Axially chiral phosphine-oxazoline ligands in silver(I)-catalyzed asymmetric Mannich reaction of N-Boc aldimines with trimethylsiloxyfuran

Article abstract of DOI:10.1016/j.tet.2011.03.046

Axially chiral phosphine-oxazoline ligand L6 was found to be a fairly effective chiral ligand in silver(I)-catalyzed asymmetric Mannich reaction of N-Boc aldimines with trimethylsiloxyfuran to give the corresponding adducts in up to 97% yield, 7:1 dr and 86% ee (major diastereoisomer).

Full text of DOI:10.1016/j.tet.2011.03.046

Tetrahedron 67 (2011) 3724e3732
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Axially chiral phosphineeoxazoline ligands in silver(I)-catalyzed asymmetric
Mannich reaction of N-Boc aldimines with trimethylsiloxyfuran
,b,
Qian-Yi Zhao a, Min Shi a
*
a Key Laboratory for Advanced Materials and Institute of Fine Chemicals, School of Chemistry and Molecular Engineering, East China University of Science and Technology,
130 Mei Long Road, Shanghai 200237, China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Axially chiral phosphineeoxazoline ligand L6 was found to be a fairly effective chiral ligand in silver(I)-
catalyzed asymmetric Mannich reaction of N-Boc aldimines with trimethylsiloxyfuran to give the cor-
responding adducts in up to 97% yield, 7:1 dr and 86% ee (major diastereoisomer).
Ó 2011 Elsevier Ltd. All rights reserved.
Received 28 January 2011
Received in revised form 14 March 2011
Accepted 17 March 2011
Available online 24 March 2011
Keywords:
N-Boc aldimines
Asymmetric Mannich reaction
Axially chiral phosphineeoxazoline ligands
Silver acetate
Trimethylsiloxyfuran
1. Introduction
which has not yet been developed. This is because asymmetric addi-
tion of nucleophiles to N-Boc-protected imines has provided
Catalytic asymmetric vinylogous Mannich (AVM)-type reaction of
trimethylsiloxyfuran with aldimines has been proved to be a very
powerfulsyntheticprotocoltopreparechiralg-butenolidederivatives
a straightforward synthetic approach to chiral amines since its pre-
cursor (BocNH2) as well as the N-Boc protected imine are easily
available and the N-protecting group (N-Boc) can be readily cleaved
underseveralconvenientacidicconditions(HClorTFA).2 Inthispaper,
we wish to report that axially chiral phosphineeoxazoline ligand L6
derived from (R)-binol is a fairly effective catalyst in the silver(I)-
catalyzed asymmetric Mannich reaction of N-Boc aldimines with
trimethylsiloxyfuran under mild conditions, providing the corre-
bearing an amino functional group in recent years.1 Many successful
examples have been reported thus far. For example, Martin and Lopez
reported the first example of catalytic asymmetric addition of tri-
alkylsilyloxyfurans to aldimines in 1999, affording the corresponding
adducts in moderate ee value along with highyield.1a A few years late,
Hoveyda and Snapper have developed a elegant asymmetric catalytic
systemwith silver(I)-based catalystusing a 2-methyloxyphenyl group
as aldimine substituent, leading to the corresponding product of AVM
(asymmetric vinylogous Mannich) reaction of trimethylsiloxyfuran
with aldimine in excellent diastereo- and enantioselectivity.1b,c Later
on, a new highly diastereo- and enantioselective catalytic asymmetric
vinylogous Mannich-type reaction system applicable to a wide range
of aldimines, which do not possess a 2-methyloxyphenyl group, with
siloxyfuran using an axially chiral phosphineeoxazoline ligand [(R,S)-
P-Oxa-Ph]/AgOAc/CF3CH2OH combination has been developed by our
group.1e During our ongoing investigation on this interesting asym-
metric catalytic system, we attempted to explore the AVM reaction of
trimethylsiloxyfuran with N-Boc (tBuOC(O))-protected aldimine,
sponding chiral N-Boc-protected g-butenolides in moderate to good
enantiomeric excesses and good to high yields as well as good
diastereoselectivities.
2. Results and discussion
Axially chiral phosphineeoxazoline ligands L1eL6 are known
compounds and were synthesized according to the previous liter-
ature.1e,3 The new chiral phosphineeoxazoline ligands L7eL12
were synthesized from (aR)-1, which is derived from (R)-binol4 and
their synthetic route has been shown in Scheme 1. The spectro-
scopic data of these new chiral ligands are indicated in the exper-
imental section.
With these above chiral ligands in hand, we set out to utilize
the Lewis acid AgOAc (10 mol %)5 combined with chiral phos-
phineeoxazoline ligands L1eL12 (10 mol %) (Fig. 1) as the catalysts
* Corresponding author. Fax: þ86 21 64166128; e-mail address: mshi@mail.
sioc.ac.cn (M. Shi).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.03.046

Q.-Y. Zhao, M. Shi / Tetrahedron 67 (2011) 3724e3732
3725
O
HPAr2
CO2Me
OTf
CO2Me
CO2H
40% KOH
MeOH, reflux
12 h
Pd(OAc)2, dppb
DMSO, DIPEA
120 oC, 24 h
P(O)Ar2
P(O)Ar2
(aR)-3a: Ar = Ph (97%)
(aR)-2a: Ar = Ph (81%)
(aR)-1
3b
(aR)- : Ar = 4-FC6H4 (97%)
(aR)-2b: Ar = 4-FC6H4 (70%)
(aR)-3c: Ar = 4-MeOC6H4 (94%)
(aR)-3d: Ar = 4-MeC6H4 (95%)
2c
(aR)- : Ar = 4-MeOC6H4 (79%)
(aR)-2d: Ar = 4-MeC6H4 (74%)
3e
(aR)- : Ar = 3,5-Me2C6H3 (92%)
2e
(aR)- : Ar = 3,5-Me2C6H3 (83%)
HO
H2N
OH
O
R
HN
R
HSiCl3
MsCl
Et3N, DCM
reflux, 12 h
HOBT, EDCI
N
R
O
Et3N, toluene
DMF, rt
12 h
P(O)Ar2
P(O)Ar2
reflux,
24 h
(aR,S)-5a: R = 2-naphthylmethyl, Ar = Ph (91%)
(aR,S)-4a: R = 2-naphthylmethyl, Ar = Ph (91%)
5b
(aR,S)- : R = benzyl, Ar = Ph (82%)
4b
(aR,S)- : R = benzyl, Ar = Ph (82%)
t
5c
t
(aR,S)- : R = Bu, Ar = 4-FC6H4 (78%)
4c
(aR,S)- : R = Bu, Ar = 4-FC6H4 (78%)
t
(aR,S)-5d: R = Bu, Ar = 4-MeOC6H4 (85%)
(aR,S)-4d: R = tBu, Ar = 4-MeOC6H4 (85%)
(aR,S)-5e: R = tBu, Ar = 4-MeC6H4 (89%)
(aR,S)-5f: R = tBu, Ar = 3,5-Me2C6H3 (98%)
(aR,S)-4e: R = tBu, Ar = 4-MeC6H4 (89%)
t
(aR,S)-4f: R = Bu, Ar = 3,5-Me2C6H3 (98%)
O
N
R
PAr2
(aR,S)-L7: R = 2-naphthylmethyl, Ar = Ph (91%)
(aR,S)-L8: R = benzyl, Ar = Ph (82%)
(aR,S)-L9: R = tBu, Ar = 4-FC6H4 (78%)
t
L10
(aR,S)-
: R = Bu, Ar = 4-MeOC6H4 (85%)
t
L11
(aR,S)-
: R = Bu, Ar = 4-MeC6H4 (89%)
(aR,S)-L12: R = tBu, Ar = 3,5-Me2C6H3 (98%)
Scheme 1. Reaction procedure for the preparation of ligands L7eL12.
and the AVM reaction of readily available N-Boc aldimine 1a
(0.15 mmol) with siloxyfuran 2 (0.27 mmol) as a model reaction in
dichloromethane (CH2Cl2) containing 0.27 mmol (1.8 equiv) of
CH3CH2OH1d,e,5a to develop the optimal reaction conditions and
the results of these experiments are summarized in Table 1. It was
found that (aR,S)-P-Oxa-tBu (L6) is the best chiral ligand in this
reaction to afford the corresponding product 3a in 97% yield and
86% ee for the major diastereoisomer (dr¼6:1) in CH2Cl2 at ꢀ78 ꢁC
for 24 h (Table 1, entry 6). Other chiral ligands L1eL5 and L7eL12
are not as effective as L6 in this reaction under identical conditions
L4
: R = Ph, Ar = Ph
O
O
i
L5
: R = Pr, Ar = Ph
t
L6
: R = Bu, Ar = Ph
N
R
N
R
L7: R = 2-naphthylmethyl, Ar = Ph
L8: R = benzyl, Ar = Ph
PPh2
PAr2
t
L9
: R = Bu, Ar = 4-FC6H4
t
L10
: R = Bu, Ar = 4-MeOC6H4
(aS,S)
L1
(aR,S)
t
L11
: R = Bu, Ar = 4-MeC6H4
: R = Ph
t
L12: R = Bu, Ar = 3,5-Me2C6H3
L2: R = iPr
L3: R = tBu
Fig. 1. Axially chiral phosphineeoxazoline ligands L1eL12.

3726
Q.-Y. Zhao, M. Shi / Tetrahedron 67 (2011) 3724e3732
drs were observed at 0 ꢁC and at room temperature (dr>20:1)
(Table 2, entries 1e5). When solvents, such as tetrahydrofuran
(THF), toluene, CH2ClCH2Cl, and CHCl2CHCl2 were used in this re-
action, lower ee value (from 77% to 57%) was realized but along
with good to excellent drs (from 11:1 to >20:1) (Table 2, entries
6e9). Previous studies have revealed that the addition of alcoholic
additives can enhance the reactivity and enantioselectivity in this
asymmetric reaction.6 The optimization studies on the effects of
different alcoholic additives in this reaction were then performed
and the results of these experiments are also summarized in Table 2
(entries 10e13). A significant decrease in enantioselectivity was
observed by adding CF3CH2OH or BnOH (1.8 equiv) into the reaction
system (Table 2, entries 10 and 11). We also examined additive
Table 1
Optimization of chiral ligands for the AVM reaction of N-Boc aldimine 1a and
siloxyfuran 2
Boc
Boc
N
HN
AgOAc (10 mol %),
L
(10 mol %)
+
OTMS
CH2Cl2, CH3CH2OH (1.8 equiv),
O
-78 oC, 24 h
O
MeO
MeO
2
O
1a
3a
Entrya
Ligand
Yield [%]b
anti:sync
anti, ee [%]d
3a
3a
3a
1
2
3
4
5
6
7
8
L1
L2
L3
L4
L5
L6
L7
L8
90
79
82
98
99
97
89
94
85
88
90
92
>20:1
7:1
47
53
52
46
51
86
61
68
65
80
79
79
5:1
t
effects of i-PrOH and BuOH in this reaction under identical con-
>20:1
>20:1
6:1
ditions, but no improvement was observed (Table 2, entries 12 and
13). Therefore, the best reaction conditions are those using 10 mol %
of AgOAc along with 10 mol % of chiral ligand L6 as the catalyst and
carrying out the reaction in CH2Cl2 at ꢀ78 ꢁC for 24 h in the pres-
ence of 1.8 equiv of CH3CH2OH.
