield after just 1 h of the reaction as a single
product. Similarly, 5c gave the expected indene 6c in 89%
yield. Similarly, other mono substituted indenes like 6d, 6f, 6i,
6o were synthesized through RCM reaction in 61% to 99%
yield. Disubstituted indenes were also formed from correꢀ
sponding dienes smoothly. When disubstituted dienes like 5a,
5f, 5g, 5n, 5p were subjected to ringꢀclosing metathesis in
presence of 1.7 mol % or less of nitroꢀHoveyda catalyst disubꢀ
stituted indenes were formed in excellent yield. Relatively
lower yields (70 to 73%) gave dienes like 5h, 5i, 5l. Finally,
the highly conjugated indene 6p was synthesized in a similar
way in 96% isolated yield.
Scheme 6. Synthesis of Deuterated Indenes
o
aConditions: CH2Cl2 (nonꢀdegassed), 40 C, [Ru-2] (1.0 mol
%: 6a, 6e, 6h-i, 6l, 6n; 1.7 mol %: 6b-d, 6f-g, 6j-k, 6m, 6o-p),
bIsolated yields after flash chromatography
A variety of triflates were subjected to the reaction, and the
corresponding products were obtained in high yields with exꢀ
cellent functional group (FG) tolerance (shown in Scheme 4).
To introduce different substituents in the five membered ring
of the indene we synthesized appropriate dienes by using difꢀ
ferently substituted (Me, Ph, CH2CH2CO2Et, paraꢀtrifluoroꢀ
phenyl) vinyl boronic pinacol esters 7a-e in Suzuki reaction.
The investigation was started with the triflate 2b (FG = orthoꢀ
Me) that gave very good yield of diene 5b when treated with
vinyl boronic pinacol ester (7b, R1 = H) in presence of Pdꢀ
catalyst. Then, scope of the reaction was studied by using
bulkier boronate i.e. isopropenyl boronic acid pinacol ester
(7c, R1 = Me). To our delight, the coupling reaction in presꢀ
ence of Pd catalyst afforded diene 5c in 82% yield. Encourꢀ
aged by these results, we then focussed on even larger FGs in
orthoꢀposition (CHO, Ph) to check the influence of the steric
effect. In all cases the triflates reacted smoothly to form correꢀ
sponding dienes in 63ꢀ87% yield (5d, 5e). It is also worth to
note that also phenyl and paraꢀtrifluorophenyl substuted vinyl
boronic pinacol esters (7d and 7e; FG = Ph and paraꢀ
CF3C6H4) can be used resulting corresponding dienes (5f, 5g,
Selectively deuterated compounds have found a number of
important applications in mechanism elucidation and other
physicoꢀchemical studies, neutron protein crystallography,
pharmacokinetic and toxicological studies, biochemistry, etc.30
Therefore, selective isotope labelling with deuterium of
whole molecules or building blocks is of growing imꢀ
portance.30 Regrettably, to the best of our knowledge methods
for the synthesis of functionalized and selectively deuterated
indenes are limited in number and scope.31 In particular, the
development of practical and general methods for selective
deuteration at the 3 position of the indene skeleton is unknown
in literature and shall be considered as challenging undertakꢀ
ing. Direct deuteration31a,d (Scheme 6) of indene is not a good
idea for accessing substituted indenes, as this process is not
selective. Therefore, we decided to try our approach in the
synthesis of substituted 3ꢀ[2H]ꢀindenes (Scheme 6). We anticiꢀ
pated that a properly constructed diene E’ would upon RCM
provide a selectively deuterated indene (3ꢀ[2H]ꢀTM). The boꢀ
ron reagent D’ required in synthesis of E’ can be prepared in
different ways. Grotjahn and coꢀworkers32 demonstrated that
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an allyl fragment in a number of substrates when treated with performed on silica gel 60 TLC plates. The spots were visualꢀ
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bifunctional catalyst [Ru-3] in the presence of D2O can underꢀ
go isomerization to a vinylic double bond with simultaneous
incorporation of deuterium with excellent regoselectivity.32
We decided to use this methodology to convert commercial
allyl boronic pinacol ester 2f to deuterated vinyl boronate deꢀ
rivative 7f’ (Scheme 7). An CD3 group present in the product
would be later drop off in the RCM step. To reduce this idea to
reality, 7f was treated in a closed tube for 16 h with 2 mol %
of Grotjahn catalyst [Ru-3] and deuterium oxide in acetoneꢀd6.
Then, without isolation, triflate 2b together with 12 mol % of
Pd(PPh3)4, K2CO3, dioxane and water were added to the same
reaction vessel and the resulted reaction mixture was heated at
ized with a UV light or by staining with KMnO4 or anisaldeꢀ
hyde solution. Flash column chromatography was performed
using silica gel 60 (particle size 0.040–0.063 mm) typically
using a nꢀhexane/ethyl acetate eluent system. FTꢀIR spectra
were recorded with Thermo ScientificTMNicoletTM iSTM50
FTꢀIR spectrometer. NMR spectra were measured at room
temperature on a Agilent Mercury 400 MHz spectrometer or
Varian Mercury 400 MHz. NMR spectra were calibrated to the
1
solvent residual signals of CDCl3. H NMR spectra were recꢀ
9
orded at 400 MHz. Data are reported as follows: chemical
shift, multiplicity (s: singlet, d: doublet, t: triplet, q: quartet,
qui: quintuplet, m: multiplet), coupling constant (J in Hz) and
integration. 13C NMR spectra were recorded at 100 MHz using
broadband proton decoupling and chemicals shifts are reported
in ppm using residual solvent peaks as reference. Carbon mulꢀ
tiplicities were assigned by DEPT techniques. High resolution
mass spectra were recorded on a MS (ESI) spectra LCMSꢀIT
TOF Shimadzu or SYNAPT G2ꢀS HDMS (Waters).
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120 C for 18 h. The resulting diene 8, isolated by column
chromatography in 74% yield was subjected to ringꢀclosing
reaction in presence of 2 mol % of nitroꢀHoveydaꢀGrubbs
catalyst [Ru-2] to afford selectively labelled ꢀmethyl(3ꢀ2H)ꢀ
1Hꢀindene 9 in 85% yield (Scheme 7). Interestingly, (3ꢀ2H)ꢀ
1Hꢀindenꢀ6ꢀyl 11 methyl ether is also synthesized in good
yield from triflate 2j.
A usual workup of the reaction mixture consists of extracꢀ
tion with ether or ethyl acetate, washing with water, brine,
drying over Na2SO4, and then concentrated under reduced
pressure on a rotary evaporator unless specified. Reported
yields are based upon isolation following purification by silica
gel column chromatography; isolated materials were judged to
be homogeneous based upon TLC and NMR.
Scheme 7. Synthesis of Substituted Deuterated Indenes
The compounds 2j,33 6b,34 6c,35 6m,36 6o37 are known in litꢀ
erature.
General Procedure for Triflation Reaction: Reactions
were carried on 8.76 mmol scale unless otherwise noted. The
substituted phenol (8.76 mmol, 1 equiv) was solubilized in a
mixture of 5 ml of pyridine and 5 mL of dry dichloromethane
at 0 °C under an argon atmosphere. To resulting mixture was
dropwise added neat trifluoromethanesulfonyl anhydride (9.64
mmol, 1.1 equiv). The reaction mixture was stirred and alꢀ
lowed to reach room temperature overnight. After this time,
the solvents were removed by rotary evaporation and the reꢀ
maining residue was taken up in ethyl acetate (100 mL) and
extracted with 5% HCl (3 x 50 mL), followed by sodium biꢀ
carbonate (2 x 50 mL), brine (100 mL) and drying over
MgSO4. Residue was concentrated in vacuum and purified
with column chromatography to obtain corresponding triflate.
CONCLUSION
We have developed an efficient approach to form the indene
skeleton that is based on Suzuki coupling followed by olefin
metathesis. Application of Pd and Ru catalysis allows to acꢀ
cess variously substituted indenes from phenols as cheap and
widely available starting materials. Utilisation of Ru isomeriꢀ
sationꢀdeuteration catalyst [Ru-3] made possible to obtain
substituted indenes selectively monodeuterated in position 3.
Due to the potential utility of functionalised indenes and the
mild conditions employed, we expect this method to be of
broad utility in organic synthesis. We expect that the develꢀ
oped method would be attractive particularly in photovoltaics
where 3ꢀindenepropionic acids functionalized fullerenes conꢀ
stitute promising alternative to common but expensive PCBM.
Further studies on application of this methodology in target
oriented synthesis are ongoing in our laboratory.
