Lewis base assisted Bronsted base catalysis: Direct asymmetric allylic alkylation of indenes

Article abstract of DOI:10.1002/ejoc.201101255

A direct, asymmetric allylic alkylation of indenes withMorita-Baylis- Hillman (MBH) carbonates has been developed based on a Lewis base assisted Bronsted base catalysis strategy. This process is promoted by a modified cinchona alkaloid hydroquinidine (ant

Full text of DOI:10.1002/ejoc.201101255

FULL PAPER
DOI: 10.1002/ejoc.201101255
Lewis Base Assisted Brønsted Base Catalysis: Direct Asymmetric Allylic
Alkylation of Indenes
Hai-Lei Cui,[a] Xun-Hao Sun,[a] Lin Jiang,[a] Lin Dong,[a] and Ying-Chun Chen*[a]
Keywords: Asymmetric catalysis / Alkaloids / Enantioselectivity / Allylation / Alkylation / Lewis bases
A
direct, asymmetric allylic alkylation of indenes with
[(DHQD)2AQN] and gives rise to multifunctional chiral in-
dene derivatives with moderate to excellent enantio-
selectivities (53–95% ee), albeit in low to modest yields (27–
71%).
Morita–Baylis–Hillman (MBH) carbonates has been devel-
oped based on a Lewis base assisted Brønsted base catalysis
strategy. This process is promoted by a modified cinchona
alkaloid hydroquinidine (anthraquinone-1,4-diyl) diether
Introduction
As a privileged scaffold, indene systems are frequently
found in an array of functional compounds, including bio-
logically active molecules,[1] ligand precursors for transition
metal complexes[2] (Scheme 1), and material science.[3] Al-
though elegant constructions of diverse indene derivatives
have been presented,[4] the asymmetric synthesis of chiral
indenes is still rare. The limited number of available exam-
ples have focused on the use of chiral sources[5] or chiral
transition metal catalysis in an indirect pathway.[6] On the
other hand, it is well established that simple indene bears a
relatively acidic C–H group [pKa = 20.1 in dimethyl sulfox-
ide (DMSO)],[7] and undergoes facile C–C bond-forming re-
actions with indenides generated in situ.[8] However, the di-
rect catalytic asymmetric modification of indenes is still an
unexplored field despite the convenience of such a strategy,
probably due to the requirement for stoichiometric amounts
of strong base and the formation of unstabilized carban-
ions.[9,10]
Scheme 1. Some chiral ligands and drug candidates containing the
indene structure.
Recently, we reported that a Lewis base assisted Brønsted
base catalysis (LBABBC) strategy was quite successful in
the direct asymmetric vinylogous alkylation of allyl phenyl
sulfone (pKa = 22.5 in DMSO).[11,12] We envisioned that the
same catalytic pattern might be also applicable to the direct
asymmetric C–C bond-forming reaction of indene com-
pounds with comparably acidic C–H groups, as outlined
in Scheme 2; thus, multifunctional chiral indene derivatives
could be efficiently constructed.
Scheme 2. Lewis base-assisted Brønsted base catalysis strategy for
direct asymmetric allylic alkylation of indene.
[a] Key Laboratory of Drug-Targeting and Drug Delivery System
of the Education Ministry, Department of Medicinal
Chemistry, West China School of Pharmacy, Sichuan
University,
Results and Discussion
Chengdu 610041, China
Fax: +86-28-85502609
E-mail: ycchenhuaxi@yahoo.com.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101255.
