Rhodium-catalyzed enantioselective alkynylative cyclization of allenyl aldehydes with terminal alkynes

Article abstract of DOI:10.1016/j.tetasy.2010.04.039

Asymmetric addition of terminal alkynes to allenyl aldehydes took place in the presence of an acetylacetonate complex [Rh(acac)L] (L = binap or segphos) as a catalyst to give indanol derivatives in high yields with high regio- and enantioselectivity. The acetylacetonate (acac) ligand on the rhodium is important for the selective formation of the indanol derivatives.

Full text of DOI:10.1016/j.tetasy.2010.04.039

Tetrahedron: Asymmetry 21 (2010) 1730–1736
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Rhodium-catalyzed enantioselective alkynylative cyclization of allenyl
aldehydes with terminal alkynes
*
*
Xun-Xiang Guo, Takahiro Sawano, Takahiro Nishimura , Tamio Hayashi
Department of Chemistry, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Asymmetric addition of terminal alkynes to allenyl aldehydes took place in the presence of an
acetylacetonate complex [Rh(acac)L*] (L* = binap or segphos) as a catalyst to give indanol derivatives
in high yields with high regio- and enantioselectivity. The acetylacetonate (acac) ligand on the rhodium
is important for the selective formation of the indanol derivatives.
Received 29 March 2010
Accepted 19 April 2010
Available online 24 May 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Dedicated to Henri Kagan on the occasion of
his 80th birthday
R
1. Introduction
Rh(acac)(C2H4)2
(5 mol % Rh)
Ph2(O)P
H
R
H
R'
(R)-binap (6 mol%)
Transition metal-catalyzed addition of terminal alkynes to
unsaturated bonds has provided a useful methodology for the syn-
thesis of internal alkynes in view of high atom efficiency,1 and a re-
cent growing attention has been paid to asymmetric alkynylations
with diverse transition-metal catalysts.2 Rhodium is one of the
most versatile metals, catalyzing the addition of terminal alkynes
to alkynes,3 allenes,4 vinyl ketones,5 aldehydes,6 and ketones.6 In
this context, we recently reported rhodium-catalyzed asymmetric
alkynylation7 of conjugate enones,8 conjugate enals,9 allenes,10
and azabenzonorbornadienes.11,12 Herein, we report rhodium-cat-
alyzed asymmetric alkynylative cyclization of allenyl aldehydes
with terminal alkynes giving indanol derivatives in high yields
with high diastereo- and enantioselectivity.
+
Ph2(O)P
Ph2P(O)OH
toluene, 80 ºC
R'
R'
H+
[Rh]
R
Ph2(O)P
I
Scheme 1.
2. Results and discussion
In our previous studies on the asymmetric addition of terminal
alkynes to diphenylphosphinylallenes, the phosphinyl substituent
on the 1,1-disubstituted allenes was essential for selective forma-
tion of exo-enynes, which is formed by regioselective protonolysis
Our initial studies were focused on the addition of (triphenylsi-
lyl)acetylene 2m to 2-(buta-2,3-dienyl)benzaldehyde 1a in the
presence of a chiral phosphine–rhodium complex as a catalyst to
find suitable reaction conditions for the formation of 1-(silylethy-
nyl)ethenyl-substituted indanol 3am (Table 1). The reaction in
the presence of 5 mol % of rhodium catalyst Rh(acac)((R)-binap)16
(acac = acetylacetonate), generated in situ from Rh(acac)(C2H4)2
and (R)-binap, at 80 °C for 24 h gave 63% yield of 3am whose enan-
tiomeric excess was 86% (entry 1). On the other hand, the use of
[Rh(OH)((R)-binap)]2, which is one of the most efficient catalysts
for the addition of terminal acetylenes8b,10,12a as well as organobo-
ronic acids,17 gave 54% yield of indanone 3am0 together with a
small amount (1%) of the indanol 3am (entry 2). The indanone
3am0, which consists of two diastereomeric isomers (dr = 1.5/1)
with lower enantioselectivity (63% ee for the major isomer and
66% ee for the minor isomer), is considered to be formed by
isomerization of indanol 3am (vide infra). The addition of acetyl-
acetone (10 mol %) to [Rh(OH)((R)-binap)]2 (5 mol %) completely
changed the selectivity, giving 64% yield of indanol 3am with
of the
p–allylrhodium(I) intermediate I involved in the catalytic
cycle (Scheme 1).10 The other substituent (R) is also important
for the formation of the addition product. For a mono-substituted
phosphinyl allene (R = H), the reaction with a terminal alkyne did
not give the corresponding hydroalkynylation product, which is
due to the oligomerization caused by the reaction of allene with
the reactive
p
–allylrhodium(I) intermediate.13 These results
prompted us to examine the alkynylation of an allenyl aldehyde
1,14,15 which has a formyl group at an appropriate position to un-
dergo the intramolecular reaction with the nucleophilic
p–allyl-
rhodium(I) intermediate giving a chiral cycloalkanol (Scheme 2).
* Corresponding authors.
E-mail addresses: tnishi@kuchem.kyoto-u.ac.jp (T. Nishimura), thayashi@
kuchem.kyoto-u.ac.jp (T. Hayashi).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.04.039

X.-X. Guo et al. / Tetrahedron: Asymmetry 21 (2010) 1730–1736
1731
Fig. 1).18 The structure of 4 indicates that this cyclization proceeds
with cis-selectivity.
OH
CHO
R
Rh catalyst
+
H
R
1
[Rh]
R
O
[Rh]
CHO
[Rh]
R
R
Scheme 2.
Table 1
Rhodium-catalyzed alkynylative cyclization of allenyl aldehyde 1aa
SiPh3
CHO
OH
[Rh] (5 mol % Rh)
ligand (6 mol %)
1,4-dioxane
80 ºC, 24 h
*
1a
*
+
3am
Figure 1. ORTEP illustration of compound 4 with thermal ellipsoids drawn at 50%
probability.
H
SiPh3
2m
SiPh3
O
O
Table 2 summarizes the results obtained for the reaction of alle-
nyl aldehydes with terminal alkynes in the presence of Rh(a-
cac)(C2H4)2/(S)-segphos catalyst. Allenyl aldehydes 1b–1d, which
have substituents on the benzene ring, were successfully applied
to the alkynylative cyclization to give the corresponding chiral ind-
anols in good yields with the enantioselectivity as high as that for 1a
(97–99% ee; entries 2–4). The reaction of 1e bearing a 1,1-disubsti-
tuted allenyl group with alkyne 2m gave indanol 3em containing
all-carbon quaternary stereocenter in 76% yield with 81% ee,
although the diastereoselectivity was moderate (cis/trans = 3/1; en-
try 5). The enantioselectivity is also very high for the reaction of alle-
nyl aldehyde 1a with (triisopropylsilyl)acetylene 2n, propargylic
ether 2o, and aromatic alkynes 2p–2r (95–99% ee; entries 6–10).