2-Allyl-4-nitrophenyl trifluoromethanesulfonate (2a) yelꢀ
low oil, 2.17 g, 86% yield, eluent: cꢀhexane/ethyl acetate 95:5;
1H NMR (400 MHz, CDCl3) δ 8.24 (d, J = 2.8 Hz, 1H), 8.19
(dd, J = 2.8, 9.0 Hz, 2H), 7.46 (d, J = 9.0 Hz, 1H), 5.91 (ddt, J
= 6.7, 10.1, 17.2 Hz, 1H), 5.31ꢀ5.18 (m, 2H), 3.55 (d, J = 6.6
Hz, 2H); 13C NMR (101 MHz, CDCl3) δ 151.5, 147.1, 135.3,
132.9, 126.8, 123.7, 122.5, 119.5, 118.6 (q, J = 318 Hz), 34.1;
IR νmax 3088, 1536, 1428, 1353, 1219, 1139, 872, 810, 742,
615 cm−1; HRMS (EI) m/z: [M]+ Calcd for C10H8F3NO5S
311.0075; Found: 311.0089. Anal. Calcd for C10H8F3NO5S: C,
38.59; H, 2.59; N, 4.50. Found: C, 38.82; H, 2.67; N, 4.43.
EXPERIMENTAL SECTION
General Information: All reactions were carried out under
argon atmosphere in ovenꢀdried glassware with magnetic stirꢀ
ring. Commercially available chemicals were used without
further purification. Grubbs II catalyst was purchased from
Aldrich (catalogue no 569747) and nitroꢀHoveydaꢀGrubbs
catalyst from Stream (catalogue no 44ꢀ0758) and TCI (cataꢀ
logue no N1060). The boronic acid pincol esters were bought
from Aldrich or synthesized from corresponding bromide
(Scheme 1). Solvents were distilled prior to use by Solvent
Purification System, Mbraun MBꢀSPSꢀ800 or by standard
methods (ref. Armarego, W L. F, and C. Chai. Purification of
Laboratory Chemicals. Oxford: Butterworth Heinemann,
2009. Print). Analytical thinꢀlayer chromatography (TLC) was
2-Allyl-6-methylphenyl trifluoromethanesulfonate (2b)
yellow oil, 10.0 mmol scale, 2.51 g, 90% yield; eluent: hexꢀ
1
ane/ethyl acetate 95:5; H NMR (400 MHz, CDCl3) δ 7.24 ꢀ
7.14 (m, 3H), 5.95ꢀ5.88 (m, 1H), 5.17ꢀ5.08 (m, 2H), 3.52 (d, J
= 6.4 Hz, 2H), 2.42 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
146.1, 135.2, 133.7, 131.9, 130.6, 129.2, 128.3, 118.7 (q, J =
329 Hz), 117.3, 34.6, 17.3; HRMS (EI) m/z: [M]+ Calcd for
C11H11F3O3S 280.0381; Found: 280.0378.
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2-Allyl-6-formylphenyl trifluoromethanesulfonate (2c)
2-Allyl-4-fluorophenyl trifluoromethanesulfonate (2i)
transparent oil, 9.36 mmol scale, 2.20 g, 79% yield; eluent: cꢀ
hexane/ethyl acetate 95:5; 1H NMR (400 MHz, CDCl3) δ 7.28ꢀ
7.19 (m, 1H), 7.07ꢀ6.92 (m, 2H), 5.88 (ddt, J = 6.7, 10.1, 16.8
Hz, 1H), 5.18 (m, 2H), 3.46 (d, J = 6.7 Hz, 2H); 13C NMR
(101 MHz, CDCl3) δ 161.7 (d, J = 247 Hz), 143.6, 135.7 (d,
J = 8 Hz), 133.9, 123.1 (d, J = 9 Hz), 118.7 (q, J = 318 Hz),
118.5, 118.0 (d, J = 24 Hz), 115.0 (d, J = 23 Hz), 34.1; 19F
NMR (376 MHz, CDCl3) δ ꢀ112.4, ꢀ73.7; HRMS (EI) m/z:
[M]+ Calcd for C10H8F4O3S 284.0130; Found: 284.0141. Anal.
Calcd for C10H8F4O3S: C, 42.26; H, 2.84; found: C, 42.19; H,
2.97.
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yellow oil, 5 mmol scale, 0.91 g, 62% yield; eluent: hexꢀ
ane/ethyl acetate 95:5; 1H NMR (400 MHz, CDCl3) δ 10.23 (s,
1H), 7.86 (dd, J = 1.6, 7.6 Hz, 1H), 7.64 ꢀ7.61 (m, 1H), 7.51ꢀ
7.49 (m, 1H), 7.89 (ddt, J = 6.4, 10.0, 17.2 Hz, 1H), 5.22ꢀ5.14
(m, 2H), 3.57 (d, J = 6.4 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ 186.9, 146.95, 137.4, 135.0, 134.2, 129.9. 129.0,
128.7, 118.7 (q, J = 318 Hz), 118.4, 33.7; HRMS (EI) m/z:
[M]+ Calcd for C11H9F3O4S 280.0381; Found: 294.0175.
3-Allyl-[1,1'-biphenyl]-2-yl
trifluoromethanesulfonate
9
(2d) orange crystals, 18.4 mmol scale, 5.42 g, 86% yield; eluꢀ
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ent: hexane/ethyl acetate 95:5; H NMR (600 MHz, CDCl3) δ
7.47ꢀ7.30 (m, 8H), 6.03 – 5.96 (m, 1H), 5.24 – 5.21 (m, 2H),
3.62 (d, J = 6.6 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ
144.9, 136.6, 135.0, 134.4, 130.6, 130.4, 129.6, 128.5, 128.4,
128.3,118.2 (q, J = 319 Hz), 117.8, 34.8; HRMS (EI) m/z:
[M]+ Calcd for C16H13F3O3S 342.0538; Found: 342.0544.
2-Allyl-4-methoxyphenyl trifluoromethanesulfonate (2j)
colourless oil, 17.7 mmol scale, 4.26 g, 81% yield; eluent:
hexane/ethyl acetate 95:5; 1H NMR (400 MHz, CDCl3) δ 7.17
(d, J = 9.0 Hz, 1H) 6.83–6.82 (m, 1H), 6.78 (dd, J = 9.0, 3.0
Hz, 1H), 5.92 (ddt, J = 6.6, 10.2, 16.8 Hz, 1H) 5.18ꢀ5.14 (m,
2H) 3.80 (s, 3H) 3.44 (d, J = 6.6 Hz, 2H); 13C NMR (100
MHz, CDCl3) δ 159.1, 141.5, 134.6, 134.3, 122.4,118.8 (q, J =
320 Hz). 117.8, 116.3, 113.0, 55.8, 34.4.
4-acetamido-2-allylphenyl
trifluoromethanesulfonate
(2e) orange crystals, 10.5 mmol scale, 2.56 g, 75% yield; eluꢀ
ent: cꢀhexane/ethyl acetate 7:3; 1H NMR (400 MHz, CDCl3) δ
7.58 – 7.44 (m, 2H), 7.35 (s, 1H), 7.20 (d, J = 8.9 Hz, 1H),
5.89 (ddt, J = 16.8, 10.2, 6.6 Hz, 1H), 5.21 – 5.07 (m, 2H),
3.44 (d, J = 6.6 Hz, 2H), 2.17 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 169.1, 143.7, 138.1, 134.3, 133.8, 122.2, 122.0,
119.3, 118.7 (q, J = 319 Hz), 117.9, 34.2, 24.6; HRMS (ESI)
m/z: [M+Na]+ Calcd for C12H12F3NO4SNa 346.0337; Found:
346.0337. Anal. Calcd for C12H12F3NO4S: C, 44.58; H, 3.74;
N, 4.33; found: C, 44.74; H, 3.78; N, 4.33.
General Procedure for Suzuki Coupling. Reactions were
carried on 1 mmol scale unless otherwise noted. A Schlenk
flask was charged with triflate 2 (1 mmol), vinyl boronic ester
7 (1.3 mmol) and K2CO3 (3 mmol). Then 10 mL of 4:1 1,4ꢀ
dioxane:water mixture was added and flask was deoxigenated
by freezeꢀpumpꢀthaw cycle three times. [Pd(PPh3)4] (0.10ꢀ0.12
mmol) was added and the sealed flask was stirred at 100 ꢀ120
°C for 18 h, resulting in an orange, transparent suspension.
After that time, the flask was cooled to RT and all volatiles
were removed under reduced pressure. The oily residue was
solubilized in AcOEt and filtered through Celite pad. Volatiles
were concentrated and separated with column chromatography
to obtain diene 5.
