Synthesis of β,β-disubstituted indanones via the Pd-catalyzed tandem conjugate addition/cyclization reaction of arylboronic acids with α,β-unsaturated esters

Article abstract of DOI:10.1021/acs.joc.7b01364

Under Pd catalysis with a newly synthesized electron-deficient heterocycle, 2-(4,5-dihydroimidazol-2-yl)- pyrimidine (as the ligand), the reaction of α,β-unsaturated esters with arylboronic acids afforded a wide range of 3,3-disubstituted indan-1-ones bearing a quaternary carbon in high yields. Mechanistic studies revealed that the reaction involves a tandem conjugate addition/1,4-Pd shift followed by a cyclization.

Full text of DOI:10.1021/acs.joc.7b01364

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Article
Synthesis of #,#-Disubstituted Indanones via the Pd-
Catalyzed Tandem Conjugate Addition/Cyclization
Reaction of Arylboronic Acids with #,#-Unsaturated Esters
Ang Gao, Xiu-Yan Liu, Hao Li, Chang-Hua Ding, and Xue-Long Hou
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b01364 • Publication Date (Web): 24 Aug 2017
Downloaded from http://pubs.acs.org on August 25, 2017
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Synthesis of β,βꢀDisubstituted Indanones via the PdꢀCatalyzed Tandem
Conjugate Addition/Cyclization Reaction of Arylboronic Acids with
α,βꢀUnsaturated Esters
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Ang Gao,† XiuꢀYan Liu,† Hao Li,† ChangꢀHua Ding,*,† and XueꢀLong Hou*,†,‡
†State Key Laboratory of Organometallic Chemistry, ‡Shanghai–Hong Kong Joint
Laboratory in Chemical Synthesis, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
xlhou@sioc.ac.cn;dingch@sioc.ac.cn
Table of Contents Graphic
Abstract: Under Pd catalysis with a newly synthesized electronꢀdeficient heterocycle,
2ꢀ(4,5ꢀdihydroimidazolꢀ2ꢀyl)pyrimidine (as the ligand), the reaction of
α,βꢀunsaturated esters with arylboronic acids afforded a wide range of
3,3ꢀdisubstituted indanꢀ1ꢀones bearing a quaternary carbon in high yields.
Mechanistic studies revealed that the reaction involves a tandem conjugate
addition/1,4ꢀPd shift followed by a cyclization.
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INTRODUCTION
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β,βꢀDisubstituted indanone subunits are common in many natural products such
as trigoxyphin M and (ꢀ)ꢀtaiwaniaquinol (Scheme 1).1 Several protocols for the
preparation of β,βꢀdisubstituted indanone derivatives have been reported in recent
years. Hayashi developed a procedure for the synthesis of β,βꢀdisubstituted indanones
by rhodiumꢀcatalyzed addition of arylzinc reagents to aryl alkynyl ketones followed
by cyclization.2 Murakami’s strategy to access β,βꢀdisubstituted indanones was a
Rhꢀcatalyzed asymmetric intramolecular addition/ringꢀopening reaction of
borylꢀsubstituted cyclobutanones.3 Ichikawa and coworkers used an intramolecular
Heckꢀtype reaction followed by βꢀfluorine elimination to prepare indanone
derivatives4, while Liu’s work utilized a Auꢀcatalyzed oxidative cyclization of
cisꢀsubstituted 3ꢀenꢀ1ꢀynes to obtain indanones.5 Gouverneur also reported a single
example of the preparation of 1ꢀindanone by the reaction of 3ꢀmethylcrotonic acid
with benzene.6 In spite of these developments, new approaches to this important
building block still remain to be explored.
Scheme 1. Some Natural Products Bearing β,βꢀDisubstituted Indanone Cores
In contrast, the palladiumꢀcatalyzed Michael addition of arylboronic reagents has
become an important synthetic tool for constructing carbonꢀcarbon bonds,7 and a
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variety of acyclic α,βꢀunsaturated ketones, aldehydes, and nitroalkanes, as well as
cyclic enones, are suitable substrates.8 α,βꢀUnsaturated esters have also been used in
this type of reaction;9 however, the addition reactions are very slow, and the oxidative
Heck reaction can become favored in some cases.10 During our studies on the
Pdꢀcatalyzed reactions of boronic acids with unsaturated compounds,11 the reaction of
(E)ꢀethylꢀ3ꢀphenylbutꢀ2ꢀenoate (1a) with phenylboronic acid (2a) was run under
Pdꢀcatalysis. Unexpectedly, 3ꢀmethylꢀ3ꢀphenylꢀindanone (3a) was obtained instead of
the desired conjugated addition product. Due to the importance of indanones, this
interesting result inspired us to study this reaction further. Herein, we would like to
report the Pdꢀcatalyzed tandem conjugate addition/cyclization reaction of arylboronic
acids with α,βꢀunsaturated esters to prepare indanones as well as the corresponding
mechanistic study.
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Results and discussion
Initially, the reaction of ethyl (E)ꢀβꢀmethylcinnamate (1a) with phenylboronic
acid (2a) in the presence of Pd(OAc)2 and 1,10ꢀphenanthroline (L1) was examined.
Surprisingly, 3ꢀmethylꢀ3ꢀphenylꢀindanone (3a) was prepared in 22% yield (entry 1,
Table 1) instead of the Michael addition product. Because of the usefulness of
indanones in organic synthesis, further investigations were carried out. Studies on the
influence of reaction parameters revealed that performing the reaction under an
oxygen atmosphere afforded a better yield of 3a (entry 2 vs entry 1, Table 1). In
contrast, trace amounts of 3a were detected when the reaction was conducted under
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argon, indicating the importance of the presence of oxygen (data not shown). The
optimum temperature for the reaction was 80 °C (entry 2 vs entries 3 and 4, Table 1).
A solvent screen showed that the reaction did not proceed in THF or toluene (entries 5
and 6, Table 1), but the reaction proceeded well in polar solvents such as DMF and
N,Nꢀdimethylacetamide (DMAc) (entries 2 and 7, Table 1). Switching the palladium
source from Pd(OAc)2 to Pd(TFA)2 slightly increased the yield (entries 8 vs entry 7,
Table 1). With Pd(TFA)2 as the catalyst in DMAc, the effect of the ligands on the
reaction was studied. Phosphine ligands such as dppe and BINAP showed no catalytic
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activity
(data
not
shown).