Based on the above considerations, simple indene 1a was
initially investigated with Morita–Baylis–Hillman (MBH)
carbonate 2a under the catalysis of 1,4-diazabicyclo[2.2.2]-
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 7366–7371

Direct Asymmetric Allylic Alkylation of Indenes
octane (DABCO) at ambient temperature. Unfortunately, with higher concentrations (Table 1, Entry 10 vs. 11). The
although both starting materials were consumed, a mixture results could not be improved by using S-BINOL as a co-
of complex products was obtained (Table 1, Entry 1). Nev- catalyst (Table 1, Entry 12). Further studies on substrate ra-
ertheless, it was pleasing to observe that a cleaner reaction tios were also unproductive (Table 1, Entries 13 and 14). Fi-
occured when 2-bromoindene[13] (1b) was applied. The de- nally, it was found that neither yield nor enantioselectivity
sired allylic alkylation product 3a was isolated in moderate were affected when (DHQD)2AQN was applied at a 5 mol-
yield, although a few unidentified minor products were also % loading, although a longer reaction time was required
detectable (Table 1, Entry 2). Subsequently, chiral tertiary (Table 1, Entry 15). In comparison, (DHQ)2AQN gave the
amines were employed to induce chirality in the product. A product with opposite configuration but with only a moder-
modified cinchona alkaloid hydroquinidine (anthraquin- ate ee value (Table 1, Entry 16).
one-1,4-diyl) diether [(DHQD)2AQN] exhibited lower cata-
With the optimal reaction conditions in hand, we ex-
lytic activity,[14] but good enantioselectivity, and a higher plored the substrate scope and limitations of the catalytic
yield was afforded (Table 1, Entry 3). Solvent screenings allylic alkylation of indenes. For 2-bromoindene (1b), a
were not beneficial, and poorer data were generally attained spectrum of MBH carbonates bearing a diverse range of
with alternative solvents (Table 1, Entries 4–6). In addition, aryl substituents could be well tolerated, and high enantio-
other modified cinchona alkaloids, such as hydroquinidine selectivities were generally obtained, although only low to
1,4-phthalazinediyl diether and hydroquinidine 2,5-di- moderate yields could be isolated due to the occurrence of
phenyl-4,6-pyrimidinediyl diether [(DHQD)2PHAL and side reactions (Table 2, Entries 1–7).[15] The indene product
(DHQD)2PYR], also delivered inferior results (Table 1, En- 3h was attained with a dramatically diminished ee value
tries 7 and 8). More reaction parameters were then exam- when 2-furyl-substituted MBH carbonate was applied
ined with (DHQD)2AQN in 1,2-dichloroethane (DCE) to (Table 2, Entry 8). MBH carbonates derived from methyl
improve the enantioselectivity and yield. Lowering of the vinyl ketone (MVK) showed better reactivity under the
reaction temperature resulted in a dramatically decreased same conditions, and similar enantiocontrol was attained
yield (Table 1, Entry 9). Substrate concentration was ex- (Table 2, Entries 9 and 10). An MBH carbonate derived
plored, and it was found that better yields could be attained from alkanecarbaldehyde and acrylonitrile could be uti-
lized, but only modest enantioselectivity with low yield was
delivered even after prolonged reaction time (Table 2, En-
try 11). On the other hand, a few substituted indene deriva-
tives were investigated, and it was found that indene 1c,
Table 1. Asymmetric allylic alkylation of indenes 1 with MBH
carbonate 2a.[a]
Table 2. Asymmetric allylic alkylation of indenes 1 with MBH
carbonates 2.[a]
Entry
Catalyst[b]
Solvent
t
[h]
Yield[c]
[%]
ee[d]
[%]
1[e,f]
2[e]
3
4
5
6
7
8
9
10
11
12
13
14
15
16
DABCO
DABCO
DCE
DCE
DCE
toluene
PhCF3
CCl4
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
24
6
–
40
50
23
43
trace
38
–
–
90
75
89
–
65
72
91
89
90
90
81
88
90
–60
(DHQD)2AQN
(DHQD)2AQN
(DHQD)2AQN
(DHQD)2AQN
(DHQD)2PHAL
(DHQD)2PYR
(DHQD)2AQN
(DHQD)2AQN
(DHQD)2AQN
(DHQD)2AQN
(DHQD)2AQN
(DHQD)2AQN
(DHQD)2AQN
(DHQ)2AQN
15
12
12
13
15
15
62
62
24
44
12
14
35
48
44
36[g]
44[h]
56[i]
56[i,j]
62[i,k]
50[i,l]
58[i,m]
55[i,m]
[a] Reagents and conditions: 1b (0.1 mmol), 2a (0.2 mmol), catalyst
(0.02 mmol), solvent (0.5 mL), 50 °C. [b] DABCO: 1,4-diazabicy-
clo[2.2.2]octane; (DHQD)2AQN: hydroquinidine (anthraquinone-
1,4-diyl) diether; (DHQD)2PHAL: hydroquinidine 1,4-phthalazine-
diyl diether; (DHQD)2PYR: hydroquinidine 2,5-diphenyl-4,6-pyr-
imidinediyl diether; (DHQ)2AQN: hydroquinine anthraquinone-
1,4-diyl diether. [c] Isolated yield. [d] Determined by chiral HPLC
analysis. [e] At room temp. [f] 1a was used. [g] At 35 °C. [h] 0.1 m.
