Diastereoselective Addition of Metal α-Fluoroenolates of Carboxylate Esters to N-tert-Butylsulfinyl Imines: Synthesis of α-Fluoro-β-amino Acids

Article abstract of DOI:10.1021/acs.joc.5b01574

We report a diastereoselective addition reaction of fluoroacetate and α-alkylated fluoroacetate to N-tert-butylsulfinyl imines. This method provides a concise route to α-fluoro-β-amino acids containing fluorinated quaternary stereogenic carbon centers with very good yields and high diastereoselectivities. This protocol has the benefit of using abundant and readily accessible starting materials and is operationally simple. Additionally, the stereochemical outcome of the present reaction was different from that of the previously known addition of comparable nonfluorinated, brominated, and chlorinated enolates to N-sulfinyl imines, suggesting that an open transition state (rather than a closed one) is involved in the current fluoroalkylation reaction.

Full text of DOI:10.1021/acs.joc.5b01574

Article
pubs.acs.org/joc
Diastereoselective Addition of Metal α‑Fluoroenolates of
Carboxylate Esters to N-tert-Butylsulfinyl Imines: Synthesis of
α‑Fluoro-β-amino Acids
Huaqi Shang, Ya Li,* Xiang Li, and Xinfeng Ren
Department of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, 333 Longteng Road, Shanghai
201620, China
S
* Supporting Information
ABSTRACT: We report a diastereoselective addition reaction
of fluoroacetate and α-alkylated fluoroacetate to N-tert-
butylsulfinyl imines. This method provides a concise route to
α-fluoro-β-amino acids containing fluorinated quaternary
stereogenic carbon centers with very good yields and high
diastereoselectivities. This protocol has the benefit of using
abundant and readily accessible starting materials and is operationally simple. Additionally, the stereochemical outcome of the
present reaction was different from that of the previously known addition of comparable nonfluorinated, brominated, and
chlorinated enolates to N-sulfinyl imines, suggesting that an open transition state (rather than a closed one) is involved in the
current fluoroalkylation reaction.
the decarboxylation process. For these reasons, a concise and
efficient synthesis of α-fluoro-β-amino acids, particularly syn-
configured α-fluoro-β-amino acids, is still highly desirable.
In the past decades, nucleophilic fluoroalkylation has been
certified as a powerful strategy for the preparation of fluorinated
compounds.2,8 In this respect, α-fluoroenolates are important in
synthetic organofluorine chemistry and have been widely used
to prepare enantiopure α-fluorinated carbonyl compounds.9,10
Particularly well developed is the use of α-fluoro-β-ketoesters as
enolate precursors, and these have been deployed in a range of
asymmetric reactions.9 For simple ketones, aldehydes, and
esters that are less acidic, their corresponding silyl α-fluoroenol
ethers are frequently used.10 However, using silyl α-fluoroenol
ethers in typical addition reactions usually results in low
stereoselectivities, and their preparation and purification is not
trivial. Very recently, α-fluorinated β-keto gem-diols were
developed to act as α-fluoroenolate equivalents in asymmetric
condensation reactions, thus providing a novel method of
constructing chiral sp3 C−F centers.11 The direct production of
α-fluorinated carbonyl compounds from metal α-fluoroenolates
generated in situ from simple fluoromethyl carbonyl com-
pounds (such as fluoroacetate and fluoromethyl ketones)
represents a highly attractive alternative, given the abundant
and readily available precursors. However, the associated
challenge of generating acyclic stereodefined enolates (of
crucial importance to achieve high levels of stereocontrol)12,13
and the relatively low stability of α-fluoro carbanions (due to
the “negative fluorine effect”)8,14 were significant obstacles to
their synthetic use. For a long time, only a few examples
describing the addition of metal α-fluoroenolates (generated in
INTRODUCTION
■
Fluorine is known to affect the biological properties of organic
compounds. The replacement of a C−H bond with a C−F
bond can make the target molecule more bioavailable,
lipophilic, and metabolically stable.1 In this context, organic
compounds with fluorine atom(s) bonded to sp3-hybridized
carbon atoms are of high importance2 as they are present in
many pharmaceuticals,1,3 including the newly approved
hepatitis C virus infection treatment drug sofosbuvir. Thus,
there is great demand for the availability of versatile fluorinated
building blocks featuring nonracemic stereogenic carbon−
fluorine centers.2,4
Fluorinated β-amino acids are an important class of
compounds as they have an integral role in bioactive molecules
and peptidomimetics.5 Proteins containing fluorinated β-amino
acid residues have also been shown to have enhanced stability
against chemical and thermal denaturation, and proteolytic
degradation.5a In this context, the asymmetric synthesis of α-
fluoro-β-amino acids has drawn a lot of attention.6 For example,
Seebach and co-workers described a multistep process starting
from natural α-amino acids, involving deoxyfluorination of 3-
amino-2-hydroxy carboxylic acid esters with DAST in the key
step. However, a fluorination rearrangement occurs during the
deoxyfluorination process, leading to a mixture of constitutional
isomers.6a Electrophilic fluorination of chiral enolates has also
been developed.6b,c However, the prerequisite chiral β-amino
esters and the use of expensive fluorination reagents (such as
NFSI) limit its practical use. Both strategies give 2,3-anti
diastereoisomers as the major products. Recently, a base-
promoted asymmetric Mannich reaction of fluorinated β-keto
acetyloxazolidinone with N-acyloxyimines, followed by decar-
boxylation, was used to prepare α-fluoro β-amino acid
derivatives.7 However, significant racemization occurred during
Received: July 9, 2015
© XXXX American Chemical Society
A
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Article
situ from fluoroacetate and fluoromethyl ketones) to aldehydes
with only low to moderate stereoselectivities were known.15 To
the best of our knowledge, the general use of a metal α-
fluoroenolate of fluoroacetate in asymmetric synthesis has not
yet been reported.16 As part of our continued efforts in the
synthesis of chiral halogenated amines,17 we herein report the
first general use of metal α-fluoroenolates of carboxylate esters
in asymmetric reactions. This enables the highly diastereose-
lective and concise synthesis of syn-configured α-fluoro-β-
amino acid derivatives from Ellman’s N-tert-butanesulfinyl
imines (Scheme 1).18
Table 1. Optimization of the Addition of Fluoroacetate to
Ellman’s Imine 2a
reactant ratio
yield
b
a
c
entry
1
2a/1a/base
solvent/additive
THF
[%]
d.r.
d
1
1a
1:1.5:1.5
(LiHMDS)
3a, <5
3a, 55
3a, 12
3a, 15
3a, 30
3a, 20
3a, 60
n.d.
Scheme 1. Synthesis of α-Fluoro-β-amino Acids from α-
Fluorinated Carboxylate Esters
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a′
1:1.2:1.2
(LiHMDS)
THF
80:13:7
42:42:16
47:40:13
87:9:4
1:1.2:1.2
(LiHMDS)
toluene
Et2O
1:1.2:1.2
(LiHMDS)
1:1.2:1.2
(KHMDS)
THF
1:1.5:1.5
(NaHMDS)
THF
31:28:23:18
73:25:2
92:6:2
1:1.2:1.2
(LiHMDS)
THF/HMPA
RESULTS AND DISCUSSION
■
1:1.2:1.2
(LiHMDS)
THF/TMEDA 3a, 65
THF/TMEDA 3a, 54
Methyl fluoroacetate 1a, an abundant feedstock chemical, was
first used as the fluorocarbon nucleophile, and its addition
reaction with N-tert-butylsulfinyl imine 2a was investigated. We
initially followed a reported procedure for the addition of
methyl fluoroacetate to aldehydes, and 2a was added to the
pregenerated enolate of 1a (formed by deprotonation of 1a
with lithium hexamethyl disilazide (LiHMDS) in THF at −70
°C).15a However, the expected product was obtained in a very
low yield with less than 10% of 1a left intact (Table 1, entry 1),
and this indicated that 1a was readily decomposed under the
reaction conditions. To our delight, when the in situ generated
fluoroenolate was subjected to the reaction with 2a (LiHMDS
was added to a mixture of 1a and 2a in this case), the addition
reaction proceeded smoothly, giving the product in 55% yield,
with a diastereoselectivity of 80:13:7 (entry 2). Evaluation of
other bases such as NaHMDS and KHMDS, and solvents
including ether and toluene, demonstrated no improvements in
yield and diastereoselectivity (entries 3−6). The inclusion of
additives such as TMEDA and HMPA was also investigated
(entries 7−12). While each was beneficial for promoting this
transformation, TMEDA gave the best yield and diastereose-
lectivity (entry 8 vs entry 7). These observations indicated that
the strong affinity of TMEDA for lithium ions plays an
important role in achieving high levels of stereocontrol in the
current fluoroalkylation reaction. Raising the temperature to
−30 °C resulted in a decreased yield, but the diastereose-
lectivity remained high (entry 9). Under the optimal reaction
conditions with the reactant ratios 2a/1a/LiHMDS = 1:1.5:1.5
in the presence of TMEDA, product 3a was afforded in 85%
yield with a diastereoselectivity up to 95:3:2 (entry 10). The
current reaction can be performed on a 10 mmol scale,
furnishing the product in undiminished yield and diastereose-
lectivity. Easily accessible t-butyl fluoroacetate 3a′ and benzyl
fluoroacetate 3a″ were also successfully subjected to the
optimal reaction conditions (entry 11 and 12), affording the
desired products with yields and diastereoselectivities com-
parable with those of methyl fluoroacetate.