Bidentate
nitrogen
ligands,
such
as
1,10ꢀphenanthrolineꢀ5,6ꢀdione (L2), bisoxazoline L3, pyridineoxazolines L4 and L5,
and pyrimidineoxazoline L6, were also unreactive under these conditions (Scheme 2
and entries 9ꢀ13, Table 1). However, the results of the reactions using ligands L4, L5,
and L6 suggested that an electronꢀdeficient ligand might be more effective in this
reaction (entries 12 vs 11; entries 13 vs 11, Table 1). Thus, a new ligand,
pyrimidineimidazoline rac-L7, was designed and synthesized by replacing the
oxazoline ring of ligand L6 with an imidazoline ring. Pleasingly, ligand rac-L7
significantly improved the yield of the reaction, affording indanone 3a in 68% yield
(entry 14, Table 2). A further increase in yield was achieved using ligand rac-L8 with
a tosyl group on the nitrogen atom, which gave 86% of 3a (entry 15, Table 1). For
comparison, a lower yield was obtained using bispyrimidine L9 (entry 16, Table 1).
These results indicated that the electronic properties of the ligand are important for
the reaction.
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Table 1. Influence of Reaction Parameters on the PdꢀCatalyzed Tandem Reaction of
Ethyl (E)ꢀβꢀmethylcinnamate (1a) and Phenylboronic Acid (2a)a
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Entry [Pd]
Solvent
DMF
T (°C)
80
Yield (%)b
22
L
1c
2
Pd(OAc)2
L1
L1
L1
L1
L1
L1
L1
L1
L2
L3
L4
L5
L6
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
DMF
80
45
3
DMF
60
36
4
DMF
120
80
45
5
THF
NR
NR
46
6
toluene
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
DMAc
80
7
80
8
80
49
9
80
trace
NR
trace
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80
80
80
80
25
rac-L7 DMAc
rac-L8 DMAc
80
68
80
86
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Pd(TFA)2
DMAc
80
40
L9
5
c
aMolar ratio 1a/2a/[Pd]/L = 100/200/5/6. bIsolated yield. Run under aerobic
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conditions.
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Scheme 2. Various Bidentate Nitrogen Ligands.
With the optimum conditions established, the substrate scope of this Pdꢀcatalyzed
tandem reaction was examined (Table 2). The reaction proceeded well for a variety of
α,βꢀunsaturated esters 1 and arylboronic acids 2, affording the corresponding
β,βꢀdisubstituted indanones in 42ꢀ95% yield. The reaction of ethyl
3ꢀmethylbutꢀ2ꢀenoate (1b) gave indanone 3b in 95% yield (entry 2, Table 2). The
reaction tolerated the arylboronic acids 2 with either electronꢀdonating or
electronꢀwithdrawing substituents at the para position of phenyl ring (entries 3ꢀ10,
Table 2). Notably, the reaction of arylboronic acid 2h, bearing a sensitive formyl
group, could be used to provide indanone 3i in 58% yield (entry 9, Table 2). The
substituent at the 2ꢀposition of the phenyl ring of arylboronic acid 2j showed a limited
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effect on the reaction (entry 11, Table 2). The cyclization step for the reaction of ester
1b and naphthalenꢀ2ꢀylboronic acid (2k) occurs regioselectively at the 3ꢀposition of
the naphthyl group (entry 12, Table 2). The yield of indanone decreased greatly if
ethyl (E)ꢀβꢀethylcinnamate (1c) was the substrate (entry 13, Table 2). Notably, the
presence of bulky groups such as isopropyl or cyclohexyl at the βꢀposition of
α,βꢀunsaturated esters 1 had a little influence on the reaction (entries 14 and 16, Table
2). Changing the R3 ester group of acrylate also had little effect on the reaction
(entries 17 and 18 vs entry 2, Table 2).
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Table 2. Substrate Scope for the PdꢀCatalyzed Tandem Reaction of α,βꢀUnsaturated
Esters 1 and Arylboronic Acids 2a
entry R1, R2, R3 (1)
Ar (2)
yield (3, %)b
86 (3a)
1
2
3
4
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7
Me, Ph, Et (1a)
Ph (2a)
Me, Me, Et (1b)
95 (3b)
2a
4ꢀMeꢀC6H4 (2b)
4ꢀMeOꢀC6H4 (2c)
85 (3c)
1b
1b
1b
1b
1b
83 (3d)
4ꢀCO2MeꢀC6H4 (2d) 70 (3e)
4ꢀFꢀC6H4 (2e)
4ꢀClꢀC6H4 (2f)
75 (3f)
77 (3g)
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4ꢀBrꢀC6H4 (2g)
4ꢀCHOꢀC6H4 (2h)
4ꢀHOꢀC6H4 (2i)
70 (3h)
58 (3i)
82 (3j)
1b
1b
1b
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11
2ꢀMeꢀC6H4 (2j)
2ꢀnaphthyl (2k)
1b
1b
82 (3k)
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13
14
15
16
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18
78 (3l)
Et, Ph, Et (1c)
42 (3m)
89 (3n)
75 (3o)
81 (3p)
88 (3b)
85 (3b)
2a
2a
2a
2a
2a
2a
Me, iPr, Et (1d)
Me, cC6H11, Et (1e)
(CH2)5, Et (1f)
Me, Me, tBu (1g)
Me, Me, Bn (1h)
aMolar ratio 1/2/Pd(TFA)2/rac-L8 = 100/200/5/6, under balloon pressure of O2.
bIsolated yield.