O
O
PPh2
PPh2
PPh2
PPh2
3am'
O
(R)-binap
Rh catalyst
(S)-segphos
Entry
Ligand
Yieldb (%)
eec (%)
1
Rh(acac)(C2H4)2
(R)-Binap
—
63
86 (1R,2S)
(63, 66)f
98 (1R,2S)
96 (1S,2R)
99 (1S,2R)
2
[Rh(OH)((R)-binap)]2
[Rh(OH)((R)-binap)]2
Rh(acac)(C2H4)2
1d (54)e
64
3g
4
—
(S)-Segphos
(S)-Segphos
74
80
5h
Rh(acac)(C2H4)2
a
Reaction conditions: allenyl aldehyde 1a (0.40 mmol), (triphenylsilyl)acetylene
(2m) (0.20 mmol), [Rh] (5 mol % of Rh), ligand (6 mol %) in 1,4-dioxane (0.4 mL) at
80 °C for 24 h.
b
Isolated yields of 3am.
Ee of 3am was determined by HPLC analysis with a chiral stationary phase
c
Table 2
column: Chiralpak AD-H.
Rhodium-catalyzed asymmetric alkynylative cyclization of allenyl aldehydes with
Determined by 1H NMR.
alkynesa
d
e
Isolated yield of 3am0 (dr = 1.5/1).
R3
CHO
R2
f
Ee of 3am0 (major, minor).
OH
g
Rh(acac)(C2H4)2 (5 mol %)
(S)-segphos (6 mol %)
CH3CO2H (5 mol %)
1,4-dioxane, 80 ºC, 24 h
Performed with acetylacetone (10 mol %).
h
Performed with acetic acid (5 mol %).
R1
1
R2
+
R1
H
R3
3
2
98% ee (entry 3). These results indicate that the acac ligand on rho-
dium is important for the selective formation of indanol 3am,
inhibiting the isomerization into indanone 3am0. The yield giving
indanol 3am was improved by use of segphos as a chiral ligand
(entry 4). The highest yield (80%) and enantioselectivity were ob-
tained in a catalyst system consisting of Rh(acac)(C2H4)2, (S)-seg-
phos, and acetic acid (5 mol %).
The absolute configuration of 3am obtained with (S)-segphos
was determined to be (1S,2R) by X-ray crystallographic analysis
of triazole 4, which was derived from 3am through copper-cata-
lyzed cycloaddition with 1-azido-4-chlorobenzene (Scheme 3,
1a: R1 = H, R2 = H
2m: R3 = SiPh3
1b: R1 = 5-MeO, R2 = H
1c: R1 = 4-MeO, R2 = H
1d: R1 = 5-F, R2 = H
1e: R1 = H, R2 = Me
2n: R3 = SiiPr3
2o: R3 = CPh2OCH2OCH3
2p: R3 = Ph
2q: R3 = (4-MeO)C6H4
2r: R3 = 1-naphthyl
Entry
1
Alkyne 2
Product
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1a
1a
1a
1a
1a
2m
2m
2m
2m
2m
2n
2o
2p
2q
2r
3am
3bm
3cm
3dm
3em
3an
3ao
3ap
3aq
3ar
80
80
62
70
76 (3/1)
81
87
50
57
99
97
99
99
81 (43)
98
95
98
99
Cl
SiPh3
O
N
OH
N
N
O
10
64
98
a—c
a
Reaction conditions: allenyl aldehyde 1 (0.40 mmol), alkyne 2 (0.20 mmol),
Rh(acac)(C2H4)2 (5 mol %), (S)-segphos (6 mol %), acetic acid (5 mol %) in 1,4-diox-
ane (0.4 mL) at 80 °C for 24 h.
3am: 99% ee
4: 99% ee (1S,2R)
b
Isolated yields. The value in parentheses is the ratio of the isomers (cis/trans).
Ee was determined by HPLC analysis with a chiral stationary phase column:
c
Scheme 3. Transformation of 3am into compound 4. Reagents and conditions: (a)
TBAF, THF, 0 °C (90%); (b) cat. CuSO4ꢀ5H2O, Na-ascorbate, 1-azido-4-chlorobenzene,
CH3CN, H2O (38%); (c) acetyl chloride, pyridine, CH2Cl2 (86%).
Chiralpak AD-H except for 3 cm (Chiralcel OG). The value in parentheses is the ee
(%) of trans-isomer.

1732
X.-X. Guo et al. / Tetrahedron: Asymmetry 21 (2010) 1730–1736
31P NMR studies demonstrated that acetic acid facilitates the
[Rh]
OH
O
O
route a
formation of alkynylrhodium species. Thus, the reaction of Rh(a-
cac)((R)-binap) with PPh3 (1.5 equiv), alkyne 2m (1.5 equiv), and
acetic acid (1.0 equiv) in 1,4-dioxane at 80 °C for 0.5 h gave 92%
yield of alkynylrhodium 5,12a while the formation of 5 was not de-
tected in the absence of acetic acid under otherwise the same con-
ditions (Scheme 4).
H
R
R
R
Hacac
+
[Rh](acac)
O
3am
3am'
R:
SiPh3
O
A
route b
O
O
R
[Rh]
R
R
R
[Rh]
H
*
H
Rh(acac)((R)-binap)
P
P
*
B
[Rh] H
[Rh] H
+
Rh
P
P
H
SiPh3
1,4-dioxane
80 ºC, 0.5 h
Scheme 6. Formation of indanol 3am and indanone 3am0.
(R)-binap
SiPh3
2m (1.5 equiv)
+
Ph3P
5
PPh3
(1.5 equiv)
with AcOH (1 equiv) 92%
without AcOH 0%
gen. NMR spectra were recorded on a JEOL JNM LA-500 spectrom-
eter (500 MHz for 1H, 125 MHz for 13C, and 202 MHz for 31P).
Chemical shifts are reported in d (ppm) referenced to an internal
SiMe4 standard for 1H NMR, chloroform-d (d 77.16) for 13C NMR,
and external H3PO4 standard for 31P NMR. The following abbrevia-
tions are used; s, singlet, d, doublet, t, triplet, q, quartet, quint,
quintet, sext, sextet, m, multiplet, br, broad. Optical rotations were
measured on a JASCO DIP-370 polarimeter or JASCO P-2200 polar-
imeter. Elemental analyses were performed at the Microanalytical
Center, Kyoto University. High-resolution mass spectra were ob-
tained with a Bruker micrOTOF spectrometer.
Scheme 4. The formation of alkynylrhodium(I) complex 5.
