Diastereoselective alkynylation of glucose-modified imines with terminal alkynes

Article abstract of DOI:10.1016/j.tetasy.2009.02.056

The copper(I)-catalyzed enantioselective alkynylation of aldimines incorporating a 2,3,4,6-tetrakis-O-pivaloyl-d-glucopyranosyl (Piv₄Glc) chiral auxiliary with terminal alkynes is reported. The present system provides a versatile tool for the c

Full text of DOI:10.1016/j.tetasy.2009.02.056

Tetrahedron: Asymmetry 20 (2009) 566–569
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Diastereoselective alkynylation of glucose-modified imines
with terminal alkynes
*
Jiangang Mao, Pengfei Zhang
College of Material, Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou 310036, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
The copper(I)-catalyzed enantioselective alkynylation of aldimines incorporating a 2,3,4,6-tetrakis-O-
pivaloyl-D-glucopyranosyl (Piv4Glc) chiral auxiliary with terminal alkynes is reported. The present sys-
tem provides a versatile tool for the construction of optically active propargylamine derivatives. Good
yields and enantiomeric excess values were achieved with an array of imines and biologically active,
propargylamine derivatives.
Received 15 December 2008
Accepted 23 February 2009
Available online 22 April 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
The enantioselective addition to C@N bonds provides a versatile
method for the synthesis of chiral nitrogen-containing scaffolds in
Chiral propargylamine derivatives that are key structural frag-
ments within biologically active materials have attracted broad
interests, particularly in the areas of synthetic methodology, bioor-
ganic and medicinal chemistry, and natural product synthesis.1,2
Rasagiline, a novel second-generation propargylamine, is a selective
and irreversible inhibitor of monoamine oxidase type B (MAO-B)
used for the treatmentof Parkinson’s disease (PD)3 and in preventing
cell death. Rasagiline and other propargylamines can prevent the
opening of permeability transition pore in insolated mitochondria,
regulate the apoptotic machinery in mitochondria, and rescue or
protect deteriorated neurons in neurodegenerativedisorders.4,5
N-Propargylamine derivatives of nitroxyls (JSAKs) can also act as
promising antioxidants and protectors of targets against ROS toxic-
ity.5,6 Propargylamine is also a new interesting medicinal agent
building block, due to the rich chemistry to which the alkyne can
be modified, the presence of a C„C bond in the desired targets offers
particularly an opportunity for further synthetic elaboration on the
chiral nitrogen-containing compounds, which are the framework
of a number of biologically active compounds and natural products.
In addition, the reaction is atom economical as the nucleophile is
generated directly.
biologically active compounds and natural products.2,10,11 Previ-
ously, we reported the enantioselective strecker reaction of
aldimines incorporating a 2,3,4,6-tetra-O-pivaloyl-b-
anosyl(Piv4Glc) chiral auxiliary and achieved several
acids and interesting medicinal agents.12 Currently, we employ
N-(2,3,4,6-tetra-O-pivaloyl-b- -glucopyranosyl) aldimine as a chi-
D
-glucopyr-
a-amino
D
ral template, and obtain desired propargylamines by the alkynyla-
tion of imines with terminal alkynes. In this process, a new bond is
formed between an sp3 carbon and an sp carbon.
2. Results and discussion
Continuing our work in C-glycoside synthesis,12 we applied the
alkynylation reaction to N-(2,3,4,6-tetra-O-pivaloyl-b-D-glucopyr-
anosyl)aldimine 1 prepared according to an already known proce-
dure.12c The alkynylation was accomplished by mixing imines 1
with 2 equiv of phenylacetylene 2 in the presence of CuOTfꢀ0.5C6H6
(10% equiv). This led to the corresponding propargylamine 3 in 95%
yield with a diastereomeric ratio of 96%.
We investigated Cu(OTf)2 as a catalyst in the reaction, but the
reaction was very slow and gave poor yields, resulting in low
conversion after 32 h at room temperature (Table 1). We also
examined other Lewis acids such as SnCl4 and ZnCl2, but the
reactions were disordered due to the formation of unknown
products.