9:1
9:1
5:1
6:1
7:1
4:1
9
L9
10
11
12
L10
L11
L12
Having established the optimal conditions, we next examined
the generality of this reaction using various N-Boc-protected imines
1 with siloxyfuran 2 and the results are summarized inTable 3. It was
found that the N-Boc-protected imines 1bei bearing an aromatic
ring (R group¼aromatic ring) could react with 2 smoothly to give the
corresponding asymmetricvinylogousMannich-typeproducts 3bei
in good to high yields (79%e97%) and good diastereoselectivities
(4:1e7:1 dr) as well as moderate to good enantiomeric excesses
(63%e83% ee) for the major diastereoisomers whether they have
electron-rich or electron-poor aromatic groups (Table 2, entries
2e9). When R is a heteroaryl group, such as 2-furyl group, similar
result was obtained, affording the desired adduct 3j in 79% yield, 80%
ee and 7:1 dr (Table 2, entry 10). As for alkyl N-Boc-protected imine
1k, the reactions also proceeded smoothly to give the corresponding
N-Boc-protected g-butenolides 3k in 75 yield and 75% ee along with
6:1 dr value (Table 2, entry 11).
The synthetic utility of the product can be displayed by removal
of the N-Boc-protecting group with trifluoroacetic acid (TFA) in
CH2Cl2 at room temperature for 4 h, affording the corresponding
free amine product 4 in 92% yield (Scheme 2). The absolute
a
Reaction conditions: 1a (0.15 mmol), 2 (0.27 mmol), CH3CH2OH (0.27 mmol),
AgOAc (10 mol %), ligand (10 mol %), CH2Cl2 (1.0 mL), and the reaction was carried
out at ꢀ78 ꢁC for 24 h.
b
Yields of the purified syn and anti product.
c
Determined by 1H NMR spectroscopic data of the crude product.
d
Determined by chiral HPLC analysis.
(Table 1, entries 1e5 and 7e12) although excellent yields and drs
were achieved when L1, L4, and L5 were used as the chiral ligands
in this reaction (Table 1, entries 1, 4, and 5).
The effects of temperature, solvents, and additives were then
investigated using the best chiral (aR,S)-P-Oxa-tBu ligand L6 in the
model reaction of 1a with 2, the results are outlined in Table 2
combined with the result obtained in DCM for comparison (Table
2, entry 5). It can be seen from Table 2, increasing the reaction
temperature from ꢀ78 ꢁC to room temperature (20 ꢁC) caused the
decrease in enantioselectivity (from 86% to 61%) although excellent
Table 2
Optimization of the temperature, solvent, and additive for the AVM reaction of
N-Boc aldimine 1a and siloxyfuran 2
Table 3
Scope and limitations of AVM reaction of N-Boc aldimines 1 and siloxyfuran 2
Boc
Boc
+
HN
*
Boc
N
HN
AgOAc (10 mol %),
AgOAc (10 mol %),
Boc
L6 (10 mol %)
N
L6 (10 mol %)
*
OTMS
+
OTMS
O
R
solvent, additive (1.8 equiv),
T, 24 h
MeO
O
2
CH2Cl2, CH3CH2OH (1.8 equiv),
-78 oC, 24 h
MeO
O
2
R
O
O
1a
3a
1
O
3
Entrya T [ꢁC] Solvent
Additive
Yield [%]b anti:sync anti, ee [%]d
Entrya
R
Yield [%]b
anti:sync
anti, ee [%]d
3a
3a
20:1
3a
3
3
3
1
2
3
4
5
6
7
8
rt
0
DCM
DCM
DCM
DCM
DCM
THF
CH3CH2OH 99
CH3CH2OH 67
CH3CH2OH 63
CH3CH2OH 90
CH3CH2OH 97
CH3CH2OH 85
CH3CH2OH 60
61
67
73
64
86
77
74
78
57
52
65
85
74
>20:1
5:1
8:1
1
2
3
4
5
6
7
8
p-MeOC6H4, 1a
m-MeOC6H4, 1b
p-MeC6H4, 1c
m-MeC6H4, 1d
3,4,5-(MeO)3C6H2, 1e
Ph, 1f
3a, 97 (83)
3b, 95 (83)
3c, 90 (72)
3d, 92 (79)
3e, 94 (78)
3f, 82 (70)
3g, 93 (80)
3h, 88 (75)
3i, 79 (69)
3j, 79 (69)
3k, 88 (75)
6:1
7:1
4:1
6:1
5:1
6:1
6:1
6:1
7:1
7:1
6:1
86
78
83
71
76
77
63
67
73
80
75
ꢀ20
ꢀ40
ꢀ78
ꢀ78
ꢀ78
ꢀ20
ꢀ20
ꢀ78
ꢀ78
ꢀ78
ꢀ78
6:1
19:1
>20:1
>20:1
11:1
6:1
Toluene
CH2ClCH2Cl CH3CH2OH 83
CHCl2CHC2 CH3CH2OH 77
DCM
DCM
DCM
DCM
p-FC6H4, 1g
9
p-BrC6H4 1 h
m-BrC6H4 1i
2-Furyl, 1j
10
11
12
13
CF3CH2OH 80
9
10
11
BnOH
i-PrOH
tBuOH
63
82
88
3:1
5:1
11:1
Cydohexyl, 1k
a
Reaction conditions: 1a (0.15 mmol), 2 (0.27 mmol), CH3CH2OH (0.27 mmol),
AgOAc (10 mol %), ligand (10 mol %), CH2Cl2 (1.0 mL), and the reaction was carried
out at ꢀ78 ꢁC for 24 h.
a
Reaction conditions: 1a (0.15 mmol), 2 (0.27 mmol), CH3CH2OH (0.27 mmol),
AgOAc (10 mol %), ligand (10 mol %), solvent (1.0 mL), and the reaction was carried
out at rt wꢀ78 ꢁC for 24 h.
b
Yields are determined by 1H NMR spectrum and in parentheses are isolated
b
Yields of the purified syn and anti product.
yields of the anti isomer.
c
c
Determined by 1H NMR spectroscopic data of the crude product.
Determined by 1H NMR spectroscopic data of the crude product.
Determined by chiral HPLC analysis.
d
d
Determined by chiral HPLC analysis.

Q.-Y. Zhao, M. Shi / Tetrahedron 67 (2011) 3724e3732
3727
configuration was assigned to be (R,S) for the products 3aek by
comparison of the free amine product 40s 1H NMR and 13C NMR
spectra data as well as optical rotation with literature values.1b,e
determined at 589 nm (sodium D line) by using a PerkineElmer-
341 MC digital polarimeter; [ ]D-values are given in unit of
a
10 degꢀ1 cm2 gꢀ11H NMR spectra were recorded on a Bruker AM-300
and AM-400 spectrometer for solution in CDCl3 with tetramethylsi-
lane (TMS) as an internal standard; coupling constants J are given in
hertz.19Fand31PNMRspectrawererecordedonaBrukerAM-300and
AM-400 spectrophotometers with complete proton decoupling
spectrophotometers. Infrared spectra were recorded on a Per-
kineElmer PE-983 spectrometer with absorption in cmꢀ1. Flash col-
umn chromatography was performed using 300e400 mesh silica gel.
For thin-layer chromatography (TLC), silica gel plates (Huanghai
GF254) were used. Chiral HPLC was performed on an SHIMADZU SPD-
10A vp series with chiral columns (Chiralpak AD-H, OJ-H, PA-H, and
IC-H columns 4.6ꢂ250 mm, (Daicel ChemicalInd., Ltd.)). Massspectra
were recorded by EI, ESI, MALDI, and HRMS was measured on an HP-
5989 instrument. Organic solvents used were dried by standard
methods when necessary. N-Boc aldimines 1aek were prepared
according to the previous reports.8 (aR)-2a and (aR)-3a are known
compounds and were prepared according to literature procedures.1e,3
O
NH2
(S)
(R)
HN
O
TFA
CH2Cl2, r.t., 4 h
O
O
O
4
, 92% yield,
O
3f
[ ]D20: -71.5 (c 1.0, CHCl3)
Scheme 2. Removal of the N-Boc group and determination of the absolute config-
uratiion of 4.
To identify the coordination pattern between L6 and AgOAc, we
treated L6 with AgOAc (1.0 equiv) at 25 ꢁC in DCM-d2 for 0.5 h, and
measured their 31P NMR spectroscopy at 25 ꢁC. A significant
chemical shift change of their 31P NMR spectroscopic signals has
been observed from ꢀ15.97 ppm (singlet) to 4.85 ppm (doublet,
J¼555 Hz) in comparison with that of L6, suggesting the co-
ordination between L6 and AgOAc (see the Supplementary data).
On the basis of previous mechanistic studies by Hoveyda and our
group,1c,e a transition-state model can be outlined in Fig. 2. In the
activated complex, to minimize the steric interactions, the sub-
strate is bound anti to the bulky substituent (tBu) on oxazoline of
L6. The catalyst-bound imine may react with the siloxyfuran by an
endo-type addition,7 and consequently, the reaction of a optically
active N-Boc imines with siloxyfuran catalyzed by AgOAc combined
with L6 provides the (R, S) stereoisomer predominantly.
4.2. Typical reaction procedure for the preparation of (aR)-2
To a solution of (aR)-14 (115 mg, 0.25 mmol), diarylphosphine
oxide (0.50 mmol), palladium diacetate (5.6 mg, 0.025 mmol), and
1,4-bis(diphenylphosphino)butane (10.7 mg, 0.025 mmol), in
1.5 mL of DMSO was added diisopropylethylamine (0.21 mL,
1.2 mmol), and the mixture was stirred at 120 ꢁC for 24 h. After
being cooled to room temperature, the reaction mixture was di-
luted with EtOAc, washed with H2O, and dried over MgSO4. Re-
moval of the solvent followed by column chromatography on silica
gel (elution with n-hexane/EtOAc¼1/2) gave compound (aR)-2.