4-Acetyl-2-allylphenyl trifluoromethanesulfonate (2f) orꢀ
ange oil, 8.51 mmol scale, 2.41 g, 91% yield; eluent: cꢀ
1
hexane/ethyl acetate 9:1; H NMR (400 MHz, CDCl3) δ 7.93
(d, J = 2.2 Hz, 1H), 7.89 (d, J = 2.2, 8.6 Hz, 1H), 7.38 (d, J =
8.5 Hz, 1H), 5.93 (ddt, J = 6.6, 10.1, 16.8 Hz, 1H), 5.18 (m,
2H), 3.53 (d, J = 6.6 Hz, 2H), 2.61 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 196.4, 150.8, 136.9, 133.9, 133.5, 131.6,
128.5, 121.6, 118.6 (q, J = 319 Hz), 118.3, 34.15, 26.79; IR
νmax 3366, 3085, 2985, 1693, 1423, 1217, 1140, 894, 857 cm−1;
HRMS (EI) m/z: [M]+ Calcd for C12H11F3O4S 308.0330;
Found: 308.0333. Anal. Calcd for C12H11F3O4S: C, 46.75; H,
3.60; found: C, 46.82; H, 3.58.
Ethyl 4-(2-allyl-4-nitrophenyl)pent-4-enoate (5a) yellow
1
oil, 216 mg, 75% yield; eluent: cꢀhexane/ethyl acetate 9:1; H
NMR (400 MHz, CDCl3) δ 8.09 (d, J = 2.4 Hz, 1H), 8.02 (dd,
J = 2.4, 8.4 Hz, 2H), 7.26 (d, J = 8.4 Hz, 1H), 5.93 (ddt, J =
6.5, 10.1, 16.6 Hz, 1H), 5.30 (dd, J = 1.5, 2.7 Hz, 1H), 5.17
(dq, J = 1.4, 10.1 Hz, 1H), 5.07 (dq, J = 1.6, 17.0 Hz, 1H),
4.98ꢀ4.96 (m, 1H), 4.12 (q, J = 7.1 Hz, 2H), 3.46 (dt, J = 1.4,
6.4 Hz, 2H), 2.66 (t, J = 7.5 Hz, 2H), 2.43 (t, J = 7.5 Hz, 2H),
1.24 (t, J = 7.1 Hz, 3H);13C NMR (101 MHz, CDCl3) δ172.7,
149.1, 146.2, 139.2, 136.2, 129.8, 124.7, 121.2, 117.6, 116.1,
60.7, 37.0, 32.7, 32.5, 14.4. IR νmax 3083, 2981, 1734, 1521,
1347, 1160, 917 cm−1; HRMS (ESI) m/z: [M+Na]+ Calcd for
C16H19NO4Na 312.1212; Found: 312.1205. Anal. Calcd for
C16H19NO4: C, 66.42; H, 6.62; N, 4.84; found: C, 66.50; H,
6.61; N, 4.86.
2-Allyl-4,5-dimethoxyphenyl trifluoromethanesulfonate
(2g) brown solid, 8.34 mmol scale, 2.66 g, 98% yield; eluent:
cꢀhexane/ethyl acetate 9:1; 1H NMR (400 MHz, CDCl3) δ 6.74
(d, J = 6.8 Hz, 2H), 5.90 (ddt, J = 6.6, 10.2, 16.8 Hz, 1H), 5.13
(m, 2H), 3.87 (d, J = 4.2 Hz, 6H), 3.40 (d, J = 6.6 Hz, 2H); 13
C
NMR (101 MHz, CDCl3) δ 148.9, 148.3, 140.5, 135.2, 124.7,
118.8 (q, J = 319 Hz), 117.4, 117.2, 112.8, 105.4, 56.4, 56.3,
33.8; IR νmax 3048, 2940s, 1641, 1590, 1516, 1419, 1213,
1142, 1066, 996, 879 cm−1; HRMS (EI) m/z: [M]+ Calcd for
C12H13F3O5S 326.0436; Found: 326.0438. Anal. Calcd for
C12H13F3O5S: C, 44.17; H, 4.02; S, 9.83; F, 17.74; found: C,
44.31; H, 4.27; S, 10.03; F, 17.64.
1-Allyl-3-methyl-2-vinylbenzene (5b) yellow oil, 1.0
mmol scale, 136 mg, 88% yield; eluent: 100% hexane, 88%
yield; 1H NMR (400 MHz, CDCl3) δ 7.13 ꢀ 7.08 (m, 3H), 6.73
(dd, J = 11.2, 18.0 Hz, 1H), 5.97 (ddt, J = 6.4, 10.0, 17.2 Hz,
1H), 5.54 (dd, J = 1.6, 11.2 Hz, 1H), 5.28 (dd, J = 2.0, 18.0
Hz, 1H), 5.07 ꢀ 4.97 (m, 2H), 3.45 – 3.43 (m, 2H), 2.33 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 138.0, 137.7, 137.6,
136.1, 135.0, 128.2, 127.2, 126.9, 119.7, 115.6, 38.1, 21.1; IR
νmax 1507, 1401, 1246, 1137, 1117 cm−1; HRMS (EI) m/z:
[M]+ Calcd for C12H14 158.1096; Found: 158.1092.
2-Allylnaphthalen-1-yl trifluoromethanesulfonate (2h)
yellow oil, 3.37 mmol scale, 8.65 g, 81% yield; eluent: hexꢀ
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ane/ethyl acetate 95:5; H NMR (400 MHz, CDCl3) δ 8.13ꢀ
8.10 (m, 1H), 7.91ꢀ7.88 (m, 1H), 7.82 (d, J = 8.8 Hz, 1H);
7.66ꢀ7.57 (m, 2H), 7.48 (d, J = 9.2 Hz, 1H), 6.10 (ddt, J = 6.0,
10.4, 17.2 Hz, 1H), 5.22ꢀ5.12 (m, 2H), 4.01 (td, J = 1.6, 6.0
Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 145.3, 134.5, 132.8,
129.3, 128.8, 128.1, 127.5, 126.8, 125.0, 119.4 (q, J = 1 Hz),
118.8 (q, J = 318 Hz), 117.0, 33.3; HRMS (EI) ) m/z: [M]+
Calcd for C14H11F3O4S 316.0379; Found: 316.0381.
1-Allyl-3-methyl-2-(prop-1-en-2-yl)benzene (5c) yellow
oil, 1 mmol scale, 141 mg, 82% yield; eluent: 100% hexane;
1H NMR (400 MHz, CDCl3) δ 7.20 ꢀ 7.12 (m, 3H), 6.02 (ddt, J
= 6.4, 9.6, 17.2 Hz, 1H), 5.36 ꢀ 5.35 (m, 1H), 5.12 ꢀ 5.08 (m,
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2H), 4.87 ꢀ 4.86 (m, 1H), 3.45 ꢀ 3.43 (m, 2H), 2.35 (s, 3H),
173.1, 168.4, 147.3, 138.3, 138.0, 137.7, 137.0, 129.4, 120.9,
2.33 (dd, J = 0.8, 1.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
144.4, 143.0, 138.5, 136.7, 135.0, 127.8, 126.7, 115.5, 115.3,
37.5, 24.4, 19.9; IR νmax 2970, 2916, 1607, 1495, 1435, 1212,
1227, 967 cm−1; HRMS (EI) m/z: [M]+ Calcd for C13H16
172.1252; Found: 172.1258.
117.9, 116.2, 115.1, 60.5, 37.2, 33.4, 32.8, 24.7, 14.4. HRMS
(ESI) m/z: [M+Na]+ Calcd for C18H23NO3Na 324.1576;
Found: 324.1568. Anal. Calcd for C18H23NO3: C, 71.73; H,
7.69; N, 4.65; found: C, 71.50; H, 7.60; N, 4.66.
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1-(3-Allyl-4-vinylphenyl)ethan-1-one (5i) transparent oil,
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147 mg, 79% yield; eluent: cꢀhexane/ethyl acetate 95:5; H
3-Allyl-2-vinylbenzaldehyde (5d) yellow oil, 0.5 mmol
1
NMR (400 MHz, CDCl3) δ 7.80 (dd, J = 1.8, 8.1 Hz, 1H), 7.76
(d, J = 1.7, 1H), 7.58 (d, J = 8.1 Hz, 1H), 6.98 (dd, J = 11.0,
17.4 Hz, 1H), 5.97 (ddt, J = 6.1, 10.1, 16.3 Hz, 1H), 5.76 (dd,
J = 1.2, 17.4 Hz, 1H), 5.42 (dd, J = 1.2, 11.0 Hz, 1H), 5.10
(dq, J = 1.5, 10.1 Hz, 1H), 4.98 (dq, J = 1.7, 17.1 Hz, 1H),
3.50 (dt, J = 1.5, 6.1 Hz, 2H), 2.59 (s, 3H); 13C NMR (101
MHz, CDCl3) δ217.2, 197.9, 141.7, 137.6, 136.6, 136.2,
134.0, 130.0, 126.9, 126.1, 118.1, 116.6, 37.5, 26.7; IR νmax
3347, 3082, 3005, 1682, 1603, 1410, 1264, 918 cm−1; HRMS
(ESI) m/z: [M+H]+ Calcd for C13H15O 187.1123; Found:
187.1115. Anal. Calcd for C13H14O: C, 83.83; H, 7.58; found:
C, 83.79; H, 7.65.
scale, 70 mg, 81% yield; eluent: 100% hexane; H NMR (400
MHz, CDCl3) δ 10.24 (s, 1H), 7.2 (dd, J = 1.6, 8.0 Hz, 1H),
7.43 ꢀ 7.36 (m, 2H), 6.98 (dd, J = 11.0, 17.6 Hz, 1H), 5.94
(ddt, J = 6.4, 10.4, 17.0 Hz, 1H), 5.78 (dd, J = 1.6, 11.2 Hz,
1H), 5.25 (dd, J = 1.2, 17.6 Hz, 1H), 5.10 (dd, J = 1.6, 10.0
Hz, 1H), 5.00 (dd, J = 2.0, 17.2 Hz, 1H), 3.45 (td, J = 1.6, 6.4
Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 193.0, 142.1, 138.9,
136.2, 134.9, 134.6, 131.6, 127.7, 126.5, 124.5, 116.6, 37.2;
HRMS (ESI) m/z: [M+H]+ Calcd for C12H13O 173.0961;
Found: 173.0958.