As a consequence of the essential role played by these N-propar-
gylamine derivatives in biological systems and their utility as
synthetic building blocks, a range of useful methodologies for the
synthesis of these compounds have been reported, such as the alky-
Next, a series of imines 1 from glucosamine were tested as
electrophilic species. The reaction was conducted in two differ-
ent solvents: dichloromethane and toluene. The best results
were obtained when aromatic imines containing an electron-
withdrawing group were used in CH2Cl2 at room temperature
(Table 1). The results indicate that the electron-withdrawing
group of aldimines reduces the electron intensity of the carbon
nylglycine skeleton was formed via the coupling of a-haloglycinates
with an excess of reactive metal alkynilides7 and of three-compo-
nent one-pot;8 particularly, catalyzed asymmetric alkynylation of
imines.9,10
* Corresponding author. Tel.: +86 571 85972894; fax: +86 571 28862867.
E-mail address: pfzhang@hznu.edu.cn (P. Zhang).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.02.056

J. Mao, P. Zhang / Tetrahedron: Asymmetry 20 (2009) 566–569
567
Table 1
Influence of different lewis acids and solvents on the alkynylation reactiona
OPiv
OPiv
CuOTf·0.5C6H6
DCM, r.t.
H
N
R2
O
O
N
H
+
R2
PivO
PivO
R1
PivO
PivO
OPiv
OPiv
R1
H
1
2
3
Entry
Catalyst
Solvent
R1
1a (Ph)
R2
Conditions
Compound
Yieldb (%)
dec (%)
1
2
3
4
5
6
7
6
7
CuOTfꢀ0.5C6H6
CuOTfꢀ0.5C6H6
CuOTfꢀ0.5C6H6
CuOTfꢀ0.5C6H6
Cu(OTf)2
CH2Cl2
CH2Cl2
2a (Ph)
2a (Ph)
2a (Ph)
2a (Ph)
2a (Ph)
2a (Ph)
2a (Ph)
2a (Ph)
2a (Ph)
2a (Ph)
2b (n-butyl)
2c (TMS)
rt, 24 h
rt, 24 h
rt, 24 h
rt, 24 h
rt, 32 h
rt, 32 h
rt, 32 h
rt, 24 h
rt, 24 h
rt, 36 h
rt, 24 h
rt, 36 h
3a
3b
3b
3c
3c
—
90
94
68
92
62
90
91
73
93
81
1b (4-NO2–C6H4)
1b (4-NO2–C6H4)
1c (4-Cl–C6H4)
1c (4-Cl–C6H4)
1c (4-Cl–C6H4)
1c (4-Cl–C6H4)
1d (3-NO2–C6H4)
1e (4-CF3–C6H4)
1f (4-CH3–C6H4)
1c (4-Cl–C6H4)
1c (4-Cl–C6H4)
Toluene
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
SnCl4
ZnCl2
—
CuOTfꢀ0.5C6H6
CuOTfꢀ0.5C6H6
CuOTfꢀ0.5C6H6
CuOTfꢀ0.5C6H6
CuOTfꢀ0.5C6H6
3d
3e
3f
3g
3h
95
91
84
72
37
96
93
92
78
28
8
9
10
a
All reactions were performed in a 0.5 mmol scale of 1 using 2 equiv of phenylacetylene 2 in 3 mL solvent with 10 mol % of catalyst at room temperature.
Isolated yield.
The enantiomeric excess was determined by HPLC with a chiral stationary phase (Daicel Chiralpak AD).
b
c
atom of aldimines, which enhances the electrophilic ability. Sub-
by N-acetylation (Ac2O, i-Pr2NEt, CH2Cl2, 2 h) to give acetamine 4
in 78% yield (Scheme 1). The acetamide 4 showed an optical rota-
sequently, we investigated the addition of different terminal al-
kynes to imine. The reaction between imine 1c and 1-hexyne
2b afforded the corresponding propargylamine 3g in 72% yield
and 78% de. Unfortunately, the methodology did not work well
with trimethylsilyl acetylene 2c, which reacted with imine 1c
to give the corresponding propargylamine 3h in 37% yield and
28% de (Table 1, entry 10).