e
f
9
1:1.5:1.5
(LiHMDS)
84:10:6
95:3:2
10
11
12
1:1.5:1.5
(LiHMDS)
THF/TMEDA 3a′,
f
85
1:1.5:1.5
(LiHMDS)
THF/TMEDA 3a′,
90:9:1
f
84
1a′′ 1:1.5:1.5
(LiHMDS)
THF/TMEDA 3a″,
79:9:6:6
f
75
a
A combination of 0.3 mL of additive (TMEDA or HMPA) and 3.0
b
mL of THF was used on a 1.0 mmol scale (for 2a). Yield was
determined by 19F NMR analysis with PhCF3 as the internal standard.
c
d
d.r. was determined by 19F NMR spectroscopy. Reaction conditions:
2a was added to the pregenerated enolate of 1a in THF at −70 °C.
e
f
The reaction was carried out at −30 °C. Isolated yield.
enolizable, aromatic, and heterocyclic imines) could be
converted to the corresponding α-fluoro-β-amino acid deriva-
tives (Table 2). Substrates with electron-withdrawing or
-donating substituents all performed well in this transformation
(Table 2, entries 1−19). Notably, the reaction conditions
tolerated a wide range of functional groups, including esters
(3g), nitriles (3i and 3i′), aryl halides (3e, 3e′, 3e″, and 3f),
and pyridines (3l). Even the strongly electronic-withdrawing
nitro group tolerated the reaction conditions, delivering the
products 3j and 3j′ in moderate to good diastereoselectivities
and high overall yield. The 2-naphthyl substrate underwent
fluoroalkylation to give 3k in 70% yield, with a diastereose-
lectivity up to a remarkable 99:0.5:0.5. Even aliphatic imines,
which can be problematic substrates under strongly basic
conditions, could be successfully transformed using the current
conditions to give 3m and 3n. More importantly, ketimines also
participated in the reaction, yielding the desired compounds
containing an amino group attached to a tertiary carbon center
(3o and 3p). From these experimental findings, fluoroacetates
1a, 1a′, and 1a″ were all shown to work well in the
fluoroalkylation reaction, and t-butyl fluoroacetate 1a′ gave
better diastereoselectivities with electron-withdrawing sub-
strates (3i vs 3i′ and 3j vs 3j′). The absolute configuration of
3e′ was determined by single-crystal X-ray analysis,19 and the
fluoro and amino substituents were found to adopt a syn
Using fluoroacetate as the fluorocarbon nucleophile, we then
evaluated the substrate scope of this reaction, and a wide array
of structurally diverse imines (including nonenolizable,
B
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Article
Table 2. Survey of the Substrate Scope in the
Fluoroalkylation of N-Sulfinylimines
Scheme 2. Synthesis of α-Fluoro-β-amino Acids Using α-
Alkylated Fluoroacetates as Nucleophiles
a
a
a
Reaction conditions: 2 (0.5 mmol), 4 (0.6 mmol), TMEDA (0.15
mL), LiHMDS (0.6 mmol), THF (1.5 mL), N2, 0.5 h, −70 °C.
b
c
Isolated yields. d.r. was determined by 19F NMR spectroscopy.
suitable for use in solid-phase peptide synthesis. First, the
removal of the N-tert-butylsulfinyl group using HCl/MeOH
gave the corresponding ammonium salt, which was taken in
crude form for Fmoc protection, affording 10 in 86% yield over
the two steps. Deprotection of the tert-butyl ester in 10 with
trifluoroacetic acid afforded enantiomerically pure 11 (Scheme
3).
Scheme 3. Synthesis of the Fmoc-Protected α-Fluoro-β-
amino Acid 11 from 3a′
a
Reaction conditions: LiHMDS (1.5 mL, 1.0 mol/L in THF) was
added slowly to a reaction mixture of 1 (1.5 mmol), 2 (1.0 mmol) and
TMEDA (0.3 mL) in THF (3.0 mL) at −70 °C. The reaction mixture
b
was stirred for 0.5 h, followed by routine workup. Isolated yields of
c
the major stereoisomers. d.r. was determined by 19F NMR
spectroscopy.
Welch and co-workers reported the addition of the metal α-
fluoroenolate of ethyl fluoroacetate to aldehydes to give the
expected aldol products with very low stereoselectivity (syn/
anti = 1:1 to 1:3). This was attributed to the low selectivity in
the Z/E enolate formation and difficulty in discriminating
between the two prochiral faces of the enolate due to the
similar size of fluorine and hydrogen.15a In sharp contrast, the
present fluoroalkylation shows remarkably high diastereoselec-
tivity for the addition reaction. On the basis of the variations in
the diastereomeric ratios (Table 2), it is reasonable to assume
that the addition reactions of E/Z fluoroenolates to N-sulfinyl
imines undergo dynamic kinetic asymmetric transformations
(or stereoconvergent processes),20 leading to the formation of
the major diastereomers with high levels of stereocontrol.
The observed diastereoselectivity can be tentatively explained
based on an open transition state (Figure 1a). As shown, the
sulfinyl oxygen of the imine is proposed to be in an s-cis
arrangement with respect to the CN bond,17c,21 and the (Z)-
enolate in an antiperiplanar orientation attacks the sterically less
hindered Si face of the imine to afford the observed
stereoselectivity. It should be pointed out that a comparable
configuration. Note that either deoxyfluorination of the 3-
amino-2-hydroxy carboxylic acid esters or fluorination of chiral
enolates, led predominantly to anti diastereomers.6 We
anticipate that the current approach will be a valuable
complement to existing synthetic methods.
The straightforward fluoroalkylation can be applied to α-
alkylated fluoroacetate nucleophiles. As shown, fluorocarbon
nucleophiles such as ethyl 4-(benzyloxy)-2-fluorobutanoate 4,
ethyl 2-fluoro-3-(naphthalen-2-yl)propanoate 5, and ethyl 2-
fluoro-3-phenylpropanoate 6 all reacted smoothly in the
fluoroalkylation reactions, leading to α-fluoro β-amino acids
7, 8, and 9 containing quaternary stereogenic sp3 C−F centers
in a highly stereoselective manner (Scheme 2). The structure of
9c was confirmed by X-ray crystallography.19 Because
quaternary carbon centers are known to provide conforma-
tional rigidity to fluorinated peptidomimetics,5 the reported α-
fluoro β-amino acids may find important applications in
medicinal and life sciences.
To further demonstrate the usefulness of the reaction,
compound 3a′ was converted to an Fmoc-protected derivative
C
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Evaporation of the solvent under vacuum, followed by flash column
chromatography on silica gel, gave the corresponding product 3.
(RS,2S,3R)-2-Fluoro-3-(2-methylpropane-2-sulfinylamino)-3-phe-
nyl-propionic Acid Methyl Ester (3a). By following the general
procedure, 3a was isolated by column chromatography on silica gel
(petroleum ether/ethyl acetate = 3/1) as a white solid (255 mg, 85%),
mp 94−95 °C; [α]2D0 = +4.18 (c = 0.52, CHCl3); 1H NMR (400 MHz,
CDCl3): δ = 7.46−7.33 (m, 5H), 5.18 (dd, J = 47.2, 2.3 Hz, 1H), 4.98
(ddd, J = 27.5, 9.3, 2.1 Hz, 1H), 4.06 (d, J = 9.3 Hz, 1H), 3.83 (s, 3H),
1.22 (s, 9H); 19F NMR (376 MHz, CDCl3): δ = −204.3 (dd, J = 47.1,
26.9 Hz); 13C NMR (101 MHz, CDCl3): δ = 163.1 (d, J = 24.7 Hz),
132.8, 124.1, 123.7, 122.4, 86.6 (d, J = 192.6 Hz), 55.9 (d, J = 18.9
Hz), 52.0, 47.8, 17.5. IR (cm−1): 3292, 2957, 1750, 1454, 1438, 1226,
1075, 796. MS (ESI) m/z: 302.1 [M + H]+. HRMS (ESI) m/z: calcd
for C14H21FNO3S+ [M + H]+ 302.1221, found 302.1213.
Figure 1. (a) Open transition-state mode proposed for the current
fluoroalkylation reaction. (b) A closed transition-state mode reported
for the addition of acetate, propionate, and bromoacetate to N-sulfinyl
imines.
(RS,2S,3R)-2-Fluoro-3-(2-methylpropane-2-sulfinylamino)-3-phe-
nyl-propionic Acid tert-Butyl Ester (3a′). By following the general
procedure, 3a′ was isolated by column chromatography on silica gel
(petroleum ether/ethyl acetate = 4/1) as a white solid (291 mg, 85%
yield), mp 107−108 °C; [α]2D0 = −16.49 (c = 0.58, CHCl3); 1H NMR
(400 MHz, CDCl3) δ = 7.42 (d, J = 7.2 Hz, 2H), 7.34 (dt, J = 21.1, 7.1
Hz, 3H), 4.98 (dd, J = 47.4, 2.8 Hz, 1H), 4.87 (ddd, J = 10.7, 9.1, 2.5
Hz, 1H), 4.02 (d, J = 8.7 Hz, 1H), 1.43 (s, 9H), 1.21 (s, 9H); 19F
NMR (376 MHz, CDCl3) δ = −199.4 (dd, J = 47.2, 24.8 Hz); 13C
NMR (101 MHz, CDCl3) δ = 166.3 (d, J = 24.5 Hz), 137.8, 128.7,
128.4, 127.4, 91.2 (d, J = 191.8 Hz), 83.5, 60.6 (d, J = 19.3 Hz), 56.8,
27.9, 22.5. IR (cm−1): 3298, 2968, 1721, 1474, 1458, 1322, 1158, 1071,
819. MS (ESI) m/z: 344.2 [M + H]+. HRMS (ESI) m/z: calcd for
C17H27FNO3S+ [M + H]+ 344.1690, found 344.1687.
transition state mode was proposed for the addition of
protected α-hydroxyacetates to N-sulfinyl imines.22 In contrast,
the stereochemical outcome of the addition of metal enolates
derived from methyl acetate and methyl propionate to N-tert-
butylsulfinyl imines has been explained by a closed chairlike
transition state (Figure 1b). The enolate attacks the Re face of
(R)-N-tert-butylsulfinyl imines to give the products.23 A similar
transition state has been used to describe the observed
stereoselectivities for the reaction of bromoacetate and
dichloroacetate with N-sulfinyl imines (Figure 1b).24,25
Evidently, introducing a single fluorine substituent imparts a
significant effect on the characteristics of metal enolates, as the
reactivity of the metal α-fluoroenolates is different from their
nonfluorinated, brominated, or chlorinated counterparts.