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3-Allyl-2-vinyl-1,1'-biphenyl (5e) yellow oil, 131 mg,
1
60% yield; eluent: cꢀhexane/ethyl acetate 95:5; H NMR (400
MHz, CDCl3) δ 7.31 (m, 8H), 6.63 (dd, J = 11.5, 17.9 Hz, 1H),
6.04 (dd, J = 10.2, 17.0 Hz, 1H), 5.32 (dd, J = 1.8, 11.5 Hz,
1H), 5.17 – 5.01 (m, 3H), 3.55 (dt, J = 6.2, 1.4 Hz, 2H).13C
NMR (100 MHz, CDCl3) δ 142.4, 141.7, 138.0, 137.7, 136.7,
135.0, 130.1, 129.0, 128.5, 127.9, 127.0, 126.7, 120.6, 116.0,
38.27. HRMS (EI) m/z: [M]+ Calcd for C17H16 220.1252;
Found: 220.1251.
1-(3-Allyl-4-(prop-1-en-2-yl)phenyl)ethan-1-one (5j) yelꢀ
low oil, 0.75 mmol scale, 137 mg, 91% yield; eluent: hexꢀ
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ane/ethyl acetate 97:3; H NMR (400 MHz, CDCl3) δ 7.81 ꢀ
7.74 (m, 2H), 7.21 (d, J = 8.0 Hz, 1H), 5.95 (ddt, J = 6.4, 10.0,
17.2 Hz, 1H), 5.24 ꢀ 5.22 (m, 1H), 5.08 (dq, J = 1.6, 10.0 Hz,
1H), 5.03 (dq, J = 1.6, 17.0 Hz, 1H), 4.88 ꢀ 4.87 (m, 1H), 3.45
(td, J = 1.6, 6.4 Hz, 2H), 2.58 (s, 3H), 2.04 ꢀ 2.03 (m, 3H); 13C
NMR (100 MHz, CDCl3) δ 198.0, 148.9, 144.5, 137.3, 137.1,
135.9, 129.7, 128.5, 126.2, 116.4, 115.7, 37.2, 26.7, 24.8; IR
νmax 2922, 1679, 1414, 1356, 1262, 1202 cm−1; HRMS (ESI)
m/z: [M+H]+ Calcd for C14H17O 201.1274; Found: 201.1284.
3-Allyl-2-(1-(4
(trifluorome-
thyl)phenyl)vinyl)benzaldehyde (5f) yellow oil, 0.5 mmol
scale, 138 mg, 87% yield; eluent: hexane/ethyl acetate 97:3;
1H NMR (400 MHz, CDCl3) δ 10.06 (s, 1H), 7.92 (dd, J = 1.6,
8.0 Hz, 1H), 7.59 ꢀ 7.32 (m, 6H), 6.26 (s, 1H), 5.78 (ddt, J =
6.4, 10.0, 16.8 Hz, 1H), 5.37 (s, 1H), 5.00 (qd, J = 1.6, 10 Hz,
1H), 4.92 (qd, J =1.6, 17.2 Hz, 1H), 3.24 (td, J = 6.4, 16.0 Hz,
2H); 13C NMR (100 MHz, CDCl3) δ 192.6, 143.1, 143.0 (d, J
= 2 Hz), 142.2, 139.4, 136.5, 135.6, 134.8, 130.3 (q, J = 33
Hz), 128.5, 126.5, 126.1, 125.8 (q, J = 4 Hz), 124.1 (q, J = 271
Hz), 120.1, 116.7, 36.9; 19F NMR (376 MHz, CDCl3) δ
−62.70; IR νmax 1690, 1616, 1588, 1322, 1114, 1065, 1014,
915 cm−1; HRMS (ESI) m/z: [M+H]+ Calcd for C19H16F3O
317.1148; Found: 317.1136.
1-(3-Allyl-4-(1-(4
(trifluorome-
thyl)phenyl)vinyl)phenyl)ethan-1-one (5k) yellow oil, 0.5
mmol scale, 144 mg, 87% yield; eluent: hexane/ethyl acetate
95:5; 1H NMR (400 MHz, CDCl3) δ 7.87 ꢀ 7.84 (m, 2H), 7.56
ꢀ 7.54 (m, 2H), 7.36 ꢀ 7.31 (m, 3H), 5.92 (d, J = 1.2 Hz, 1H),
5.78 (ddt, J = 6.4, 10.0, 17.0 Hz, 1H), 5.36 (d, J = 1.2 Hz, 1H),
5.00 ꢀ 4.88 (m, 2H), 3.20 ꢀ 2.18 (m, 2H), 2.63 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 198.0, 147.1, 145.5, 143.5, 138.7,
137.0, 136.3, 130.8, 130.0 (q, J = 30 Hz), 129.7, 126.8, 126.5,
125.5 (q, J = 268 Hz), 125.6 (q, J = 4 Hz), 118.1, 116.7, 37.6,
26.8; 19F NMR (376 MHz, CDCl3) δ −62.59; IR νmax 1683,
1356, 1322, 114, 1084, 848 cm−1; HRMS (ESI) m/z: [M+H]+
Calcd for C20H18OF3 331.1304; Found: 331.1306.
2-Allyl-4-nitro-1-(1-(4
(trifluorome-
thyl)phenyl)vinyl)benzene (5g) yellow oil, 0.5 mmol scale,
145 mg, 87% yield; eluent: hexane/ethyl acetate 95:5; 1H
NMR (400 MHz, CDCl3) δ 8.14 ꢀ 8.11 (m, 2H), 7.59 ꢀ 7.56
(m, 2H), 7.41 ꢀ 7.33 (m, 3H), 5.98 (d, J = 0.4 Hz, 1H), 5.77
(ddt, J = 6.4, 10.0, 16.8 Hz, 1H), 5.40 (s, 1H), 5.06 (dq, J =
1.6, 10.0 Hz, 1H), 4.95 (dq, J =1.6, 17.2 Hz, 1H), 3.22 (dt, J =
1.6, 6.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 147.9, 147.2,
146.2, 142.8 (d, J = 1 Hz), 140.3, 135.2, 131.4, 130.3 (q, J =
33 Hz), 126.8, 125.7 (q, J = 4 Hz), 124.7, 124.1 (q, J = 271
Hz), 121.7, 118.8, 117.7, 37.4; 19F NMR (376 MHz, CDCl3) δ
−62.66; IR νmax 1520, 1348, 1324, 1166, 1117, 1067, 850
cm−1; HRMS (EI) m/z: [M]+ Calcd for C18H14F3NO2 333.0977;
Found: 333.0975.
1-Allyl-4,5-dimethoxy-2-(1-phenylvinyl)benzene (5l) yelꢀ
low oil, 0.6 mmol scale, 102 mg, 61% yield; eluent: cꢀ
1
hexane/ethyl acetate 9:1; H NMR (400 MHz, CDCl3) δ 7.29
(m, 5H), 6.73 (d, J = 6.2 Hz, 2H), 5.86 – 5.70 (m, 2H), 5.20 (d,
J = 1.4 Hz, 1H), 4.98 – 4.86 (m, 2H), 3.90 (s, 3H), 3.85 (s,
3H), 3.12 (d, J = 6.6 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ
148.7, 148.5, 147.2, 141.1, 137.9, 133.7, 130.4, 128. 5, 127.8,
126.8, 124.7, 115.5, 115.3, 113.7, 112.6, 56.2, 56.0, 37.4; IR
νmax 3078, 2999, 2933, 2843, 1511, 1252, 1221, 907, 782 cm−1;
HRMS (ESI) m/z: [M+Na]+ Calcd for C19H20O2Na 303.1361;
Found: 303.1354. Anal. Calcd for C19H20O2: C, 81.40; H, 7.19;
found: C, 81.17; H, 7.05.