The reaction of allenyl aldehyde 1a with alkynylrhodium(I)
complex 5 indicates that the catalytic cycle of the present reaction
involves an alkynylrhodium(I) species (Scheme 5). Thus, treatment
of complex 5 with allenyl aldehyde 1a (5 equiv) in the presence of
acetylacetone (2 equiv) in 1,4-dioxane at 80 °C for 12 h gave inda-
nol 3am in 75% yield together with the formation of Rh(acac)(bin-
ap),16 which was confirmed by 31P NMR. The enantiomeric excess
of the isolated 3am was 99% and its absolute configuration was
(1R,2S), which is consistent with that obtained in the catalytic
reaction with (R)-binap ligand. The same reaction without acetyl-
acetone mainly gave indanone 3am0 (51% yield (dr = 2/1)), where
indanol 3am was not detected.
4.2. Materials
1,4-Dioxane was purified by passing through a neutral alumina
column under N2. Rhodium complexes, [Rh(OH)((R)-binap)]217 and
Rh(acac)(C2H4)2,19 were prepared according to the reported proce-
dures. Alkynylrhodium complex 5 was prepared according to the
reported procedure.12a
It is most likely that indanone 3am0 is formed through b-hydro-
gen elimination from rhodium alkoxide A which is generated by
the addition of a p–allylrhodium intermediate to aldehyde moiety
(see Scheme 2). The b-hydrogen elimination from A followed by
addition of the resulting rhodium hydride to the olefinic double
bond and subsequent b-hydrogen elimination–readdition leads to
4.3. Preparation of allenyl aldehyde 1
indanone 3am0 by way of the oxa-
p–allylrhodium B (Scheme 6,
4.3.1. 2-(Buta-2,3-dienyl)benzaldehyde 1a
route b). In the presence of acetylacetone (Hacac), rhodium alkoxide
Allenyl aldehyde 1a was prepared according to the following
procedures starting with 2-(2-allylphenyl)-1,3-dioxolane s1,20
which was prepared from 2-bromobenzaldehyde. To a mixture of
s1 [96689-74-6] (7.6 g, 40 mmol), bromoform (80.9 g, 320 mmol),
and benzyltrimethylammonium chloride (0.46 g, 2 mmol) was
added dropwise a solution of sodium hydroxide (24.0 g, 600 mmol)
in H2O (48 mL) at 60 °C over a period of 1.5 h, and the mixture was
stirred at 60 °C for 8 h.21 After cooling to room temperature, the
mixture was passed through a pad of Celite. The organic layer
was washed with H2O and brine, dried over MgSO4, filtered, and
concentrated on a rotary evaporator. The residue was subjected
to flash column chromatography on silica gel with ethyl acetate/
hexane (1/10) as eluent to give 2-(2-((2,2-dibromocyclopro-
A undergoes protonolysis with Hacac to give indanol 3am (route a).
3. Conclusion
In conclusion, we developed a rhodium-catalyzed asymmetric
addition of terminal alkynes to allenyl aldehydes giving indanol
derivatives in high yields with high regio- and enantioselectivity.
It was found that the use of a rhodium catalyst with acac ligand
is important for the selective formation of the indanol derivatives
without isomerization into the indanones.
4. Experimental
4.1. General
pyl)methyl)phenyl)-1,3-dioxolane s2 as
a white solid (8.0 g,
22 mmol; 55% yield). 1H NMR (CDCl3) d 1.43 (dd, J = 7.6, 7.3 Hz,
1H), 1.81 (dd, J = 10.4, 7.3 Hz, 1H), 1.92–2.00 (m, 1H), 2.88 (dd,
J = 15.7, 7.0 Hz, 1H), 3.19 (dd, J = 15.7, 6.7 Hz, 1H), 4.00–4.20 (m,
4H), 5.96 (s, 1H), 7.25–7.43 (m, 3H), 7.57 (d, J = 7.0 Hz, 1H); 13C
All anaerobic and moisture-sensitive manipulations were
carried out with standard Schlenk techniques under predried nitro-
SiPh3
OH
*
P
P
CHO
Hacac (2 equiv)
Rh
+
+ Rh(acac)((R)-binap)
1,4-dioxane
Ph3P
80 ºC, 12 h
SiPh3
O
5
1a (5 equiv)
O
3am (1R,2S)
75% yield, 99% ee
*
P
P
(R)-binap
Hacac
Scheme 5. Reaction of alkynylrhodium(I) complex 5 with allenyl aldehyde 1a.

X.-X. Guo et al. / Tetrahedron: Asymmetry 21 (2010) 1730–1736
1733
NMR (CDCl3) d 28.6, 29.5, 31.6, 34.4, 65.3, 65.4, 102.2, 126.7, 129.3,
129.6, 135.1, 138.0. HRMS (ESI) calcd for C13H14Br2NaO2 (M+Na)+
382.9253, found 382.9259. To a solution of s2 (5.4 g, 15 mmol) in
diethyl ether (15 mL) was added methyllithium in diethyl ether
(1.13 M, 15 mL, 17 mmol) at ꢁ40 °C, and the mixture was stirred
at the same temperature for 2 h. The mixture was allowed to warm
to room temperature, the reaction was quenched with saturated
aqueous NH4Cl, and the mixture was extracted with diethyl ether.
The combined organic layer was washed with brine, dried over
MgSO4, filtered, and concentrated on a rotary evaporator. The
crude 2-(2-(buta-2,3-dienyl)phenyl)-1,3-dioxolane s3 thus ob-
tained was used directly for the next step without purification. A
mixture of crude s3 and p-toluenesulfonic acid monohydrate
(143 mg, 0.75 mmol) in acetone (60 mL) was stirred at room
temperature for 5 h. The mixture was concentrated under vacuum,
and the residue was extracted with diethyl ether. The ether
extracts were washed with saturated aqueous sodium bicarbonate,
brine, dried over MgSO4, filtered, and concentrated on a rotary
evaporator. The residue was subjected to flash column chromatog-
raphy on silica gel with ethyl acetate/hexane (1/10) as eluent to
give 1a as colorless oil (1.6 g, 10 mmol; 67% yield). 1H NMR (CDCl3)
d 3.76 (dt, J = 6.7, 3.3 Hz, 2H), 4.66 (dt, J = 6.4, 3.3 Hz, 2H), 5.37 (tt,
J = 6.7, 6.4 Hz, 1H), 7.33 (d, J = 7.6 Hz, 1H), 7.40 (td, J = 7.6, 0.9 Hz,
1H), 7.53 (td, J = 7.6, 1.2 Hz, 1H), 7.85 (dd, J = 7.6, 1.2 Hz, 1H),
10.27 (s, 1H); 13C NMR (CDCl3) d 31.8, 76.2, 89.8, 127.1, 131.0,
131.5, 134.0 (2C), 142.5, 192.4, 209.0. Anal. Calcd for C11H10O: C,
83.51; H, 6.37. Found: C, 83.25; H, 6.28.
overall yield from 2-bromobenzaldehyde). 1H NMR (CDCl3) d 1.74
(t, J = 3.2 Hz, 3H), 3.67 (t, J = 3.3 Hz, 2H), 4.50 (sext, J = 3.3 Hz,
2H), 7.27 (dd, J = 7.5, 0.6 Hz, 1H), 7.38 (ddd, J = 7.7, 7.5, 0.6 Hz,
1H), 7.51 (td, J = 7.5, 1.5 Hz, 1H), 7.87 (d, J = 7.7, 1.5 Hz, 1H),
10.28 (s, 1H); 13C NMR (CDCl3) d 18.7, 36.9, 75.4, 99.2, 127.1,
130.2, 131.4, 133.7, 134.5, 142.0, 192.0, 206.9. Anal. Calcd for
C12H12O: C, 83.69; H, 7.02. Found: C, 83.70; H, 7.04.
