Ni/AntPohs-Catalyzed Stereoselective Asymmetric Intramolecular Reductive Coupling of N-1,6-Alkynones

Article abstract of DOI:10.1021/acs.joc.1c00079

An efficient nickel-catalyzed stereoselective asymmetric intramolecular reductive coupling of N-1,6-alkynones is reported. A P-chiral monophosphine ligand AntPhos was found to be a privileged catalyst for constructing versatile functionalized chiral pyrro

Full text of DOI:10.1021/acs.joc.1c00079

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Ni/AntPohs-Catalyzed Stereoselective Asymmetric Intramolecular
Reductive Coupling of N‑1,6-Alkynones
Wanjun Chen,§ Yaping Cheng,§ Tao Zhang, Yu Mu, Wenqi Jia, and Guodu Liu*
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ABSTRACT: An efficient nickel-catalyzed stereoselective asymmetric intramolecular reductive coupling of N-1,6-alkynones is
reported. A P-chiral monophosphine ligand AntPhos was found to be a privileged catalyst for constructing versatile functionalized
chiral pyrrolidine rings using triethylsilane as the reducing reagent. Concise synthesis of pyrrolidines with chiral tertiary allylic
alcohols was achieved in high yields (99%), excellent stereoselectivity (>99:1 E/Z), and enantioselectivity (>99:1 er) with very
broad substrate scope. Totally, thirty-five N-1,6-alkynones were synthesized and applied in this reaction successfully. This reaction
can be scaled up to gram scale without loss of its enantioselectivity. Ligand effects and reaction mechanism are investigated in detail.
While the developed asymmetric synthesis of pyrrolidine with chiral tertiary allylic alcohols is anticipated to find wider applications
in organic synthesis and chemical biology, the discovered new reactions of N-1,6-alkynone with AntPhos using different catalyst
systems would further expanded its new research fields and attract more detailed explorations in the future.
ophthalmology. Hygrine has antispasmodic activity. Domic
acid has a powerful neuroexcitatory property.2 Nifeviroc is a
novel antagonist for CCR5 in clinical development for HIV
infection treatment.3 Norsecurinamine A showed significant
biological activities on the central nervous system and
cytotoxicity.4 Many chiral pyrrolidine-related compounds
display a wide variety of biological activity and are prevalent
in active pharmaceutical ingredients. Therefore, new methods
for the synthesis of chiral pyrrolidines in enantiomerically
enriched form are valuable. Although numerous catalytic
enantioselective reactions to give the chiral pyrrolidine
derivatives have been described,5 methods for the pyrrolidines
with chiral tertiary allylic alcohols are limited due to steric and
electronic constraints regarding the substrates and reagents,
and hence, it is still a challenge to establish a high level of
asymmetric induction as well as a high stereoselectivity.
Transition metal-catalyzed coupling of alkynes with carbon-
yls6 is a highly powerful and practical method for direct
construction of new carbon−carbon bonds with allylic
INTRODUCTION
■
Chiral pyrrolidines are privileged substructures of numerous
biologically active natural products and drugs (Figure 1). L-
Proline is natural cyclic chiral amino acid playing a pivotal role
in the protein structure. Its derivatives were used as efficient
ligands for asymmetric synthesis.1 Nicotine is the second most
widely used recreational drug after caffeine. Anisomycin is an
anticancer antibiotic inhibiting protein synthesis. Cocaine was
widely used as a topical anesthetic in dentistry and in
Received: January 12, 2021
Published: March 24, 2021
Figure 1. Chiral pyrrolidines in natural products and drugs.
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alcohols, valuable building blocks in organic synthesis that
commonly occur as key subunits embedded within bioactive
natural products as well as versatile precursors for a variety of
synthetic transformations.7 Although catalysts based on Pd,6b,8
Rh,9 Ru,10 and Ir,11 and so forth have been successfully
employed in coupling of alkynes with various carbonyls in the
past years, these metals are very expensive as their reserves are
declining, limiting their application in the industry. Thus,
earth-abundant transition metal Ni-catalyzed reactions have
become more attractive as nickel is abundant, inexpensive, and
environmentally friendly for its further industrial utilization.