(RS,2S,3R)-2-Fluoro-3-(2-methylpropane-2-sulfinylamino)-3-phe-
nyl-propionic Acid Benzyl Ester (3a″). By following the general
procedure, 3a″ was isolated by column chromatography on silica gel
(petroleum ether/ethyl acetate = 4/1) as a yellow oil (283 mg, 75%);
[α]2D0 = −3.63 (c = 0.40, CHCl3); H NMR (400 MHz, CDCl3) δ =
1
CONCLUSIONS
■
7.62−7.30 (m, 10H), 5.38−5.14 (m, 3H), 4.99 (ddd, J = 26.5, 9.2, 2.5
Hz, 1H), 4.06 (d, J = 9.2 Hz, 1H), 1.18 (s, 9H); 19F NMR (376 MHz,
CDCl3) δ = −202.97 (dd, J = 47.1, 26.4 Hz); 13C NMR (101 MHz,
CDCl3) δ = 162.4(d, J = 24.8 Hz), 132.7, 129.7, 124.2, 124.1, 124.0,
123.9, 123.9, 123.8, 123.8, 123.7, 86.6 (d, J = 192.7 Hz), 62.9, 55.9 (d,
J = 18.9 Hz), 52.0, 17.6. IR (cm−1): 3329, 2960, 1760, 1497, 1455,
1364, 1263, 1202, 1063, 966, 746. MS (ESI) m/z: 378.2 [M + H]+.
HRMS (ESI) m/z: calcd for C20H25FNO3S+ [M + H]+ 378.1534,
found 378.1536.
We have successfully developed a concise, highly diastereose-
lective synthesis of α-fluoro-β-amino acid derivatives, based on
a straightforward addition of metal α-fluoroenolates of
carboxylate esters to N-tert-butylsulfinyl imines. The reaction
uses abundant and readily available starting materials, has broad
substrate scope, tolerates a variety of functional groups, and is
operationally simple. Additionally, the stereochemical outcome
of the reaction is different from that of the addition of
comparable nonfluorinated, brominated, and chlorinated
enolates to N-sulfinyl imines, demonstrating a marked fluorine
effect. Further explorations of the applications of metal α-
fluoroenolates in asymmetic fluoroalkylation reactions are
underway in our laboratory and will be reported in due course.
(RS,2S,3R)-2-Fluoro-3-(2-methylpropane-2-sulfinylamino)-3-p-
tolyl-propionic Acid Methyl Ester (3b). By following the general
procedure, 3b was isolated by column chromatography on silica gel
(petroleum ether/ethyl acetate = 3/1) as a white solid (252 mg, 80%),
mp 91−92 °C; [α]2D0 = +5.20 (c = 0.50, CHCl3); 1H NMR (400 MHz,
CDCl3) δ = 7.33 (d, J = 8.0 Hz, 2H), 7.21 (d, J = 8.0 Hz, 2H), 5.15
(dd, J = 47.2, 2.4 Hz, 1H), 4.93 (ddd, J = 27.5, 9.3, 2.2 Hz, 1H), 4.00
(d, J = 9.2 Hz, 1H), 3.82 (s, 3H), 2.36 (s, 3H), 1.21 (s, 9H); 19F NMR
(376 MHz, CDCl3) δ = −204.2 (dd, J = 46.9, 28.3 Hz); 13C NMR
(101 MHz, CDCl3) δ = 167.9 (d, J = 24.8 Hz), 138.3, 134.5, 129.5,
127.1, 91.5 (d, J = 192.3 Hz), 60.5 (d, J = 18.9 Hz), 56.7, 52.5, 22.4,
21.0. IR (cm−1): 3321, 2956, 1740, 1473, 1315, 1274, 1076, 880. MS
(ESI) m/z: 338.1 [M + Na]+. HRMS (ESI) m/z: calcd for
C15H23FNO3S+ [M + H]+ 316.1377, found 316.1371.
EXPERIMENTAL SECTION
■
Unless otherwise mentioned, all commercial reagents and solvents
were used directly as purchased without further purification. THF was
distilled from sodium/benzophenone. TMEDA was treated with 4 Å
molecular sieves before use. Melting points were uncorrected. Optical
rotations were measured with a sodium lamp. NMR spectra were
recorded on a spectrometer at 400 MHz (1H NMR), 100 MHz (13C
NMR), and 376 MHz (19F NMR). Chemical shifts (δ) are reported in
parts per million (ppm), and coupling constants (J) are given in Hertz
(Hz). HRMS data using ESI were obtained on an ESI-FTMS mass
spectrometer.
(RS,2S,3R)-2-Fluoro-3-(2-methylpropane-2-sulfinylamino)-3-p-
tolyl- propionic acid tert-butyl ester (3b′). By following the general
procedure, 3b′ was isolated by column chromatography on silica gel
(petroleum ether/ethyl acetate = 4/1) as a white solid (282 mg, 79%),
Typical Procedure for the Diastereoselective Addition of
Fluoroacetate 1 to N-tert-Butylsulfinyl Imine 2. Under a N2
atmosphere, LiHMDS (1.5 equiv, 1.5 mL, 1.0 mol/L in THF) was
added slowly to a mixture of fluoroacetate 1 (1.5 mmol, 1.5 equiv),
imine 2 (1.0 mmol, 1.0 equiv), TMEDA (0.3 mL), and THF (3 mL) at
−70 °C. Reaction mixtures were stirred at this temperature for 30 min.
Then, 1 N HCl (4 mL) was added, and the quenched reaction mixture
was extracted three times with ethyl acetate (20 mL × 3). The
combined organic layers were dried over anhydrous MgSO4.
mp 112−113 °C; [α]2D0 = −19.85 (c = 0.61, CHCl3); H NMR (400
1
MHz, CDCl3) δ = 7.30 (d, J = 7.8 Hz, 2H), 7.17 (d, J = 7.8 Hz, 2H),
4.96 (dd, J = 47.5, 2.8 Hz, 1H), 4.83 (ddd, J = 25.1, 8.6, 2.3 Hz, 1H),
3.96 (d, J = 8.6 Hz, 1H), 2.33 (s, 3H), 1.44 (s, 9H), 1.21 (s, 9H); 19F
NMR (376 MHz, CDCl3) δ = −199.9 (dd, J = 47.2, 25.0 Hz); 13C
NMR (101 MHz, CDCl3) δ = 166.3 (d, J = 24.8 Hz), 138.2, 134.9,
129.4, 127.3, 91.3 (d, J = 191.4 Hz), 83.4, 60.5 (d, J = 19.1 Hz), 56.7,
28.0, 22.6, 21.1. IR (cm−1): 3298, 2968, 1721, 1474, 1322, 1260, 1158,
D
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1071, 819. MS (ESI) m/z: 358.2 [M + H]+. HRMS (ESI) m/z: calcd
for C18H29FNO3S+ [M + H]+ 358.1847, found 358.1844.
Hz), 56.9, 28.0, 22.5. IR (cm−1): 3309, 2964, 1720, 1496, 1474, 1319,
1261, 1070, 882. MS (ESI) m/z: 379.0 [M + H]+. HRMS (ESI) m/z:
calcd for C17H25ClFNO3SNa+ [M + Na]+ 400.1120, found 400.1139.
(RS,2S,3R)-3-(4-Chloro-phenyl)-2-fluoro-3-(2-methylpropane-2-
sulfinylamino)-propionic Acid Benzyl Ester (3e″). By following the
general procedure, 3e″ was isolated by column chromatography on
silica gel (petroleum ether/ethyl acetate = 5/1) as a white solid (321
(RS,2S,3R)-2-Fluoro-3-(2-methylpropane-2-sulfinylamino)-3-m-
tolyl-propionic Acid Methyl Ester (3c). By following the general
procedure, 3c was isolated by column chromatography on silica gel
(petroleum ether/ethyl acetate = 3/1) as a white solid (233 mg, 74%),
mp 89−90 °C; [α]2D0 = +0.23 (c = 0.53, CHCl3); 1H NMR (400 MHz,
CDCl3) δ = 7.27 (dd, J = 9.4, 6.1 Hz, 1H), 7.21 (d, J = 6.3 Hz, 2H),
7.13 (d, J = 7.2 Hz, 1H), 5.13 (dd, J = 47.3, 1.8 Hz, 1H), 4.90 (dd, J =
27.6, 9.3 Hz, 1H), 3.99 (d, J = 9.1 Hz, 1H), 3.80 (s, 3H), 2.36 (s, 3H),
1.19 (s, 9H); 19F NMR (376 MHz, CDCl3) δ = −204.3 (dd, J = 47.3,
27.4 Hz); 13C NMR (101 MHz, CDCl3) δ = 167.9 (d, J = 24.8 Hz),
138.5, 137.5, 129.2, 128.7, 127.9, 124.2, 91.4 (d, J = 192.6 Hz), 60.7
(d, J = 18.7 Hz), 56.7, 52.5, 22.4, 21.4. IR (cm−1): 3295, 2851, 1750,
1456, 1355, 1297, 1072, 794. MS (ESI) m/z: 338.1 [M + Na]+. HRMS
(ESI) m/z: calcd for C15H22FNO3SNa+ [M + Na]+ 338.1197, found
338.1194.