4.4. A typical procedure for rhodium-catalyzed asymmetric
alkynylative cyclization of allenyl aldehyde 1a with alkyne 2m
To a mixture of Rh(acac)(C2H4)2 (2.6 mg, 0.010 mmol) and
(S)-segphos (7.3 mg, 0.012 mmol) in a screw cap test tube was
added 1,4-dioxane (0.4 mL) under N2, and the mixture was stirred
at room temperature for 10 min. To the solution were added (tri-
phenylsilyl)acetylene (2m) (56.9 mg, 0.20 mmol), allenyl aldehyde
1a (63.3 mg, 0.40 mmol), and acetic acid (0.6 lL, 0.010 mmol), and
the tube was capped tightly. The mixture was stirred at 80 °C for
24 h. The reaction mixture was concentrated under vacuum, and
the residue was subjected to column chromatography on silica
gel with ethyl acetate/hexane (1/5) as eluent to give indanol 3am
(70.8 mg, 0.16 mmol; 80% yield). The absolute configuration of
3am was determined to be (1S,2R) by X-ray crystallographic anal-
ysis of compound 4 derived from compound 3am (vide infra). For
others, they were assigned by consideration of the stereochemical
pathway.
4.4.1. (1S,2R)-2-(4-(Triphenylsilyl)but-1-en-3-yn-2-yl)indan-1-
ol 3am
4.3.2. 2-(Buta-2,3-dienyl)-5-methoxybenzaldehyde 1b
This compound was prepared using 2-bromo-5-methoxybenzal-
dehyde22 instead of 2-bromobenzaldehyde, following the procedures
for 1a (18% overall yield from 2-bromo-5-methoxybenzaldehyde). 1H
NMR (CDCl3) d 3.68 (dt, J = 6.6, 3.3 Hz, 2H), 3.85 (s, 3H), 4.66 (dt,
J = 6.6, 3.3 Hz, 2H), 5.34 (quint, J = 6.6 Hz, 1H), 7.08 (dd, J = 8.4,
2.9 Hz, 1H), 7.22 (d, J = 8.4 Hz, 1H), 7.37 (d, J = 2.9 Hz, 1H), 10.26 (s,
1H); 13C NMR (CDCl3) d 30.8, 55.6, 76.3, 90.5, 113.6, 120.9, 132.2,
134.8, 135.0, 158.7, 191.7, 209.0. HRMS (ESI) calcd for C12H12NaO2
(M+Na)+ 211.0730, found 211.0720.
The enantiomeric excess was measured by HPLC (Chiralpak AD–
H
column, 0.5 mL/min, hexane/2-propanol = 9/1, 254 nm,
t1 = 20.2 min (1R,2S), t2 = 39.3 min (1S,2R)). ½a D20
¼ ꢁ45 (c 0.99,
ꢂ
CHCl3) for 99% ee. 1H NMR (CDCl3) d 1.98 (d, J = 6.1 Hz, 1H), 3.03
(ddd, J = 13.7, 9.7, 4.3 Hz, 1H), 3.24–3.35 (m, 2H), 5.25 (dd, J = 6.1,
5.5 Hz, 1H), 5.60 (s, 1H), 5.83 (s, 1H), 7.16–7.23 (m, 3H), 7.31–
7.44 (m, 10H), 7.57–7.61 (m, 6H); 13C NMR (CDCl3) d 34.3, 51.2,
76.9, 90.8, 109.3, 124.9, 125.1, 126.1, 127.1, 128.1, 128.9, 129.8,
130.1, 133.4, 135.6, 142.6, 143.5. HRMS (ESI) calcd for C31H26NaOSi
(M+Na)+ 465.1645, found 465.1642.
4.3.3. 2-(Buta-2,3-dienyl)-4-methoxybenzaldehyde 1c
This compound was prepared from 2-bromo-4-methoxybenzal-
dehyde,23 following the procedures for 1a (6% overall yield from
2-bromo-4-methoxybenzaldehyde). 1H NMR (CDCl3) d 3.74 (dt,
J = 7.0, 3.0 Hz, 2H), 3.88 (s, 3H), 4.68 (dt, J = 6.7, 3.0 Hz, 2H), 5.35
(tt, J = 7.0, 6.7 Hz, 1H), 6.82 (d, J = 2.5 Hz, 1H), 6.88 (dd, J = 8.5,
2.5 Hz, 1H), 7.80 (d, J = 8.5 Hz, 1H), 10.11 (s, 1H); 13C NMR (CDCl3)
d 32.1, 55.6, 76.0, 89.4, 112.0, 116.3, 127.6, 134.6, 145.1, 164.0,
190.8, 209.1. HRMS (ESI) calcd for C12H12NaO2 (M+Na)+ 211.0730,
found 211.0738.
4.4.2. (1S,2R)-6-Methoxy-2-(4-(triphenylsilyl)but-1-en-3-yn-2-
yl)indan-1-ol 3bm
The enantiomeric excess was measured by HPLC (Chiralpak AD–H
column, 0.5 mL/min, hexane/2-propanol = 9/1, 254 nm, t1 = 24.5 min
(1S,2R), t2 = 33.4 min (1R,2S)). ½a D20
¼ ꢁ14 (c 0.98, CHCl3) for 97% ee.