Ethyl 4-(4-acetamido-2-allylphenyl)pent-4-enoate (5h)
beige solid, 0.6 mmol scale, 102 mg, 68% yield; eluent: cꢀ
2-Allyl-4-fluoro-1-(prop-1-en-2-yl)benzene (5m) yellow
oil, 1 mmol scale, 145 mg, 82% yield; eluent: 100% hexane;
1H NMR (400 MHz, CDCl3) δ 7.09 (dd, J = 6.0, 8.4 Hz, 1H),
6.94 ꢀ 6.85 (m, 2H), 5.93 (ddt, J = 6.4, 11.2, 16.8 Hz, 1H),
5.22 ꢀ 5.21 (m, 1H), 5.12 ꢀ 5.03 (m, 2H), 4.85 ꢀ 4.84 (m, 1H),
3.40 (dd, J = 1.6, 6.4 Hz, 2H), 2.33 (dd, J = 0.8, 1.6 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 161.9 (d, J = 244 Hz), 144.6,
1
hexane/ethyl acetate 7:3; H NMR (400 MHz, CDCl3) δ 7.39
(dd, J = 1.8, 8.1 Hz, 1H), 7.25 (m, 2H), 7.05 (d, J = 8.2 Hz,
1H), 5.91 (ddt, J =16.7, 10.2, 6.5 Hz, 1H), 5.26 – 4.83 (m,
4H), 4.11 (q, J = 7.1 Hz, 2H), 3.35 (d, J = 6.4 Hz, 2H), 2.63 (t,
J = 7.6 Hz, 2H), 2.39(dd, J = 8.5, 6.8 Hz, 2H), 2.16 (s, 3H),
1.24 (dt, J = 9.2, 6.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ
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139.6 (d, J = 3 Hz), 139.0 (d, J = 7 Hz), 137.3, 130.0 (d, J = 8
4-Methyl-1H-indene (6b) yellow oil, 0.872 mmol scale,
102 mg, 90% yield; eluent: 100% hexane; 1H NMR (400
MHz, CDCl3) δ 7.35 ꢀ 7.32 (m, 1H), 7.15 ꢀ 7.01 (m, 3H), 6.58
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Hz), 116.4, 116.03 (d, J = 21 Hz) 115.7, 112.9 (d, J = 21 Hz),
37.3 (d, J = 2 Hz), 25.3; 19F NMR (376 MHz, CDCl3) δ
−116.27; IR νmax 2927, 1487, 1435, 1243, 1086 cm−1; HRMS
(EI) m/z: [M]+ Calcd for C12H13F 176.1001; Found: 176.0988.
(td, J = 2.0, 5.6 Hz, 1H), 3.44 ꢀ 3.43 (m, 2H), 2.49 (s, 3H); 13
C
NMR (100 MHz, CDCl3) δ 143.8, 143.7, 133.6, 130.3, 130.3,
127.4, 124.7, 121.3, 39.5, 18.7.
Ethyl 4-(2-allyl-4-fluorophenyl)pent-4-enoate (5n) yellow
oil, 0.5 mmol scale, 78 mg, 60% yield; eluent: cꢀhexane/ethyl
3,4-Dimethyl-1H-indene (6c) yellow oil, 0.872 mmol scale,
112 mg, 89% yield; eluent: 100% hexane; 1H NMR (400
MHz, CDCl3) δ 7.32 ꢀ 7.30 (m, 1H), 7.12 ꢀ 7.04 (m, 2H), 6.18
(dd, J = 1.6, 3.6 Hz, 1H), 3.29 ꢀ 3.28 (m, 2H), 2.36 (s, 3H),
2.39 (dd, J = 2.0, 4.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
145.6, 143.5, 141.6, 131.1, 129.9, 128.8, 124.7, 121.8, 37.4,
20.0, 17.8.
1
acetate 95:5; H NMR (400 MHz, CDCl3) δ 7.05 (dd, J = 6.0,
8.4 Hz, 1H), 6.98ꢀ6.80 (m, 2H), 5.90 (ddt, J = 6.5, 10.1, 16.7
Hz, 1H), 5.22 (q, J = 1.5 Hz, 1H), 5.12ꢀ4.98 (m, 2H), 4.93ꢀ
4.87 (m, 1H), 4.11 (q, J = 7.1 Hz, 2H), 3.36 (d, J = 6.5 Hz,
2H), 2.63 (t, J = 7.6 Hz, 2H), 2.40 (t, J = 7.6 Hz, 2H), 1.24 (t,
J = 7.1 Hz, 3H);13C NMR (101 MHz, CDCl3) δ 173.0, 162.1
(d, J = 244 Hz), 147.1, 139.5 (d, J = 7 Hz), 138.0 (d, J = 3
Hz), 137.2, 130.2 (d, J = 8 Hz), 116.6, 116.2 (d, J = 22 Hz),
115.4, 112.9 (d, J = 21 Hz), 60.6, 37.2, 33.4, 32.7, 14.4. 19F
NMR (376 MHz, CDCl3) δ −115.76. HRMS (EI) m/z: [M]+
Calcd for C16H19FO2 262.1369; Found: 262.1369. 2-Allyl-1-
vinylnaphthalene (5o) yellow oil, 0.5 mmol scale, 79 mg,
81% yield; eluent: 100% hexane; 1H NMR (400 MHz, CDCl3)
δ 8.08 ꢀ 8.05 (m, 1H), 7.85 ꢀ 7.83 (m, 1H), 7.78 ꢀ 7.69 (m,
2H), 7.56 ꢀ 7.45 (m, 2H), 7.26ꢀ 7.18 (m, 1H), 6.10 (ddt, J =
5.6, 10.0, 17.2 Hz, 1H), 5.80 (dd, J = 1.6, 17.2 Hz, 1H), 5.45
(t, J = 1.6, 10.8 Hz, 1H), 5.08 (dq, J = 1.6, 10.0 Hz, 1H), 4.95
(dq, J = 1.6. 17.0 Hz, 1H), 3.95 (td, J = 2.0, 5.6 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ 135.2, 134.0, 133.5, 132.5, 132.4,
128.6, 127.2, 127.1, 125.6, 124.6, 124.1, 116.5, 116.1, 32.3;
IR νmax 3042, 2925, 2853, 1584, 1509, 1454, 1395, 1375,
1337, 1162, 906, 859, 815, 746 cm−1; HRMS (EI) m/z: [M]+
Calcd for C15H14 194.1096; Found: 194.1090.
9
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17
18
19
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1H-Indene-4-carbaldehyde (6d) yellow oil, 0.348 mmol
1
scale, 46 mg, 92% yield; eluent: hexane/ethyl acetate 95:5; H
NMR (400 MHz, CDCl3) δ 10.2 (s, 1H), 7.74 ꢀ 7.66 (m, 3H),
7.34 (t, J = 3.6 Hz, 1H), 6.86 – 6.83 (m, 1H ), 3.42 ꢀ 3.41 (m,
2H); 13C NMR (100 MHz, CDCl3) δ 192.5, 145.4, 145.3,
138.9, 130.4, 129.9, 128.9, 128.8, 124.8, 38.6; IR νmax 2727,
1690, 1587, 1387, 1270, 1219, 987, 770 cm−1; HRMS (EI)
m/z: [M]+ Calcd for C10H8O 144.0575; Found: 144.0572.
4-Phenyl-1H-indene (6e) transparent oil, 0.3 mmol scale,
1
35 mg, 61% yield; eluent: cꢀhexane 100%; H NMR (400
MHz, CDCl3) δ 7.57 – 7.27 (m, 8H), 7.10 – 7.04 (m, 1H), 6.60
(dt, J = 5.6, 2.0 Hz, 1H), 3.49 (t, J = 1.8 Hz, 2H); 13C NMR
(101 MHz, CDCl3) δ144.5, 142.7, 141.1, 135.4, 134.6, 131.3,
129.1, 128.6, 127.1, 126.8, 125.0, 122.9, 39.6; HRMS (EI)
m/z: [M]+ Calcd for C15H12 192.0939; Found: 192.0938. Anal.
Calcd for C15H12: C, 93.71; H, 6.29; found: C, 93.49; H, 6.46.
3-(4-(Trifluoromethyl)phenyl)-1H-indene-4-
2-Allyl-1-(1-(4-
carbaldehyde (6f) yellow oil, 0.417 mmol scale, 116 mg,
(trifluoromethyl)phenyl)vinyl)naphthalene (5p) yellow oil,
1
96% yield; eluent: hexane/ethyl acetate 95:5; H NMR (400
1
0.5 mmol scale, 155 mg, 92% yield; eluent: 100% hexane; H
MHz, CDCl3) δ 9.91 (d, J = 0.8 Hz, 1H), 7.89 (d, J = 1.2, 8.0
Hz, 1H), 7.76 ꢀ 7.69 (m, 3H), 7.57 – 7.55 (m, 2H), 7.41ꢀ 7.37
(m, 1H), 6.70 (t, J = 2.0 Hz, 1H), 3.61 (d, J = 2.0 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ 190.4, 145.9, 144.3, 142.4 (d, J = 2
Hz), 138.1, 130.6, 130.2 (q, J = 32 Hz), 129.4, 128.4, 126.0 (q,
J = 4 Hz), 125.9, 125.8, 124.1 (q, J = 271 Hz), 38.6; 19F NMR
(376 MHz, CDCl3) δ −62.57; IR νmax 2933, 1324, 1230, 1158,
1124, 1104, 1066, 847 cm−1; HRMS (EI) m/z: [M]+ Calcd for
C17H11F3O 288.0762; Found: 288.0757.