The ring formation could be occurring on either of the aryl rings in the
cyclization step of the reaction of βꢀalkylꢀβꢀarylꢀα,βꢀunsaturated esters with
arylboronic acids. Two control experiments were performed to determine which aryl
ring is involved in the cyclization step (eqs 1 and 2). The reaction of ethyl
(E)ꢀβꢀmethylcinnamate (1a) and (4ꢀmethoxyphenyl)boronic acid (2c) gave the
mixture of 3q and 3q’ in a ratio of 2.7/1 (eq 1). In contrast, the reaction of ester 1i
with phenylboronic acid (2a) afforded the mixture of 3q and 3q’ in a ratio of 1/2.7 (eq
2). These results indicate that cyclization mainly occurred on the aryl ring of the
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boronic acid, and no common intermediate was involved in this step.
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Some experiments were carried out using deuteriumꢀlabeled phenylboronic acid
(2a) to gain insight into the plausible reaction mechanism. Treatment of PhB(OD)2
2aꢀD with the ester 1b in the presence of Pd(TFA)2/rac-L8 gave the deuterated
indanone 3bꢀD in 95% yield (eq 3). 1H NMR spectroscopy of 3bꢀD showed that 40%
of the αꢀposition of the carbonyl group and 40% of the 4ꢀposition were deuterated.
The deuteration at the 4ꢀposition of the indanone was unexpected and was proposed to
be produced through a reversible 1,4ꢀpalladium migration (vide infra).12 The
employment of phenyl deuterated boronic acid d5ꢀ2a led to indanone d4ꢀ3b, in which
there was 15% deuteration at the αꢀposition of the carbonyl group and 47% deuterium
incorporation at the 4ꢀposition (eq 4). In addition, boronic acid d5ꢀ2a was recovered in
20% yield without loss of deuterium. A competitive reaction was performed using
equivalent amounts of boronic acid 2a and d5ꢀ2a; indanones 3b and d4ꢀ3b were
produced in a ratio of 1/1, and a 52% loss of deuterium at the 4ꢀposition of d4ꢀ3b was
observed (eq 5). These results were consistent with eqs 3 and 4. Furthermore, ester 1i
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bearing an aryl group reacted with PhB(OD)2 2aꢀD to give a mixture of 3qꢀD and
3q’ꢀD in 47% yield in a ratio of 1/2.3 (eq 6). 1H NMR spectroscopy of 3q'ꢀD showed
that 35% of the 4ꢀposition and 45% of the two oꢀpositions of the methoxyphenyl ring
were deuterated. For product 3qꢀD, 1H NMR spectroscopy showed that a total of 1.32
aryl protons were deuterated; deuteration should be occurring at the same position as
that of 3q'ꢀD, although the position could not be assigned. The above results provided
further support of a reversible 1,4ꢀpalladium migration (vide infra).12 The ethyl
3ꢀmethylꢀ3ꢀphenylbutanoate, a possible conjugate addition product of PhB(OH)2 to
ester 1b, was subjected to the standard reaction conditions (eq 7).13 No indanone 3b
was observed, which suggests the indanone was not produced from the conjugate
addition product.
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Based on the above observations and literature precedent, a plausible reaction
mechanism was proposed (Scheme 3). The transmetallation of the Pd catalyst and
phenylboronic acid generate PhꢀPdꢀLn species A, which undergoes conjugate addition
to α,βꢀunsaturated ester 1 to form intermediate B. A 1,4ꢀpalladium migration in B
produces the aryl palladium intermediate C.12 Intramolecular cyclization of
intermediate C provides indanone 3 as the final product. it is worth noting that the
reaction may proceed through a Pd(II) catalysis, but the presence of O2 should be
important. It seems that the role of O2 should oxidaze the Pd(0) species formed in
some side reactions such as the homocoupling of arylboronic acids in the presence of
Pd(II) species.14
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Scheme 3. Proposed Catalytic Cycle of the PdꢀCatalyzed Tandem Reaction of
α,βꢀUnsaturated Ester 1 and Arylboronic Acid 2a
During the studies of the impact of ligands on the reaction, some chiral ligands
were used. A 65% ee of 3n was obtained using chiral ligand L10, while 56% ee and
63% ee were observed using ligands (R,R)ꢀL7 and (R,R)ꢀL8, respectively (eq 8). Thus,
some other chiral ligands (L11—L13) were tested. However, lower ee percentages for
3n were observed in all cases. Methods for improving the enantioselectivity of this
reaction should be investigated further.
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CONCLUSION
We have developed a new Pdꢀcatalyzed reaction of β,βꢀdisubstituted
α,βꢀunsaturated esters with aryl boronic acids to synthesize 1ꢀindanone derivatives.
The use of a newly synthesized electronꢀdeficient ligand improved the efficiency of
the reaction significantly. A plausible mechanism involves a tandem conjugate
addition/1,4ꢀPd shift/intramolecular cyclization process. Investigations regarding why
the cyclization step mainly occurs at the aryl ring of the boronic acid and regarding a
detailed mechanism as well as optimization of the asymmetric variant of the reaction
are currently underway.
EXPERIMENTAL SECTION
General Methods. Commercially available reagents were used without further
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purification. Solvents were purified prior to use according to the standard methods.
Column chromatography was performed on silica gel (300–400 mesh) using a forced
flow of eluent. NMR spectra were recorded at room temperature on an NMR
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instrument operating at 400 MHz. Chemical shifts for H NMR are reported in parts
per million with the solvent resonance as the internal standard (7.26 ppm for CHCl3).
The data were reported as follows: chemical shift, multiplicity (s = singlet, d =
doublet, t = triplet, q = quartet, sep = septet, bs = broad singlet, m = multiplet),
coupling constants (Hz), and integration. 13C NMR spectra were recorded on an NMR
instrument operating at 100 MHz with complete proton decoupling. Chemical shifts
were reported in parts per million with the solvent resonance as the internal standard
(77.1 ppm for CDCl3). MS and HRMS were measured in EI or ESI mode, and the
mass analysis mode of the HRMS was TOF. Infrared spectra were recorded from thin
films of pure samples. Melting points were measured on an XTꢀ4 micromelting point
apparatus. Thin layer chromatography was performed on precoated glassꢀbacked
plates and visualized with UV light at 254 nm. Enantiomeric ratios were determined
by chiral HPLC analysis in comparison with authentic racemic materials.