ꢂ
1H NMR (CDCl3) d 2.01 (d, J = 7.0 Hz, 1H), 2.98 (dd, J = 15.2, 7.6 Hz,
1H), 3.19 (dd, J = 15.2, 7.3 Hz, 1H), 3.33 (ddd, J = 7.6, 7.3, 6.4 Hz, 1H),
3.75 (s, 3H), 5.22 (t, J = 6.4 Hz, 1H), 5.59 (s, 1H), 5.81 (s, 1H), 6.78
(dd, J = 8.2, 2.7 Hz, 1H), 6.94 (d, J = 2.7 Hz, 1H), 7.08 (d, J = 8.2 Hz,
1H), 7.32–7.45 (m, 9H), 7.54–7.60 (m, 6H); 13C NMR (CDCl3) d 33.6,
51.7, 55.6, 77.2, 90.8, 109.2, 109.7, 115.7, 125.6, 126.2, 128.1, 129.9,
130.1, 133.4, 134.3, 135.6, 144.9, 159.2. HRMS (ESI) calcd for
4.3.4. 2-(Buta-2,3-dienyl)-5-fluorobenzaldehyde 1d
This compound was prepared from 2-bromo-5-fluorobenzalde-
hyde, following the procedures for 1a (31% overall yield from 2-bro-
mo-5-fluorobenzaldehyde). 1H NMR (CDCl3) d 3.71 (dt, J = 6.6,
3.4 Hz, 2H), 4.66 (dt, J = 6.6, 3.4 Hz, 2H), 5.36 (quint, J = 6.6 Hz, 1H),
7.23 (td, J = 8.4, 2.3 Hz, 1H), 7.29 (dd, J = 8.4, 5.1 Hz, 1H), 7.54 (dd,
J = 8.8, 2.8 Hz, 1H), 10.23 (d, J = 2.2 Hz, 1H); 13C NMR (CDCl3) d
30.8, 76.6, 90.0 (d, JF–C = 1.0 Hz), 116.3 (d, JF–C = 21.7 Hz), 120.9 (d,
JF–C = 21.2 Hz), 132.8 (d, JF–C = 7.2 Hz), 135.5 (d, JF–C = 5.7 Hz), 138.2
(d, JF–C = 3.6 Hz), 161.7 (d, JF–C = 247.5 Hz), 190.5 (d, JF–C = 2.1 Hz),
209.0. HRMS (ESI) calcd for C11H9FNaO (M+Na)+ 199.0530, found
199.0526.
C
32H28NaO2Si (M+Na)+ 495.1751, found 495.1750.
4.4.3. (1S,2R)-5-Methoxy-2-(4-(triphenylsilyl)but-1-en-3-yn-2-
yl)indan-1-ol 3cm
The enantiomeric excess was measured by HPLC (Chiralcel OGcol-
umn, 0.5 mL/min, hexane/2-propanol = 95/5, 254 nm, t1 = 35.5 min
(1S,2R), t2 = 41.0 min (1R,2S)). ½a D20
¼ ꢁ39 (c 0.77, CHCl3) for 99% ee.
ꢂ
1H NMR (CDCl3) d 1.94 (br s, 1H), 2.98 (dd, J = 14.5, 6.3 Hz, 1H),
3.21–3.33 (m, 2H), 3.73 (s, 3H), 5.19 (br s, 1H), 5.59 (s, 1H), 5.82 (s,
1H), 6.72–6.78 (m, 2H), 7.28 (d, J = 8.0 Hz, 1H), 7.32–7.44 (m, 9H),
7.56–7.62 (m, 6H); 13C NMR (CDCl3) d 34.4, 51.6, 55.5, 76.3, 90.7,
109.4, 110.0, 113.2, 125.96, 125.99, 128.1, 130.0, 130.1, 133.4,
135.6, 136.0, 144.5, 160.6. HRMS (ESI) calcd for C32H28NaO2Si
(M+Na)+ 495.1751, found 495.1764.
4.3.5. 2-(2-Methylbuta-2,3-dienyl)benzaldehyde 1e
This compound was prepared by way of 2-((2-methyl-2-prope-
nyl)phenyl)-1,3-dioxolane, following the procedures for 1a (28%

1734
X.-X. Guo et al. / Tetrahedron: Asymmetry 21 (2010) 1730–1736
4.4.4. (1S,2R)-6-Fluoro-2-(4-(triphenylsilyl)but-1-en-3-yn-2-yl)
indan-1-ol 3dm
The enantiomeric excess was measured by HPLC (Chiralpak AD–H
column, 0.5 mL/min, hexane/2-propanol = 9/1, 254 nm, t1 = 26.6 min
4.4.8. (1S,2R)-2-(4-Phenylbut-1-en-3-yn-2-yl)indan-1-ol 3ap
The enantiomeric excess was measured by HPLC (Chiralpak AD–H
column, 0.5 mL/min, hexane/2-propanol = 9/1, 254 nm, t1 = 19.4 min
(1R,2S), t2 = 33.4 min (1S,2R)). ½a D20
¼ ꢁ33 (c 0.93, CHCl3) for 98% ee.
ꢂ
(1R,2S), t2 = 30.5 min (1S,2R)). ½a D20
ꢂ
¼ ꢁ35 (c 0.74, CHCl3) for 99% ee.
1H NMR (CDCl3) d 2.08 (d, J = 6.7 Hz, 1H), 3.07 (dd, J = 15.5, 7.3 Hz,
1H), 3.28 (dd, J = 15.5, 7.3 Hz, 1H), 3.35 (td, J = 7.3, 6.4 Hz, 1H), 5.31
(dd, J = 6.7, 6.4 Hz, 1H), 5.54 (s, 1H), 5.70 (s, 1H), 7.22–7.32 (m, 8H),
7.45 (d, J = 7.3 Hz, 1H); 13C NMR (CDCl3) d 34.5, 51.7, 77.0, 88.9,
91.1, 122.8, 124.0, 124.9, 125.0, 127.1, 128.4, 128.5, 128.8, 130.0,
131.8, 142.7, 143.8. HRMS (ESI) calcd for C19H16NaO (M+Na)+
283.1093, found 283.1090.
1H NMR (CDCl3) d 2.08 (d, J = 6.7 Hz, 1H), 2.98 (dd, J = 15.6, 7.7 Hz,
1H), 3.18 (dd, J = 15.6, 7.0 Hz, 1H), 3.34 (ddd, J = 7.7, 7.0, 6.2 Hz, 1H),
5.20 (br t, J = 6.2 Hz, 1H), 5.58 (s, 1H), 5.81 (s, 1H), 6.86 (ddd, J = 8.8,
8.4, 2.4 Hz, 1H), 7.05 (dd, J = 8.4, 2.6 Hz, 1H), 7.08 (dd, J = 8.4, 5.0 Hz,
1H), 7.32–7.44 (m, 9H), 7.52–7.60 (m, 6H); 13C NMR (CDCl3) d 33.8,
51.7, 76.7 (d, JF–C = 2.1 Hz), 91.3, 108.9, 111.9 (d, JF–C = 22.2 Hz),
115.9 (d, JF–C = 22.2 Hz), 125.9 (d, JF–C = 8.8 Hz), 126.5, 128.1, 129.5,
130.1, 133.3, 135.6, 137.7 (d, JF–C = 2.6 Hz), 145.5 (d, JF–C = 7.2 Hz),
162.3 (d, JF–C = 243.9 Hz). HRMS (ESI) calcd for C31H25FNaOSi
(M+Na)+ 483.1551, found 483.1553.