NMR (400 MHz, CDCl3) δ 8.12 ꢀ 8.10 (m, 1H), 7.93 ꢀ0 7.90
(m, 1H), 7.82 ꢀ 7.79 (m, 1H), 7.60 ꢀ 7.31 (m, 7H), 6.03 (d, J =
1.2 Hz, 1H), 5.93 (ddt, J = 6.0, 10.4, 17.2 Hz, 1H), 5.44 (d, J =
0.8 Hz, 1H), 5.00 (qd, J = 1.6, 10 Hz, 1H), 4.87 (qd, J =1.6,
17.2 Hz, 1H), 3.24 (td, J = 2.0, 5.6 Hz, 2H); 13C NMR (100
MHz, CDCl3) δ 147.8, 144.2 (d, J = 2 Hz), 138.3, 137.0,
133.5, 133.3, 132.6, 129.8 (q, J = 32 Hz), 128.7, 128.2, 127.9,
127.1, 126.4, 125.8, 125.4 (q, J = 4 Hz), 125.2, 124.3 (q, J =
271 Hz), 117.6, 116.0, 34.1; 19F NMR (376 MHz, CDCl3) δ
−62.47; IR νmax 1615, 1322, 1264, 1163, 1114, 1064, 1014,
848 cm−1; HRMS (EI) m/z: [M]+ Calcd for C22H17F3 338.1282;
Found: 338.1286.
6-Nitro-3-(4-(trifluoromethyl)phenyl)-1H-indene
(6g)
yellow oil, 0.35 mmol scale, 101 mg, 95% yield; eluent: hexꢀ
ane/ethyl acetate 95:5; 1H NMR (400 MHz, CDCl3) δ 8.39 (t, J
= 0.8, 2.0 Hz, 1H), 8.24 (ddd, J = 0.8, 2.0, 8.4 Hz, 1H), 7.77 ꢀ
7.67 (m, 4H), 7.61 (dd, J = 0.8, 8.8 Hz, 1H), 6.98 (t, J = 2.4
Hz, 1H), 3.68 (d, J = 2.4 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ 149.6, 146.1, 145.4, 143.9, 138.4 (d, J = 2 Hz),
138.2, 130.4 (q, J = 32 Hz), 128.1, 125.8 (d, J = 4 Hz), 124.2
(q, J = 271 Hz), 122.9 (d, J = 1 Hz), 120.2, 120.0, 38.8; 19F
NMR (376 MHz, CDCl3) δ −62.60; IR νmax 1507, 1335, 1319,
1275, 1174, 1130,1062 cm−1; HRMS (ESI) m/z: [M−H]− Calcd
for C16H10F3NO2 304.0591; Found: 304.0598.
General Procedure for Ring closing metathesis. The
diene (1 mmol unless otherwise noted) was dissolved in 5 mL
dry CH2Cl2 and nitroꢀHoveydaꢀGrubbs catalyst [Ru-2] (1ꢀ1.7
mol %) was added and refluxed for 1 h. Then reaction mixture
was concentrated and purified by column chromatography.
Ethyl 3-(6-nitro-1H-inden-3-yl)propanoate (6a) beige solꢀ
id, 0.43 mmol scale, 113mg, quantitative yield; eluent: cꢀ
1
hexane/ethyl acetate 9:1 ; H NMR (400 MHz, CDCl3) δ 8.26
(s, 1H), 8.21 (d, J = 8.3 Hz, 1H), 7.43 (d, J = 8.4 Hz, 1H), 6.55
(s, 1H), 4.15 (q, J = 7.1 Hz, 2H), 3.43 (s, 2H), 2.90 (t, J = 7.1
Ethyl 3-(6-acetamido-1H-inden-3-yl)propanoate (6h)
beige solid, 0.17mmol scale, 32 mg, 71% yield; eluent: cꢀ
hexane/ethyl acetate 7:3; 1H NMR (400 MHz, CDCl3) δ 7.74
(s, 1H), 7.59 (s, 1H), 7.33 – 7.15 (m, 2H), 6.15 (s, 1H), 4.15
(q, J = 7.1 Hz, 2H), 3.28 (s, 2H), 2.84 (t, J = 7.0 Hz, 2H), 2.66
(dd, J = 18.0, 11.0 Hz, 2H), 2.16 (s, 3H), 1.25 (t, J = 7.1 Hz,
3H); 13C NMR (101 MHz, CDCl3) δ 173.4, 168.6, 145.5,
142.6, 141.6, 135.4, 127.7, 118.9, 118.3, 116.6, 60.6, 38.0,
Hz, 2H), 2.70 (t, J = 7.5 Hz, 2H), 1.24 (t, J = 7.1 Hz, 3H); 13
C
NMR (101 MHz, CDCl3) δ 172.8, 151.4, 145.9, 145.0, 142.8,
134.4, 122.8, 119.0, 118.9, 77.5, 77.2, 76.8, 60.7, 38.2, 32.7,
22.9, 14.3; IR νmax 3068, 2981, 2934, 1731, 1514, 1339, 1172,
1065, 884, 816, 763 cm−1; HRMS (ESI) m/z: [M+Na]+ Calcd
for C14H15NO4Na 284.0899; Found: 284.0896.
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32.9, 24.6, 23.1, 14.3; HRMS (ESI) m/z: [M+Na]+ Calcd for
Page 8 of 10
2.0 Hz, 2H), 2.86 (ddd, J = 8.1, 5.0, 1.4 Hz, 2H), 2.76 – 2.63
(m, 2H), 1.26 (dd, J = 9.3, 4.9 Hz, 3H); 13C NMR (101 MHz,
CDCl3) δ 173.2, 161.7 (d, J = 241 Hz), 146.5 (d, J = 8 Hz),
142.5, 141.1 (d, J = 2 Hz), 127.6 (d, J = 3 Hz), 119.4 (d, J =
8 Hz), 113.1 (d, J = 23 Hz), 111.6 (d, J = 23 Hz), 60.6, 37.9
(d, J = 3 Hz), 32.9, 23.2, 14.4; 19F NMR (376 MHz, CDCl3) δ
−118.96; HRMS (EI) m/z: [M]+ Calcd for C14H15FO2
234.1056; Found: 234.1060. Anal, Calcd for C14H15FO2: C
71.78; H 6.45; found: C 71.67; H 6.52.
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6
7
8
C16H19NO3Na 296.1263; Found: 296.1253.
1-(1H-Inden-6-yl)ethan-1-one (6i) yellow solid, 0.54
mmol scale, 82 mg, 70% yield; eluent: cꢀhexane/ethyl acetate
9:1; 1H NMR (400 MHz, CDCl3) δ 8.14 – 8.03 (m, 1H), 7.97 –
7.86 (m, 1H), 7.46 (d, J = 7.9 Hz, 1H), 7.01 – 6.87 (m, 1H),
6.78 (dt, J = 5.5, 2.0 Hz, 1H), 3.47 (t, J = 1.7 Hz, 2H), 2.63 (s,
3H); 13C NMR (101 MHz, CDCl3) δ 198.4, 149.8, 143.9,
138.6, 134.1, 132.0, 127.7, 123.6, 120.9, 39.4, 26.9; IR νmax
3438, 2919, 1677, 1607, 1426, 1260, 833 cm−1; HRMS (ESI)
m/z: [M+Na]+ Calcd for C11H10ONa 181.0629; Found:
181.0621.
3H-Cyclopenta[a]naphthalene (6o) yellow solid, 0.386
9
mmol scale, 62 mg, 96% yield; eluent: hexane/ethyl acetate
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1
98:2; H NMR (400 MHz, CDCl3) δ 8.01 – 7.99 (m, 1H),
7.91ꢀ7.80 (m, 2H) 7.64 ꢀ 7.42 (m, 3H), 7.06 (td, J = 2.0 Hz,
1H), 6.68 (td, J = 2.0 Hz, 1H), 3.75 (d, J = 2.0 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ 142.4, 140.3, 133.8, 132.8, 131.6,
130.2, 128.0, 127.2, 126.3, 124.6, 123.6, 120.6, 38.2.