General Experimental Procedure for the Synthesis of β,βꢀDisubstituted
Indanones. Pd(OOCCF3) (0.01 mmol, 3.4 mg), racꢀL8 (0.012 mmol, 5.5 mg), and
DMAc (1.0 mL) were added to a Schlenk tube that contained a stir bar. The resulting
solution was stirred for one hour at room temperature. α,βꢀUnsaturated ester 1 (0.2
mmol) and arylboronic acid 2 (0.4 mmol) were then added sequentially. The reaction
atmosphere was carefully exchanged with oxygen three times. Then, an oxygen
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balloon was installed in the reaction tube, and the mixture was stirred for 24 hours at
80 °C. The reaction mixture was cooled to room temperature and ethyl acetate (15.0
mL), and water (5.0 mL) were added. The organic phase was washed with water (5.0
mL x 3) and brine (5.0 mL). The combined water phase was reꢀextracted with ethyl
acetate (5.0 mL). The combined organic phase was dried over anhydrous Na2SO4.
After concentration under reduced pressure, the residue was purified by column
chromatography (hexane/EA) to give β,βꢀdisubstituted indanone 3.
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3ꢀmethylꢀ3ꢀphenylꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀone (3a):15 colorless oil, 86% yield
(38.2 mg); 1H NMR (400 MHz, CDCl3): δ 1.85 (s, 3H), 2.86 (d, J = 19.0 Hz, 1H),
2.98 (d, J = 19.5 Hz, 1H), 7.17–7.23 (m, 3H), 7.26–7.31 (m, 3H), 7.40–7.45 (m, 1H),
7.58–7.62 (m, 1H), 7.77–7.81 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 28.3, 46.0,
55.8, 123.4, 125.6, 126.2, 126.4, 127.8, 128.5, 135.2, 135.8, 147.3, 162.8, 205.8; MS
(EI): 207 (100), 222 (41), 178 (27), 208 (16), 115 (14).
3,3ꢀdimethylꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀone (3b):15 colorless oil, 95% yield (30.4
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mg); H NMR (400 MHz, CDCl3): δ 1.41 (s, 6H), 2.58 (s, 2H), 7.34–7.38 (m, 1H),
7.48–7.51 (m, 1H), 7.59–7.63 (m, 1H), 7.68–7.71 (m, 1H); 13C NMR (100 MHz,
CDCl3): δ 29.9, 38.5, 52.9, 123.2, 123.5, 127.3, 134.9, 135.2, 163.8, 205.8; MS (EI):
145 (100), 115 (44), 160 (42), 117 (40), 91 (20).
3,3,6ꢀtrimethylꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀone (3c):15 colorless oil, 85% yield
1
(29.6 mg); H NMR (400 MHz, CDCl3): δ 1.39 (s, 6H), 2.39 (s, 3H), 2.57 (s, 2H),
7.37–7.40 (m, 1H), 7.42–7.45 (m, 1H), 7.49–7.51 (m, 1H); 13C NMR (100 MHz,
CDCl3): δ 21.0, 30.0, 38.2, 53.2, 123.2 (2C), 135.4, 136.1, 137.3, 161.3, 206.0; MS
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(EI): 159 (100), 174 (39), 131 (35), 91 (26), 115 (26).
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6ꢀMethoxyꢀ3,3ꢀdimethylꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀone (3d):16 colorless oil, 83%
yield (31.5 mg); 1H NMR (400 MHz, CDCl3): δ 1.38 (s, 6H), 2.59 (s, 2H), 3.81 (s,
3H), 7.10 (d, J = 4.0 Hz, 1H), 7.20 (dd, J = 4.0 Hz, 8.0 Hz, 1H), 7.38 (d, J = 8 Hz,
1H); 13C NMR (100 MHz, CDCl3): δ 30.0, 37.9, 53.4, 55.5, 104.4, 124.1, 124.3, 136.4,
156.7, 159.3, 205.6; MS (EI): 175 (100), 190 (34), 91 (23), 115 (15), 176 (12).
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Methyl
1,1ꢀdimethylꢀ3ꢀoxoꢀ2,3ꢀdihydroꢀ1Hꢀindeneꢀ5ꢀcarboxylate
(3e):17
colorless oil, 70% yield (30.5 mg); 1H NMR (400 MHz, CDCl3): δ 1.43 (s, 6H), 2.63
(s, 2H), 3.92 (s, 3H), 7.55 (dd, J = 8.1 Hz, 1H), 8.29 (dd, J = 1.6, 8.1 Hz, 1H), 8.34 (d,
J = 1.6 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 29.8, 38.9, 52.3, 53.0, 123.7, 125.0,
129.9, 135.5, 135.8, 166.2, 168.0, 204.8; MS (EI): 203 (100), 115 (38), 218 (34), 116
(20), 91 (19).
6ꢀFluoroꢀ3,3ꢀdimethylꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀone (3f):17 colorless oil, 75%
yield (26.7 mg); 1H NMR (400 MHz, CDCl3): δ 1.41 (s, 6 H), 2.62 (s, 2 H), 7.30–7.35
(m, 2 H), 7.45–7.49 (m, 1 H); 19F NMR (376 MHz, CDCl3): δ ꢀ114.8; 13C NMR (100
MHz, CDCl3): δ 30.0, 38.2, 53.3, 108.9(d, J = 21.7 Hz), 122.5(d, J = 23.7 Hz),
125.1(d, J= 8.1 Hz), 137.1(d, J = 7.2 Hz), 159.3(d, J = 2.1), 162.3(d, J = 246.5 Hz),
204.5(d, J = 2.9 Hz); MS (EI): 163 (100), 135 (43), 178 (35), 133 (30), 115 (27).
6ꢀChloroꢀ3,3ꢀdimethylꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀone (3g):15 colorless oil, 77%
yield (29.9 mg); 1H NMR (400 MHz, CDCl3): δ 1.41 (s, 6H), 2.61 (s, 2H), 7.43 (d, J =
13
8.5 Hz, 1H), 7.55 (dd, J = 8.0, 2.5 Hz, 1H), 7.64 (d, J = 1.5 Hz, 1H); C NMR (100
MHz, CDCl3): δ 29.9, 38.4, 53.0, 123.1, 124.9, 133.8, 134.9, 136.8, 161.9, 204.4; MS
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(EI): 179 (100), 115 (58), 116 (39), 194 (37), 181 (32).