1
mg, 78%), mp 102−103 °C; [α]2D0 = +7.01 (c = 0.50, CHCl3); H
NMR (400 MHz, CDCl3) δ = 7.41−7.35 (m, 9H), 5.23 (dd, J = 29.7,
12.0 Hz, 2H), 5.16 (dd, J = 47.1, 2.5 Hz, 1H), 4.95 (ddd, J = 26.0, 9.5,
2.4 Hz, 1H), 4.06 (d, J = 9.5 Hz, 1H), 1.17 (s, 9H); 19F NMR (376
MHz, CDCl3) δ = −202.60 (dd, J = 48.7, 27.3 Hz); 13C NMR (101
MHz, CDCl3) δ = 167.0 (d, J = 24.7 Hz), 140.8, 135.9, 134.5, 134.3,
129.0, 128.8, 128.7, 128.7, 128.5, 127.6, 126.9, 91.1 (d, J = 193.3 Hz),
67.7, 65.3, 60.1 (d, J = 19.2 Hz), 56.8, 22.3. IR (cm−1): 3329, 3029,
1739, 1494, 1455, 1358, 1172, 1089, 885. MS (ESI) m/z: 434.1 [M +
Na]+. HRMS (ESI) m/z: calcd for C20H23ClFNO3SNa+ [M + Na]+
434.0963, found 434.0977.
(RS,2S,3R)-2-Fluoro-3-(2-methylpropane-2-sulfinylamino)-3-m-
tolyl-propionic Acid tert-Butyl Ester (3c′). By following the general
procedure, 3c′ was isolated by column chromatography on silica gel
(petroleum ether/ethyl acetate = 4/1) as a white solid (289 mg, 81%),
(RS,2S,3R)-3-(4-Bromo-phenyl)-2-fluoro-3-(2-methylpropane-2-
sulfinylamino)-propionic Acid tert-Butyl Ester (3f). By following the
general procedure, 3f was isolated by column chromatography on silica
gel (petroleum ether/ethyl acetate = 5/1) as a white solid (321 mg,
mp 118−119 °C; [α]2D0 = −22.25 (c = 0.53, CHCl3); H NMR (400
1
76%), mp 124−125 °C; [α]2D0 = −5.60 (c = 0.58, CHCl3); H NMR
1
MHz, CDCl3) δ = 7.30−7.19 (m, 3H), 7.12 (d, J = 7.1 Hz, 1H), 4.96
(dd, J = 47.5, 3.1 Hz, 1H), 4.81 (ddd, J = 24.5, 8.5, 2.8 Hz, 1H), 3.97
(d, J = 8.5 Hz, 1H), 2.35 (s, 3H), 1.43 (s, 9H), 1.21 (s, 9H); 19F NMR
(376 MHz, CDCl3) δ = −199.2 (dd, J = 47.3, 24.7 Hz); 13C NMR
(101 MHz, CDCl3) δ = 166.3 (d, J = 24.5 Hz), 138.4, 136.6, 129.2,
128.6, 128.1, 124.5, 91.2 (d, J = 191.6 Hz), 83.4, 60.7 (d, J = 19.2 Hz),
56.7, 27.9, 22.5, 21.4. IR (cm−1): 3285, 2978, 1742, 1473, 1368, 1055,
843, 796. MS (ESI) m/z: 358.2 [M + H]+. HRMS (ESI) m/z: calcd for
C18H29FNO3S+ [M + H]+ 358.1847, found 358.1843.
(400 MHz, CDCl3) δ = 7.50 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.2 Hz,
2H), 4.95 (dd, J = 47.3, 2.5 Hz, 1H), 4.83 (ddd, J = 25.0, 9.4, 2.2 Hz,
1H), 4.05 (d, J = 9.4 Hz, 1H), 1.45 (s, 9H), 1.20 (s, 9H); 19F NMR
(376 MHz, CDCl3) δ = −199.9 (dd, J = 47.1, 24.8 Hz); 13C NMR
(101 MHz, CDCl3) δ = 166.0 (d, J = 24.2 Hz), 136.9, 131.8, 129.2,
122.6, 90.8 (d, J = 192.5 Hz), 83.8, 60.0 (d, J = 19.4 Hz), 56.9, 28.0,
22.5. IR (cm−1): 3308, 2987, 1719, 1491, 1362, 1296, 1070, 832. MS
(ESI) m/z: 422.1 [M + H]+. HRMS (ESI) m/z: calcd for
C17H26BrFNO3S+ [M + H]+ 422.0795, found 422.0793.
(RS,2S,3R)-2-Fluoro-3-(2-methylpropane-2-sulfinylamino)-3-o-
tolyl-propionic Acid Methyl Ester (3d). By following the general
procedure, 3d was isolated by column chromatography on silica gel
(petroleum ether/ethyl acetate = 3/1) as a white solid (239 mg, 76%),
mp 65−66 °C; [α]2D0 = +3.46 (c = 0.52, CHCl3); 1H NMR (400 MHz,
CDCl3) δ = 7.26 (dd, J = 9.1, 6.6 Hz, 1H), 7.21 (d, J = 6.6 Hz, 2H),
7.13 (d, J = 7.3 Hz, 1H), 5.13 (dd, J = 47.2, 2.1 Hz, 1H), 4.90 (dd, J =
27.6, 9.1 Hz, 1H), 3.98 (d, J = 9.3 Hz, 1H), 3.80 (s, 3H), 2.36 (s, 3H),
1.19 (s, 9H); 19F NMR (376 MHz, CDCl3) δ = −204.3 (dd, J = 46.9,
28.5 Hz); 13C NMR (101 MHz, CDCl3) δ = 167.9 (d, J = 24.7 Hz),
138.5, 137.5, 129.2, 128.7, 127.9, 124.2, 91.4 (d, J = 192.6 Hz), 60.7
(d, J = 18.7 Hz), 56.7, 52.5, 22.4, 21.4. IR (cm−1): 3296, 2926, 1613,
1441, 1355, 1226, 1095, 794, 721. MS (ESI) m/z: 338.1 [M + Na]+.
HRMS (ESI) m/z: calcd for C15H22FNO3SNa+ [M + Na]+ 338.1197,
found 338.1194.
(RS,2S,3R)-4-[2-Fluoro-2-methoxycarbonyl-1-(2-methylpropane-
2-sulfinylamino)-ethyl]-benzoic Acid Methyl Ester (3g). By following
the general procedure, 3g was isolated by column chromatography on
silica gel (petroleum ether/ethyl acetate = 3/1) as a white solid (233
mg, 65%), mp 62−63 °C; [α]2D0 = +12.2 (c = 0.42, CHCl3); 1H NMR
(400 MHz, CDCl3) δ = 8.06 (d, J = 8.3 Hz, 2H), 7.51 (d, J = 8.1 Hz,
2H), 5.16 (dd, J = 47.2, 1.9 Hz, 1H), 5.01 (dd, J = 27.3, 10.0 Hz, 1H),
4.14 (d, J = 9.6 Hz, 1H), 3.91 (s, 3H), 3.82 (s, 3H), 1.19 (s, 9H); 19F
NMR (376 MHz, CDCl3) δ = −204.2 (dd, J = 47.0, 28.0 Hz); 13C
NMR (101 MHz, CDCl3) δ = 167.5 (d, J = 24.6 Hz), 166.5, 142.4,
130.3, 130.1, 127.3, 91.1 (d, J = 193.4 Hz), 60.2 (d, J = 19.0 Hz), 56.9,
52.7, 52.2, 22.4. IR (cm−1): 3426, 2921, 1769, 1436, 1366, 1277, 1042,
927. MS (ESI) m/z: 382.1 [M + Na]+. HRMS (ESI) m/z: calcd for
C16H22FNO5SNa+ [M + Na]+ 382.1095, found 382.1087.
(RS,2S,3R)-3-(4-Chloro-phenyl)-2-fluoro-3-(2-methylpropane-2-
sulfinylamino)-propionic Acid Methyl Ester (3e). By following the
general procedure, 3e was isolated by column chromatography on
silica gel (petroleum ether/ethyl acetate = 3/1) as a white solid (279
mg, 83%), mp 77−78 °C; [α]2D0 = −14.8 (c = 0.55, CHCl3); 1H NMR
(400 MHz, CDCl3) δ = 7.60−7.32 (m, 4H), 5.15 (dd, J = 47.2, 2.3 Hz,
1H), 4.95 (ddd, J = 27.4, 9.7, 2.2 Hz, 1H), 4.06 (d, J = 9.7 Hz, 1H),
3.84 (s, 3H), 1.21 (s, 9H) ; 19F NMR (376 MHz, CDCl3) δ = −204.3
(dd, J = 46.9, 28.2 Hz); 13C NMR (101 MHz, CDCl3) δ = 167.6 (d, J
= 24.3 Hz), 136.0, 134.5, 129.0, 128.6, 91.1 (d, J = 192.9 Hz), 60.0 (d,
J = 19.0 Hz), 56.8, 52.6, 22.3. IR (cm−1): 3325, 2960, 1771, 1496,
1456, 1276, 1018, 837, 811. MS (ESI) m/z: 358.1 [M + Na]+. HRMS
(ESI) m/z: calcd for C14H20ClFNO3S+ [M + H]+ 336.0831, found
336.0840.