1-(3-Methyl-1H-inden-6-yl)ethan-1-one (6j) colourless
oil, 0.649 mmol scale, 101 mg, 90% yield; eluent: hexꢀ
1
ane/ethyl acetate 95:5; H NMR (400 MHz, CDCl3) δ 8.03 ꢀ
7.93 (m, 2H), 7.36 (d, J = 8.0, 1H), 6.41 ꢀ 6.40 (m, 1H), 3.37 ꢀ
3.35 (m, 2H), 2.62 (s, 3H), 2.19 ꢀ 2.17 (m, 3H); 13C NMR (100
MHz, CDCl3) δ 198.4, 151.0, 144.4, 139.9, 133.8, 133.2,
127.4, 123.4, 118.7, 37.9, 26.9, 13.1; IR νmax 1681, 1610,
1424, 1357, 1260, 1176, 1093 cm−1; HRMS (ESI) m/z:
[M+H]+ Calcd for C12H13O 173.0961; Found: 173.0963.
1-(4-(Trifluoromethyl)phenyl)-3H-
cyclopenta[a]naphthalene (6p) yellow solid, 0.429 mmol
scale, 128 mg, 96% yield; eluent: hexane/ethyl acetate 98:2;
1H NMR (400 MHz, CDCl3) δ 8.04 (dq, J = 0.8, 8.0 Hz, 1H),
7.93 ꢀ 7.90 (m, 1H), 7.85 ꢀ 7.83 (m, 1H), 7.78 ꢀ 7.69 (m, 5H),
7.56 ꢀ 7.52 (m, 1H), 7.48ꢀ 7.43 (m, 1H), 6.75 (t, J = 2.0 Hz,
1H), 3.87 (d, J = 2.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ
145.0, 141.6, 140.7, 139.9 (q, J = 1 Hz), 131.9, 131.8, 130.4,
129.8 (q, J = 32 Hz), 129.0, 128.1, 127.4, 126.6, 125.7 (q, J =
4.0 Hz), 125.2, 124.4 (q, J = 271 Hz), 123.7, 119.3, 38.6; 19F
NMR (376 MHz, CDCl3) δ −62.44; IR νmax 3054, 1613, 1513,
1408, 1324, 1164, 1066 cm−1; HRMS (EI) m/z: [M]+ Calcd for
C20H13F3 310.0969; Found: 310.0963.
1-(3-(4-(Trifluoromethyl)phenyl)-1H-inden-6-yl)ethan-1-
one (6k) yellow solid, 0.40 mmol scale, 111 mg, 92% yield;
eluent: hexane/ethyl acetate 95:5; 1H NMR (400 MHz, CDCl3)
δ 8.14 (dd, J = 0.8, 1.6 Hz, 1H), 7.98 ꢀ 7.96 (m, 1H), 7.74 ꢀ
7.67 (m, 4H), 8.14 (dd, J = 0.8, 8.0 Hz, 1H), 6.86 (t, J = 2.4
Hz, 1H), 3.61 (d, J = 2.4 Hz, 2H), 2.65 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 198.2, 148.0, 144.8, 144.0, 139.1 (d, J = 2
Hz), 136.5 (d, J = 2 Hz), 134.4, 130.0 (q, J = 32 Hz), 128.1,
127.6, 125.8 (d, J = 4 Hz), 124.1 (d, J = 2 Hz), 124.3 (q, J =
271 Hz), 120.0 (q, J = 2 Hz), 38.7, 26.9 (d, J = 3 Hz); 19F
NMR (376 MHz, CDCl3) δ −62.53; IR νmax 1685, 1359, 1326,
1267, 1167, 1125, 1067 cm−1; HRMS (ESI) m/z: [M+H]+
Calcd for C18H14F3O 303.0991; Found: 303.0994.
General Method for Isomerisation-Deuteration of Al-
lylboronic Acid Pinacol Ester:
In a schlenk tube acetoneꢀD6 (2 mL), allylboronic acid pinaꢀ
col ester 7f (1 mmol), D2O (40 mmol) were taken and deoxyꢀ
genated and then catalyst [Ru-3] (2 mol %) dissolved in aceꢀ
toneꢀD6 (0.5 mL) was added and kept the mixture for 12ꢀ16 h
in the globeꢀbox. Isomerisation and disappearance of protons
was checked by NMR. Then, the whole reaction mixture was
used in next reaction without purification. Triflate 2 (0.5
mmol), Pd(PPh3)4 (12 mol %) and 10 mL of dioxaneꢀwater
(4:1) were added to the same Schlenk tube and after deoxyꢀ
genation of the whole solution heated for 18 h at 120 oC. After
that time, the flask was cooled at roomꢀtemperature and all
volatiles were removed under reduced pressure. The oily resiꢀ
due was solubilized in ethyl acetate and filtrated through a
Celite pad. Volatiles were concentrated in vacuo and purified
by column chromatography (2% EA/hexane) to afford pure
product.
5,6-Dimethoxy-3-phenyl-1H-indene (6l) beige solid, 0.36
mmol scale, 66 mg, 73% yield; after workꢀup product was
1
purified by triple recrystallization from methanol; H NMR
(400 MHz, CDCl3) δ 7.63 – 7.56 (m, 2H), 7.47 (t, J = 7.4 Hz,
2H), 7.38 (ddd, J = 6.4, 4.5, 1.2 Hz, 1H), 7.13 (d, J = 7.0 Hz,
2H), 6.48 (t, J = 2.1 Hz, 1H), 3.94 (s, 3H), 3.89 (s, 3H), 3.45
(d, J = 1.8 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ148.4,
147.7, 145.2, 137.4, 136.9, 136.6, 129.7, 128.8, 127.7, 127.7,
108.5, 104.4, 56.5, 38.2; IR νmax 2936, 2830, 1493, 1345, 1274,
1204, 1081, 854, 821, 749, 700 cm−1; HRMS (ESI) m/z:
[M+Na]+ Calcd for C17H16O2Na 275.1048; Found: 275.1042.
Anal. Calcd for C17H16O2: C, 80.93; H, 6.39; found: C, 80.87;
H, 6.29.
1-Allyl-3-methyl-2-(prop-1-en-1-yl-1,3,3,3-d4)benzene
6-Fluoro-3-methyl-1H-indene (6m) yellow oil, 0.248
mmol scale, 35 mg, 83% yield; eluent: 100% hexane; 1H NMR
(400 MHz, CDCl3) δ 7.26 ꢀ 7.14 (m, 2H), 7.04 ꢀ 6.99 (m, 1H),
6.17 (t, J = 2.0 Hz, 1H), 3.30 (d, J = 2.0 Hz, 2H), 2.17 ꢀ 2.15
(m, 3H); 13C NMR (100 MHz, CDCl3) δ 161.6 (d, J = 241 Hz),
146.5 (d, J = 8 Hz), 142.2 (d, J = 2 Hz), 139.4, 128.4 (d, J = 4
Hz), 119.3 (d, J = 8 Hz), 112.9 (d, J = 23 Hz), 111.4 (d, J = 23
Hz), 37.8 (d, J = 2 Hz), 13.2; 19F NMR (376 MHz, CDCl3) δ
−119.54.
1
(8) yellow oil, 0.5 mmol scale, 65 mg, 74% yield; H NMR
(400 MHz, CDCl3) δ 7.10ꢀ7.03 (m, 3H), 6.05ꢀ 5.91 (m, 1H),
5.68 ꢀ 5.66 (m, 1H), 5.06 – 4.96 (m, 2H), 3.42 (td, J = 1.6, 6.4
Hz, 2H) 2.29 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 137.9,
137.7, 136.4, 130.4, 128.1, 127.0, 126.5, 115.5, 38.3, 21.2; IR
νmax 2924, 2854, 1682, 1465, 1378, 1261, 1044, 994, 764 cmꢀ1;
HRMS (EI) m/z: [M]+ Calcd for C13H12D4 176.1503; Found:
176.1503.
2-Allyl-4-methoxy-1-(prop-1-en-1-yl-1,3,3,3-d4)benzene
Ethyl 3-(6-fluoro-1H-inden-3-yl)propanoate (6n) transꢀ
parent oil, 0.19 mmol scale, 44 mg, 99% yield; eluent: cꢀ
hexane/ethyl acetate 95:5; 1H NMR (400 MHz, CDCl3) δ 7.33
– 7.22 (m, 1H), 7.16 (dd, J = 8.8, 2.2 Hz, 1H), 7.07 – 6.93 (m,
1H), 6.28 – 6.11 (m, 1H), 4.16 (q, J = 7.1 Hz, 2H), 3.31 (d, J =
1
(10) yellow oil, 0.5 mmol scale, 62% yield; H NMR (400
MHz, CDCl3) δ 7.38ꢀ7.54 (m, 2H), 6.76ꢀ 6.52 (m, 3H), 6.01 ꢀ
5.93 (m, 2H), 5.09 – 4.99 (m, 2H), 3.79 (s, 3H), 3.41 (d, J =
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6.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 158.7, 136.9,
127.1, 127.0, 116.0, 114.9, 112.1, 55.3, 37.8.