[i] 0.4 m. [j] S-BINOL (10 mol-%) was added. [k] 1a (2 equiv.) was
used. [l] 2a (3 equiv.) was used. [m] Catalyst (5 mol-%) was applied.
[a] Reagents and conditions: 1 (0.2 mmol), 2 (0.4 mmol), (DHQD)2-
AQN (5 mol-%), DCE (0.5 mL), 50 °C. [b] Isolated yield. [c] Deter-
mined by chiral HPLC analysis. [d] The desired product was not
isolated. Similar results were observed when indenes 1e–i were
applied.
Eur. J. Org. Chem. 2011, 7366–7371
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Y.-C. Chen et al.
FULL PAPER
containing a methoxycarbonyl group at the C2 position, re- cascade enables the formation of a quaternary ammonium
acted smoothly to provide the expected alkylation product cation and the generation of a strong Brønsted base that
with good data (Table 2, Entries 12 and 13). Unfortunately, facilitates the deprotonation of indene. The Si face of this
either no reaction took place or complex mixtures of prod- complex is blocked in the generated chiral environment,
ucts were observed when other indenes 1d–i were applied thus favoring attack from the Re face. A subsequent
under the current catalytic conditions (Table 2, Entry 14). Michael addition, elimination, and isomerization cascade
We propose that an electron-withdrawing group at the C2 would deliver the observed chiral product.
position is necessary for the generation and stabilization of
the corresponding indenides.
To determine the stereochemistry of the allylic alkylation
products, a diastereoselective dipolar [3+2] cycloaddition
Conclusions
was carried out between 3a and nitrile N-oxide generated
in situ. Crystals of the major diastereomer of cycloadduct
4 that were suitable for X-ray crystallographic analysis
We have demonstrated that a Lewis base assisted
Brønsted base catalysis strategy could be applied for the
direct asymmetric C–C bond-forming reaction of indene
compounds, as exemplified with the first allylic alkylation
by using MBH carbonates. A variety of multifunctional chi-
ral indene derivatives were obtained in moderate to excel-
could be obtained from a solution of petroleum ether and
ethyl acetate,[16] which facilitated the determination of the
absolute configuration of 3a (Scheme 3).[17]
lent enantioselectivities (up to 95% ee), albeit with low to
modest yields due to some side reactions. An expansion of
the synthetic applications of the chiral indene products is
underway in our laboratory.
Experimental Section
General: Cinchona alkaloid catalysts (DHQD)2PHAL, (DHQD)2-
PYR, (DHQD)2AQN, and (DHQ)2AQN were purchased from Al-
drich Chemical Company. MBH carbonates[18] and substituted in-
denes were prepared according to literature procedures.[19] Dicholo-
roethane was distilled from CaH2. All other chemicals were used
without purification as commercially available.