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6ꢀBromoꢀ3,3ꢀdimethylꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀone (3h):18 colorless oil, 70%
yield (33.5 mg); 1H NMR (400 MHz, CDCl3): δ 1.40 (s, 6H), 2.59 (s, 2H), 7.37 (d, J =
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8.0 Hz, 1H), 7.71 (dd, J = 4.0, 8.0 Hz, 1H), 7.81 (d, J = 4.0 Hz, 1H); C NMR (100
MHz, CDCl3): δ 29.8, 38.5, 52.9, 121.7, 125.3, 126.3, 137.2, 137.7, 162.3, 204.3; MS
(EI): 116 (100), 222 (95), 224 (88), 115 (64), 237 (33), 239 (31).
1,1ꢀDimethylꢀ3ꢀoxoꢀ2,3ꢀdihydroꢀ1Hꢀindeneꢀ5ꢀcarbaldehyde (3i): white solid,
o
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58% yield (21.8 mg), mp 97 – 98 C; H NMR (400 MHz, CDCl3): δ 1.45 (s, 6H),
2.66 (s, 2H), 7.64 (d, J = 8.0 Hz, 1H), 8.14–8.16 (m, 2H), 10.05 (s, 1H); 13C NMR
(100 MHz, CDCl3): δ 29.7, 39.1, 52.9, 124.5, 126.2, 134.5, 136.0, 136.0, 169.5, 191.1,
204.6; IR (KBr, film): 2961, 2932, 2850, 2748, 1696, 1607, 1163, 1121, 1100, 837,
722; MS (EI): 173 (100), 115 (50), 188 (49), 117 (37), 91 (22); HRMS (ESI) Calcd
for C12H13O2 [M+H]+ = 189.0910, found 189.0911.
6ꢀHydroxyꢀ3,3ꢀdimethylꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀone (3j):17 colorless oil, 82%
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yield (28.9 mg); H NMR (400 MHz, CDCl3): δ 1.35 (s, 6H), 2.60 (s, 2H), 7.19ꢀ7.22
(m, 2H), 7.31 (d, J = 8.2 Hz, 1H), 7.97 (brs, 1H); 13C NMR (100 MHz, CDCl3): δ
30.0, 38.2, 53.5, 108.4, 124.4, 124.6, 136.2, 156.3, 157.7, 207.9; MS (EI): 161 (100),
176 (38), 105 (28), 133 (21), 77 (15).
3,3,4ꢀTrimethylꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀone (3k):15 colorless oil, 82% yield
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(25.8 mg); H NMR (400 MHz, CDCl3): δ 1.51 (s, 6H), 2.52 (s, 3H), 2.61 (s, 2H),
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7.25 (t, J = 7.2 Hz, 1H), 7.35 (d, J = 7.5 Hz, 1H), 7.56 (d, J = 7.5 Hz, 1H); C NMR
(100 MHz, CDCl3): δ 19.6, 28.0, 39.9, 54.7, 121.4, 127.7, 135.4, 136.3, 137.7, 159.9,
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206.3; MS (EI): 159 (100), 174 (38), 131 (36), 91 (26), 115 (22).
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3,3ꢀDimethylꢀ2,3ꢀdihydroꢀ1Hꢀcyclopenta[b]naphthalenꢀ1ꢀone (3l): colorless
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oil, 78% yield (32.8 mg); H NMR (400 MHz, CDCl3): δ 1.52 (s, 6H), 2.70 (s, 2H),
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7.47–7.60 (m, 2H), 7.88–7.99 (m, 3H), 8.28 (s, 1H); 13C NMR (100 MHz, CDCl3): δ
30.7, 38.4, 53.7, 121.9, 124.2, 126.1, 128.0, 128.5, 130.4, 132.4, 133.5, 137.4, 157.2,
206.3; IR (KBr, film): 3055, 2957, 1711, 1628, 1602, 1240, 1162, 1128, 1089, 857,
781; MS (EI): 195 (100), 210 (50), 167 (35), 165 (30), 152 (25); HRMS (ESI) Calcd
for C15H15O [M+H]+: 211.1117, found: 211.1118.
3ꢀEthylꢀ3ꢀphenylꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀone (3m): colorless oil, 42% yield
(19.9 mg); 1H NMR (400 MHz, CDCl3): δ 0.75 (t, J = 8.0 Hz, 3H), 2.17–2.39 (m, 2H),
2.92 (d, J = 8.0 Hz, 2H), 7.18–7.34 (m, 6H), 7.42 (t, J = 8.0 Hz, 1H), 7.61 (t, J = 8.0
Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 9.3, 32.5, 50.3,
52.4, 123.3, 126.2, 126.4, 126.5, 127.8, 128.5, 134.9, 136.9, 146.8, 160.4, 205.9; IR
(KBr, film): 2967, 1711, 1600, 1460, 1323, 758, 699; MS (EI): 207 (100), 178 (26),
208 (17), 179 (8); HRMS (ESI) Calcd for C17H17O [M+H]+: 237.1274, found:
237.1277.