4.4.9. (1S,2R)-2-(4-(4-Methoxyphenyl)but-1-en-3-yn-2-yl)indan-
1-ol 3aq
The enantiomeric excess was measured by HPLC (Chiralpak AD–H
column, 0.5 mL/min, hexane/2-propanol = 9/1, 254 nm, t1 = 27.9 min
(1R,2S), t2 = 43.5 min (1S,2R)). ½a D20
¼ ꢁ58 (c 0.65, CHCl3) for 99% ee.
ꢂ
4.4.5. 2-Methyl-2-(4-(triphenylsilyl)but-1-en-3-yn-2-yl)indan-
1-ol 3em
1H NMR (CDCl3) d 2.11 (d, J = 6.6 Hz, 1H), 3.07 (dd, J = 15.5, 7.4 Hz,
1H), 3.27 (dd, J = 15.5, 7.4 Hz, 1H), 3.34 (td, J = 7.4, 6.2 Hz, 1H), 3.79
(s, 3H), 5.31 (dd, J = 6.6, 6.2 Hz, 1H), 5.50 (s, 1H), 5.66 (s, 1H), 6.79
(d, J = 8.9 Hz, 2H), 7.18–7.32 (m, 5H), 7.46 (d, J = 7.2 Hz, 1H); 13C
NMR (CDCl3) d 34.6, 51.8, 55.4, 77.1, 87.6, 91.3, 114.0, 114.9, 123.2,
124.9, 125.0, 127.0, 128.8, 130.1, 133.3, 142.8, 143.9, 159.9. Anal.
Calcd for C20H18O2: C, 82.73; H, 6.25. Found: C, 82.71; H, 6.30.
Compound 3em and its trans-isomer trans-3emwereseparatedby
preparative TLC (silica gel, CHCl3). Compound 3em (cis-isomer): The
enantiomeric excess was measured by HPLC (Chiralpak AD–H col-
umn, 0.5 mL/min, hexane/2-propanol = 9/1, 254 nm, t1 = 15.1 min
(1R,2S), t2 = 33.7 min (1S,2R)). ½a D20
¼ ꢁ32 (c 0.70, CHCl3) for 81% ee.
ꢂ
1H NMR (CDCl3) d 1.26 (s, 3H), 2.20 (d, J = 5.2 Hz, 1H), 2.69 (d,
J = 15.4 Hz, 1H), 3.47 (d, J = 15.4 Hz, 1H), 4.82 (d, J = 5.2 Hz, 1H), 5.59
(s, 1H), 5.81 (s, 1H), 7.15–7.25 (m, 4H), 7.32–7.45 (m, 9H), 7.58–
7.67 (m, 6H); 13C NMR (CDCl3) d 25.9, 41.3, 53.1, 82.7, 91.0, 109.2,
124.6, 125.3, 125.8, 127.0, 128.2, 128.9, 130.1, 133.5, 135.4, 135.6,
142.7, 142.9. HRMS (ESI) calcd for C32H28NaOSi (M+Na)+ 479.1802,
found 479.1800. Compound trans-3em: The enantiomeric excess
was measured by HPLC (Chiralpak AD–H column, 0.5 mL/min, hex-
ane/2-propanol = 9/1, 254 nm, t1 = 10.7 min (minor), t2 = 12.2 min
4.4.10. (1S,2R)-2-(4-(Naphthalen-1-yl)but-1-en-3-yn-2-yl)indan-
1-ol 3ar
The enantiomeric excess was measured by HPLC (Chiralpak AD–H
column, 0.5 mL/min, hexane/2-propanol = 9/1, 254 nm, t1 = 21.7 min
(1R,2S), t2 = 32.3 min (1S,2R)). ½a D20
¼ ꢁ65 (c 0.80, CHCl3) for 98% ee.
ꢂ
1H NMR (CDCl3) d 2.10 (d, J = 6.5 Hz, 1H), 3.15 (dd, J = 15.5, 7.5 Hz,
1H), 3.38 (dd, J = 15.5, 7.6 Hz, 1H), 3.46 (ddd, J = 7.6, 7.5, 6.3 Hz, 1H),
5.39 (dd, J = 6.5, 6.3 Hz, 1H), 5.62 (d, J = 1.3 Hz, 1H), 5.85 (d,
J = 0.8 Hz, 1H), 7.27–7.34 (m, 3H), 7.38 (dd, J = 8.2, 7.2 Hz, 1H),
7.47–7.55 (m, 4H), 7.79–7.82 (m, 2H), 8.07–8.12 (m, 1H); 13C NMR
(CDCl3) d 34.6, 51.6, 77.1, 89.1, 93.8, 120.5, 124.3, 125.0, 125.2,
125.3, 126.2, 126.5, 127.0, 127.1, 128.4, 128.9, 129.0, 130.2, 130.9,
133.23, 133.24, 142.7, 143.8. HRMS (ESI) calcd for C23H18NaO
(M+Na)+ 333.1250, found 333.1251.
(major)). ½a 2D0
ꢂ
¼ þ9 (c 0.98, CHCl3) for 43% ee. 1H NMR (CDCl3) d
1.18 (s, 3H), 2.05 (d, J = 6.7 Hz, 1H), 2.77 (d, J = 15.4 Hz, 1H), 3.34 (d,
J = 15.4 Hz, 1H), 5.41 (d, J = 6.3 Hz, 1H), 5.60 (d, J = 1.0 Hz, 1H), 5.73
(d, J = 1.0 Hz, 1H), 7.15–7.26 (m, 3H), 7.30–7.42 (m, 10H), 7.59–7.63
(m, 6H); 13C NMR (CDCl3) d 19.1, 43.0, 53.7, 81.1, 91.5, 109.5, 123.0,
124.2, 124.9, 126.9, 128.1, 128.2, 130.1, 133.5, 135.6, 137.6, 139.8,
143.3. HRMS (ESI) calcd for C32H28NaOSi (M+Na)+ 479.1802, found
479.1802.