4.2.1. Compound (aR)-2b. Yield: 70%, 96 mg, white solid, mp
O
79e80 ꢁC; IR (neat):
n
3056, 2949, 2884, 2835, 1718, 1589, 1497,
1277, 1225, 1190, 1158, 1113, 877, 828, 766, 662 cmꢀ1 1H NMR
(400 MHz, CDCl3, TMS): 3.55 (3H, s), 6.70e6.75 (2H, m), 6.86e6.91
N
Ph
;
d
H
Ag
(2H, m), 6.97 (1H, d, J¼8.4 Hz), 7.05e7.20 (3H, m), 7.30e7.40 (3H,
m), 7.45e7.51 (3H, m), 7.64 (1H, dd, J¼8.8, 12.0 Hz), 7.72 (1H, d,
J¼8.0 Hz), 7.78 (1H, d, J¼8.4 Hz), 7.89 (1H, d, J¼8.4 Hz), 7.95 (1H, d,
J¼8.8 Hz), 8.05 (1H, d, J¼8.4 Hz); 31P NMR (161.94 MHz, CDCl3, 85%
N
P
CH3
Si
Ph
O
Ph
CH3
CH3
26.24; 19F NMR (376 MHz, CDCl3, CFCl3):
d
ꢀ107.4 to 107.5
O
H3PO4):
d
O
O
(1F, m), ꢀ107.8 to 107.9 (1F, m); MS (ESI) m/z 549.5 (MþHþ, 100).
HRMS (MALDI) calcd for C34H24O3F2P requires (MþHþ) 549.1426,
20 þ19.8 (c 0.44, CH2Cl2).
CH3CH2OH
found: 549.1439; [a]
D
Fig. 2. Plausible transition-state model.
4.2.2. Compound (aR)-2c. Yield: 79%, 113 mg, white solid, mp
85e68 ꢁC; IR (neat):
3057, 2976, 2885, 2836,1719,1595,1501,1277,
1244, 1177, 1115, 1023, 828, 800, 766, 695, 646 cmꢀ1 1H NMR
(400 MHz, CDCl3, TMS): 3.53 (3H, s), 3.71 (3H, s), 3.77 (3H, s), 6.58
n
3. Conclusion
;
d
In summary, we have reported a silver(I)-catalyzed catalytic
asymmetric Mannich reaction of N-Boc imines with trimethylsi-
loxyfuran in the presence of chiral phosphineeoxazoline ligand L6
in CH2Cl2 under mild conditions, affording the corresponding ad-
ducts in good to high yields and good diastereoselectivities along
with moderate to good enantioselectivities. Since the N-Boc group
can be easily cleaved under several convenient acidic conditions
(2H, dd, J¼2.4, 8.8 Hz), 6.68 (1H, dd, J¼2.4, 8.8 Hz), 6.97e7.02 (2H,
m), 7.09e7.13 (1H, m), 7.18e7.27 (3H, m), 7.33e7.41 (3H, m), 7.49
(1H, t, J¼8.0 Hz), 7.68e7.78 (3H, m), 7.90e7.95 (2H, m), 8.03 (1H, d,
J¼8.8 Hz); 31P NMR (161.93 MHz, CDCl3, 85% H3PO4):
d 27.44; MS
(MALDI) m/z 573.5 (MþHþ, 100). HRMS (ESI) calcd for C36H30O5P
requires (MþHþ) 573.1825, found: 573.1828; [
a]
þ15.8 (c 0.40,
20
D
CH2Cl2).
(HCl or TFA),2 the chiral N-Boc-protected
g-butenolides synthe-
sized in this paper will be more useful in organic synthesis.
4.2.3. Compound (aR)-2d. Yield: 74%, 100 mg, white solid, mp
79e80 ꢁC; IR (neat):
3056, 2986, 2877, 2837, 1720, 1599, 1433,
1276, 1241, 1186, 1132, 809, 765, 747, 658, 645 cmꢀ1 1H NMR
(300 MHz, CDCl3, TMS): 2.20 (3H, s), 2.30 (3H, s), 3.53 (3H, s), 6.83
n
4. Experimental section
4.1. General remarks
;
d
(2H, dd, J¼2.4, 7.8 Hz), 6.95e7.11 (5H, m), 7.16e7.25 (3H, m),
7.34e7.40 (3H, m), 7.48 (1H, t, J¼7.8 Hz), 7.63e7.70 (2H, m), 7.76
(1H, d, J¼9.0 Hz), 7.89e7.94 (2H, m), 8.02 (1H, d, J¼9.0 Hz); 31P NMR
Melting points were determined on a digital melting point appa-
ratus and temperatures were uncorrected. Optical rotations were
(121.45 MHz, CDCl3, 85% H3PO4):
d 28.82; MS (ESI) m/z 541.6

3728
Q.-Y. Zhao, M. Shi / Tetrahedron 67 (2011) 3724e3732
(MþHþ, 100). HRMS (MALDI) calcd for C36H30O3P requires (MþHþ)
for C37H31O3PNa requires (MþNaþ) 577.1903, found: 577.1911;
20
541.1927, found: 541.1918; [
a
]
20 þ6.0 (c 0.58, CH2Cl2).
[a
]
þ127.4 (c 1.0, CH2Cl2).
D
D
4.2.4. Compound (aR)-2e. Yield: 83%, 118 mg, white solid, mp
107e110 ꢁC; IR (CH2Cl2):
3048, 2948, 2918, 2859, 1724, 1597, 1455,
1433, 1276, 1243, 1190, 1132, 871, 852, 767, 733, 696 cmꢀ1; 1H NMR
(400 MHz, CDCl3, TMS): 2.06 (6H, s), 2.20 (6H, s), 3.59 (3H, s), 6.70
n
4.4. Typical reaction procedure for the preparation of (aR)-4
d
A mixture of compound (aR)-3 (1.0 mmol), chiral aminoalcohol
(2.0 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hy-
drochloride (576 mg, 3.0 mmol), and 1-hydroxy-benzotriazole
(542 mg, 4.00 mmol) in N,N-dimethylformamide (20 mL) was
stirred at room temperature overnight. Then, the solvent was re-
moved from the flask under reduced pressure. The resulting residue
was diluted with CH2Cl2, washed with saturated NaCl solution
twice, and extracted by CH2Cl2. The organic layer was dried over
anhydrous Na2SO4 and concentrated under reduced pressure. The
residue was chromatographed on silica gel (elution with petroleum
ether/EtOAc¼1:1) to give compound (aR,S)-4.
(1H, s), 6.89 (1H, d, J¼12 Hz), 6.95e7.02 (3H, m), 7.11e7.29 (5H, m),
7.36 (1H, td, J¼1.2, 7.2 Hz), 7.49 (1H, t, J¼7.2 Hz), 7.68e7.75 (3H, m),
7.90e7.95 (2H, m), 8.03 (1H, d, J¼8.4 Hz); 31P NMR (161.94 MHz,
CDCl3, TMS):
d
27.08; MS (ESI) m/z 569.4 (MþHþ, 100). HRMS (ESI)
calcd for C38H33O3PNa requires (MþNaþ) 591.2060, found:
20
591.2071; [
a]
ꢀ8.2 (c 1.0, CH2Cl2).
D
4.3. Typical reaction procedure for the preparation of (aR)-3
To a solution of (aR)-2 (0.20 mmol) in 2.5 mL of methanol (dioxane
for (aR)-2b) was added 500 mL of 40% KOH solution and the mixture
was refluxed for 13 h. The reaction mixture was acidified to pH¼2 by
addition of concd HCl at 0 ꢁC and extracted with CH2Cl2 (2ꢂ20 mL).
The combined organic layers were dried over anhydrous Na2SO4 and
concentrated under reduced pressure. The crude product was
recrystallizedinCH2Cl2 andpetroleumethertogivecompound(aR)-3.
4.4.1. Compound (aR,S)-4a. Yield: 91%, 620 mg, white solid, mp
229e230 ꢁC; IR (neat):
n
3367, 3296, 3057, 3022, 2946, 2877, 2825,
1651, 1537, 1435, 1297, 1147, 1112, 872, 822, 750, 721, 687, 639 cmꢀ1
1H NMR (300 MHz, CDCl3, TMS):
;
d
1.86 (1H, dd, J¼5.1, 13.5 Hz), 2.13
(1H, dd, J¼10.2, 13.5 Hz), 3.32e3.40 (1H, m), 3.70e3.74 (1H, m),
4.00e4.02 (1H, m), 4.24e4.29 (1H, m), 6.66e6.73 (3H, m),
6.89e6.96 (2H, m), 7.06e7.13 (4H, m), 7.19e7.28 (2H, m), 7.34e7.38
(3H, m), 7.45 (1H, t, J¼7.2 Hz), 7.52e7.64 (7H, m), 7.70e7.86 (4H, m),
7.91e7.98 (3H, m), 8.97 (1H, d, J¼7.5 Hz); 31P NMR (121.45 MHz,
4.3.1. Compound (aR)-3b. Yield: 97%, 104 mg, white solid, mp
ꢁ
148e150 C; IR (neat):
n 3057, 2989, 2884, 2829, 1588, 1497, 1386,
1226, 1159, 1134, 1013, 807, 772, 745, 663 cmꢀ1; 1H NMR (400 MHz,
CDCl3, TMS):
d
6.28 (1H, d, J¼8.4 Hz), 6.62e6.65 (2H, m), 6.80 (1H, t,
CDCl3, 85% H3PO4):
d
31.41; MS (ESI) m/z 682.6 (MþHþ, 100). HRMS
J¼7.2 Hz), 7.12e7.20 (5H, m), 7.26e7.34 (3H, m), 7.54 (1H, t, J¼8.0 Hz),
(MALDI) calcd for C46H37NO3P requires (MþHþ) 682.2506, found:
20
7.68e7.77 (4H, m), 7.89e7.97 (3H, m); 31P NMR (161.94 MHz, CDCl3,
682.2510; [
a]
ꢀ28.3 (c 1.1, CH2Cl2).
D
85% H3PO4):
d
33.26 (t, J¼1.6 Hz); 19F NMR (376 MHz, CDCl3, CFCl3):
d
ꢀ104.9 to 105.0 (1F, m), ꢀ106.2 to 106.3 (1F, m); MS (ESI) m/z 535.5
4.4.2. Compound (aR,S)-4b. Yield: 82%, 517 mg, white solid, mp
ꢁ
(MþHþ, 100). HRMS (MALDI) calcd for C33H21O3F2PNa requires
262e263 C; IR (neat):
1543, 1435, 1295, 1147, 1090, 943, 875, 832, 816, 753, 707, 641 cmꢀ1
1H NMR (300 MHz, CDCl3, TMS):
n 3406, 3263, 3059, 2995, 2879, 2825, 1649,
(MþNaþ) 557.1089, found: 557.1089; [
a]
20 ꢀ78.7 (c 1.0, CH2Cl2).