3ꢀIsopropylꢀ3ꢀmethylꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀone (3n):3 colorless oil, 89%
yield (33.5 mg); 1H NMR (400 MHz, CDCl3): δ 0.56 (d, J = 4.0 Hz, 3H), 0.92 (d, J =
4.0 Hz, 3H), 1.95ꢀ2.03 (m, 1H), 2.25 (d, J = 20.0 Hz, 1H), 2.69 (d, J = 20.0 Hz, 1H),
7.32 (t, J = 8.0 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.55 (t, J = 8.0 Hz, 1H), 7.67 (d, J =
8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 18.1, 18.3, 27.3, 36.6, 45.5, 46.4, 123.2,
124.1, 127.3, 134.7, 136.2, 162.7, 206.4; MS (EI): 115 (100), 146 (91), 144 (68), 188
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3ꢀCyclohexylꢀ3ꢀmethylꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀone (3o):19 colorless oil, 75%
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yield (34.2 mg); H NMR (400 MHz, CDCl3): δ 0.71–0.88 (m, 2H), 0.97–1.28 (m,
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4H), 1.40 (s, 3 H), 1.59–1.63 (m, 3H), 1.75–1.80 (m, 1H), 1.89–1.93 (m, 1H), 2.23 (d,
J = 20.0 Hz, 1H), 2.71 (d, J = 20.0 Hz, 1H), 7.32 (t, J = 8.0 Hz, 1H), 7.43 (d, J = 8.0
Hz, 1H), 7.56 (t, J = 8.0 Hz, 1H), 7.66 (d, J = 8.0 Hz, 1H); 13C NMR (100 MHz,
CDCl3): δ 26.3, 26.5, 26.7, 26.8, 27.8, 28.3, 45.4, 47.0, 47.6, 123.1, 124.2, 127.3,
134.7, 136.3, 162.7, 206.5; MS (EI): 146 (100), 131 (30), 145 (22), 115 (22), 228 (8).
Spiro[cyclohexaneꢀ1,1'ꢀinden]ꢀ3'(2'H)ꢀone (3p):20 colorless oil, 81% yield (32.4
mg); 1H NMR (400 MHz, CDCl3): δ 1.26ꢀ1.53 (m, 5H), 1.70ꢀ1.78 (m, 5H), 2.57 (s,
2H), 7.35 (t, J = 7.4 Hz, 1H), 7.49 (d, J = 7.7 Hz, 1H), 7.58 (t, J = 7.1 Hz, 1H), 7.69
(d, J = 7.7 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 23.8, 25.5, 38.4, 43.1, 48.4, 123.4,
124.0, 127.5, 134.8, 135.5, 164.2, 206.2; MS (EI): 144 (100), 200 (38), 115 (34), 145
(33), 129 (32).
6ꢀMethoxyꢀ3ꢀmethylꢀ3ꢀphenylꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀone (3q): colorless oil,
56% yield mixed with 3q’ (28.2 mg); The pure sample of 3q was obtained by
preparative HPLC separation. 1H NMR (400 MHz, CDCl3): δ 1.80 (s, 3H), 2.90 (dd, J
= 20.0, 44.0 Hz, 2H), 3.85 (s, 3H), 7.16–7.29 (m, 8H); 13C NMR (100 MHz, CDCl3):
δ 28.4, 45.4, 55.6, 56.3, 104.3, 124.6, 126.1, 126.3, 126.4, 128.4, 137.0, 147.5, 155.7,
159.6, 205.7; IR (KBr, film): 2962, 2835, 1706, 1486, 1328, 1277, 1244, 1088, 1066,
1030, 740, 699; MS (EI): 237 (100), 252 (39), 237 (18), 165 (16), 115 (9); HRMS
(ESI) Calcd for C17H17O2 [M+H]+: 253.1223, found: 253.1225.
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3ꢀ(4ꢀMethoxyphenyl)ꢀ3ꢀmethylꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀone (3q’):21 colorless
oil, 56% yield mixed with 3q (28.2 mg); The pure sample of 3q’ was obtained by
preparative HPLC separation. 1H NMR (400 MHz, CDCl3): δ 1.79 (s, 3H), 2.86 (dd, J
= 20.0, 44.0 Hz, 2H), 3.76 (s, 3H), 6.79 (d, J = 8.0 Hz, 2H), 7.07 (d, J = 8 Hz, 2H),
7.25–7.28 (m, 1 H), 7.39 (t, J = 8.0 Hz. 1H), 7.57 (t, J = 8.0 Hz, 1H), 7.77 (d, J = 8.0
Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 28.5, 45.4, 55.2, 55.8, 113.7, 123.3, 125.5,
127.3, 127.7, 135.2, 135.6, 139.4, 157.9, 163.1, 206.0; MS (EI): 237 (100), 252 (39),
237 (18), 165 (15), 115 (9).
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Procedure for the Reaction of Ester 1b and Boronic Acid 2aꢀD (eq 3). The
reaction was performed according to general experimental procedure for the synthesis
of β,βꢀdisubstituted indanones using ester 1b (25.6 mg, 0.2 mmol) and boronic acid
2aꢀD (49.6 mg, 0.4 mmol). 3,3ꢀDimethylꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀoneꢀ2,4ꢀd2 (3bꢀD)
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was obtained as a colorless oil in 95% yield (30.4 mg). H NMR (400 MHz, CDCl3):
δ 1.40 (s, 6H), 2.57 (m, 1.6H), 7.34–7.38 (m, 1H), 7.48–7.51 (m, 0.6H), 7.59–7.63 (m,
1H), 7.68–7.71 (m, 1H); 13C NMR (100 MHz, CDCl3): δ major component: 29.9, 38.5,
52.9, 123.3, 123.5, 127.4, 134.9, 135.3, 163.8, 206.0; observable signals of the minor
component: 38.4, 52.6 (t, J = 19.0 Hz), 134.8, 163.8 (t, J = 4.0 Hz), 206.0; MS (EI):
145 (36), 146 (42), 147 (20), 115 (21), 116 (17), 117 (18), 160 (C11H12O [M]+, 16),
161 (C11H11DO [M]+, 20), 162 (C11H10D2O [M]+, 7); HRMS (EI) Calcd for
C11H10D2O [M]+: 162.1014, found: 162.1011.
Procedure for the Reaction of Ester 1b and Boronic Acid d5ꢀ2a (eq 4). The
reaction was performed according to general experimental procedure for the synthesis
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of β,βꢀdisubstituted indanones using ester 1b (25.6 mg, 0.2 mmol) and boronic acid
d5ꢀ2a (50.8 mg, 0.4 mmol). 3,3ꢀDimethylꢀ2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀoneꢀ2,4,5,6,7ꢀd5
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(d4ꢀ3b) was obtained as a colorless oil in 82% yield (26.7 mg). H NMR (400 MHz,
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CDCl3): δ 1.40 (s, 6H), 2.57, (s, 1.85H), 7.48(s, 0.53H); 13C NMR (100 MHz, CDCl3):
δ 30.0, 38.5, 52.9, 122.9 (t, J = 24.9 Hz), 123.4, 126.9 (t, J = 24.9 Hz), 134.4 (t, J =
24.2 Hz), 135.2, 163.7, 205.9; MS (EI): 149 (100), 148 (77), 118 (26), 119 (15), 120
(24), 121 (19), 163 (C11H9D3O [M]+, 33), 164 (C11H8D4O [M]+, 27), 165 (C11H7D5O
[M]+, 6); HRMS (EI) Calcd for C11H7D5O [M]+: 165.1202, found: 165.1201.