The absolute configurations of propargylamines 3were deter-
mined by transforming compound 3 into known acetamide 4
(Scheme 1). The major isomer 3 from the nucleophilic addition
reaction was treated with dried HCl in HCOOH for 10 h, followed
tion of ½a 2D0
¼ þ11:6 (c 0.054, CHCl3), which allowed us to assign
ꢁ
the (R)-configuration to the stereogenic center. The (R)-enantiomer
has been described to have a specific rotation of ½a D22
¼ þ36:1 (c
ꢁ
0.82, CHCl3).13 This result is consistent with our previous work,12b,c
the Piv4Glc group plays a significant role in controlling the diaste-
reoselective addition of phenylacetylene 2 to imine 1. On the basis
of the presented results, we proposed the key transition state
shown in (Fig. 1). Herein, CuI is coordinated to both the N-atom
of the imine and O-atoms of glucopyranose cycle and carbonyl
group of the 2-O-pivaloyl group. This complexation decreased the
OPiv
H
1. HCl, HCO2H
2. Ac2O
O
AcHN
N
PivO
PivO
OPiv
4
3
Scheme 1.
OPiv
H
OPiv
O
Cu
N
PivO
PivO
O
PivO
PivO
N
OPiv
O
H
O
Figure 1. Proposed models for the diastereoselective addition of terminal alkyne 3.

568
J. Mao, P. Zhang / Tetrahedron: Asymmetry 20 (2009) 566–569
electron density at the C-atom of the C@N moiety and led to an at-
tack of the terminal alkyne.
8.08 (d, J = 8.8, 1H), 7.67 (d, J = 8.8, 2H), 7.44–7.27 (m, 4H), 5.45 (m,
1H), 5.27 (t, J = 6.8, 1H), 5.22 (d, J = 12.0, 1H), 5.12 (dd, J = 9.6, 3.6,
1H), 4.92 (d, J = 9.2, 1H), 4.65 (d, J = 9.2, 1H), 4.23 (t, J = 9.2, 1H),
3.93 (t, J = 8.0, 1H), 2.52 (s, 1H), 1.30–1.11 (m, 36H). 13C NMR
(100 MHz, CDCl3): 177.9, 177.4, 177.0, 176.8, 148.4, 147.4, 128.6,
128.5, 128.3, 128.2, 127.7, 124.1, 86.3, 81.7, 76.9, 73.0, 72.4, 70.7,
67.4, 61.1, 55.9, 38.8, 38.7, 38.5, 27.3, 27.1, 27.0. HR-MS: calcd
for [C41H54N2O11+Na]+ 773.3625, found: 773.3629.
3. Conclusions
In conclusion, the diastereoselective addition of phenylacety-
lene to N-(2,3,4,6-tetra-O-pivaloyl-b-D-glucopyranosyl)aldimines
under CuI catalysis was proven to occur cleanly in good yields
(84–95%) and diastereoselectivities (89–96%). This has opened up
access to various chiral propargylamines.
4.2.3. N-(2,3,4,6-Tetra-O-pivaloyl-b-D-glucopyranosyl)-1-(4-
chlorophenyl)-3-phenylprop-2-ynylamine 3c
Yield (0.460 mmol, 0.340 g, 92%). ½a D20
¼ þ36:6 (c 0.023, CHCl3).
ꢁ
1H NMR (400 MHz, CDCl3): 7.52(d, J = 8.0, 1H), 7.41–7.36 (m, 2H),
7.33–7.30 (m, 6H), 5.34 (t, J = 9.6, 1H), 5.23 (dd, J = 12.4, 8.0, 1H),
5.10 (t, J = 9.2, 1H), 4.94–4.86 (m, 1H), 4.78–4.76 (d, J = 8.0, 1H),
4.61–4.59 (d, J = 8.0, 1H), 4.45–4.40 (t, J = 9.6, 1H), 4.14 (s, 1H),
2.19 (s, 1H), 1.28–1.02 (m, 36H). 13C NMR (100 MHz, CDCl3):
177.8, 177.3, 176.8, 176.4, 139.7, 133.5, 130.0, 129.4, 128.6,
128.4, 128.3, 128.2, 124.7, 86.2, 81.8, 76.1, 73.2, 72.4, 70.6, 65.8,
62.2, 51.7, 38.8, 38.7, 38.5, 27.2, 27.1, 27.0. HR-MS: calcd for
[C41H54ClNO9+Na]+ 762.3385, found: 762.3381.