;
D
d
1.68 (1H, dd, J¼5.1, 13.5 Hz), 1.94
4.3.2. Compound (aR)-3c. Yield: 94%, 105 mg, white solid, mp
116e117 ꢁC; IR (neat):
3058, 2964, 2892, 2837,1711,1594,1501,1404,
1254, 1116, 1022, 800, 746, 650 cmꢀ1 1H NMR (400 MHz, CDCl3,
TMS):
(1H, dd, J¼10.2, 13.5 Hz), 3.27e3.36 (1H, m), 3.68e3.73 (1H, m),
3.83e3.91 (1H, m), 4.22e4.26 (1H, m), 6.67e6.75 (3H, m), 6.89e6.97
(4H, m), 7.07e7.13 (6H, m), 7.20e7.33 (2H, m), 7.52e7.65 (6H, m), 7.79
(2H, dd, J¼8.4, 30.0 Hz), 7.90e8.02 (4H, m), 8.85 (1H, d, J¼7.8 Hz); 31P
n
;
d
3.68 (3H, s), 3.87 (3H, s), 6.18 (1H, d, J¼8.4 Hz), 6.43 (2H, dd,
J¼2.0, 8.8 Hz), 6.68e6.72 (1H, m), 7.00e7.05 (4H, m), 7.10 (1H, d,
J¼8.4 Hz), 7.18 (1H, t, J¼8.0 Hz), 7.24e7.28 (1H, m), 7.34 (1H, dd, J¼8.4,
12.4 Hz), 7.51 (1H, t, J¼8.0 Hz), 7.66e7.74 (4H, m), 7.87e7.94 (3H, m);
NMR (121.45 MHz, CDCl3, 85% H3PO4): d 31.49; MS (ESI) m/z 632.6
(MþHþ, 100). HRMS (MALDI) calcd for C42H35NO3P requires (MþHþ)
632.2349, found: 632.2342; [
a
]
20 ꢀ26.3 (c 0.74, CH2Cl2).
D
31P NMR (161.93 MHz, CDCl3, 85% H3PO4):
d 34.53; MS (ESI) m/z 559.4
(MþHþ, 100). HRMS (ESI) calcd for C35H27NaO5P requires (MþNaþ)
4.4.3. Compound (aR)-4c. Yield: 78%, 494 mg, white solid, mp
225e226 ꢁC; IR (neat):
3431, 3224, 3065, 2965, 2880, 2836, 1647,
1591, 1495, 1397, 1227, 1184, 1093, 1058, 847, 825, 680 cmꢀ1 1H
NMR (300 MHz, CDCl3, TMS): 0.24 (9H, s), 3.26e3.34 (1H, m),
581.1488, found: 581.1507; [
a]
D
20 þ86.4 (c 0.59, CH2Cl2).
n
;
4.3.3. Compound (aR)-3d. Yield: 95%, 100 mg, white solid, mp
d
ꢁ
245e246 C; IR (neat):
1284, 1115, 1086, 1019, 826, 806, 752, 680, 649 cmꢀ1
(300 MHz, CDCl3, TMS): 2.16 (3H, s), 2.44 (3H, s), 6.18 (1H, d,
n
3049, 2984, 2883, 2833, 1717, 1599, 1404,
3.69e3.82 (2H, m), 4.25 (1H, t, J¼6.0 Hz), 6.36e6.43 (2H, m), 6.54
(1H, d, J¼9.0 Hz), 6.97e7.11 (3H, m), 7.19e7.25 (3H, m), 7.30e7.43
(3H, m), 7.49e7.62 (3H, m), 7.77 (1H, d, J¼9.0 Hz), 7.83e8.02 (4H,
m), 8.12 (1H, d, J¼8.4 Hz); 31P NMR (121.45 MHz, CDCl3, 85%
;
1H NMR
d
J¼8.7 Hz), 6.63e6.73 (3H, m), 6.96e7.03 (2H, m), 7.09e7.20 (2H, m),
7.24e7.37 (4H, m), 7.51 (1H, t, J¼7.5 Hz), 7.63e7.73 (4H, m),
7.86e7.93 (3H, m); 31P NMR (121.45 MHz, CDCl3, 85% H3PO4):
H3PO4):
d
28.66 (t, J¼1.6 Hz); 19F NMR (282 MHz, CDCl3, CFCl3):
d
ꢀ106.3 to 106.5 (1F, m), ꢀ108.0 to 108.1 (1F, m); MS (ESI) m/z
d
35.79; MS (ESI) m/z 527.6 (MþHþ, 100). HRMS (MALDI) calcd for
634.7 (MþHþ, 100). HRMS (MALDI) calcd for C39H34NO3F2PNa re-
20
C35H28O3P requires (MþHþ) 527.1771, found: 527.1766; [
a]
20 þ119.5
quires (MþNaþ) 656.2137, found: 656.2126; [
a]
ꢀ34.0 (c 0.29,
D
D
(c 0.7, CH2Cl2).
CH2Cl2).
4.3.4. Compound (aR)-3e. Yield: 92%, 102 mg, white solid, mp
325e328 ꢁC; IR (CH2Cl2):
3054, 2918, 2859, 2461, 1923, 1718, 1599,
1502, 1466, 1402, 1272, 1232, 1157, 1134, 1104, 878, 852, 766, 738,
693, 644 cmꢀ1; 1H NMR (400 MHz, CDCl3, TMS):
2.00 (6H, s), 2.36
4.4.4. Compound (aR)-4d. Yield: 85%, 558 mg, white solid, mp
191e192 ꢁC; IR (neat):
3429, 3302, 3241, 3068, 2958, 2900, 2836,
1642, 1594, 1522, 1499, 1249, 1169, 1113, 1022, 799, 765, 667,
643 cmꢀ1; 1H NMR (400 MHz, CDCl3, TMS):
0.25 (9H, s), 3.44 (1H,
n
n
d
d
(6H, s), 6.24 (1H, d, J¼8.0 Hz), 6.62 (1H, s), 6.70 (2H, d, J¼12.8 Hz),
6.77 (1H, t, J¼8.0 Hz), 7.10e7.17 (2H, m), 7.24e7.30 (3H, m),
7.34e7.42 (3H, m), 7.53 (1H, t, J¼8.0 Hz), 7.65 (1H, d, J¼8.0 Hz), 7.72
(1H, d, J¼8.0 Hz), 7.88e7.95 (3H, m); 31P NMR (161.94 MHz, CDCl3,
dd, J¼6.4, 11.6 Hz), 3.64 (3H, s), 3.73e3.81 (2H, m), 3.85 (3H, s), 6.22
(2H, dd, J¼2.4, 8.8 Hz), 6.48 (1H, d, J¼8.4 Hz), 6.90e7.03 (5H, m),
7.20e7.31 (3H, m), 7.52e7.59 (3H, m), 7.74e7.81 (3H, m), 7.90e7.96
(3H, m), 8.09 (1H, d, J¼8.8 Hz); 31P NMR (161.93 MHz, CDCl3, 85%
TMS):
d
34.02; MS (ESI) m/z 555.4 (MþHþ, 100). HRMS (ESI) calcd
H3PO4):
d
29.25; MS (ESI) m/z 658.6 (MþHþ, 100). HRMS (ESI) calcd

Q.-Y. Zhao, M. Shi / Tetrahedron 67 (2011) 3724e3732
3729
20
for C41H41NO5P requires (MþHþ) 658.2717, found: 658.2714; [
ꢀ43.7 (c 0.39, CH2Cl2).
a
]
D
1236,1158,1099,1058,1112, 817, 741 cmꢀ1; 1H NMR (300 MHz, CDCl3,
TMS):
d
0.57 (9H, s), 3.55 (1H, t, J¼8.4 Hz), 3.70 (1H, t, J¼9.3 Hz), 3.93
(1H, t, J¼9.3 Hz), 6.72e6.83 (4H, m), 7.05e7.27 (4H, m), 7.31e7.43
(5H, m), 7.50 (1H, t, J¼7.5 Hz), 7.69e7.77 (3H, m), 7.88e7.97 (3H, m);
4.4.5. Compound (aR)-4e. Yield: 89%, 557 mg, white solid, mp
ꢁ
117e118 C; IR (neat):
2830, 1645, 1550, 1502, 1308, 1165, 1113, 1093, 810, 748, 661,
646 cmꢀ1; 1H NMR (400 MHz, CDCl3, TMS):
0.24 (9H, s), 2.07 (3H, s),
n
3425, 3305, 3239, 3055, 2973, 2950, 2877,
31P NMR (121.45 MHz, CDCl3, 85% H3PO4):
d
27.52 (t, J¼1.8 Hz); 19F
NMR (282 MHz, CDCl3, CFCl3):
d
ꢀ108.4 to 108.5 (2F, m); MS (ESI) m/z
d
616.6 (MþHþ, 100). HRMS (MALDI) calcd for C39H33NO2F2P requires
2.41 (3H, s), 3.44 (1H, dd, J¼6.0, 11.2 Hz), 3.74e3.82 (2H, m), 4.41 (1H,
s), 6.48 (3H, d, J¼8.4 Hz), 6.88e6.98 (3H, m), 7.19e7.33 (5H, m),
7.50e7.60 (3H, m), 7.72e7.80 (3H, m), 7.90e7.96 (3H, m), 8.08 (1H, d,
(MþHþ) 616.2212, found: 616.2211; [
a]
D
20 þ72.6 (c 0.42, CH2Cl2).