Procedure for the Reaction of Ester 1b, Boronic Acid 2a, and Boronic Acid
d5ꢀ2a (eq 5). The reaction was performed according to general experimental
procedure for the synthesis of β,βꢀdisubstituted indanones using ester 1b (25.6 mg,
0.2 mmol), boronic acid 2a (24.4 mg, 0.2 mmol), and boronic acid d5ꢀ2a (25.4 mg, 0.2
mmol). The mixture of 3b and d4ꢀ3b (1/1 ratio) was obtained as a colorless oil in 82%
yield (26.5 mg). 1H NMR (400 MHz, CDCl3): δ 1.40 (s, 6H), 2.57 (s, 2H), 7.32–7.36
(m, 0.5H), 7.47–7.49 (m, 0.76H), 7.57–7.61 (m, 0.5H), 7.66–7.68 (m, 0.5H).
Procedure for the Reaction of Ester 1i and Boronic Acid 2aꢀD (eq 6). The
reaction was performed according to general experimental procedure for the synthesis
of β,βꢀdisubstituted indanones using ester 1i (44.0 mg, 0.2 mmol) and boronic acid
2aꢀD (49.6 mg, 0.4 mmol). The mixture of 3qꢀD and 3q’ꢀD (1/2.3 ratio) was obtained
as a colorless oil in 47% yield (23.7 mg).
1
3qꢀD: The pure sample of 3qꢀD was obtained by preparative HPLC separation. H
NMR (400 MHz, CD3COCD3): δ 1.83 (s, 3H), 2.88 (s, 2H), 3.89 (s, 3H), 7.14–7.31
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(m, 6.68); 13C NMR (100 MHz, CDCl3): δ 28.3, 45.4, 55.6, 56.3, 104.3, 124.6, 126.1,
126.3, 126.4, 128.4, 137.0, 147.4 (t, J =7.3 Hz), 155.7, 159.6, 205.7; observable
signals of the minor component: 128.3, 155.8, 205.8; MS (EI): 237 (19), 238 (30),
239 (30), 240 (12), 252 (C17H16O2 [M]+, 6), 253 (C17H15DO2 [M]+, 10), 254
(C17H14D2O2 [M]+, 7), 255 (C17H13D3O2 [M]+, 4); HRMS (EI) Calcd for C17H16O2
[M]+: 252.1150, found: 252.1160.
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3q’ꢀD: The pure sample of 3q’ꢀD was obtained by preparative HPLC separation. H
NMR (400 MHz, CD3COCD3): δ 1.83 (s, 3H), 2.86 (s, 2H), 3.75 (s, 3H), 6.85 (d, J =
3.6 Hz, 2H), 7.13 (d, J = 8.5 Hz, 1.1H), 7.37 (d, J = 7.6 Hz. 0.65H), 7.47 (t, J = 7.6
Hz, 1H), 7.65ꢀ7.69 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 28.5, 45.4, 55.2, 55.8,
113.7, 123.3, 125.5, 127.3, 127.7, 135.2, 135.7, 139.4 (t, J = 7.7 Hz), 157.9, 163.1,
206.0; observable signals of the minor component: 113.8, 127.2, 135.1, 163.0; MS
(EI): 237 (45), 238 (99), 239 (100), 240 (55), 252 (C17H16O2 [M]+, 18), 253
(C17H15DO2 [M]+, 36), 254 (C17H14D2O2 [M]+, 37), 255 (C17H13D3O2 [M]+, 21);
HRMS (EI) Calcd for C17H13D3O2 [M]+: 255.1339, found: 255.1332.
The Synthesis of Ligands (R,R)ꢀL7 and (R,R)ꢀL8. The ligands (R,R)ꢀL7 and
(R,R)ꢀL8 were prepared according to methods in the literature with minor
modifications.22,23 2ꢀCyanopyrimidine (1.32 g, 12.5 mmol) was added to a 50 mL
flameꢀdried Schlenk flask that contained a stir bar. Then, CH3OH (25 mL) and sodium
methoxide (67.5 mg, 0.1 equiv) were added at 0 °C. The resulting mixture was stirred
for 10 min at 0 °C, and then the reaction mixture was stirred at room temperature for
24 hours until the solution turned wine red. The volatiles were removed in vacuo to
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give pyrimidineꢀ2ꢀcarboximidate as a red liquid, which was used in the next step
without purification.
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In a flameꢀdried sealed tube, a mixture of the above pyrimidineꢀ2ꢀcarboximidate (571
mg, 4.0 mmol), (1R,2R)ꢀ1,2ꢀdiphenylethyleneꢀdiamine (471 mg, 2.22 mmol) and
CH2Cl2 (10 mL) was stirred at 50 °C for 48 hours. The resulting red solution was
added to 30 mL CH2Cl2 and then washed with water (10.0 mL x 3). The aqueous
layers were extracted with CH2Cl2 (10.0 mL). The combined organic layers were
acidified with 1 M HCl (aq.) until the solution reached a pH of 1.0. Water was added
to dissolve the solid precipitate. After separation, the aqueous phase was basified with
1 M NaOH (aq.) until the pH was 14. CH2Cl2 was added to dissolve the solid
precipitate. The oil layer was separated and dried with anhydrous Na2SO4. After
concentration under reduced pressure, the residue was purified by column
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chromatography
(CH2Cl2/MeOH
=
20:1,
Rf
=
0.2)
to
obtain
2ꢀ((4R,5R)ꢀ4,5ꢀdiphenylꢀ4,5ꢀdihydroꢀ1Hꢀimidazolꢀ2ꢀyl)
pyrimidine
(L7):
25
white/yellow solid, 25% yield (157 mg), mp 233ꢀ234 °C (decomposed). [α]D
=
1
82.74 (c 1.0, CHCl3); H NMR (400 MHz, CDCl3): δ 5.10 (s, 2H), 7.32–7.37 (m,
10H), 7.43 (t, J = 4.0 Hz, 1H), 8.88 (d, J = 4.0 Hz, 2H); 13C NMR (100 MHz, CDCl3):
δ 121.9, 126.8, 127.5, 128.6, 142.9, 157.1, 157.4, 161.1; IR (KBr, film): 3056, 3020,
2906, 1559, 1492, 1451, 1411, 696; MS (EI): 195 (100), 300 (43), 89 (26), 90 (19),
196 (15); HRMS (ESI) Calcd for C19H17N4 [M+H]+: 301.1448, found: 301.1451.