4. Experimental
4.1. General
N-(2,3,4,6-Tetra-O-pivaloyl-b-D-glucopyranosyl)aldimines 1a–f
were prepared as previously described.12c Other reagents were
commercially obtained at highest commercial quality and were
used without further purification. Dichloromethane and toluene
were freshly distilled from CaH2 under nitrogen prior to use. All
non-aqueous reactions were carried out under anhydrous condi-
tions within a nitrogen atmosphere. Column chromatography
was performed on silica gel grade 60 (230–400 mesh). Analytical
TLC: Silica Gel 60, F254 plates from Merck, which were visualised
by UV and phosphomolybdic acid staining. Melting points were re-
corded on X4-Data microscopic melting-point apparatus; uncor-
rected. Optical rotation values were measured on a PerkinElmer
P241 polarimeter. 1H and 13C NMR spectra were recorded on a Bru-
ker Avance DRX-400 spectrometer and all measurements were
performed with tetramethylsilane as an internal standard; d in
ppm, J in hertz. Mass spectra were acquired on Bruker Esquire
3000 plus spectrometer; in m/z.
4.2.4. N-(2,3,4,6-Tetra-O-pivaloyl-b-D-glucopyranosyl)-1-(3-
nitrophenyl)-3-phenylprop-2-ynylamine 3d
Yield (0.475 mmol, 0.356 g, 95%). ½a D20
¼ þ16:9 (c 0.043, CHCl3).
ꢁ
1H NMR (400 MHz, CDCl3): 8.70 (s, 2H), 8.50–8.47 (m, 2H), 8.24 (d,
J = 7.6, 2H), 7.78 (t, J = 7.6, 2H), 7.29 (s, 1H), 5.30 (t, J = 9.6, 1H), 5.05
(t, J = 9.6, 1H), 4.80 (t, J = 10.0, 1H), 4.24 (t, J = 8.4, 1H), 4.15 (d,
J = 3.6, 1H), 4.07 (d, J = 2.8, 2H), 3.67–3.63 (m, 1H), 3.01 (t, J = 8.0,
1H), 1.24–1.09 (m, 36H). 13C NMR (100 MHz, CDCl3): 178.0,
177.4, 177.1, 176.9, 149.2, 142.1, 135.5, 130.1, 128.5, 128.4,
128.3, 125.3, 124.3, 122.2, 86.5, 82.2, 77.0, 73.0, 72.6, 70.3, 65.4,
62.1, 55.8, 38.8, 38.6, 38.5, 27.3, 27.2, 27.0. HR-MS: calcd for
[C41H54N2O11+Na]+ 773.3625, found: 773.3630.
4.2. General procedure for the synthesis of propargylamines 3
4.2.5. N-(2,3,4,6-Tetra-O-pivaloyl-b-D-glucopyranosyl)-1-(4-
trifluoromethyl)penyl-3-phenylprop-2-ynylamine 3e
Imines 1 (0.5 mmol) and CuOTfꢀ0.5C6H6 (0.025 g, 0.05 mmol)
were added to a dried 5-mL reaction flask containing a magnetic
stirring bar. Freshly distilled and well-degassed CH2Cl2 (3 mL)
was added, and the mixture was stirred at room temperature for
1 h. Phenylacetylene (0.102 g, 1.0 mmol) was sequentially added
under vigorous stirring. The resulting solution was stirred at room
temperature until TLC showed the completion of the reaction. The
resulting mixture was then filtered through a short plug of silica
gel and purified by column chromatography on silica gel neutral-
ized with triethylamine to afford the desired alkynylation product
3 as a light yellow oil.