4.5.4. Compound (aR,S)-5d. Yield: 85%, 543 mg, white solid, mp
96e97 ꢁC; IR (neat):
3058, 2950, 2895, 2836, 1637, 1595, 1501,
1292, 1251, 1117, 1114, 1024, 823, 750, 663 cmꢀ1; 1H NMR (300 MHz,
CDCl3, TMS):
J¼8.8 Hz); 31P NMR (161.93 MHz, CDCl3, 85% H3PO4):
d
31.01; MS (ESI)
n
m/z 626.7 (MþHþ,100). HRMS (MALDI) calcd for C41H41NO3P requires
(MþHþ) 626.2819, found: 626.2818; [
a]
D
20 ꢀ41.7 (c 0.52, CH2Cl2).
d
0.56 (9H, s), 3.51 (1H, t, J¼8.4 Hz), 3.69 (1H, t,
J¼8.4 Hz), 3.75 (3H, s), 3.76 (3H, s), 3.91 (1H, dd, J¼8.4, 9.9 Hz),
6.56e6.65 (4H, m), 7.03e7.22 (4H, m), 7.26e7.39 (5H, m), 7.47 (1H,
t, J¼7.8 Hz), 7.68e7.96 (6H, m); 31P NMR (121.45 MHz, CDCl3, 85%
4.4.6. Compound (aR)-4f. Yield: 98%, 640 mg, white solid, mp
275e278 ꢁC; IR (CH2Cl2):
3434, 3055, 2957, 2866, 1649, 1551, 1503,
1272, 1175, 1164, 1152, 1162, 876, 852, 718, 748, 696 cmꢀ1; 1H NMR
(300 MHz, CDCl3, TMS): 0.25 (9H, s), 1.93 (6H, s), 2.36 (6H, s),
n
H3PO4):
d
29.04; MS (ESI) m/z 640.7 (MþHþ, 100). HRMS (MALDI)
d
calcd for C41H39NO4P requires (MþHþ) 640.2611, found: 640.2624;
20
3.40e3.48 (1H, m), 3.73e3.81 (2H, m), 4.33 (1H, t, J¼7.2 Hz), 6.45
(1H, s), 6.50 (1H, d, J¼8.1 Hz), 6.65 (1H, d, J¼12.6 Hz), 6.97 (1H, t,
J¼6.9 Hz), 7.16e7.31 (4H, m), 7.50e7.66 (5H, m), 7.75 (1H, d,
J¼8.7 Hz), 7.91e8.00 (3H, m), 8.10 (1H, d, J¼8.7 Hz); 31P NMR
[a
]
þ42.0 (c 0.28, CH2Cl2).
D
4.5.5. Compound (aR,S)-5e. Yield: 89%, 540 mg, white solid, mp
83e84 ꢁC; IR (neat):
3050, 2973, 2898, 2868, 2836, 1635, 1600,
1359, 1186, 1112, 1055, 973, 808, 749, 658 cmꢀ1; 1H NMR (400 MHz,
CDCl3, TMS): 0.56 (9H, s), 2.25 (3H, s), 2.26 (3H, s), 3.51 (1H, t,
n
(121.45 MHz, CDCl3, TMS):
d
24.77; MS (ESI) m/z 654.4 (MþHþ,100).
HRMS (ESI) calcd for C43H45NO3P requires (MþHþ) 654.3132,
d
20
found: 654.3145; [
a
]
ꢀ30.1 (c 1.0, CH2Cl2).
J¼8.4 Hz), 3.67 (1H, t, J¼9.6 Hz), 3.90 (1H, dd, J¼8.4, 9.6 Hz),
6.88e6.91 (4H, m), 7.03e7.11 (3H, m), 7.17e7.37 (6H, m), 7.47 (1H, t,
J¼8.0 Hz), 7.66e7.77 (3H, m), 7.86e7.93 (3H, m); 31P NMR
D
4.5. Typical reaction procedure for the preparation of (aR)-5
(161.93 MHz, CDCl3, 85% H3PO4):
d 28.46; MS (ESI) m/z 608.7
To a mixture of compound (aR)-4 (1.0 mmol), 4-dimethylamino-
pyridine (1.22 mg, 0.01 mmol), and triethylamine (1.8 mL, 2.0 mmol) in
dichloromethane (15 mL) was added methanesulfonyl chloride
(0.4 mL, 2.0 mmol) at 0 ꢁC, and the solution was stirred for 0.5 h at this
temperature. Then anotherportion of triethylamine (1.4 mL, 9.0 mmol)
was added to the solution, and it was refluxed until the initially formed
mesylationproduct disappeared (checked by TLC plates). On cooling to
room temperature, the reaction mixture was diluted with CH2Cl2, then
washed with saturated NaHCO3 solution and extracted by CH2Cl2. The
organic layer was dried over anhydrous Na2SO4 and concentrated
under reduced pressure. The residue was chromatographed on silica
gel (elution with EtOAc) to give compound (aR,S)-5.
(MþHþ, 100). HRMS (MALDI) calcd for C41H39NO2P requires
(MþHþ) 608.2713, found: 608.2714; [
a
]
D
20 þ41.9 (c 0.45, CH2Cl2).
4.5.6. Compound (aR,S)-5f. Yield: 98%, 622 mg, white solid, mp
121e126 ꢁC; IR (CH2Cl2):
3050, 2954, 2865, 1640, 1600, 1477, 1360,
1271, 1191, 1124, 978, 870, 853, 824, 749, 669, 642 cmꢀ1 1H NMR
(300 MHz, CDCl3, TMS): 0.55 (9H, s), 2.13 (6H, s), 2.14 (6H, s), 3.54
n
;
d
(1H, t, J¼9.3 Hz), 3.72 (1H, t, J¼9.3 Hz), 3.98 (1H, t, J¼8.7 Hz), 6.85
(2H, d, J¼13.2 Hz), 6.96e7.22 (8H, m), 7.36 (1H, t, J¼7.5 Hz), 7.47
(1H, t, J¼7.5 Hz), 7.66e7.78 (3H, m), 7.86e7.93 (3H, m); 31P NMR
(121.45 MHz, CDCl3, TMS):
d
23.80; MS (EI) m/z (%): 635 [Mþ] (7.6),
578 (22.7), 378 (79.0), 365 (45.6), 257 (91.5), 210 (100.0), 209 (31.5),
183 (76.3), 91 (42.1), 57 (25.7), 43 (18.2); HRMS (EI) calcd for
4.5.1. Compound (aR,S)-5a. Yield: 91%, 603 mg, white solid, mp
C43H42NO2P requires (Mþ) 635.2953, found: 635.2956; [
(c 1.0, CH2Cl2).
a
]
20 þ41.7
D
ꢁ
106e107 C; IR (neat):
n
3050, 2986, 2888, 2836, 1631, 1504, 1435,
1363, 1308, 1189, 1113, 1057, 971, 815, 747, 697 cmꢀ1
(300 MHz, CDCl3, TMS):
;
1H NMR
d
2.45 (1H, dd, J¼8.4, 13.8 Hz), 3.02 (1H, dd,
4.6. Typical reaction procedure for the preparation of L7eL12
J¼5.4, 13.8 Hz), 3.58 (1H, t, J¼7.8 Hz), 3.91 (1H, t, J¼8.4 Hz),
4.25e4.36 (1H, m), 6.99e7.22 (10H, m), 7.27e7.52 (10H, m),
7.60e7.77 (6H, m), 7.84e7.89 (2H, m), 7.99 (1H, d, J¼8.4 Hz); 31P
To a mixture of compound (aR,S)-5 (1.0 mmol) and triethylamine
(4.2 mL, 30 mmol) in toluene (20 mL) was added trichlorosilane
(1.0mL,10.0mmol)at0 ꢁC,and thesolutionwasstirredfor0.5hatthis
temperature. It was then refluxed for 24 h under nitrogen atmo-
sphere. After cooling to room temperature, the mixture was diluted
with EtOAc and quenched with small amount of saturated NaHCO3.
The resulting suspension was filtered through Celite and the filter
cake was washed with EtOAc. The combined organic layer was dried
over anhydrous Na2SO4 and concentrated under reduced pressure.
The crude product was purified by silica gel column chromatography
NMR (121.45 MHz, CDCl3, 85% H3PO4):
d 28.41; MS (ESI) m/z 664.6
(MþHþ, 100). HRMS (MALDI) calcd for C46H35NO2P requires
20
(MþHþ) 664.2400, found: 664.2399; [
a]
þ8.0 (c 0.30, CH2Cl2).
D
4.5.2. Compound (aR,S)-5b. Yield: 82%, 503 mg, white solid, mp
94e95 ꢁC; IR (neat):
3053, 2987, 2886, 2828, 1634, 1496, 1436,
1310, 1190, 1113, 1056, 973, 818, 748, 697 cmꢀ1; 1H NMR (400 MHz,
CDCl3, TMS):
n
d
2.23 (1H, dd, J¼8.8, 14.0 Hz), 2.87 (1H, dd, J¼5.6,
14.0 Hz), 3.51 (1H, t, J¼8.0 Hz), 3.92 (1H, t, J¼8.8 Hz), 4.16e4.22 (1H,
m), 6.94 (2H, d, J¼6.4 Hz), 7.02e7.07 (3H, m), 7.10e7.21 (8H, m),
7.23e7.30 (2H, m), 7.34e7.39 (3H, m), 7.45 (2H, dd, J¼8.0, 11.6 Hz),
7.53 (1H, t, J¼7.2 Hz), 7.65e7.72 (3H, m), 7.91e7.95 (3H, m); 31P
(elution petroleum ether/EtOAc¼4:1) to give chiral ligands L7eL12.
ꢁ
L7. 589 mg, Yield: 91%, white solid, mp 67e68 C; IR (neat):
n
3049, 2973, 2889, 2837, 1632, 1504, 1477, 1432, 1308, 1261, 1091,
1055, 1024, 815, 741, 694 cmꢀ1 1H NMR (400 MHz, CDCl3, TMS):
;
NMR (161.93 MHz, CDCl3, 85% H3PO4):
d
27.53; MS (ESI) m/z 614.6
d
2.26 (1H, dd, J¼8.8,13.6 Hz), 2.91 (1H, dd, J¼5.2,13.6 Hz), 3.36 (1H,
(MþHþ, 100). HRMS (MALDI) calcd for C42H33NO2P requires
t, J¼8.0 Hz), 3.60 (1H, t, J¼8.8 Hz), 4.05e4.14 (1H, m), 6.96e7.29
(15H, m), 7.34 (1H, s), 7.40e7.49 (5H, m), 7.65e7.69 (2H, m), 7.75
(1H, d, J¼8.0 Hz), 7.83e7.91 (3H, m), 8.02 (1H, d, J¼8.4 Hz), 8.16 (1H,
(MþHþ) 614.2243, found: 614.2235; [
a
]
20 þ13.4 (c 0.57, CH2Cl2).