General Procedure for Asymmetric Allylic Alkylation Reaction: To a
solution of indene 1b or 1c (0.2 mmol) and (DHQD)2AQN (8.6 mg,
5 mol-%) in dry DCE (0.5 mL), was added MBH carbonate 2
(0.4 mmol). The reaction mixture was stirred at 50 °C and moni-
tored by TLC analysis. After completion, purification by silica gel
flash chromatography (EtOAc/petroleum ether) gave the chiral in-
dene product 3.
Methyl (R)-2-[(2-Bromo-1H-inden-3-yl)(phenyl)methyl]acrylate (3a):
58% yield. [α]2D0 = –25.5 (c = 0.70 in CH2Cl2); 90% ee, determined
Scheme 3. The [3+2] dipolar cycloaddition of indene derivative 3a.
by HPLC analysis [Daicel Chiralcel OD, n-hexane/iPrOH = 99:1,
1.0 mL/min, λ = 254 nm]: tR = 14.19 (major), 16.53 (minor) min.
1H NMR (400 MHz, CDCl3): δ = 7.35–7.34 (m, 1 H), 7.31–7.22
(m, 5 H), 7.16–7.09 (m, 3 H), 6.48 (s, 1 H), 5.61 (s, 1 H), 5.52 (s, 1
H), 3.72 (s, 3 H), 3.67 (s, 2 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 167.1, 143.2, 142.3, 140.9, 140.4, 139.1, 128.6, 128.4, 128.0,
126.8, 126.3, 124.6, 123.9, 123.1, 120.5, 52.1, 46.2, 45.0 ppm.
HRMS (ESI): calcd. for C20H17BrO2Na 391.0310; found 391.0324.
As shown in Scheme 4, a plausible transition state is pro-
posed that can rationalize the observed stereocontrol.[11]
The Lewis base promoted Michael addition/elimination
Methyl
(S)-2-[(2-Bromo-1H-inden-3-yl)(2-bromophenyl)methyl]-
acrylate (3b): 46% yield. [α]2D0 = +70.5 (c = 0.80 in CHCl3); 91%
ee, determined by HPLC analysis [Daicel Chiralcel OD, n-hexane/
iPrOH = 80:20, 1.0 mL/min, λ = 220 nm]: tR = 10.11 (major), 6.11
(minor) min. 1H NMR (400 MHz, CDCl3): δ = 7.60 (d, J = 7.6 Hz,
1 H), 7.38–7.34 (m, 2 H), 7.24–7.12 (m, 2 H), 7.16–7.09 (m, 3 H),
6.51 (s, 1 H), 5.79 (s, 1 H), 5.41 (s, 1 H), 3.73 (s, 3 H), 3.68 (s, 2
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 166.7, 143.7, 142.1,
139.2, 139.1, 138.4, 133.3, 130.3, 128.7, 128.3, 127.3, 126.5, 125.3,
124.8, 124.6, 123.1, 119.8, 52.2, 46.4, 45.4 ppm. HRMS (ESI):
calcd. for C20H16Br2O2Na 468.9415; found 468.9427.
Scheme 4. Proposed transition state for the formation of 3a.
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 7366–7371

Direct Asymmetric Allylic Alkylation of Indenes
Methyl (R)-2-[(2-Bromo-1H-inden-3-yl)(4-chlorophenyl)methyl]ac-
rylate (3c): 43% yield. [α]2D0 = –53.9 (c = 1.30 in CHCl3); 95% ee,
determined by HPLC analysis [Daicel Chiralcel OD, n-hexane/iP-
min. 1H NMR (400 MHz, CDCl3): δ = 7.36–7.14 (m, 5 H), 6.45 (s,
1 H), 6.32 (s, 1 H), 6.14 (d, J = 2.4 Hz, 1 H), 5.63 (s, 2 H), 3.74 (s,
3 H), 3.66 (s, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 166.7,
rOH = 90:10, 1.0 mL/min, λ = 254 nm]: tR = 5.06 (major), 6.36 152.1, 142.8, 142.2, 141.9, 138.8, 138.0, 127.8, 126.4, 124.8, 124.5,
(minor) min. 1H NMR (400 MHz, CDCl3): δ = 7.36–7.32 (m, 1 H),
123.1, 120.3, 110.3, 108.0, 52.2, 45.0, 40.4 ppm. HRMS (ESI):
7.27–7.19 (m, 4 H), 7.14–7.11 (m, 3 H), 6.49 (s, 1 H), 5.58 (s, 1 H), calcd. for C18H15BrO3Na 381.0102; found 381.0104.