(RS,2S,3R)-2-Fluoro-3-(2-methylpropane-2-sulfinylamino)-3-(3-
trifluoromethyl-phenyl)-propionic Acid Methyl Ester (3h). By
following the general procedure, 3h was isolated by column
chromatography on silica gel (petroleum ether/ethyl acetate = 3/1)
as a white solid (284 mg, 77%), mp 63−65 °C; [α]2D0 = +7.64 (c =
1
0.50, CHCl3); H NMR (400 MHz, CDCl3) δ = 7.65 (d, J = 9.1 Hz,
2H), 7.60 (d, J = 7.5 Hz, 1H), 7.52 (t, J = 7.5 Hz, 1H), 5.16 (dd, J =
47.1, 1.2 Hz, 1H), 5.01 (dd, J = 27.4, 9.7 Hz, 1H), 4.13 (d, J = 9.8 Hz,
1H), 3.82 (s, 3H), 1.18 (s, 9H); 19F NMR (376 MHz, CDCl3) δ =
−62.6 (s, 3F), −204.5 (dd, J = 47.1, 26.9 Hz, 1F); 13C NMR (101
MHz, CDCl3) δ = 167.4 (d, J = 24.4 Hz), 138.6, 130.9, 129.4, 125.4
(d, J = 3.7 Hz), 124.0 (d, J = 3.5 Hz), 91.0 (d, J = 193.3 Hz), 60.2 (d, J
= 18.9 Hz), 57.0, 52.7, 29.6, 22.3. IR (cm−1): 3315, 2917, 1748, 1440,
1323, 1086, 1076, 819. MS (ESI) m/z: 392.1 [M + Na]+. HRMS (ESI)
m/z: calcd for C15H19F4NO3SNa+ [M + Na]+ 392.0914, found
392.0904.
(RS,2S,3R)-3-(4-Chloro-phenyl)-2-fluoro-3-(2-methylpropane-2-
sulfinylamino)-propionic Acid tert-Butyl Ester (3e′). By following the
general procedure, 3e′ was isolated by column chromatography on
silica gel (petroleum ether/ethyl acetate = 5/1) as a white solid (299
(RS,2S,3R)-2-Fluoro-3-(2-methylpropane-2-sulfinylamino)-3-(3-
trifluoromethyl-phenyl)-propionic Acid tert-Butyl Ester (3h′). By
following the general procedure, 3h′ was isolated by column
chromatography on silica gel (petroleum ether/ethyl acetate = 3/1)
as a white solid (345 mg, 84%), mp 99−100 °C; [α]2D0 = −2.57 (c =
mg, 79%), mp 123−124 °C; [α]2D0 = +29.10 (c = 0.53, CHCl3); H
1
NMR (400 MHz, CDCl3) δ = 7.36 (q, J = 8.7 Hz, 4H), 4.95 (dd, J =
47.4, 2.2 Hz, 1H), 4.87−4.78 (m, 1H), 4.05 (d, J = 9.3 Hz, 1H), 1.45
(s, 9H), 1.21 (s, 9H); 19F NMR (376 MHz, CDCl3) δ = −199.6 (dd, J
= 48.6, 25.8 Hz); 13C NMR (101 MHz, CDCl3) δ = 166.0 (d, J = 24.2
Hz), 136.4, 134.4, 128.9, 90.9 (d, J = 192.6 Hz), 83.7, 59.9 (d, J = 19.5
1
0.52, CHCl3); H NMR (400 MHz, CDCl3) δ = 7.66 (d, J = 7.5 Hz,
2H), 7.60 (d, J = 7.5 Hz, 1H), 7.51 (t, J = 7.6 Hz, 1H), 4.99 (dd, J =
47.1, 2.7 Hz, 1H), 4.94 (ddd, J = 24.3, 9.4, 2.5 Hz, 1H), 4.16 (d, J = 9.3
E
DOI: 10.1021/acs.joc.5b01574
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Hz, 1H), 1.44 (s, 9H), 1.22 (s, 9H); 19F NMR (376 MHz, CDCl3) δ =
−62.6 (s, 3F), −199.1 (dd, J = 48.8, 25.5 Hz, 1F); 13C NMR (101
MHz, CDCl3) δ = 165.9 (d, J = 24.2 Hz), 138.8, 131.1, 129.3, 125.3
(d, J = 3.5 Hz), 124.2 (d, J = 2.6 Hz), 90.7 (d, J = 193.1 Hz), 83.9,
77.2, 60.0 (d, J = 19.6 Hz), 57.0, 27.9, 22.5. IR (cm−1): 3323, 2975,
1744, 1473, 1333, 1171, 1129, 1043, 873. MS (ESI) m/z: 412.2 [M +
H]+. HRMS (ESI) m/z: calcd for C18H26F4NO3S+ [M + H]+
412.1564, found 412.1559.
(d, J = 9.3 Hz, 1H), 3.82 (s, 3H), 1.20 (s, 9H); 19F NMR (376 MHz,
CDCl3) δ = −204.0 (dd, J = 47.0, 28.2 Hz); 13C NMR (101 MHz,
CDCl3) δ = 167.8 (d, J = 24.8 Hz), 134.9, 133.1, 128.8, 128.2, 127.6,
126.6, 126.5, 126.4, 124.7, 91.4 (d, J = 192.7 Hz), 60.7 (d, J = 18.8
Hz), 56.8, 52.6, 22.4. IR (cm−1): 3296, 2958, 1439, 1353, 1285, 1073,
931, 875, 800. MS (ESI) m/z: 374.1 [M + Na]+. HRMS (ESI) m/z:
calcd for C18H22FNO3SNa+ [M + Na]+ 374.1197, found 374.1189.
(RS,2S,3R)-2-Fluoro-3-(2-methylpropane-2-sulfinylamino)-3-pyri-
din-2-yl-propionic Acid Methyl Ester (3l). By following the general
procedure, 3l was isolated by column chromatography on silica gel
(petroleum ether/ethyl acetate = 1/2) as a white solid (212 mg, 70%),
(RS,2S,3R)-3-(4-Cyano-phenyl)-2-fluoro-3-(2-methylpropane-2-
sulfinylamino)-propionic Acid Methyl Ester (3i). By following the
general procedure, 3i was isolated by column chromatography on silica
gel (petroleum ether/ethyl acetate = 3/1) as a white solid (231 mg,
1
mp 110−111 °C; [α]2D0 = +4.77 (c = 0.57, CHCl3); H NMR (400
71%), mp 113−114 °C; [α]2D0 = +29.1 (c = 0.53, CHCl3); H NMR
MHz, CDCl3) δ = 8.58 (d, J = 4.7 Hz, 1H), 7.72 (t, J = 7.7 Hz, 1H),
7.54 (d, J = 7.8 Hz, 1H), 7.20−7.24 (m, 1H), 5.47 (dd, J = 46.9, 2.4
Hz, 1H), 5.07 (dd, J = 26.2, 9.2 Hz, 1H), 4.89 (d, J = 9.1 Hz, 1H), 3.80
(s, 3H), 1.26 (s, 9H); 19F NMR (376 MHz, CDCl3) δ = −204.5 (dd, J
= 46.8, 26.1 Hz); 13C NMR (101 MHz, CDCl3) δ = 167.9 (d, J = 24.5
Hz), 155.8, 149.0, 137.0, 123.1, 122.0, 91.0 (d, J = 191.4 Hz), 62.0 (d, J
= 19.8 Hz), 56.7, 52.4, 22.5. IR (cm−1): 3251, 2959, 1760, 1592, 1438,
1347, 1234, 1075, 993. MS (ESI) m/z: 303.1 [M + H]+. HRMS (ESI)
m/z: calcd for C13H20FN2O3S+ [M + H]+ 303.1173, found 303.1170.
(RS,2S,3R)-2-Fluoro-4-methyl-3-(2-methylpropane-2-sulfinylami-
no)-pentanoic Acid tert-Butyl Ester (3m). By following the general
procedure, 3m was isolated by column chromatography on silica gel
(dichloromethane/methanol = 100/1) as a white solid (260 mg, 84%),
1
(400 MHz, CDCl3) δ = 7.68 (d, J = 8.3 Hz, 2H), 7.56 (d, J = 8.2 Hz,
2H), 5.15 (dd, J = 47.1, 1.9 Hz, 1H), 4.99 (dd, J = 27.3, 10.2 Hz, 1H),
4.16 (d, J = 10.2 Hz, 1H), 3.82 (s, 3H), 1.18 (s, 9H); 19F NMR (376
MHz, CDCl3) δ = −204.3 (dd, J = 47.0, 27.8 Hz); 13C NMR (101
MHz, CDCl3) δ = 167.2 (d, J = 24.5 Hz), 142.7, 132.6, 128.1, 118.2,
112.5, 90.8 (d, J = 193.8 Hz), 60.4 (d, J = 19.1 Hz), 57.0, 52.8, 22.3. IR
(cm−1): 3307, 2961, 2226, 1735, 1444, 1360, 1291, 1061, 850. MS
(ESI) m/z: 327.1 [M + H]+. HRMS (ESI) m/z: calcd for
C15H19FN2O3SNa+ [M + Na]+ 349.0993, found 349.0986.