Yield (0.455 mmol, 0.352 g, 91%). ½a D20
¼ þ31:4 (c 0.027, CHCl3).
ꢁ
1H NMR (400 MHz, CDCl3): 7.73 (dd, J = 13.6, 8.4, 1H), 7.62 (s, 2H),
7.53 (t, J = 7.6, 1H), 7.45–7.29 (m, 5H), 5.53–5.41 (m, 1H), 5.37 (d,
J = 4.0, 1H), 5.30–5.24 (m, 1H), 5.19 (t, J = 6.8, 1H), 5.11 (q, J = 8.0,
1H), 4.96 (t, J = 8.8, 1H), 4.28–4.05 (m 2H), 3.58 (q, J = 4.4, 1H),
1.27–1.12 (m, 36H). 13C NMR (100 MHz, CDCl3): 177.9, 177.5,
177.1, 176.7, 146.2, 129.5, 128.5, 128.4, 128.3, 128.1, 128.0,
125.7, 125.2, 123.0, 87.1, 81.2, 76.0, 73.3, 71.7, 70.2, 65.7, 62.5,
51.1, 38.8, 38.7, 38.5, 27.3, 27.1, 27.0. HR-MS: calcd for
[C42H54F3NO9+Na]+ 796.3648, found: 796.3652.
4.2.6. N-(2,3,4,6-Tetra-O-pivaloyl-b-D-glucopyranosyl)-1-(4-
4.2.1. N-(2,3,4,6-Tetra-O-pivaloyl-b-
diphenylprop-2-ynylamine 3a
D
-glucopyranosyl)-1,3-
methylphenyl)-3-phenylprop-2-ynylamine 3f
Yield (0.420 mmol, 0.302 g, 84%). ½a D20
¼ þ17:2 (c 0.073, CHCl3).
ꢁ
Yield (0.450 mmol, 0.317 g, 90%).
½ ꢁ
a 2D0
¼ þ30:55 (c 0.036,
1H NMR (400 MHz, CDCl3): 7.29–7.26 (d, J = 2.8, 1H), 7.22–7.20 (d,
J = 6.8, 1H), 7.13–7.08 (m, 4H), 6.64 (d, J = 8.0, 2H), 6.45 (d, J = 7.6,
1H), 5.57 (t, J = 8.8, 1H), 5.34 (t, J = 7.6, 1H), 5.14 (d, J = 9.6, 1H), 4.85
(t, J = 9.6, 1H), 4.42 (t, J = 9.6, 1H), 4.34 (q, J = 8.4, 1H), 4.20–4.15 (m,
1H), 3.79–3.75 (t, J = 5.2, 1H), 2.46 (s, 3H), 1.19–1.14 (m, 36H). 13C
NMR (100 MHz, CDCl3): 177.7, 177.4, 177.1, 176.5, 138.6, 137.4,
129.0, 128.7, 128.5, 128.3, 128.2, 123.5, 86.0, 80.5, 76.1, 73.0,
72.2, 70.1, 65.7, 62.4, 52.3, 38.8, 38.6, 38.5, 27.2, 27.1, 27.0. 23.8.
HR-MS: calcd for [C42H57NO9+Na]+ 742.3931, found: 742.3934.
CHCl3). 1H NMR (400 MHz, CDCl3): 7.59 (d, J = 6.8, 2H), 7.46–7.26
(m, 8H), 5.48 (t, J = 12.0, 1H), 5.22 (t, J = 9.2, 1H), 5.07 (m, 1H),
4.92 (d, J = 13.2, 1H), 4.77 (s, 1H), 4.63 (d, J = 9.2, 1H), 4.26–4.05
(m, 1H), 3.85 (d, J = 8.8, 1H) , 2.05 (br, 1H), 1.07–1.35 (m, 36H).