Ni-catalyzed reductive couplings of alkynes with aldehydes
have been first developed by Montgomery12 and Jamison,13
but the enantioselective synthesis has not been achieved until
chiral N-heterocyclic carbenes14 and chiral phosphorus
ligands15 were applied for this kind of reactions. While limited
Ni-catalyzed reductive coupling of alkynes with ketones have
been reported,16 a practical stereoselective asymmetric Ni-
catalyzed intramolecular reductive coupling of N-1,6-alky-
nones17 is yet to be explored (Scheme 1).
prepared in situ from 10 mol % Ni(cod)2, 10 mol %
monophosphorus ligand/5 mol % bisphosphorus ligand, and
3 equiv Et3SiH; the produced silyl ether was treated with
TBAF (tetra-n-butylammonium fluoride) to get the alcohol. As
shown in Table 1, achiral mono-phosphorus ligands PPh3,
a
Table 1. Ligand Effects and Reaction Optimization
Scheme 1. Transition-Metal-Catalyzed Asymmetric
Intramolecular Reductive Coupling for the Construction of
Cyclic Allylic Alcohols
AntPhos was an efficient ligand for catalytic enantioselective
synthesis. It was successfully applied in the catalytic
enantioselective intramolecular reactions, such as reductive
cyclization16b and dearomatic cyclization.18 It is proposed that
the pyrrolidines with chiral tertiary allylic alcohols could be
prepared by the reductive cyclization of N-1,6-alkynones
catalyzed by this ligand. Herein, we reported an efficient
stereoselective asymmetric nickel-catalyzed intramolecular
reductive coupling of N-1,6-alkynones to give pyrrolidines
bearing chiral tertiary allylic alcohols with >99:1 E/Z
stereoselectivity and >99:1 er using privileged monophosphine
ligand AntPhos under mild conditions.
a
Conditions: 1a (0.2 mmol), Ni(cod)2 (X mol %), ligand (Y mol %),
b
Et3SiH (0.6 mmol), N2 in dioxane (0.5 mL), 24 h. Isolated yields.
c
d
1
E/Z ratio confirmed by H NMR. The enantiomeric ratio (er) was
e
determined by HPLC with CHIRALCEL columns. The solvent was
dioxane/THF (1:1). The reaction was run in 2 mmol scale of 1a.
f
PCy3, S-Phos (L1), Ru-Phos (L2), and X-Phos (L3) gave the
cyclized product 2a in a racemic form with high to excellent
yields (PPh3: 98%; PCy3: 82%; S-Phos: 98%; Ru-Phos: 95%;
X-Phos: 85%, entries 1−5), showed that a simple mono-
phosphine ligand has good reactivity for this reaction. Chiral
bisphosphine ligand L4 [(R,R)-DIOP], L5 [(S,S)-BDPP], L6
[(R)-(S)-JosiPhos], L7 [(R)-SegPhos], and L8 [(R)-BINAP]
were further tested. Although L4 showed mediate reactivity
(48% yield) but no enantioselectivity was achieved (entry 6),
L5, L6, and L7 has no reactivity while L8 has a trace product
which cannot be detected for its enantioselectivity (entries 7−
RESULTS AND DISCUSSION
■
We are interested in the phosphorous ligand effects on this
type of reductive coupling reactions. Various ligands including
achiral ligands and chiral ligands were investigated for their
activity and enantioselectivity. Standard N-1,6-alkynone (1a)
was chosen for the nickel-catalyzed intramolecular reductive
coupling of N-1,6-alkynones using triethylsilane (Et3SiH) as
the reducing reagent. The reactions were performed under
nitrogen in dioxane for 24 h in the presence of a nickel catalyst
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a
10), which proved that bisphosphine ligands are not applicable
to this reaction. As estimated, chiral monophosphine ligand L9
[(R)-MOP], L10 [(R,R)-], L11 [(R)-BIDIME], and L12
[(R)-AntPhos] showed mediate to excellent reactivity and
enantioselectivity for this coupling (L9: 87% yield, 25:75 er;
L10: 53% yield, 80:20 er; L11: 99% yield, 96:4 er; L12: 99%
yield, 98:2 er; entries 11−14). We are excited to explore the
potential of (R)-AntPhos (L12) in consideration of its catalyst
loading and enantioselectivity. To our surprise, decreasing the
temperature to 0 °C, the enantioselectivity was enhanced to
99:1 er; gradually decreasing the catalyst loading to 1 mol %,
31% yield with 99:1 er was obtained for the desired product
(entries 15−17). Interestingly, although different ligands were
applied for the transformation of alkyne to alkene, the E/Z
stereoselectivity of the cyclized allylic alcohol was >99:1, no
matter how much its enantioselectivity was conducted. Hence,
with (R)-AntPhos, the best result is 99% yield, >99:1 E/Z
stereoselectivity and 99:1 er with highest nickel catalyst TON
of 30. On the basis of these results, the conditions of entry 16
were selected for following experiments. The absolute
configuration of 2a was assigned as S by referencing the
reported physical data in the literature.16b
Table 2. Substrate Scope of Different Alkynes
The substrate scope of this process for the enantioselective
synthesis of pyrrolidines with chiral tertiary allylic alcohols was
then explored in detail with ligand (R)-AntPhos under the
optimized reaction conditions (Table 1, entry 16). First of all,
different R1 groups of aromatic alkynes were found tolerable
with very high E/Z stereoselectivity and enantioselectivity in
good yield (Table 2, see details in Supporting Information). All
the N-1,6-alkynones were coupled to cyclized alkenes with
>99:1 E/Z as only one product was observed afterward.