5.54 (s, 1 H), 3.73 (s, 3 H), 3.67 (s, 2 H) ppm. 13C NMR (100 MHz,
(R)-3-[(2-Bromo-1H-inden-3-yl)(phenyl)methyl]but-3-en-2-one (3i):
62% yield. [α]2D0 = +18.2 (c = 1.70 in CHCl3); 90% ee, determined
by HPLC analysis [Daicel Chiralpak IC, n-hexane/iPrOH = 95:5,
CDCl3): δ = 167.0, 142.9, 142.3, 140.5, 139.8, 137.7, 132.6, 130.0,
128.7, 128.3, 126.4, 124.8, 124.3, 123.3, 120.4, 52.2, 45.6, 45.1 ppm.
HRMS (ESI): calcd. for C20H16BrClO2Na 424.9920; found
424.9912.
1
1.0 mL/min, λ = 254 nm]: tR = 7.12 (major), 8.29 (minor) min. H
NMR (400 MHz, CDCl3): δ = 7.34–7.21 (m, 5 H), 7.14–7.10 (m, 3
H), 6.31 (d, J = 1.8 Hz, 1 H), 5.67 (d, J = 1.8 Hz, 1 H), 5.64 (s, 1
H), 3.64 (s, 2 H), 2.41 (s, 3 H) ppm. 13C NMR (50 MHz, CDCl3):
δ = 198.6, 149.2, 143.7, 142.3, 141.1, 139.3, 128.9, 128.5, 127.7,
126.8, 126.3, 124.7, 123.6, 123.2, 120.3, 45.3, 45.1, 26.2 ppm.
HRMS (ESI): calcd. for C20H17BrONa 375.0360; found 375.0354.
Methyl
(R)-2-[(2-Bromo-1H-inden-3-yl)(m-tolyl)methyl]acrylate
(3d): 60% yield. [α]2D0 = –12.7 (c = 0.88 in CHCl3); 94% ee, deter-
mined by HPLC analysis [Daicel Chiralcel OD, n-hexane/iPrOH =
90:10, 1.0 mL/min, λ = 254 nm]: tR = 4.55 (major), 5.64 (minor)
1
min. H NMR (400 MHz, CDCl3): δ = 7.35–7.34 (m, 1 H), 7.20–
7.03 (m, 7 H), 6.47 (s, 1 H), 5.58 (s, 1 H), 5.52 (s, 1 H), 3.72 (s, 3
H), 3.67 (s, 2 H), 2.30 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 16.7.2, 143.3, 142.3, 141.0, 140.4, 139.0, 138.0, 129.4, 128.3,
127.9, 127.6, 126.3, 125.8, 124.6, 123.9, 123.1, 120.6, 52.1, 46.1,
45.0, 21.5 ppm. HRMS (ESI): calcd. for C20H19BrO2Na 405.0466;
found 405.0475.