13C NMR (100 MHz, CDCl3): 178.1, 177.4, 177.0, 176.5, 139.4,
131.7, 128.7, 128.5, 128.4, 128.3, 127.6, 127.4, 122.8, 87.8, 81.5,
77.0, 73.1, 72.6, 68.3, 67.0, 62.3, 50.1, 38.8, 38.7, 38.5, 27.2, 27.1,
27.0. HR-MS: calcd for [C41H55NO9+Na]+ 728. 3775, found:
728.3779.
4.2.7. N-(2,3,4,6-Tetra-O-pivaloyl-b-D-glucopyranosyl)-1-(4-
4.2.2. N-(2,3,4,6-Tetra-O-pivaloyl-b-D-glucopyranosyl)-1-(4-
chlorophenyl)-hept-2-ynylamine 3g
Yield (0.390 mmol, 0.281 g, 78%). ½a D20
ꢁ
¼ þ11:9 (c 0.056, CHCl3).
nitrophenyl)-3-phenylprop-2-ynylamine 3b
Yield (0.470 mmol, 0.353 g, 94%). ½a D20
¼ þ32:4 (c 0.032, CHCl3).
ꢁ
1H NMR (400 MHz, CDCl3): d 7.41 (d, J = 8.4, 2H), 7.10 (d, J = 8.4,
2H), 5.34 (t, J = 9.6, 1H), 5.22 (dd, J = 12.0, 8.0, 1H), 5.11 (t, J = 9.2,
1H NMR (400 MHz, CDCl3): 8.40 (d, J = 8.4, 1H), 8.20 (d, J = 8.4, 1H),

J. Mao, P. Zhang / Tetrahedron: Asymmetry 20 (2009) 566–569
569
1H), 4.93–4.85 (m, 1H), 4.78–4.77 (d, J = 8.0, 1H), 4.61–4.58 (d,
References
J = 8.0, 1H), 4.45–4.41 (t, J = 9.6, 1H), 4.14 (s, 1H), 2.28 (tt, J = 7.2,
2.4, 2H), 2.19 (s, 1H), 1.45–1.38 (m, 2H), 1.36–1.30 (m, 2H), 1.27–
1.01 (m, 36H), 0.86 (t, J = 7.6, 3H). 13C NMR (100 MHz, CDCl3):
177.8, 177.4, 176.8, 176.3, 139.4, 133.2, 129.9, 129.4, 128.6, 83.4,
81.7, 74.6, 73.3, 72.4, 70.6, 65.7, 62.2, 51.7, 38.8, 38.7, 38.5, 31.0,
27.2, 27.1, 27.0, 22.1, 18.6, 13.5. HR-MS: calcd for [C39H58ClNO9+-
Na]+ 742.3698, found: 742.3695.
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1988, 44, 5451.
Yield (0.185 mmol, 0.136 g, 37%). ½a D20
¼ þ9:4 (c 0.039, CHCl3).
ꢁ
1H NMR (400 MHz, CDCl3): 7.40 (d, J = 8.4, 2H), 7.08 (d, J = 8.4,
2H), 5.33 (t, J = 9.6, 1H), 5.23 (dd, J = 12.4, 8.4, 1H), 5.10 (t, J = 9.2,
1H), 4.94–4.85 (m, 1H), 4.79–4.76 (d, J = 8.0, 1H), 4.63–4.59 (d,
J = 8.0, 1H), 4.45–4.41 (t, J = 9.6, 1H), 4.14 (s, 1H), 2.20 (s, 1H),
1.27–1.02 (m, 36H), 0.06 (s, 9H). 13C NMR (100 MHz, CDCl3):
177.8, 177.3, 176.8, 176.4, 139.7, 133.1, 129.6, 129.2, 128.8,
100.5, 91.5, 81.7, 73.2, 72.4, 70.6, 65.8, 62.3, 51.7, 38.8, 38.7,
38.5, 27.3, 27.1, 27.0, 0.8. HR-MS: calcd for [C38H58ClNO9Si+Na]+
758.3467, found: 758.3471.
4.3. Synthesis of N-[(R)-1.3-diphenylprop-2-ynyl)acetamide
412c,13
8. (a) Li, C.-J.; Wei, C. Chem. Commun. 2002, 268; (b) Li, Z.; Li, C.-J. J. Am. Chem. Soc.