Substrates bearing either an electron-donating or electron-
withdrawing group at the p-position of the aromatic ring were
converted into their corresponding products in up to 96% yield
with excellent enantioselectivities (2b−2c, 2f, 2g; er: 99:1),
however, the bulky iPr-group and electron-withdrawing F- and
CF3-group showed a few decrease of the yields and
enantioselectivities (2d, 2e, 2h; yield: 79, 83, 79%; er: 96:4,
95:5 and 98:2). m-Substituted aromatic alkynes were found to
give the desired pyrrolidines with chiral tertiary allylic alcohols
in excellent yields (up to 96% yield) and enantioselectivities
(2i−2l; yield: 96, 86, 96, 96%; er: 96:4, 95:5 and 98:2), except
the CF3-group showed a decrease of the yield and
enantioselectivity (2m: 72% yield, 97:3 er). When the
substituent group was present at the o-positions (2n−2p),
the corresponding products bearing the electron-withdrawing
group (F- and Cl-) were obtained with moderate to good
yields and excellent enantioselectivities (2n, 2o; yield: 72, 79%;
er: 92:8, >99:1), while the substrates bearing electron-donating
groups (MeO-) afforded excellent yield and enantioselectivity
(2p: 96% yield, 99:1 er). Disubstituted substrates were also
examined in the reductive coupling, affording excellent results
(2q: 92% yield, 95:5 er); p-phenyl substituted 1,6-alkynone
products 2r showed less reactivity (73% yield) with excellent er
(98:2). When the benzene ring was replaced by thiophenyl
groups, good yields and excellent enantioselectivities were
obtained (2s, 2t; yield: 87, 81%; er: 99:1, 99:1). Although the
reason for the difference of yields and enantioselectivities
influenced by electron-withdrawing groups, such as F-, Cl- and
CF3-, at different positions are still not clear, most of their
enantioselectivities are >97:3 er.
a
Conditions: 1 (0.2 mmol), Ni(cod)2/L12 (5 mol %), Et3SiH (0.6
b
mmol), N2 in dioxane/THF(1:1, 0.5 mL), 0 °C, 24 h. The reactions
were run in 2 mmol scale of 1a. Isolated yields. Isolated E/Z ratio
confirmed by H NMR analysis. The enantiomeric ratio (er) was
determined by HPLC with CHIRALCEL columns. The absolute
configuration of 2b−2t was assigned the same as 2a.
c
d
e
1
enantioselective synthesis of pyrrolidines with chiral tertiary
allylic alcohols under the same reaction conditions as above
mentioned with ligand (R)-AntPhos (Table 3). Different R2
groups of ketones can afford the corresponding products with
very high E/Z stereoselectivity and enantioselectivity in good
to excellent yield (see details in Supporting Information). All
the different ketones were cyclized to give the alkenes with
>99:1 E/Z as only one product was determined by isolation
and NMR. Substrates of an electron-donating or electron-
withdrawing group at the p-position of the aromatic ring were
converted into their corresponding products in up to 95% yield
with excellent enantioselectivities (2u−2y; er: >99:1); only an
electron-withdrawing Cl-group decrease its yield to 82%. m-
Substituted aromatic ketones were found to give the desired
pyrrolidines with chiral tertiary allylic alcohols in good yields
and enantioselectivities (2z−2ab; yield: 87, 78, 85%; er: >99:1,
Further substrate scope was extended by different ketones.