(R)-3-[(2-Bromo-1H-inden-3-yl)(p-tolyl)methyl]but-3-en-2-one (3j):
56% yield. [α]2D0 = +12.2 (c = 0.41 in CHCl3); 92% ee, determined
by HPLC analysis [Daicel Chiralpak AD, n-hexane/iPrOH = 90:10,
1
1.0 mL/min, λ = 254 nm]: tR = 4.54 (major), 5.00 (minor) min. H
NMR (400 MHz, CDCl3): δ = 7.35–7.32 (m, 1 H), 7.18–7.07 (m, 7
H), 6.30 (d, J = 1.8 Hz, 1 H), 5.67 (d, J = 1.8 Hz, 1 H), 5.59 (s, 1
H), 3.64 (s, 2 H), 2.41 (s, 3 H), 2.30 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 198.7, 149.3, 143.6, 142.3, 141.1, 136.3,
136.1, 129.8, 129.2, 128.6, 127.6, 126.3, 124.6, 123.3, 120.3, 45.1,
44.7, 26.3, 21.0 ppm. HRMS (ESI): calcd. for C21H19BrONa
389.0517; found 389.0522.
Methyl (R)-2-[(2-Bromo-1H-inden-3-yl)(4-methoxyphenyl)methyl]-
acrylate (3e): 65% yield. [α]2D0 = –18.1 (c = 1.04 in CH2Cl2); 89%
ee, determined by HPLC analysis [Daicel Chiralcel OD, n-hexane/
iPrOH = 90:10, 1.0 mL/min, λ = 254 nm]: tR = 6.81 (major), 7.89
(minor) min. 1H NMR (400 MHz, CDCl3): δ = 7.35–7.33 (m, 1 H),
7.19–7.10 (m, 5 H), 6.82 (d, J = 8.8 Hz, 1 H), 6.45 (s, 1 H), 5.53
(s, 1 H), 5.51 (s, 1 H), 3.76 (s, 3 H), 3.70 (s, 3 H), 3.65 (s, 2 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 167.2, 158.3, 143.3, 142.3,
141.0, 140.7, 131.1, 129.6, 127.8, 126.3, 124.6, 123.7, 123.1, 120.6,
113.8, 55.1, 52.1, 45.5, 45.0 ppm. HRMS (ESI): calcd. for
C21H19BrO3Na 421.0415; found 421.0419.
(R)-3-(2-Bromo-1H-inden-3-yl)-2-methylenepentanenitrile (3k): 27%
yield. [α]2D0 = –26.0 (c = 0.96 in CHCl3); 56% ee, determined by
HPLC analysis [Daicel Chiralcel OD, n-hexane/iPrOH = 95:5,
1
1.0 mL/min, λ = 254 nm]: tR = 6.04 (major), 5.57 (minor) min. H
NMR (400 MHz, CDCl3): δ = 7.40 (d, J = 7.2 Hz, 1 H),7.36–7.34
(m, 1 H), 7.25–7.17 (m, 2 H), 6.00 (d, J = 2.2 Hz, 1 H), 5.83 (d, J
= 2.2 Hz, 1 H), 3.86–3.81 (m, 1 H), 3.69 (s, 2 H), 2.19–2.06 (m, 3
H), 0.92 (t, J = 7.6 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 142.4, 141.2, 139.1, 131.1, 126.4, 125.8, 125.1, 123.8, 123.6,
120.1, 118.3, 45.0, 44.3, 23.4, 12.0 ppm. HRMS (ESI): calcd. for
C15H14BrNNa 310.0207; found 310.0205.
Methyl
(R)-2-[Benzo[d][1,3]dioxol-5-yl(2-bromo-1H-inden-3-yl)-
methyl]acrylate (3f): 54% yield. [α]2D0 = –42.5 (c = 0.86 in CHCl3);
94% ee, determined by HPLC analysis [Daicel Chiralcel OD, n-
hexane/iPrOH = 90:10, 1.0 mL/min, λ = 254 nm]: tR = 7.25
(major), 8.75 (minor) min. 1H NMR (400 MHz, CDCl3): δ = 7.35–
7.13 (m, 4 H), 6.76 (s, 1 H), 6.74 (s, 2 H), 6.46 (s, 1 H), 5.92 (s, 2
H), 5.55 (s, 1 H), 5.51 (s, 1 H), 3.72 (s, 3 H), 3.66 (s, 2 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 167.1, 147.7, 146.4, 143.2, 142.3,
140.9, 140.4, 132.9, 127.9, 126.3, 124.7, 123.8, 123.2, 121.6, 120.5,
109.2, 108.2, 101.0, 52.2, 50.7, 45.9 ppm. HRMS (ESI): calcd. for
C21H17BrO4Na 435.0208; found 435.0213.