D
4.5.3. Compound (aR,S)-5c. Yield: 78%, 480 mg, white solid, mp
80e81 ꢁC; IR (neat):
3059, 2978, 2953, 2838,1640,1589,1498,1355,
d, J¼8.4 Hz); 31P NMR (161.93 MHz, CDCl3, 85% H3PO4):
d
ꢀ15.38;
n
MS (MALDI) m/z 648.6 (MþHþ, 100). HRMS (ESI) calcd for

3730
Q.-Y. Zhao, M. Shi / Tetrahedron 67 (2011) 3724e3732
20
C46H35NOP requires (MþHþ) 648.2451, found: 648.2457; [
a
]
D
1 (0.15 mmol), CH3CH2OH (16 mL, 0.27 mmol) was added followed
ꢀ29.9 (c 0.54, CH2Cl2).
by another 0.5 mL of DCM. The mixture was cooled to ꢀ78 ꢁC, and
ꢁ
L8. 490 mg, Yield: 82%, white solid, mp 65e66 C; IR (neat):
n
stirred for 0.5 h, then 2-trimethylsiloxyfuran (2) (46 mL, 0.27 mmol)
3050, 2975, 2885, 2831, 1633, 1495, 1478, 1432, 1262, 1093, 1054,
was added. The mixture was allowed to stir at ꢀ78 ꢁC for 24 h, and
then it was allowed to warm to room temperature (22 ꢁC). A sat-
urated aqueous solution of NaHCO3 was added and the aqueous
layer was washed with EtOAc (3ꢂ5 mL), dried over MgSO4, and the
volatiles were removed under reduced pressure and the residue
was purified by flash column chromatography on silica gel (elution
with petroleum ether/EtOAc¼4:1) to give 3.
1025, 971, 816, 741, 694 cmꢀ1 1H NMR (400 MHz, CDCl3, TMS):
;
d
2.08 (1H, dd, J¼8.8,13.6 Hz), 2.75 (1H, dd, J¼4.2,13.6 Hz), 3.30 (1H,
t, J¼8.0 Hz), 3.62 (1H, t, J¼8.8 Hz), 3.95e4.03 (1H, m), 6.89 (2H, d,
J¼6.8 Hz), 6.95e7.05 (4H, m), 7.10e7.27 (13H, m), 7.39e7.49 (3H,
m), 7.84e7.91 (3H, m), 8.01 (1H, d, J¼8.8 Hz), 8.13 (1H, d, J¼8.8 Hz);
31P NMR (161.93 MHz, CDCl3, 85% H3PO4):
d
ꢀ15.32; MS (ESI) m/z
598.6 (MþHþ, 100). HRMS (MALDI) calcd for C42H33NOP requires
(MþHþ) 598.2294, found: 598.2274; [
a
]
20 ꢀ24.1 (c 0.61, CH2Cl2).
4.7.1. Compound anti-3a. Yield: 83%, 40 mg, white solid, mp
D
ꢁ
ꢁ
L9. 467 mg, Yield: 78%, white solid, mp 59e60 C; IR (neat):
n
138e139 C; IR (neat):
n
3364, 2990, 2938, 2841, 1767, 1693, 1506,
1H NMR
d 1.43 (9H, s), 3.77 (3H, s), 5.01e5.02 (1H, m),
3058, 2958, 2899, 2867, 1639, 1586, 1493, 1359, 1224, 1158, 1097,
1282, 1242, 1152, 1091, 1030, 906, 826, 787, 634 cmꢀ1
(400 MHz, CDCl3, TMS):
;
1054, 1014, 811, 747 cmꢀ1; 1H NMR (400 MHz, CDCl3, TMS):
d
0.52
(9H, s), 3.45 (1H, t, J¼8.0 Hz), 3.61 (1H, t, J¼8.0 Hz), 3.71 (1H, t,
J¼8.8 Hz), 6.78e6.83 (3H, m), 6.93e7.00 (5H, m), 7.21e7.24 (4H, m),
7.35e7.45 (3H, m), 7.84e7.88 (3H, m), 7.99 (1H, d, J¼8.8 Hz), 8.10
(1H, d, J¼8.8 Hz); 31P NMR (161.93 MHz, CDCl3, 85% H3PO4):
5.39e5.41 (2H, m), 5.97 (1H, s), 6.84 (2H, d, J¼8.4 Hz), 7.15 (2H, d,
J¼8.4 Hz), 7.34 (1H, d, J¼5.6 Hz); 13C NMR (CDCl3, 100 MHz):
d 28.2,
55.1, 55.8, 80.2, 84.6, 114.0 (2C), 122.8, 127.5, 128.2 (2C), 153.2, 154.9,
159.4,172.4; MS (ESI) m/z 337.2 (MþNH4
þ,100). HRMS (ESI) calcd for
20
d
ꢀ17.54 (t, J¼4.5 Hz); 19F NMR (282 MHz, CDCl3, CFCl3):
d
ꢀ112.9 to
C17H21NO5Na requires (MþNaþ) 342.1312, found: 342.1318; [
a]
D
113.0 (1F, m), ꢀ113.4 to 113.5 (1F, m); MS (ESI) m/z 600.6 (MþHþ,
ꢀ100.7 (c 1.0, CH2Cl2, 86% ee). Enantiomeric excess was determined
by HPLC with a Chiralcel PA-H column (n-hexane/i-PrOH¼50/50,
0.7 mL/min, 214 nm, tminor¼21.02 min, tmajor¼16.99 min).
100). HRMS (MALDI) calcd for C39H33NOF2P requires (MþHþ)
20
600.2262, found: 600.2268; [
a
]
þ11.9 (c 0.31, CH2Cl2).
D
ꢁ
L10. 530 mg, Yield: 85%, white solid, mp 68e69 C; IR (neat):
n
3059, 2960, 2899, 2834, 1635, 1592, 1496, 1282, 1244, 1176, 1093,
4.7.2. Compound anti-3b. Yield: 83%, 40 mg, white solid, mp
1028, 821, 796, 649 cmꢀ1; 1H NMR (400 MHz, CDCl3, TMS):
d
0.52
128e129 ꢁC; IR (neat):
n
3389, 2977, 2934, 2836,1748,1687,1599,1516,
1494, 1249, 1161, 1101, 1039, 884, 830, 750, 663 cmꢀ1 1H NMR
(400 MHz, CDCl3, TMS): 1.39 (9H, s), 3.81 (3H, s), 5.06e5.13 (2H, m),
(9H, s), 3.44 (1H, t, J¼8.0 Hz), 3.57 (1H, dd, J¼8.0, 10.0 Hz), 3.70 (1H,
dd, J¼8.0, 10.0 Hz), 3.71 (3H, s), 3.77 (3H, s), 6.64 (2H, d, J¼8.0 Hz),
6.81e6.86 (3H, m), 6.90e6.97 (3H, m), 7.16e7.24 (4H, m), 7.33e7.46
(3H, m), 7.81e7.86 (3H, m), 7.97 (1H, d, J¼8.8 Hz), 8.11 (1H, d,
;
d
5.33 (1H, s), 6.15 (1H, dd, J¼2.0, 6.0 Hz), 6.86 (1H, dd, J¼2.0, 8.0 Hz),
6.94e6.99 (2H, m), 7.27e7-31 (1H, m), 7.53 (1H, s); 13C NMR (CDCl3,
J¼8.4 Hz); 31P NMR (161.94 MHz, CDCl3, 85% H3PO4):
d
ꢀ18.36; MS
100 MHz): d 28.1, 55.1, 55.2, 80.2, 85.1, 113.0, 113.5, 119.3, 122.2, 129.9,
(ESI) m/z 624.7 (MþHþ, 100). HRMS (MALDI) calcd for C41H39NO3P
139.4, 154.4, 155.2, 159.9, 172.9; MS (ESI) m/z 342.3 (MþNaþ, 100).
20
requires (MþHþ) 624.2662, found: 624.2661; [
a]
ꢀ18.1 (c 0.32,
HRMS (ESI) calcd for C17H21NO5Na requires (MþNaþ) 342.1312, found:
D
CH2Cl2).
342.1320; [
a
]
20 ꢀ83.6 (c 1.0, CH2Cl2, 78% ee). Enantiomeric excess was
D
ꢁ
L11. 526 mg, Yield: 89%, white solid, mp 71e72 C; IR (neat):
3047, 2971, 2896, 2836,1634,1496,1359,1262,1099,1054, 972, 804,
746, 693 cmꢀ1; 1H NMR (400 MHz, CDCl3, TMS):
0.52 (9H, s), 2.25
n
determined by HPLC with a Chiralcel AD-H column (n-hexane/i-
PrOH¼70/30, 0.6mL/min, 214nm, tminor¼12.77 min, tmajor¼10.15 min).
d
(3H, s), 2.32 (3H, s), 3.42 (1H, t, J¼8.4 Hz), 3.54 (1H, t, J¼9.6 Hz), 3.67
(1H, dd, J¼8.4, 9.6 Hz), 6.90e6.91 (5H, m), 6.95e7.00 (1H, m), 7.08
(2H, d, J¼7.6 Hz), 7.14e7.20 (4H, m), 7.35e7.43 (2H, m), 7.48 (1H, dd,
J¼2.8, 8.4 Hz), 7.82 (2H, d, J¼8.4 Hz), 7.87 (1H, d, J¼8.0 Hz), 7.98 (1H,
d, J¼8.8 Hz), 8.11 (1H, d, J¼8.8 Hz); 31P NMR (161.93 MHz, CDCl3,
4.7.3. Compound anti-3c. Yield: 72%, 33 mg, white solid, mp
ꢁ
153e154 C; IR (neat):
n
3377, 2977, 2925, 2854, 1770, 1696, 1511,
1H NMR
1.43 (9H, s), 2.31 (3H, s), 5.03 (1H, s), 5.31
1361, 1277, 1248, 1160, 1089, 1049, 909, 815, 743 cmꢀ1
(400 MHz, CDCl3, TMS):
;
d
(1H, d, J¼8.4 Hz), 5.41 (1H, s), 5.96 (1H, s), 7.09e7.13 (4H, m), 7.32
85% H3PO4):
d
ꢀ17.06; MS (MALDI) m/z 592.7 (MþHþ, 100). HRMS
(1H, d, J¼6.4 Hz); 13C NMR (CDCl3, 75 MHz):
d 21.0, 28.2, 56.0, 80.3,
84.6, 122.9, 126.9 (2C), 129.3 (2C), 132.4, 138.1, 153.1, 154.9, 172.4;
(ESI) calcd for C41H39NOP requires (MþHþ) 592.2764, found:
20
592.2762; [
a
]
ꢀ11.2 (c 0.5, CH2Cl2).
MS (ESI) m/z 326.3 (MþNaþ, 100). HRMS (ESI) calcd for
D
L12. 607 mg, Yield 98%, white solid, mp 86e91 ꢁC; IR (CH2Cl2):
n
C17H21NO4Na requires (MþNaþ) 326.1363, found: 326.1362; [
a]
D
20
3050, 2953, 2866, 1640, 1598, 1582, 1477, 1359, 1264, 1124, 1101,
ꢀ101.6 (c 1.0, CH2Cl2, 83% ee). Enantiomeric excess was determined
by HPLC with a Chiralcel OJ-H column (n-hexane/i-PrOH¼80/20,
0.7 mL/min, 230 nm, tminor¼14.18 min, tmajor¼11.63 min).