2004, 126, 11810; (c) Luo, Y.; Li, Z.; Li, C.-J. Org. Lett. 2005, 7, 2675; (d)
Gommermann, N.; Knochel, P. Chem. Commun. 2005, 4175; (e) Knoepfel, T. F.;
Aschwanden, P.; Ichikawa, T.; Watanabe, T.; Carreira, E. M. Angew. Chem., Int.
Ed. 2004, 43, 5971; (f) Kidwai, M.; Bansal, V.; Kumar, A.; Mozumdar, S. Green
Chem. 2007, 9, 742; (g) Gommermann, N.; Knochel, P. Chem. Eur. J. 2006, 12,
4380; (h) Niu, M. Y.; Yin, Z. M.; Fu, H.; Jiang, Y. Y.; Zhao, Y. F. J. Org. Chem. 2008,
73, 3961.
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124, 5638; (g) Koradin, C.; Gommermann, N.; Polborn, K.; Knochel, P. Chem. Eur.
J. 2003, 9, 2797; (h) Koradin, C.; Polborn, K.; Knochel, P. Angew. Chem., Int. Ed.
2002, 41, 2535.
Anhydrous HCl gas was bubbled through a soln. of 3a (0.212 g,
0.3 mmol) in formic acid (4 mL) for 10 h at rt. The soln was concen-
trated in vacuo and the residue was dissolved in 2 mL of dichloro-
methane. To this solution stirred at 0 °C were added successively
diisopropylethylamine (105
lL, 0.6 mmol, 2 equiv) and acetic
anhydride (90 L, 0.9 mmol, 3 equiv). After 30 min at 0 °C and
l
2 h at room temperature, the resulting solution was extracted with
water, and the organic layer was dried over magnesium sulfate.
The solvent was removed under reduced pressure, and the product
was used in the next step without purification: white solid
(0.234 mmol, 0.059 g, 78%); mp: 173–174 °C; ½a D22
¼ þ11:6 (c
ꢁ
0.054, CHCl3); ½a D22
ꢁ
¼ þ36:1 (c 0.82, CHCl3).13 1H NMR (400 MHz,
10. (a) Fujimori, S.; Carreira, E. M. Angew. Chem., Int. Ed. 2007, 46, 4964; (b) Motoki,
R.; Kanai, M.; Shibasaki, M. Org. Lett. 2007, 9, 2997; (c) Asano, Y.; Hara, K.; Ito,
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R. Chem. Rev. 1998, 98, 1407; (c) Knöpfel, T. F.; Zarotti, P.; Ichikawa, T.; Carreira,
E. M. J. Am. Chem. Soc. 2005, 127, 9682.
CDCl3): 2.11 (s, 3H), 6.28 (s, 2H), 7.35 (m, 6H), 7.43 (m, 2H),
7.60(d, J = 9.2, 2H); 13C NMR (100 MHz, CDCl3): 23.8, 45.0, 84.6,
87.3, 122.7, 127.4, 128.2, 128.4, 128.6, 128.7, 128.9, 132.4, 139.2,
169.0.
12. (a) Zhou, G. B.; Guan, Y. Q.; Shen, C.; Wang, Q.; Liu, X. M.; Zhang, P. F.; Li, L. L.
Synthesis 2008, 13, 1994; (b) Wang, D.; Zhang, P. F.; Yu, B. Helv. Chim. Acta 2007,
90, 938; (c) Zhoua, G. B.; Zheng, W. X.; Wang, D.; Zhang, P. F.; Pan, Y. J. Helv.
Chim. Acta 2006, 89, 520; (d) Zhou, G. B.; Zhang, P. F.; Pan, Y. J. Tetrahedron
2005, 61, 5671.
Acknowledgment
This work was supported by the Natural Science Foundation of
Zhejiang Province (No. R406378).
13. Turcaud, S.; Berhal, F.; Royer, J. J. Org. Chem. 2007, 72, 7893.