Methyl
(S)-3-[2-(Methoxycarbonyl)-1-phenylallyl]-1H-indene-2-
carboxylate (3l): 64% yield. [α]2D0 = –14.0 (c = 1.12 in CHCl3); 88%
ee, determined by HPLC analysis [Daicel Chiralcel OD, n-hexane/
iPrOH = 95:5, 1.0 mL/min, λ = 254 nm]: tR = 9.98 (major), 7.85
(minor) min. 1H NMR (400 MHz, CDCl3): δ = 7.46 (d, J = 7.6 Hz,
1 H), 7.36 (d, J = 8.0 Hz, 1 H), 7.30–7.14 (m, 7 H), 6.62 (s, 1 H),
6.45 (s, 1 H), 5.44 (s, 1 H), 3.81 (s, 3 H), 3.73 (d, J = 5.6 Hz, 2 H),
3.67 (s, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 167.3, 165.7,
153.9, 144.0, 141.8, 140.1, 131.3, 128.8, 128.05, 127.5, 127.2, 126.7,
126.4, 124.2, 124.1, 52.1, 51.4, 45.0, 39.0, 29.7 ppm. HRMS (ESI):
calcd. for C22H20O4Na 371.1259; found 371.1247.
Methyl (R)-2-[(2-Bromo-1H-inden-3-yl)(naphthalen-1-yl)methyl]ac-
rylate (3g): 71% yield. [α]2D0 = –37.9 (c = 0.78 in CH2Cl2); 92% ee,
determined by HPLC analysis [Daicel Chiralcel OD, n-hexane/iP-
rOH = 95:5, 1.0 mL/min, λ = 254 nm]: tR = 9.11 (major), 10.92
(minor) min. 1H NMR (400 MHz, CDCl3): δ = 8.00–7.98 (m, 1 H),
7.88–7.85 (m, 1 H), 7.80 (d, J = 8.0 Hz, 1 H), 7.51–7.40 (m, 4 H),
7.36 (d, J = 6.0 Hz, 1 H), 7.18 (d, J = 7.6 Hz, 1 H), 7.14–7.09 (m,
2 H), 6.52 (s, 1 H), 6.28 (s, 1 H), 5.47 (s, 1 H), 3.74 (s, 3 H), 3.70
(s, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 167.2, 143.7,
142.2, 139.9, 134.9, 134.0, 131.8, 128.8, 128.5, 128.0, 126.4, 126.3,
126.2, 125.7, 125.1, 124.7, 124.5, 123.8, 123.2, 122.8, 119.2, 52.2,
45.2, 43.0 ppm. HRMS (ESI): calcd. for C24H19BrO2Na 441.0466;
found 441.0469.