(RS,2S,3R)-3-(4-Cyano-phenyl)-2-fluoro-3-(2-methylpropane-2-
sulfinylamino)-propionic Acid tert-Butyl Ester (3i′). By following the
general procedure, 3i′ was isolated by column chromatography on
silica gel (petroleum ether/ethyl acetate = 3/1) as a white solid (276
mp 82−83 °C; [α]2D0 = −32.70 (c = 0.53, CHCl3); H NMR (400
1
mg, 75%), mp 121−122 °C; [α]2D0 = +1.75 (c = 0.55, CHCl3); H
MHz, CDCl3) δ = 4.88 (d, J = 47.9 Hz, 1H), 3.53 (qd, J = 15.4, 9.2 Hz,
2H), 2.07 (dd, J = 12.9, 6.7 Hz, 1H), 1.48 (s, 9H), 1.21 (s, 9H), 1.06
(dd, J = 12.1, 4.4 Hz, 6H); 19F NMR (376 MHz, CDCl3) δ = −203.1
(dd, J = 47.9, 31.0 Hz); 13C NMR (101 MHz, CDCl3) δ = 167.2 (d, J
= 25.1 Hz), 88.7 (d, J = 188.1 Hz), 83.1, 62.9 (d, J = 17.9 Hz), 56.7,
32.0, 28.1, 22.7, 19.5, 18.7. IR (cm−1): 3256, 2978, 1756, 1559, 1469,
1360, 1280, 1148, 860. MS (ESI) m/z: 310.2 [M + H]+. HRMS (ESI)
m/z: calcd for C14H29FNO3S+ [M + H]+ 310.1847, found 310.1845.
(RS,2S,3R)-2-Fluoro-4,4-dimethyl-3-(2-methylpropane-2-sulfinyla-
mino)-pentanoic Acid tert-Butyl Ester (3n). By following the general
procedure, 3n was isolated by column chromatography on silica gel
(petroleum ether/ethyl acetate = 3/1) as a white solid (265 mg, 82%),
1
NMR (400 MHz, CDCl3) δ = 7.67 (d, J = 8.3 Hz, 2H), 7.57 (d, J = 8.2
Hz, 2H), 4.98 (dd, J = 47.0, 2.3 Hz, 1H), 4.93 (ddd, J = 15.8, 11.8, 2.2
Hz, 1H), 4.20 (d, J = 9.8 Hz, 1H), 1.46 (s, 9H), 1.21 (s, 9H); 19F
NMR (376 MHz, CDCl3) δ = −199.5 (dd, J = 46.5, 23.4 Hz); 13C
NMR (101 MHz, CDCl3) δ = 165.7 (d, J = 23.9 Hz), 143.1, 132.4,
128.3, 118.3, 112.4, 90.4 (d, J = 193.9 Hz), 84.1, 60.2 (d, J = 19.6 Hz),
57.1, 28.0, 22.5. IR (cm−1): 3334, 2978, 2231, 1750, 1473, 1355, 1252,
1156, 881. MS (ESI) m/z: 369.2 [M + H]+. HRMS (ESI) m/z: calcd
for C18H26FN2O3S+ [M + H]+ 369.1643, found 369.1636.
(RS,2S,3R)-2-Fluoro-3-(2-methylpropane-2-sulfinylamino)-3-(4-
nitro-phenyl)-propionic Acid Methyl Ester (3j). By following the
general procedure, 3j was isolated by column chromatography on silica
gel (petroleum ether/ethyl acetate = 3/1) as a white solid (197 mg,
57%), mp 80−81 °C; [α]D20 = +28.0 (c = 0.53, CHCl3); 1H NMR (400
MHz, CDCl3) δ = 8.25 (d, J = 8.8 Hz, 2H), 7.63 (d, J = 8.7 Hz, 2H),
5.17 (dd, J = 47.2, 2.0 Hz, 1H), 5.05 (dd, J = 27.4, 10.4 Hz, 1H), 4.21
(d, J = 10.2 Hz, 1H), 3.83 (s, 3H), 1.19 (s, 9H); 19F NMR (376 MHz,
CDCl3) δ = −204.2 (dd, J = 46.9, 28.1 Hz); 13C NMR (101 MHz,
CDCl3) δ = 167.2 (d, J = 24.4 Hz), 147.9, 144.5, 128.4, 124.0, 90.82
(d, J = 193.9 Hz), 60.1 (d, J = 19.1 Hz), 57.1, 52.8, 22.3. IR (cm−1):
3119, 2965, 1737, 1525, 1439, 1348, 1275, 1008, 932. MS (ESI) m/z:
368.9 [M + Na]+. HRMS (ESI) m/z: calcd for C14H19FN2O5SNa+ [M
+ Na]+ 369.0891, found 369.0900.
(RS,2S,3R)-2-Fluoro-3-(2-methylpropane-2-sulfinylamino)-3-(4-
nitro-phenyl)-propionic Acid tert-Butyl Ester (3j′). By following the
general procedure, 3j′ was isolated by column chromatography on
silica gel (petroleum ether/ethyl acetate = 3/1) as a white solid (260
mg, 67%), mp 99−100 °C; [α]2D0 = +7.90 (c = 0.57, CHCl3). 1H NMR
(400 MHz, CDCl3) δ = 8.23 (d, J = 8.7 Hz, 2H), 7.63 (d, J = 8.6 Hz,
2H), 5.10−4.86 (m, 2H), 4.25 (d, J = 9.9 Hz, 1H), 1.47 (s, 9H), 1.22
(s, 9H); 19F NMR (376 MHz, CDCl3) δ = −199.8 (dd, J = 47.2, 24.3
Hz); 13C NMR (101 MHz, CDCl3) δ = 165.7 (d, J = 23.9 Hz), 147.8,
145.0, 128.6, 123.8, 90.4 (d, J = 194.1 Hz), 84.2, 59.9 (d, J = 19.6 Hz),
57.1, 28.0, 22.5. IR (cm−1): 3342, 2981, 1752, 1473, 1357, 1253, 1156,
848, 765. MS (ESI) m/z: 389.2 [M + H]+. HRMS (ESI) m/z: calcd for
C17H26FN2O5S+ [M + H]+ 389.1541, found 389.1533.
mp 111.2−111.5 °C; [α]D20 = −42.38 (c = 0.62, CHCl3); H NMR
1
(400 MHz, CDCl3) δ = 4.99 (d, J = 47.9 Hz, 1H), 3.61 (d, J = 9.3 Hz,
1H), 3.46 (dd, J = 28.3, 9.2 Hz, 1H), 1.49 (s, 9H), 1.22 (s, 9H), 1.08
(s, 9H); 19F NMR (376 MHz, CDCl3) δ = −202.7 (dd, J = 47.8, 28.6
Hz); 13C NMR (101 MHz, CDCl3) δ = 162.7 (d, J = 25.1 Hz), 83.3
(d, J = 188.1 Hz), 78.3, 60.9 (d, J = 17.0 Hz), 52.2, 29.8, 23.4, 23.2,
22.6, 18.1. IR (cm−1): 3254, 2958, 1762, 1475, 1368, 1234, 1159, 1062,
998. MS (ESI) m/z: 324.2 [M + H]+. HRMS (ESI) m/z: calcd for
C15H31FNO3S+ [M + H]+ 324.2003, found 324.2002.
(RS,2S,3R)-2-Fluoro-3-(2-methylpropane-2-sulfinylamino)-4,4-di-
phenyl- butyric Acid Methyl Ester (3o). By following the general
procedure, 3o was isolated by column chromatography on silica gel
(petroleum ether/ethyl acetate = 3/1) as a white solid (267 mg, 71%),
mp 112−113 °C; [α]2D0 = −23.01 (c = 0.57, CHCl3); H NMR (400
1
MHz, CDCl3) δ = 7.63 (d, J = 7.8 Hz, 2H), 7.29−7.42 (m, 6H), 7.12−
7.28 (m, 2H), 5.72 (d, J = 47.5 Hz, 1H), 5.50 (s, 1H), 3.46 (s, 3H),
1.23 (s, 9H); 19F NMR (376 MHz, CDCl3) δ = −185.73 (d, J = 47.2
Hz); 13C NMR (101 MHz, CDCl3) δ = 169.0 (d, J = 23.2 Hz), 139.3,
138.3, 129.3, 128.8, 128.7, 128.4, 128.2, 128.0, 92.3 (d, J = 206.8 Hz),
69.2 (d, J = 20.8 Hz), 56.5, 52.5, 22.9. IR (cm−1): 3316, 2853, 1446,
1301, 1172, 1069, 867, 821. MS (ESI) m/z: 400.1 [M + Na]+. HRMS
(ESI) m/z: calcd for C20H24FNO3SNa+ [M + Na]+ 400.1353, found
400.1365.