1055, 974, 846, 818, 746, 693, 524; 1H NMR (300 MHz, CDCl3, TMS):
d
0.51 (9H, s), 2.10 (6H, s), 2.23 (6H, s), 3.48 (1H, t, J¼7.8 Hz), 3.63
(1H, t, J¼9.6 Hz), 3.77 (1H, dd, J¼7.8, 9.6 Hz), 6.60 (2H, d, J¼7.8 Hz),
6.76 (1H, s), 6.83e6.98 (5H, m), 7.19e7.21 (2H, m), 7.35e7.45 (2H,
m), 7.54 (1H, dd, J¼5.7, 8.4 Hz), 7.85 (3H, t, J¼8.4 Hz), 7.98 (1H, d,
J¼8.4 Hz), 8.10 (1H, d, J¼8.4 Hz); 31P NMR (121.45 MHz, CDCl3,
4.7.4. Compound syn-3c. Yield: 18%,
144e145 ꢁC; IR (neat):
3384, 2981, 2923, 2851,1748, 1687, 1509,1367,
1246, 1161, 1099, 1040, 888, 815, 750, 651 cmꢀ1; 1H NMR (400 MHz,
CDCl3,TMS):
9 mg, white solid, mp
n
TMS):
d
ꢀ13.69; MS (EI) m/z (%): 619 [Mþ] (27.9), 535 (100.0), 493
d
1.39 (9H, s), 2.35 (3H, s), 4.97 (1H, d, J¼9.2Hz), 5.03e5.05
(49.4), 430 (50.4), 408 (84.7), 378 (22.2), 362 (27.7), 281 (20.4), 241
(1H, m), 5.32 (1H, s), 6.15 (1H, dd, J¼2.0, 5.6 Hz), 7.18 (2H, d, J¼8.0 Hz),
(29.3), 57 (45.2), 41 (23.3); HRMS (EI) calcd for C43H42NOP (Mþ):
7.29 (2H, d, J¼8.0Hz),7.53(1H,d, J¼4.8 Hz); 13CNMR(CDCl3,100MHz):
619.3004, found: 619.3010; [
a]
20 ꢀ8.0 (c 1.0, CHCl3).
d 21.1, 28.2, 54.9, 80.2, 85.3, 122.2, 127.0 (2C), 129.5 (2C), 134.9, 138.2,
D
154.5,155.2,172.9; MS (ESI) m/z 326.3 (MþNaþ,100). HRMS (ESI) calcd
20
4.7. General procedure for the reaction of N-Boc aldimines 1
with siloxyfuran 2 in the presence of AgOAc and chiral
phosphineeoxazoline ligand L6
for C17H21NO4Na requires (MþNaþ) 326.1363, found: 326.1367; [
a]
D
ꢀ1.7 (c 0.50, CH2Cl2, 7% ee). Enantiomeric excess was determined by
HPLC with a Chiralcel IC-H column (n-hexane/i-PrOH¼80/20, 1.0 mL/
min, 214 nm, tminor¼22.73 min, tmajor¼10.58 min).
AgOAc (2.50 mg, 0.015 mmol) and chiral phosphineeoxazoline
ligand L6 (8.4 mg, 0.015 mmol) were added into a Schlenk tube and
then DCM (0.5 mL) was added into the reaction vessel. The resulting
solution was stirred for 0.5 h at room temperature. N-Boc aldimine
4.7.5. Compound anti-3d. Yield: 79%, 36 mg, white solid, mp
146e147 ꢁC; IR (neat):
n 3374, 2984, 2922, 2851, 1780, 1755, 1690, 1514,
1
1362, 1246, 1151, 1091, 885, 832, 703, 641 cmꢀ1; H NMR (300 MHz,

Q.-Y. Zhao, M. Shi / Tetrahedron 67 (2011) 3724e3732
3731
CDCl3, TMS):
d
1.43 (9H, s), 2.32 (3H, s), 5.02 (1H, s), 5.36e5.39 (2H, m),
1490, 1368, 1245, 1168, 1060, 1010, 922, 888, 833, 797, 650 cmꢀ1; 1H
NMR (300 MHz, CDCl3, TMS): 1.40 (9H, s), 4.98e5.07 (2H, m), 5.33
5.97 (1H, d, J¼2.1 Hz), 7.01e7.03 (2H, m), 7.09 (1H, d, J¼7.5 Hz), 7.18e7-
d
23 (1H, m), 7.34 (1H, d, J¼5.4 Hz); 13C NMR (CDCl3, 100 MHz):
d
21.3,
(1H, s), 6.19 (1H, dd, J¼2.0, 5.6 Hz), 7.24e7.28 (1H, m), 7.34e7.36
28.2, 56.3, 80.3, 84.5, 122.8, 124.0, 127.7, 128.5, 129.1, 135.5, 138.4, 153.0,
(1H, m), 7.46e7.49 (1H, m), 7.52e7.57 (2H, m); 13C NMR (CDCl3,
154.9, 172.3; MS (ESI) m/z 326.3 (MþNaþ, 100). HRMS (ESI) calcd for
75 MHz): d 28.2, 54.5, 80.6, 84.8, 122.6, 125.8, 130.2, 130.5, 131.5,
20
C17H21NO4Na requires (MþNaþ) 326.1363, found: 326.1360; [
a]
133.9, 140.2, 154.1, 155.1, 172.6; MS (ESI) m/z 390.3 (MþNaþ, 100).
D
ꢀ79.5 (c 1.0, CH2Cl2, 71% ee). Enantiomeric excess was determined by
HPLC with a Chiralcel IC-H column (n-hexane/i-PrOH¼70/30, 0.7 mL/
min, 214 nm, tminor¼29.48 min, tmajor¼12.13 min).
HRMS (ESI) calcd for C16H18NO4BrNa requires (MþNaþ) 390.0311,
found: 390.0315; [
a
]
20 ꢀ71.7 (c 0.34, CH2Cl2, 73% ee). Enantiomeric
D
excess was determined by HPLC with a Chiralcel IC-H column (n-
hexane/i-PrOH¼70/30, 0.6 mL/min, 230 nm, tminor¼14.66 min,
tmajor¼12.26 min).
4.7.6. Compound anti-3e. Yield: 78%, 44 mg, white solid, mp
68e69 ꢁC; IR (neat):
n
3366, 2972, 2930, 2851, 1751, 1697, 1595, 1509,
1461,1286,1237,1160,1124,1094,1054,1109, 828, 683 cmꢀ1; 1H NMR
(400 MHz, CDCl3, TMS): 1.45 (9H, s), 3.81 (3H, s), 3.84 (6H, s), 4.98
4.7.11. Coꢁmpound anti-3j. Yield: 69%, 29 mg, white solid, mp
d
136e137 C; IR (neat): n 3385, 2956, 2923, 2852, 1758, 1690, 1520,
(1H, s), 5.33 (1H, d, J¼7.2 Hz), 5.45 (1H, s), 6.00 (1H, s), 6.45 (2H, s),
1362, 1290, 1156, 1092, 1053, 1005, 894, 833, 778, 756, 690 cmꢀ1; 1H
NMR (400 MHz, CDCl3, TMS): 1.45 (9H, s), 5.20e5.21 (2H, m), 5.36
7.32 (1H, d, J¼5.6 Hz); 13C NMR (CDCl3, 100 MHz):
d
28.2, 56.1 (2C),
d
56.5, 60.7, 80.5, 84.4, 104.1 (2C), 122.9, 131.3, 137.9, 153.0, 153.4 (2C),
(1H, s), 6.10 (1H, d, J¼3.2 Hz), 6.27 (1H, d, J¼2.8 Hz), 6.32 (1H, s),
154.9, 172.4; MS (ESI) m/z 402.4 (MþNaþ, 100). HRMS (ESI) calcd for
7.34 (1H, s), 7.42 (1H, dd, J¼1.2, 6.0 Hz); 13C NMR (CDCl3, 75 MHz):
20
C19H25NO7Na requires (MþNaþ) 402.1523, found: 402.1527; [
a]
d 28.2, 50.5, 80.7, 83.5, 108.3, 110.5, 123.1, 142.5, 149.1, 152.6, 154.8,
D
ꢀ30.1 (c 1.0, CH2Cl2, 76% ee). Enantiomeric excess was determined by
HPLC with a Chiralcel AD-H column (n-hexane/i-PrOH¼90/10,
0.5 mL/min, 214 nm, tminor¼13.89 min, tmajor¼11.64 min).
172.2; MS (ESI) m/z 302.1 (MþNaþ, 100). HRMS (ESI) calcd for
C14H17NO5Na requires (MþNaþ) 302.0999, found: 302.1013; [
a]
D
20
ꢀ42.7 (c 0.5, CH2Cl2, 80% ee). Enantiomeric excess was determined
by HPLC with a Chiralcel AD-H column (n-hexane/i-PrOH¼70/30,
0.7 mL/min, 214 nm, tminor¼12.48 min, tmajor¼11.02 min).
4.7.7. Compound anti-3f. Yield: 70%, 30 mg, white solid, mp
ꢁ
159e160 C; IR (neat):
n 3385, 2984, 2924, 2852, 1751, 1686, 1513,
1498, 1355, 1246, 1165, 1102, 889, 825, 804, 702, 653, 680 cmꢀ1; 1H
NMR (300 MHz, CDCl3, TMS): 1.39 (9H, s), 5.02e5.12 (2H, m), 5.36
4.7.12. Compound anti-3k. Yield: 75%, 33 mg, white solid, mp
ꢁ
d
163e164 C; IR (neat):
n
3366, 2981, 2920, 2852, 1740, 1694, 1518,
(1H, s), 6.17 (1H, dd, J¼1.8, 5.7 Hz), 7.34e7.41 (5H, m), 7.56 (1H, d,
1366, 1285, 1163, 1094, 1039, 1021, 901, 836, 779, 703, 616 cmꢀ1; 1H
NMR (400 MHz, CDCl3, TMS): 1.16e1.191 (H, m),1.27e1.31 (1H, m),
J¼5.1 Hz); 13C NMR (CDCl3, 75 MHz):
d
28.1, 55.1, 80.3, 85.2, 122.2,
d
127.1 (2C), 128.3, 128.9 (2C), 137.8, 154.5, 155.2, 172.9; MS (ESI) m/z
312.2 (MþNaþ, 100). HRMS (ESI) calcd for C16H19NO4Na requires
1.45 (9H, s), 1.61e1.80 (9H, m), 3..60e3.65 (1H, m), 4.57 (1H, d,
J¼9.2 Hz), 5.00 (1H, d, J¼7.6 Hz), 6.17 (1H, dd, J¼1.6, 5.6 Hz), 7.49
(MþNaþ) 312.1206, found: 312.1212; [
a
]
20 ꢀ71.3 (c 1.0, CH2Cl2, 77%
(1H, d, J¼5.2 Hz); 13C NMR (CDCl3, 100 MHz):
d 25.8, 25.9, 26.0, 27.0,
28.2, 30.3, 38.6, 56.8, 80.0, 83.0, 122.0, 154.9, 155.5, 172.6; MS (ESI)
D
ee). Enantiomeric excess was determined by HPLC with a Chiralcel
OD-H column (n-hexane/i-PrOH¼80/20, 0.6 mL/min, 214 nm,
tminor¼13.53 min, tmajor¼10.93 min).
m/z 318.3 (MþNaþ, 100). HRMS (ESI) calcd for C16H25NO4Na re-
20
quires (MþNaþ) 318.1676, found: 318.1681; [
a
]
ꢀ40.0 (c 0.5,
D
CH2Cl2, 75% ee). Enantiomeric excess was determined by HPLC with
a Chiralcel AD-H column (n-hexane/i-PrOH¼90/10, 0.6 mL/min,
214 nm, tminor¼25.72 min, tmajor¼18.54 min).