Methyl (S)-3-[1-(Benzo[d][1,3]dioxol-5-yl)-2-(methoxycarbonyl)all-
yl]-1H-indene-2-carboxylate (3m): 60% yield. [α]2D0 = –35.5 (c = 1.2
in CHCl3); 92% ee, determined by HPLC analysis [Daicel Chiralcel
OD, n-hexane/iPrOH = 90:10, 1.0 mL/min, λ = 254 nm]: tR = 12.40
1
(major), 9.83 (minor) min. H NMR (400 MHz, CDCl3): δ = 7.46
(d, J = 7.2 Hz, 1 H), 7.40 (d, J = 7.6 Hz, 1 H), 7.28 (t, J = 7.6 Hz,
1 H), 7.18 (t, J = 7.6 Hz, 1 H), 6.78–6.71 (m, 3 H), 6.53 (s, 1 H),
Methyl (R)-2-[(2-Bromo-1H-inden-3-yl)(furan-2-yl)methyl]acrylate 6.43 (s, 1 H), 5.90 (d, J = 2.4 Hz, 2 H), 5.48 (s, 1 H), 3.82 (s, 3 H),
(3h): 52% yield. [α]2D0 = +9.8 (c = 1.66 in CHCl3); 53% ee, deter-
mined by HPLC analysis [Daicel Chiralpak IB, n-hexane/iPrOH =
95:5, 1.0 mL/min, λ = 254 nm]: tR = 5.15 (major), 5.47 (minor)
3.70 (d, J = 4.0 Hz, 2 H), 3.67 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 167.2, 165.7, 153.9, 147.7, 146.2, 143.9, 143.7, 141.8,
133.8, 131.0, 127.4, 127.3, 126.4, 124.2, 124.1, 121.8, 109.4, 108.2,
Eur. J. Org. Chem. 2011, 7366–7371
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7369

Y.-C. Chen et al.
FULL PAPER
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C23H20O6Na 415.1158; found 415.1152.
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Procedure for Dipolar [3 + 2] Cycloaddition: A solution of choro-
benzaldoxime (67.5 mg, 0.43 mmol) in anhydrous CH2Cl2 (1.5 mL)
was cooled to –40 °C, and DIPEA (59.5 μL, 0.36 mmol) was added.
After stirring for 10 min, a solution of 3a (133.0 mg, 0.36 mmol) in
CH2Cl2 (1.0 mL) was added dropwise. The reaction mixture was
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poured into saturated aqueous NH4Cl (5 mL), and extracted with
CH2Cl2 (2ϫ5 mL). The combined organic phases were washed
with water (2ϫ5 mL) and brine (2ϫ5 mL), dried with anhydrous
Na2SO4, filtered, and concentrated. Purification by silica gel flash
chromatography (EtOAc/petroleum ether = 1:20) gave 4 (mixture
of diastereomers, 4.2:1) as a white semi-solid (143.3 mg, 81%);
[α]2D0 = –147.5 (c = 1.11 in CHCl3).
Methyl (R)-5-[(S)-(2-Bromo-1H-inden-3-yl)(phenyl)methyl]-3-phen-
yl-4,5-dihydroisoxazole-5-carboxylate (Major Isomer of 4): 94% ee,
determined by HPLC analysis [Daicel Chiralpak AD, n-hexane/
iPrOH = 90:10, 1.0 mL/min, λ = 254 nm]: tR = 31.80 (major), 31.14
(minor) min. 1H NMR (400 MHz, CDCl3): δ = 7.61 (d, J = 7.6 Hz,
2 H), 7.48 (d, J = 7.2 Hz, 2 H), 7.36–7.02 (m, 8 H), 7.11–7.02 (m,
2 H), 5.42 (s, 1 H), 3.70 (d, J = 4.0 Hz, 2 H), 3.67 (s, 3 H), 3.61 (d,
J = 3.6 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 156.0,
141.9, 140.2, 136.9, 130.3, 129.6, 128.8, 128.7, 128.6, 128.5, 128.4,
127.1, 126.8, 126.3, 124.8, 123.1, 122.6, 90.7, 53.1, 49.8, 44.8, 44.3,
43.3 ppm. HRMS (ESI): calcd. for C27H22BrNO3Na 510.0681;
found 510.0684.
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We are grateful for financial support from the National Natural
Science Foundation of China (20972101 and 21021001) and the
National Basic Research Program of China (973 Program,
2010CB833300).
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www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 7366–7371

Direct Asymmetric Allylic Alkylation of Indenes
[16] CCDC-842448 (4) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[17] More synthetic transformations with the obtained chiral in-
dene products have been explored but, unfortunately, with lim-
ited success.
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Organometallics 2000, 19, 5464.
Received: August 29, 2011
Published Online: October 19, 2011
Eur. J. Org. Chem. 2011, 7366–7371
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7371