(RS,2S,3R)-3,3-Bis(4-chloro-phenyl)-2-fluoro-3-(2-methylpropane-
2-sulfinylamino)-propionic Acid Methyl Ester (3p). By following the
general procedure, 3p was isolated by column chromatography on
silica gel (petroleum ether/ethyl acetate = 4/1) as a white solid (366
(RS,2S,3R)-2-Fluoro-3-(2-methylpropane-2-sulfinylamino)-3-
naphthalen-2-yl-propionic Acid Methyl Ester (3k). By following the
general procedure, 3k was isolated by column chromatography on
silica gel (petroleum ether/ethyl acetate = 3/1) as a white solid (246
mg, 82%), mp 101−102 °C; [α]2D0 = −3.98 (c = 0.58, CHCl3); H
1
NMR (400 MHz, CDCl3) δ = 7.58 (d, J = 7.6 Hz, 2H), 7.33 (dd, J =
8.7, 4.9 Hz, 4H), 7.13 (d, J = 8.5 Hz, 2H), 5.63 (d, J = 47.5 Hz, 1H),
5.52 (s, 1H), 3.53 (s, 3H), 1.22 (s, 9H); 19F NMR (376 MHz, CDCl3)
δ = −186.0 (d, J = 47.1 Hz); 13C NMR (101 MHz, CDCl3) δ = 168.8
mg, 70%), mp 111−113 °C; [α]2D0 = +16.17 (c = 0.51, CHCl3); H
1
NMR (400 MHz, CDCl3) δ = 7.95−7.78 (m, 4H), 7.61−7.44 (m,
3H), 5.25 (d, J = 47.2 Hz, 1H), 5.12 (dd, J = 27.5, 9.2 Hz, 1H), 4.16
F
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Article
(d, J = 22.8 Hz), 137.5, 136.2, 134.8, 134.5, 131.1, 130.7, 130.2, 130.1,
128.6, 128.3, 92.0 (d, J = 208.2 Hz), 68.7 (d, J = 20.9 Hz), 56.7, 52.8,
22.9. IR (cm−1): 3319, 2956, 1770, 1493, 1402, 1300, 1281, 1095, 873.
MS (ESI) m/z: 445.9 [M + H]+. HRMS (ESI) m/z: calcd for
C20H22Cl2FNO3SNa+ [M + Na]+ 468.0574, found 468.0551.
Typical Procedure for the Diastereoselective Addition of α-
Alkylated Fluoroacetate to N-tert-Butylsulfinyl Imines. Under
N2 atmosphere, LiHMDS (0.6 mL, 1.0 mol/L in THF, 1.2 equiv) was
added slowly to a mixture of α-alkylated fluoroacetate (0.6 mmol, 1.2
equiv), imine 2 (0.5 mmol, 1.0 equiv), TMEDA (0.15 mL), and THF
(1.5 mL) at −70 °C. Reaction mixtures were stirred at this
temperature for 30 min. Then, 1 N HCl (2 mL) was added, and
the quenched reaction mixture was extracted three times with ethyl
acetate (10 mL × 3). The combined organic layers were dried over
anhydrous MgSO4. Evaporation of the solvent under vacuum, followed
by flash column chromatography on silica gel, gave the corresponding
product 7, 8, or 9.
(dd, J = 4.3, 2.6 Hz, 2H), 4.74 (dd, J = 25.2, 10.8 Hz, 1H), 3.88−4.17
(m, 3H), 2.96 (dd, J = 39.3, 14.4 Hz, 1H), 2.65 (t, J = 13.7 Hz, 1H),
1.15 (s, 9H), 1.05 (t, J = 7.1 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ
= −177.55 (br); 13C NMR (101 MHz, CDCl3) δ = 169.0 (d, J = 25.4
Hz), 135.4, 134.8, 133.3, 129.9, 129.1, 128.2, 127.3, 99.8 (d, J = 199.0
Hz), 64.8 (d, J = 19.0 Hz), 61.8, 56.6, 41.4 (d, J = 20.8 Hz), 22.3, 13.9.
IR (cm−1): 3327, 2956, 1730, 1496, 1367, 1139, 1095, 1014, 844. MS
(ESI) m/z: 440.1 [M + H]+. HRMS (ESI) m/z: calcd for
C22H28ClFNO3S+ [M + H]+ 440.1451, found 440.1448.
(RS,2S,3R)-2-Benzyl-2-fluoro-3-(2-methylpropane-2-sulfinylami-
no)-3-p-tolyl-propionic Acid Ethyl Ester (9c). By following the general
procedure, 9c was isolated by column chromatography on silica gel
(petroleum ether/ethyl acetate = 3/1) as a white solid (159 mg, 76%),
mp 110−111 °C; [α]2D0 = −3.70 (c = 0.52, CHCl3); H NMR (400
1
MHz, CDCl3) δ = 7.32 (d, J = 7.6 Hz, 2H), 7.12−7.25 (m, 5H), 7.09
(d, J = 7.1 Hz, 2H), 4.72 (dd, J = 26.0, 10.5 Hz, 1H), 4.01 (dd, J =
14.6, 7.4 Hz, 2H), 2.57−3.12 (m, 2H), 2.35 (s, 3H), 1.14 (s, 9H), 1.06
(t, J = 7.1 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ = −177.8 (br);
13C NMR (101 MHz, CDCl3) δ = 169.4, 138.5, 133.9, 133.7, 129.9,
(RS,2S,3R)-4-Benzyloxy-2-fluoro-2-[(2-methylpropane-2-sulfinyla-
mino)-phenyl-methyl]-butyric Acid Ethyl Ester (7). By following the
general procedure, 7 was isolated by column chromatography on silica
gel (petroleum ether/ethyl acetate = 3/1) as a white solid (184 mg,
129.6, 128.3, 128.1, 127.1, 100.1 (d, J = 198.8 Hz), 65.3 (d, J = 18.7
Hz), 61.6, 56.4, 41.4 (d, J = 20.8 Hz), 22.3, 21.1, 13.9. IR (cm−1):
3324, 2955, 2853, 1759, 1496, 1277, 1192, 1079, 856. MS (ESI) m/z:
420.2 [M + H]+. HRMS (ESI) m/z: calcd for C23H31FNO3S+ [M +
H]+ 420.1998, found 420.1994.
82%), mp 123.5−124.2 °C; [α]2D0 = −8.85 (c = 0.57, CHCl3); H
1
NMR (400 MHz, CDCl3) δ = 7.26−7.39 (m, 10H), 4.61 (dd, J = 26.3,
10.6 Hz, 1H), 4.37 (s, 2H), 3.99−4.11 (m, 3H), 3.47 (dddd, J = 18.6,
13.9, 9.4, 4.5 Hz, 2H), 2.08−2.32 (m, 2H), 1.19 (t, J = 7.2 Hz, 3H),
1.15 (s, 9H); 19F NMR (376 MHz, CDCl3) δ = −180.9 (t, J = 30.7
Hz); 13C NMR (101 MHz, CDCl3) δ = 169.7 (d, J = 26.3 Hz), 137.7,
136.9, 128.7, 128.6, 128.5, 128.2, 127.8, 127.6, 97.5 (d, J = 195.1 Hz),
73.2, 65.5 (d, J = 18.7 Hz), 64.1 (d, J = 4.0 Hz), 61.7, 56.5, 35.3 (d, J =
21.4 Hz), 22.3, 13.9. IR (cm−1): 3321, 2962, 1730, 1470, 1322, 1221,
1151, 1098, 1030, 879. MS (ESI) m/z: 450.2 [M + H]+. HRMS (ESI)
m/z: calcd for C24H33FNO4S+ [M + H]+ 450.2109, found 450.2100.
(RS,2S,3R)-2-Fluoro-3-(2-methylpropane-2-sulfinylamino)-2-
naphthalen-2-ylmethyl-3-phenyl-propionic Acid Ethyl Ester (8). By
following the general procedure, 8 was isolated by column
chromatography on silica gel (petroleum ether/ethyl acetate = 3/1)
as a white solid (153 mg, 67%), mp 147.9−148.7 °C; [α]2D0 = +7.11 (c
= 0.52, CHCl3); 1H NMR (400 MHz, CDCl3) δ = 7.63−7.87 (m, 3H),
7.55 (s, 1H), 7.32−7.51 (m, 7H), 7.22 (d, J = 8.4 Hz, 1H), 4.81 (dd, J
= 25.7, 10.5 Hz, 1H), 4.10 (d, J = 10.7 Hz, 1H), 3.99 (q, J = 7.1 Hz,
2H), 3.14 (dd, J = 39.3, 14.5 Hz, 1H), 2.82 (t, J = 13.7 Hz, 1H), 1.16
(s, 9H), 0.98 (t, J = 7.1 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ =
−177.4 (br); 13C NMR (101 MHz, CDCl3) δ = 169.2 (d, J = 25.6 Hz),
136.9, 133.1, 132.5, 131.2, 128.9, 128.8, 128.8, 128.5, 127.9, 127.8,
127.5, 127.5, 125.9, 125.7, 100.1 (d, J = 198.9 Hz), 65.6 (d, J = 18.7
Hz), 61.7, 56.6, 41.6 (d, J = 20.9 Hz), 22.3, 13.9. IR (cm−1): 3319,
2959, 1716, 1508, 1457, 1328, 1223, 1083, 885. MS (ESI) m/z: 456.2
[M + H]+. HRMS (ESI) m/z: calcd for C26H31FNO3S+ [M + H]+
456.2003, found 456.1993.
Procedure for the Synthesis of the Fmoc-Protected α-
Fluoro-β-amino Acid tert-Butyl Ester 10. Into a 10 mL flask was
placed 3a′ (171.5 mg, 0.5 mmol) and 1.25 N HCl/MeOH (1.0 mL).
The reaction mixture was stirred at rt for 30 min and was then
concentrated to near dryness. Diethyl ether was added to precipitate
out the ammonium hydrochloride. The precipitate was suspended in a
mixture of CH3CN (0.5 mL) and 10% NaHCO3 (1.0 mL) at 0 °C.