4.4.11. 2-(4-(Triphenylsilyl)but-3-yn-2-yl)indan-1-one 3am0
A major isomer (Table 1, entry 2): The enantiomeric excess was
measured by HPLC (Chiralcel OD–H column ꢃ 2, 0.5 mL/min, hex-
ane/2-propanol = 9/1, 254 nm, t1 = 22.9 min (major), t2 = 25.8 min
4.4.6. (1S,2R)-2-(4-(Triisopropylsilyl)but-1-en-3-yn-2-yl)indan-
1-ol 3an
(minor)). ½a 2D0
ꢂ
¼ þ27 (c 1.00, CHCl3) for 63% ee. 1H NMR (CDCl3)
The enantiomeric excess was measured by HPLC (Chiralpak AD–H
column, 0.5 mL/min, hexane/2-propanol = 95/5, 254 nm, t1 =
d 1.43 (d, J = 7.1 Hz, 3H), 2.72 (dt, J = 7.7, 4.0 Hz, 1H), 3.25 (dd,
J = 17.3, 7.7 Hz, 1H), 3.31 (dd, J = 17.3, 4.2 Hz, 1H), 3.49 (qd,
J = 7.1, 4.0 Hz, 1H), 7.20–7.42 (m, 17H), 7.54 (t, J = 7.6 Hz, 1H),
7.75 (d, J = 7.7 Hz, 1H); 13C NMR (CDCl3) d 20.1, 28.9, 29.4, 51.9,
81.4, 112.2, 124.2, 126.6, 127.5, 127.9, 129.7, 133.8, 135.0, 135.4,
137.0, 154.4, 206.7. HRMS (ESI) calcd for C31H26NaOSi (M+Na)+
465.1645, found 465.1640. A minor isomer: The enantiomeric ex-
cess was measured by HPLC (Chiralcel OD–H column ꢃ 2, 0.5 mL/
min, hexane/2-propanol = 9/1, 254 nm, t1 = 20.9 min (major),
14.1 min (1R,2S), t2 = 16.2 min (1S,2R)). ½a D20
¼ ꢁ55 (c 0.80, CHCl3)
ꢂ
for 98% ee. 1H NMR (CDCl3) d 0.97–1.12 (m, 21H), 2.16 (d, J = 6.1 Hz,
1H), 2.96–3.05 (m, 1H), 3.20–3.28 (m, 2H), 5.24 (t, J = 5.7 Hz, 1H),
5.50 (s, 1H), 5.68 (s, 1H), 7.19–7.29 (m, 3H), 7.44 (d, J = 7.3 Hz, 1H);
13C NMR (CDCl3) d 11.3, 18.7, 34.2, 51.2, 76.9, 92.4, 106.7, 124.7,
124.9, 125.3, 127.0, 128.9, 130.1, 142.8, 143.6. HRMS (ESI) calcd for
C
22H32NaOSi (M+Na)+ 363.2115, found 363.2116.
t2 = 21.8 min (minor)). ½a D20
ꢂ
¼ ꢁ58 (c 0.90, CHCl3) for 66% ee. 1H
4.4.7. (1S,2R)-2-(5-(Methoxymethoxy)-5,5-diphenylpent-1-en-
3-yn-2-yl)indan-1-ol 3ao
NMR (CDCl3) d 1.20 (d, J = 7.0 Hz, 3H), 3.05 (dt, J = 8.3, 4.0 Hz,
1H), 3.20 (dd, J = 17.6, 4.0 Hz, 1H), 3.34 (dd, J = 17.6, 8.3 Hz, 1H),
3.43 (qd, J = 7.0, 4.0 Hz, 1H), 7.20–7.44 (m, 11H), 7.46 (d,
J = 7.6 Hz, 1H), 7.54–7.60 (m, 6H), 7.73 (d, J = 7.5 Hz, 1H); 13C
NMR (CDCl3) d 15.9, 28.2, 29.7, 50.7, 80.6, 114.4, 124.0, 126.7,
127.6, 128.0, 129.9, 134.0, 135.0, 135.6, 137.5, 154.2, 206.2. HRMS
(ESI) calcd for C31H26NaOSi (M+Na)+ 465.1645, found 465.1647.
The enantiomeric excess was measured by HPLC (Chiralpak AD–
H
column, 0.5 mL/min, hexane/2-propanol = 9/1, 254 nm,
t1 = 17.6 min (1R,2S), t2 = 29.6 min (1S,2R)). ½a D20
¼ ꢁ20 (c 0.94,
ꢂ
CHCl3) for 95% ee. 1H NMR (CDCl3) d 2.98–3.07 (m, 1H), 3.24–
3.32 (m, 3H), 3.27 (s, 3H), 4.67 (d, J = 7.1 Hz, 1H), 4.80 (d,
J = 7.1 Hz, 1H), 5.21 (dd, J = 8.2, 6.4 Hz, 1H), 5.52 (s, 1H), 5.68 (s,
1H), 7.18–7.32 (m, 9H), 7.40–7.44 (m, 3H), 7.48–7.52 (m, 2H);
13C NMR (CDCl3) d 34.7, 51.1, 56.0, 77.3, 80.0, 89.0, 90.2, 93.5,
124.4, 124.8, 125.4, 126.8, 126.9, 127.0, 127.8, 127.9, 128.28,
128.32, 128.7, 130.2, 142.5, 143.6, 143.9, 144.0. HRMS (ESI) calcd
for C28H26NaO3 (M+Na)+ 433.1774, found 433.1771.
4.5. Transformation of compound 3am into 4
To a solution of 3am (132.8 mg, 0.30 mmol, 99% ee) in THF (6 mL)
was added tetrabutylammonium fluoride (TBAF) solution (0.30 mL,

X.-X. Guo et al. / Tetrahedron: Asymmetry 21 (2010) 1730–1736
1735
1.0 M in THF) at 0 °C, and the mixture was stirred for 1 h. The reac-
tion was quenched with H2O and the mixture was extracted with
CH2Cl2. The combined organic layer was washed with brine, dried
over MgSO4, filtered, and concentrated on a rotary evaporator. The
residue was subjected to preparative thin-layer chromatography
on silica gel (ethyl acetate/hexane = 1/5) to give (1S,2R)-2-(but-1-
en-3-yn-2-yl)indan-1-ol s4 as a white solid (49.6 mg, 0.27 mmol;
90%). The enantiomeric excess was measured by HPLC (Chiralpak
AD–H column, 0.5 mL/min, hexane/2-propanol = 9/1, 254 nm,
4.6. The reaction of Rh(acac)((R)-binap) with silylacetylene 2m
(Scheme 4)
A mixture of Rh(acac)(C2H4)2 (13.0 mg, 0.050 mmol) and (R)-bin-
ap (37.4 mg, 0.060 mmol) in 1,4-dioxane (1.0 mL) in a Schlenk tube
was stirred at room temperature for 10 min. To the mixture were
added PPh3 (19.7 mg, 0.075 mmol), 2m (21.3 mg, 0.075 mmol),
and acetic acid (3 lL, 0.05 mmol), and the mixture was heated at
80 °C for 0.5 h. After the mixture was quickly cooled to room tem-
perature, 31P NMR of the mixture was measured using methyldiphe-
nylphosphine oxide (10.8 mg, 0.05 mmol) as an internal standard.