4.7.8. Compound anti-3g. Yield: 80%, 37 mg, white solid, mp
ꢁ
151e152 C; IR (neat):
n 3387, 2983, 2920, 2851, 1754, 1682, 1504,
1349, 1277,1249,1226,1158,1102, 888, 822, 805, 680 cmꢀ1; 1H NMR
(400 MHz, CDCl3, TMS): 1.39 (9H, s), 5.03e5.08 (2H, m), 5.32 (1H,
d
4.8. General procedure for the removal of N-Boc group
s), 6.17 (1H, dd, J¼1.2, 6.0 Hz), 7.07 (2H, t, J¼8.4 Hz), 7.38e7.42 (2H,
m), 7.54 (1H, d, J¼2.4 Hz); 13C NMR (CDCl3, 75 MHz):
d
28.1, 54.4,
A solution of anti-3f (233 mg, 0.81 mmol) in dichloromethane
(25 mL) and TFA (5 mL) was stirred at ambient temperature for 4 h
and then the solution was concentrated under reduced pressure.
The residue was purified by flash column chromatography on silica
gel (elution with petroleum ether/EtOAc¼4:1) to provide the title
compound 4 (141 mg, 92%).
80.4, 85.0, 115.7 (2C, d, J¼20.9 Hz), 122.3, 128.9 (2C, d, J¼8.2 Hz),
133.8 (d, J¼3.1 Hz), 154.3, 155.1, 162.4 (d, J¼246.2 Hz), 172.8; 19F
NMR (376 MHz, CDCl3, CFCl3):
d
ꢀ113.9 to 114.0 (1F, m); MS (ESI) m/
z 330.3 (MþNaþ, 100). HRMS (ESI) calcd for C16H18FNO4Na requires
(MþNaþ) 330.1112, found: 330.1113; [
a
]
20 ꢀ65.7 (c 1.0, CH2Cl2, 63%
D
ee). Enantiomeric excess was determined by HPLC with a Chiralcel
OJ-H column (n-hexane/i-PrOH¼90/10, 0.7 mL/min, 230 nm,
tminor¼24.37 min, tmajor¼28.97 min).
This is a known compound.1b,e 141 mg, Yield: 92%, orange oil; IR
(CH2Cl2):
1029, 897, 825, 764, 702 cmꢀ1
1.64 (2H, s), 4.45 (1H, d, J¼4.8 Hz), 5.22 (1H, ddd, J¼1.2, 2.0,
n
3381, 3318, 1754, 1600, 1494, 1453, 1331, 1161, 1089,
;
1H NMR (400 MHz, CDCl3, TMS):
d
4.7.9. Compound anti-3h. Yield: 75%, 41 mg, white solid, mp
4.8 Hz), 6.13 (1H, dd, J¼2.0, 6.0 Hz), 7.31 (1H, dd, J¼1.2, 6.0 Hz),
ꢁ
165e166 C; IR (neat):
n
3347, 2978, 2924, 2852, 1752, 1683, 1517,
7.32e7.40 (5H, m); 13C NMR (100 MHz, CDCl3, TMS):
d
56.9, 87.0,
1494, 1367, 1276, 1167, 1063, 1018, 922, 886, 833, 797, 655 cmꢀ1; 1H
NMR (300 MHz, CDCl3, TMS): 1.39 (9H, s), 5.04e5.07 (2H, m), 5.31
(1H, s), 6.18 (1H, dd, J¼2.1, 5.4 Hz), 7.29 (2H, d, J¼8.4 Hz), 7.49e7.52
(3H, m); 13C NMR (CDCl3, 75 MHz):
28.1, 54.5, 80.5, 84.8, 122.3,
123.2, 126.6, 128.1, 128.8, 139.3, 153.2, 172.7; [a]
ꢀ71.5 (c 1.0,
20
D
d
CHCl3); MS (EI) m/z (100): 172 [MþꢀNH3] (6.2), 144 (1.8), 115 (4.6),
107 (8.6), 106 (100), 104 (7.8), 79 (30.7), 77 (16.3); HRMS (EI) calcd
for C11H11NO2 (Mþ): 189.0790, found: 189.0792.
d
122.5, 128.9 (2C), 132.0 (2C), 137.0, 154.1, 155.1, 172.7; MS (ESI) m/z
366.2 (MꢀHþ, 100). HRMS (ESI) calcd for C16H17NO4Br requires
Acknowledgements
(MꢀHþ) 366.0346, found: 366.0359; [
a
]
20 ꢀ40.5 (c 0.5, CH2Cl2, 67%
D
ee). Enantiomeric excess was determined by HPLC with a Chiralcel
IC-H column (n-hexane/i-PrOH¼70/30, 0.6 mL/min, 230 nm,
tminor¼36.59 min, tmajor¼32.47 min).
We thank the Shanghai Municipal Committee of Science and
Technology (08dj1400100-2), National Basic Research Program of
China (973)-2010CB833302, the Fundamental Research Funds for
the Central Universities and the National Natural Science Founda-
tion of China for financial support (21072206, 20872162, 20672127,
20732008, 20821002, and 20702013).
4.7.10. Compound anti-3i. Yield: 69%, 38 mg, white solid, mp
ꢁ
161e162 C; IR (neat):
n 3347, 2960, 2923, 2849, 1754, 1685, 1518,

3732
Q.-Y. Zhao, M. Shi / Tetrahedron 67 (2011) 3724e3732
2. (a) Greene, T. W.; Wuts, P. G. Protective Groups in Organic Synthesis; John Wiley &
Sons: New York, NY, 1999; 518e525; (b) The use of -carbamoyl sulfones for the
Supplementary data
a
in situ generation of N-Boc imines, see: Petrini, M. Chem. Rev. 2005, 105,
3949e3977; (c) Liu, Z.; Shi, M. Tetrahedron 2010, 66, 2619e2623.
3. (a) Ogasawara, M.; Yoshida, K.; Kamei, H.; Kato, K.; Uozumi, Y.; Hayashi, T. Tet-
rahedron: Asymmetry 1998, 9, 1779e1787; (b) Hatano, M.; Yamanaka, M.;
Mikami, K. Eur. J. Org. Chem. 2003, 2552e2555.
4. Ko, D.-H.; Kim, K. H.; Ha, D.-C. Org. Lett. 2002, 4, 3759e3762.
5. (a) Zhao, Q.-Y.; Yuan, Z.-L.; Shi, M. Tetrahedron: Asymmetry 2010, 21, 943e951
Reviews for the silver-catalyzed asymmetric reactions, please see: (b) Naodovic,
M.; Yamamoto, H. Chem. Rev. 2008, 108, 3132e3148; (c) Yanagisawa, A.; Arai, T.
Chem. Commun. 2008, 1165e1172; (d) Kaur, P.; Pindi, S.; Wever, W.; Rajale, T.; Li,
G. Chem. Commun. 2010, 4330e4333; (e) Kaur, P.; Pindi, S.; Wever, W.; Rajale, T.;
Li, G. J. Org. Chem. 2010, 75, 5144e5148; (f) Pindi, S.; Kaur, P.; Shakya, G.; Li, G.
Chem. Biol. Drug Des. 2011, 75, 20e25.
6. (a) See Ref. 1g; For a review on the effect of additives in asymmetric catalysis,
please see: (b) Vogl, E. M.; Groger, H.; Shibasaki, M. Angew. Chem., Int. Ed. 1999,
38, 1570e1577; (c) Giera, D. S.; Sichert, M.; Schneider, C. Org. Lett. 2008, 10,
4259e4262.
7. Burr, S. K.; Martin, S. F. Org. Lett. 2000, 2, 3445e3447.
8. (a) Wenzel, A. G.; Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 12964e12965; (b)
Song, J.; Wang, Y.; Deng, L. J. Am. Chem. Soc. 2006, 128, 6048e6049.
Spectroscopic data and chiral HPLC traces of the compounds
shown in Tables 1e3 are included in the Supplementary data.
Supplementary data related to this article can be found online at
doi:10.1016/j.tet.2011.03.046.
References and notes
1. Successful examples on the asymmetric vinylogous Mannich (AVM)-type re-
actions: (a) Martin, S. F.; Lopez, O. D. Tetrahedron Lett. 1999, 40, 8949e8953; (b)
Carswell, E. L.; Snapper, M. L.; Hoveyda, A. H.; Tang, J. Angew. Chem., Int. Ed. 2006,
45, 7230e7233; (c) Mandai, H.; Mandai, K.; Snapper, M. L.; Hoveyda, A. H. J. Am.
Chem. Soc. 2008, 130, 17961e17969; (d) Yuan, Z. L.; Jiang, J. J.; Shi, M. Tetrahedron
2009, 65, 6001e6007; (e) Deng, H. P.; Wei, Y.; Shi, M. Adv. Synth. Catal. 2009, 351,
2897e2902; (f) Liu, T. Y.; Cui, H. L.; Long, J.; Li, B. J.; Wu, Y.; Ding, L. S.; Chen, Y. C.
J. Am. Chem. Soc. 2007, 129, 1878e1879; (g) Sichert, M.; Schneider, C. Angew.
Chem., Int. Ed. 2008, 47, 3631e3634 For a review, see: (h) Martin, S. F. Acc. Chem.
Res. 2002, 35, 895e904.