E. Coord. Chem. Rev. 1999, 193, 147. (f) Kravchenko, R.; Masood,
A.; Waymouth, R. M. Organometallics 1997, 16, 3635.
3. For recent examples of biologically active indene derivaꢀ
1
2
3
4
5
6
7
8
RCM: The diene (0.34 mmol) was dissolved in 5 mL
CH2Cl2 and Nitro catalyst [Ru-2] (2 mol %) was added and
refluxed for 1 h. Then reaction mixture was concentrated and
purified by column chromatography (using 2% EA/hexane).
tives, see: a) Banothu, J.; Basavoju, S.; Bavantula, R. J. Heterocycl.
Chem. 2015, 52, 853. b) ElꢀSheshtawy, H. S.; Baker, A. M. A., Kuꢀ
mar, J. Mol. Struct. 2014, 1067, 225. c) Kahlon, A. K.; Negi, A. S.;
Kumari, R.; Srivastava, K. K.; Darokar, S. M. P.; Sharma, A. Appl.
Microbiol. Biotechnol. 2014, 98, 2041. d) Li, Y.; Yan, X.; Chen, D.;
Shun, L. Chin. J. Org. Chem. 2013, 33, 1490. e) Norrgård, M. A.;
Mannervik, B.; J. Mol. Biol. 2011, 412, 111. f) Huang,C.; Moree, W.
J.; ZamaniꢀKord, S.; Li, B. F.; Tucci, F. C.; Malany, S.; Wen, J.;
Wang, H.; Hoare, S. R.; Yang, C.; Madan, A.; Crowe, P. D.; Beaton,
G. Bioorg. Med. Chem. Lett. 2011, 21, 947. g) Alcalde, E.; Mesquida,
N.; Frigola, J.; LópezꢀPérez, S.; Mercè, R. Org. Biomol. Chem. 2008,
6, 3795.
4-Methyl-1H-indene-3-d (9) yellow oil, 0.34 mmol scale,
1
38 mg, 85% yield; H NMR (400 MHz, CDCl3) δ 7.35 ꢀ 7.32
(m, 1H), 7.15 ꢀ 7.09 (m, 2H), 6.59ꢀ6.57 (m, 1H), 3.44 ꢀ 3.43
(m, 2H), 2.48 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 143.8,
143.7, 133.6, 130.3 (t, J = 3 Hz), 128.5 (t, J = 24 Hz), 127.3,
124.8, 121.3 (t, J = 2 Hz), 39.5, 18.7; IR νmax 2924, 2854,
1720, 1601, 1465, 1379, 1268, 1201, 1041, 971, 772 cmꢀ1;
HRMS (EI) m/z: [M]+ Calcd for C10H9D 131.0845; Found:
131.0845.
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4.
(a) Das, B. G.; Chirila, A.; Tromp, M.; Reek, J. N. H.;
Bruin, B. de J. Am. Chem. Soc. 2016, 138, 8968. (b) Gabriele, B.;
Mancuso, R.; Veltri, L. Chem. Eur. J. 2016, 22, 5056. c) Enders, M.;
Baker, R. W. Curr. Org. Chem. 2006, 10, 937. (d) Ivchenko ,N. B.;
Ivchenko, P. V.; Nifanťev, I. E. Russ. J. Org. Chem. 2000, 36, 609.
6-Methoxy-1H-indene-3-d (11) yellow oil, 0.208 mmol
scale, 27 mg, 88% yield; 1H NMR (400 MHz, CDCl3) δ 7.31 ꢀ
7.28 (m, 1H), 7.09 ꢀ 7.08 (m, 1H), 6.86ꢀ6.81 (m, 1H), 6.43 –
6.41 (m, 1H), 3.84 (s, 3H), 3.38 ꢀ 3.37 (m, 2H),; 13C NMR
(100 MHz, CDCl3) δ 157.9, 145.7, 138.1, 131.9, 131.6, 130.5
(t, J = 23 Hz), 121.2, 112.0, 110.4, 95.7, 39.3; IR νmax 2935,
2833, 1608, 1478, 1290, 1255, 1201, 1032, 809 cmꢀ1; HRMS
(EI) m/z: [M]+ Calcd for C10H9DO 147.0794; Found:
147.0789.
5.
(a) Gassman, P. G.; Ray, J. A.; Wenthold, P. G.; Mickelꢀ
son, J. W. J. Org. Chem. 1991, 56, 5143. (b) Prough, J. D.; Alberts,
A. W.; Deana, A. A.; Gilfillian, J. L.; Huff, J. W.; Smith, R. L.; Wigꢀ
gins, J. M. J. Med. Chem. 1990, 33, 758.
6.
(a) Usanov, D. L.; Yamamoto, H. Org. Lett. 2012, 14, 414.
(b) Panteleev, J.; Huang, R. Y.; Lui, H. E. K.; Lautens, M. Org. Lett.
2011, 13, 5314. (c) Smith, C. D.; Rosocha, G.; Mui, L.; Batey, R. A.
J. Org. Chem. 2010, 75, 4716. (d) Xi, Z. F.; Guo, R. Y.; Mito, S.;
Yan, H. L.; Kanno, K, I.; Nakajima, K.; Takahashi, T. J. Org. Chem.
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ASSOCIATED CONTENT
Supporting Information
7.
(a) Shi, M.; Lu, J.ꢀM.; Wei, Y.; Shao, L.ꢀX. Acc. Chem.
Res. 2012, 45, 641. (b) Semmelhack, M. F.; Ho, S.; Cohen, D.; Steiꢀ
gerwald, M.; Lee, M. C.; Lee, G.; Gilbert, A. M.; Wulff, W. D.; Ball,
R. G. J. Am. Chem. Soc. 1994, 116, 7108.
The Supporting Information is available free of charge on the
ACS Publications website. NMR spectra (PDF)
8.
Pd: (a) Bi, H.ꢀP.; Liu, X.ꢀY.; Gou, F.ꢀR.; Guo, L.ꢀN.;
Duan, X.ꢀH.; Liang, Y.ꢀM. Org. Lett. 2007, 9, 3527. (b) Zhang, D.;
Liu, Z.; Yum, E. K.; Larock, R. C. J. Org. Chem. 2007, 72, 251. (c)
Zhang, D. H.; Yum, E. K.; Liu, Z. J.; Larock, R. C. Org. Lett. 2005, 7,
4963. (d) Gevorgyan, V.; Quan, L. G.; Yamamoto, Y. Tetrahedron
Lett. 1999, 40, 4089. (e) Quan, L. G.; Gevorgyan, V.; Yamamoto, Y.
J. Am. Chem. Soc. 1999, 121, 3545.
AUTHOR INFORMATION
Corresponding Author
*K.G.: tel, +48ꢀ22ꢀ8220211 ext. 420; fax, +48ꢀ22ꢀ8220211;
email: prof.grela@gamil.com
Author Contributions
9.
Ni: (a) Deng, R.; Sun, L.; Li, Z. Org. Lett. 2007, 9, 5207.
§ these authors contributed equally
Notes
(b) Rayabarapu, D. K.; Yang, C.ꢀH.; Cheng, C.ꢀH. J. Org. Chem.
2003, 68, 6726. (c) Rayabarapu, D. K.; Cheng, C.ꢀH. Chem. Commun.
2002, 942.
The authors declare no competing financial interest.
10.
11.
Pt: Zhao, J.; Clark, D. A. Org. Lett. 2012, 14, 1668.
Co: (a) Chang, K.ꢀJ.; Rayabarapu, D. K.; Cheng, C.ꢀH. J.
ACKNOWLEDGMENT
Org. Chem. 2004, 69, 4781. (b) Chang, K.ꢀJ.; Rayabarapu, D. K.;
Cheng, C.ꢀH. Org. Lett. 2003, 5, 3963.
The authors would like to thank the PolishꢀSingapore Grant
(3/3/ENGꢀSIN/2012) "Green and Sustainable Catalysts for Chemꢀ
ical, Agrochemical and Pharmaceutical Industry" 2012ꢀ2015
NCBR.
12.
Au: (a) Sanz, R.; Miguel, D.; Rodriguez, F. Angew. Chem.,
Int. Ed. 2008, 47, 7354. (b) Ye, L.; Wang, Y.; Aue, D. H.; Zhang, L.
J. Am. Chem. Soc. 2011, 134, 31.
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D.ꢀJ.; Li, C. N.; Tian, S.ꢀK. Org. Lett. 2010, 12, 3832.
14. Bacha, J.D.; Schulz, J.G.D.; Onopchenko, A., J. Org.
Chem. 1979, 44, 648.
Fe: Liu, C.ꢀR.; Yang, F.ꢀL.; Jin, Y.ꢀZ.; Ma, X. T.; Cheng,
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