A solution of pꢀtoluenesulfonyl chloride (75.7 mg, 0.4 mmol) was added dropwise to
a solution of (R,R)ꢀL7 (100 mg, 0.33 mmol) and 4ꢀ(dimethylamino) pyridine (73.1 mg,
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0.6 mmol) in dichloromethane (3.0 mL) at 0 °C. The reaction mixture was allowed to
warm to room temperature and was stirred for 12 h. Evaporation of the volatile
components gave a yellow solid that was purified by column chromatography on
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silica
gel
(CH2Cl2/MeOH
=
20:1,
Rf
=
0.7)
to
obtain
2ꢀ((4R,5R)ꢀ4,5ꢀdiphenylꢀ1ꢀtosylꢀ4,5ꢀdihydroꢀ1Hꢀimidazolꢀ2ꢀyl)pyrimidine
(L8):
white solid, 70% yield (101 mg); mp 249–252 °C (decomposed). [α]D25 = 4.20 (c 1.0,
CHCl3); 1H NMR (400 MHz, CDCl3): δ 2.38 (s, 3H), 5.13ꢀ5.18 (m, 2H), 7.05ꢀ7.14 (m,
4H), 7.25–7.35 (m, 8H), 7.45 (t, J = 4.0 Hz, 1H), 7.51 (d, J = 8.0 Hz, 2H), 8.92 (d, J =
4.0 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 21.6, 71.5, 79.6, 121.6, 126.4, 126.6,
127.8, 128.0, 128.2, 128.8, 129.0, 129.3, 135.0, 135.4, 140.6, 140.6, 144.2, 156.4,
157.1, 159.4; IR (KBr, film): 2925, 2853, 1562, 1158, 695, 665; MS (EI): 195 (100),
300 (52), 454 (35), 89 (33), 91 (32); HRMS (ESI) Calcd for C26H23N4O2S [M+H]+:
455.1536, found: 455.1537.
The Synthesis of Deuterated Phenylboronic Acid (2aꢀD). D2O (20 mL) was
heated to 75 °C in a 50 mL roundꢀbottomed flask. Triphenyl boroxine was added until
the solution was saturated. The resulting solution was stirred at this temperature for 3
hours. The solution was filtered while it was still hot. The filtrate was cooled to room
temperature, and deuterated phenylboronic acid was obtained as a white solid. After
filtration, the white solid was dried in an infrared drying oven under vacuum for 3
hours (note: drying for a long period will lead to decomposition back to triphenyl
boroxine). Deuterated phenylboronic acid (2aꢀD) (>90% D) containing 30 mol%
triphenyl boroxine was obtained. 1H NMR (400 MHz, d6ꢀdmso): δ 7.30–7.40 (m, 3H),
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7.77–7.79 (m, 2H), 8.07 (s, 0.06H). (δ 7.87–7.89 are signals of triphenyl boroxine).
PdꢀCatalyzed Tandem Reaction of (E)ꢀEthyl 3,4ꢀdimethylpentꢀ2ꢀenoate (1d)
and Phenylboronic Acid (2a) Using Chiral Ligand L10. Pd(OOCCF3) (0.01 mmol,
3.4 mg), L10 (0.012 mmol, 3.3 mg), and DMAc (1.0 mL) were added to a Schlenk
tube that contained a stir bar. The resulting solution was stirred for one hour at room
temperature. Then, (E)ꢀethyl 3,4ꢀdimethylpentꢀ2ꢀenoate (1d) (31.2 mg, 0.2 mmol) and
phenylboronic acid (2a) (48.8 mg, 0.4 mmol) were added sequentially. The reaction
atmosphere was carefully exchanged with oxygen three times. Then, an oxygen
balloon was installed in the reaction tube, and the mixture was stirred for 24 hours at
80 °C. The reaction mixture was cooled to room temperature, and ethyl acetate (15.0
mL) and water (5.0 mL) were added. The organic phase was washed with water (5.0
mL x 3) and brine (5.0 mL). The combined water phase was reꢀextracted with ethyl
acetate (5.0 mL). The combined organic phase was dried with anhydrous Na2SO4.
After concentration under reduced pressure, the residue was purified by column
chromatography (hexane/EA = 20/1) to give 2,3ꢀdihydroꢀ1Hꢀindenꢀ1ꢀone 3n (30.8 mg,
82% yield, 65% ee). Chiral HPLC (Chiralcel IC, 0.46 cm × 250 mm,
nꢀhexane/2ꢀpropanol 99.4/0.6, flow rate 0.5 mL/min, UV 214 nm): tR = 36.7 min
(major), 38.4 min (minor).
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ACKNOWLEDGMENTS
This paper is dedicated to Professor Yang Jie Wu on the occasion of his 90th
birthday. Financial support by National Natural Science Foundation of China (NSFC)
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(21472214, 21372242, 21532010, 21421091), the Strategic Priority Research Program
of the Chinese Academy of Sciences (XDB20030100), the NSFC and the Research
Grants Council of Hong Kong Joint Research Scheme (21361162001), the
Technology Commission of Shanghai Municipality, and the Croucher Foundation of
Hong Kong.
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Supporting Information
The spectra of compounds 3aꢀ3q, (R,R)ꢀL7 and (R,R)ꢀL8. This material is
available free of charge via the Internet at http://pubs.acs.org.
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