Then, a solution of 9-fluorenylmethyl N-succinimidyl carbonate (202
mg, 0.6 mmol) in CH3CN (0.5 mL) was added slowly. The resulting
mixture was stirred at rt for 4 h, diluted with H2O (10 mL), and
extracted three times with ethyl acetate (10 mL × 3). The combined
organic layers were dried over anhydrous MgSO4. Evaporation of the
solvent under vacuum, followed by flash column chromatography on
silica gel (petroleum ether/ethyl acetate = 3/1), gave the
corresponding product 10.
(2S,3R)-3-(9H-Fluoren-9-ylmethoxycarbonylamino)-2-fluoro-3-
phenyl-propionic Acid tert-Butyl Ester (10). White solid (198 mg,
86%), mp 100.6−101.2 °C; [α]2D0 = +17.70 (c = 0.53, CHCl3); H
1
NMR (400 MHz, CDCl3) δ = 7.79 (d, J = 7.4 Hz, 2H), 7.59 (d, J = 4.8
Hz, 2H), 7.30−7.46 (m, 9H), 5.74 (d, J = 9.5 Hz, 1H), 5.41 (dd, J =
28.7, 10.1 Hz, 1H), 5.09 (d, J = 47.9 Hz, 1H), 4.31−4.58 (m, 3H),
4.23 (t, J = 6.9 Hz, 1H), 1.48 (s, 9H).); 19F NMR (376 MHz, CDCl3)
δ = −201.6 (dd, J = 47.4, 28.7 Hz); 13C NMR (101 MHz, CDCl3) δ =
166.2 (d, J = 24.9 Hz), 155.5, 143.7, 143.6, 141.2, 137.4, 128.7, 128.1,
127.7, 127.0, 126.7, 125.0, 119.9, 90.3 (d, J = 191.1 Hz), 83.8, 67.2,
55.8 (d, J = 19.0 Hz), 47.1, 29.7, 27.8. IR (cm−1): 3380, 3067, 2923,
1748, 1518, 1477, 1297, 1159, 1094, 842. MS (ESI) m/z: 479.2 [M +
(RS,2S,3R)-2-Benzyl-2-fluoro-3-(2-methylpropane-2-sulfinylami-
no)-3-phenyl-propionic Acid Ethyl Ester (9a). By following the
general procedure, 9a was isolated by column chromatography on
silica gel (petroleum ether/ethyl acetate = 3/1) as a white solid (150
mg, 74%), mp 107.5−108.6 °C; [α]2D0 = −9.43 (c = 0.55, CHCl3); 1H
NMR (400 MHz,CDCl3) δ = 7.36−7.54 (m, 5H), 7.21−7.27 (m, 3H),
7.06−7.18 (m, 2H), 4.79 (dd, J = 25.6, 10.5 Hz, 1H), 4.01−4.10 (m,
3H), 2.99 (dd, J = 39.3, 14.5 Hz, 1H), 2.46−2.80 (m, 1H), 1.18 (s,
9H), 1.09 (t, J = 7.2 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ =
−177.82 (br); 13C NMR (101 MHz, CDCl3) δ = 169.2 (d, J = 25.6
Hz), 136.9, 133.6, 129.9, 128.8, 128.7, 128.5, 128.1, 127.2, 100.0 (d, J
= 199.1 Hz), 65.5 (d, J = 18.8 Hz), 61.6, 56.5, 41.6, 41.4, 22.3, 13.9. IR
(cm−1): 3321, 2981, 1760, 1472, 1299, 1183, 1061, 871, 780. MS
(ESI) m/z: 406.1 [M + H]+. HRMS (ESI) m/z: calcd for
C22H29FNO3S+ [M + H]+ 406.1847, found 406.1846.
(RS,2S,3R)-2-Benzyl-3-(4-chloro-phenyl)-2-fluoro-3-(2-methylpro-
pane-2-sulfinylamino)-propionic Acid Ethyl Ester (9b). By following
the general procedure, 9b was isolated by column chromatography on
silica gel (petroleum ether/ethyl acetate = 3/1) as a white solid (143
mg, 65%), mp 99−100 °C; [α]2D0 = +2.67 (c = 0.57, CHCl3); 1H NMR
(400 MHz, CDCl3) δ = 7.33−7.48 (m, 4H), 7.18−7.25 (m, 3H), 7.08
+
NH4]+. HRMS (ESI) m/z: calcd for C28H32FN2O4 [M + NH4]+
479.2341, found 479.2332.
Procedure for Synthesis of the Fmoc-Protected α-Fluoro-β-
amino Acid 11. In a 10 mL flask, TFA (0.9 mL) was added to a
stirred solution of 10 (198 mg, 0.43 mmol) in DCM (2.0 mL) at rt,
and the resulting mixture was stirred at rt for 16 h. Saturated
NaHCO3−H2O (10 mL) were then added, and the aqueous layer was
extracted with DCM (10 mL × 2). The combined organic extracts
were then concentrated under vacuum to give 11.
(2S,3R)-3-(9H-Fluoren-9-ylmethoxycarbonylamino)-2-fluoro-3-
phenyl-propionic Acid (11). White solid (146 mg, 84%), mp 186.1−
1
186.7 °C; [α]2D0 = +13.36 (c = 0.61, CHCl3); H NMR (400 MHz, d-
DMSO) δ = 8.03 (d, J = 8.0 Hz, 1H), 7.89 (d, J = 8.0 Hz, 2H), 7.73−
7.78 (m, 2H), 7.28−7.46 (m, 8H), 5.28 (dd, J = 48.0, 4.0 Hz, 1H),
5.26 (dd, J = 32.0, 8.0 Hz, 1H), 4.18−4.28 (m, 3H); 19F NMR (376
MHz, CDCl3) δ = −188.0 (br); 13C NMR (101 MHz, d-DMSO) δ =
170.1(d, J = 19.4 Hz), 155.8, 144.4, 144.0, 141.1, 141.0, 128.3, 128.0,
127.5, 127.2, 125.7, 125.6, 120.5, 92.5 (d, J = 188.7 Hz), 66.0, 56.5 (d,
J = 21.6 Hz), 47.1. IR (cm−1): 3386, 2936, 1752, 1683, 1528, 1477,
G
DOI: 10.1021/acs.joc.5b01574
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1299, 1226, 1074, 977. MS (ESI) m/z: 406.1 [M + H]+. HRMS (ESI)
M.; March, T. L. J. Org. Chem. 2010, 75, 7365−7372. (c) Peddie, V.;
Abell, A. D. Helv. Chim. Acta 2012, 95, 2460−2472. (d) Jing, Z.-T.;
Huang, Y.-G.; Qing, F.-L. Chin. Chem. Lett. 2011, 22, 919−922.
(e) Andrews, P. C.; Bhaskar, V.; Bromfield, K. M.; Dodd, A. M.;
Duggan, P. J.; Duggan, S. A. M.; McCarthy, T. D. Synlett 2004, 0791−
0794. (f) Tang, C.-Y.; Wang, G.; Yang, X.-Y.; Wu, X.-Y.; Sha, F.
Tetrahedron Lett. 2014, 55, 6447−6450. (g) Somekh, L.; Shanzer, A. J.
+
m/z: calcd for C24H21FNO4 [M + H]+ 406.1449, found 406.1442.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.5b01574.
Am. Chem. Soc. 1982, 104, 5836−5837. (h) Groth, U.; Schollkopf, U.
̈
1
Copies of H, 19F, and 13C NMR spectra of all new
Synthesis 1983, 1983, 673−675. (i) Ayi, A. I.; Guedj, R. J. Chem. Soc.,
Perkin Trans. 1 1983, 2045−2051. For the synthesis of α,α-difluoro-β-
amino acids, see: (j) March, T. L.; Johnston, M. R.; Duggan, P. J. Org.
Lett. 2012, 14, 182−185. (k) Soloshonok, V. A.; Ohkura, H.;
Sorochinsky, A.; Voloshin, N.; Markovsky, A.; Belik, M.; Yamazaki,
T. Tetrahedron Lett. 2002, 43, 5445−5448. (l) Sorochinsky, A.;
Voloshin, N.; Markovsky, A.; Belik, M.; Yasuda, N.; Uekusa, H.; Ono,
T.; Berbasov, D. O.; Soloshonok, V. A. J. Org. Chem. 2003, 68, 7448−
7454. (m) Staas, D. D.; Savage, K. L.; Homnick, C. F.; Tsou, N. N.;
Ball, R. G. J. Org. Chem. 2002, 67, 8276−8279.
(7) Pan, Y.; Zhao, Y.; Ma, T.; Yang, Y.; Liu, H.; Jiang, Z.; Tan, C.-H.
Chem. - Eur. J. 2010, 16, 779−782.
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(10) (a) Huang, X.-T.; Chen, Q.-Y. J. Org. Chem. 2002, 67, 3231−
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(e) Saadi, J.; Akakura, M.; Yamamoto, H. J. Am. Chem. Soc. 2011, 133,
compounds
(PDF)
X-ray crystal structure of compound 3e′
(CIF)
X-ray crystal structure of compound 9c
(CIF)
AUTHOR INFORMATION
Corresponding Author
*E-mail: ya.li@sues.edu.cn.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Support of our work by the National Natural Science
Foundation of China (21102089) and the Innovation Program
of Shanghai University of Engineering Science (2012td09,
14KY0407) is gratefully acknowledged.
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