t1 = 19.6 min (1R,2S), t2 = 30.3 min (1S,2R)). ½a D20
¼ ꢁ96 (c 0.93,
ꢂ
CHCl3) for 99% ee. 1H NMR (CDCl3) d 1.97 (d, J = 5.8 Hz, 1H), 2.94 (s,
1H), 2.98 (dd, J = 14.9, 6.9 Hz, 1H), 3.16–3.22 (m, 1H), 3.25 (dd,
J = 14.9, 8.7 Hz, 1H), 5.22 (t, J = 5.8 Hz, 1H), 5.54 (s, 1H), 5.73 (s,
1H), 7.21–7.30 (m, 3H), 7.42 (d, J = 7.1 Hz, 1H); 13C NMR (CDCl3) d
33.8, 51.1, 76.8, 78.4, 83.6, 124.9, 125.2, 125.4, 127.0, 128.9, 129.1,
142.8, 143.5. HRMS (ESI) calcd for C13H12NaO (M+Na)+ 207.0780,
4.7. The reaction of complex 5 with allenyl aldehyde 1a in an
NMR tube (Scheme 5)
To a solution of complex 5 (12.7 mg, 0.010 mmol) in 1,4-diox-
ane (0.50 mL) in an NMR tube were added allenyl aldehyde 1a
(7.9 mg, 0.050 mmol) and acetylacetone (2.0 mg, 0.020 mmol) un-
der Ar. The mixture was heated at 80 °C for 12 h. After cooling to
room temperature, 31P NMR was measured to show the complete
conversion of 5 with the formation of Rh(acac)((R)-binap). The
mixture was passed through a short silica gel column eluting with
Et2O and the eluate was concentrated under vacuum. The residue
was subjected to preparative TLC (silica gel, CHCl3) to give 3am,
whose yield was determined by 1H NMR using CH3NO2 as an inter-
nal standard.
found 207.0771. To
a solution of p-chloroaniline (51.0 mg,
0.40 mmol) in CH3CN (1.0 mL) at 0 °C was added isopentyl nitrite
(70.3 mg, 0.60 mmol) followed by Me3SiN3 (55.3 mg, 0.48 mmol)
dropwise at the same temperature. The resulting solution was stir-
red at room temperature for 2 h. To the mixture were added com-
pound s4 (36.8 mg, 0.20 mmol) in CH3CN (1.0 mL), an aqueous
solution (0.2 mL) of CuSO4ꢀ5H2O (5.0 mg, 0.020 mmol), and sodium
L-ascorbate (15.8 mg, 0.080 mmol), and the mixture was stirred for
24 h. The solvent was removed on a rotary evaporator and the resi-
due was subjected to preparative thin-layer chromatography on sil-
ica gel (ethyl acetate/hexane = 1/2) to give (1S,2R)-2-(1-(1-(4-
chlorophenyl)-1,2,3-triazol-4-yl)vinyl)indan-1-ol s5 as a white so-
lid (25.7 mg, 0.076 mmol; 38% yield). The enantiomeric excess was
measured by HPLC (Chiralcel OJ–H column, 0.8 mL/min, hexane/2-
propanol = 4/1, 254 nm, t1 = 28.5 min (1S,2R), t2 = 40.6 min
Acknowledgment
This work was supported by Grant-in-Aid for Scientific Re-
search (S) (19105002) from MEXT, Japan.
(1R,2S)). ½a 2D0
ꢂ
¼ ꢁ67 (c 1.00, CHCl3) for 99% ee. 1H NMR (CDCl3) d
2.59 (br s, 1H), 3.07 (dd, J = 15.7, 7.6 Hz, 1H), 3.38 (dd, J = 15.7,
8.8 Hz, 1H), 3.79 (q, J = 7.3 Hz, 1H), 5.40 (br s, 1H), 5.41 (s, 1H),
5.88 (s, 1H), 7.21–7.34 (m, 3H), 7.43–7.54 (m, 3H), 7.65–7.72 (m,
2H), 8.02 (s, 1H); 13C NMR (CDCl3) d 34.1, 49.6, 76.2, 116.2, 118.5,
121.8, 124.8, 125.5, 127.1, 128.8, 130.1, 134.8, 135.5, 136.7, 142.8,
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143.9, 149.6. HRMS (ESI) calcd for
C
19H16ClN3NaO (M+Na)+
360.0874, found 360.0863. To a solution of compound s5 (20.5 mg,
0.060 mmol, 99% ee) in CH2Cl2 (2 mL) were added pyridine
(23.7 mg, 0.30 mmol) and acetyl chloride (23.6 mg, 0.30 mmol),
and the mixture was stirred at room temperature for 1 h. The reac-
tion was quenched with H2O and the mixture was extracted with
CH2Cl2. The organic layer was washed with brine, dried over MgSO4,
filtered, and concentrated on a rotary evaporator. The residue was
subjected to preparative thin-layer chromatography on silica gel
with ethyl acetate/hexane (1/3) as eluent to give 4 as a white solid
(19.6 mg, 0.052 mmol; 86% yield). The enantiomeric excess was
measured by HPLC (Chiralpak AD–H column, 0.5 mL/min, hexane/
2-propanol = 9/1, 254 nm, t1 = 49.7 min (1S,2R), t2 = 72.3 min
(1R,2S)). ½a 2D0
ꢂ
¼ ꢁ232 (c 0.35, CHCl3) for 99% ee. 1H NMR (CDCl3) d
1.86 (s, 3H), 3.15 (dd, J = 15.5, 7.3 Hz, 1H), 3.44 (dd, J = 15.5, 9.3 Hz,
1H), 3.87–3.93 (m, 1H), 5.41 (s, 1H), 6.01 (s, 1H), 6.42 (d, J = 5.7 Hz,
1H), 7.22–7.28 (m, 1H), 7.31–7.36 (m, 2H), 7.43–7.52 (m, 3H),
7.65–7.71 (m, 2H), 7.89 (s, 1H); 13C NMR (CDCl3) d 21.2, 34.6, 47.7,
77.1, 115.6, 117.9, 121.8, 124.8, 126.3, 127.1, 129.4, 130.0, 134.6,
135.59, 135.64, 140.7, 143.8, 149.1, 170.6. HRMS (ESI) calcd for
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C
21H18ClN3NaO2 (M+Na)+ 402.0980, found 402.0979. Colorless crys-
tals of compound 4 suitable for X-ray crystallographic analysis were
obtained by recrystallization from ethyl acetate/hexane. The crystal
structure has been deposited at the Cambridge Crystallographic
Data Centre (deposition number: CCDC 675500). Crystal data for
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4:
C21H18ClN3O2, Mw = 379.83, space group P21 (No. 4),
a = 7.802(3) Å, b = 18.451(7) Å, c = 13.419(4) Å, V = 1862.7(12) Å3,
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1736
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