Substituted phenyl, alkyl groups were examined for the
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a
were carried on to confirm these possibilities. Each experiment
was run at the standard conditions as above (Scheme 2). (1)
Table 3. Substrate Scope of Different Ketones
Scheme 2. Control Experiments of Nickel-Catalyzed
Stereoselective Asymmetric Reductive Coupling of N-1,6-
Alkynones
Without reductant Et3SiH, the reactions could not be
processed, the catalyzed cycle could not be generated, and
the starting material 1a was recovered; (2) without ligand (R)-
AntPhos, the nickel precursor Ni(cod)2 is not enough to
generate the active intermediate with N-1,6-alkynone; even
with the reductant Et3SiH, the starting material 1a could not
be reduced to simple secondary alcohol and was also
recovered; (3) when the reductant was changed to ZnEt2, no
influence was found for the yield (99%) and E/Z stereo-
selectivity (>99%), but the enantioselectivity was decreased to
(92:8 er). Thus, we conclude that the monophosphine ligand
(R)-AntPhos and reductant are necessary for this nickel-
catalyzed stereoselective asymmetric reductive coupling of N-
1,6-alkynones, and different reductants may have different
effects on this type of coupling reactions. We also proposed
that other transition metal precursors (such as Cu, Co, Pd, Rh,
and so forth) accelerated with AntPhos type ligands may start
up many new reactions afterward.
a
Conditions: 1 (0.2 mmol), Ni(cod)2/L12 (5 mol %), Et3SiH (0.6
b
mmol), N2 in dioxane/THF(1:1, 0.5 mL), 0 °C, 24 h. Isolated yields.
c
d
Isolated E/Z ratio confirmed by 1H NMR analysis. The
On the base of theoretical and computational studies19 on
Ni-catalyzed alkyne-aldehyde reductive coupling by Hou-
k,19a,c,d Jamison,19a and Montgomery,19b−d the mechanism of
Ni-catalyzed alkyne−ketone (alkynone) reductive coupling has
been depicted.16b,17 We thus proposed the catalytic cycle of
our asymmetric reductive coupling of N-1,6-alkynones with
(R)-AntPhos as the monomeric metallacyclic model, which
was illustrated in Figure 2. Before adding the substrate 1a, (R)-
AntPhos was coordinated with Ni(cod)2 to form the Ni(0)
species I; then, addition of N-1,6-alkynone 1a generated the
cyclization process through the stage II and provided Ni(II)
metallacycle III. At this stage, the detailed stereochemical
model of Ni(II) metallacycle III presented two possible
formation with opposite enantiomeric selectivity at the tertiary
C−O bond position. The enantioselectivity and stereo-
selectivity is apparently determined at the cycloaddition
stage. Conformational analysis of metallacycle III with (R)-
AntPhos indicates that the conformer IIIB is unflavored as its
big steric hindrance between the phenyl group of the bicycle
ring and the anthracenyl moiety of (R)-AntPhos. Thus, the
favored conformer IIIA generates Ni(II) hydride species IV by
coordination and δ-bond metathesis of Et3SiH. Reductive
elimination of IV regenerates the Ni(0) catalyst I and provides
2a as the cyclization product with S configuration, which is in
accordance with referenced data,16b which was determined by
X-ray crystallography.
enantiomeric ratio (er) was determined by HPLC with CHIRALCEL
columns. The absolute configuration of 2u−2ai was assigned the same
as 2a.
99:1 and 98:2). When the electron-donating OMe-group was
present at the o-positions, the corresponding product (2ac)
was obtained with moderate yield (64%) and excellent
enantioselectivity (98:2 er). Disubstituted aromatic ketones
were also tested, affording excellent results (2q: 61% yield,
99:1 er); p-phenyl substituted aromatic ketone product 2ae
showed less reactivity (61% yield) with excellent er (99:1).
Naphthyl ketone products 2af showed excellent yield (87%)
with excellent er (99:1), when the bulky alkyl tBu-,
cyclopropyl- and adamantyl-groups were found to afford the
corresponding pyrrolidines in good yields and excellent
enantioselectivities (2ag−2ai; yield: 79, 81, 76%; er: 98:2,
99:1, 99:1). Although several examples showed moderate
yields, most of their enantioselectivities are >98:2 er.
Having established the synthetic method efficiently,
attention was then turned to understanding how the reactions
operate in the presence of (R)-AntPhos, especially the
mechanism for the stereochemical and enantiomeric control
of allylic tertiary alcohols. Based on previous experiments, we
reasoned that ligand activation of the N-1,6-alkynones must
play a key role for this process. Several control experiments
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Scheme 3. Gram-Scale Reductive Coupling with (R)-
AntPhos
reactions were discovered with good reactivity and enantiose-
lectivity using 1,6-alkynone as the substrate (Scheme 4). (a) by
Scheme 4. New Asymmetric Couplings with (R)-AntPhos
and N-1,6-Alkynone
Figure 2. Proposed mechanism and stereochemical model.
Ni catalyzed reductive cyclization using HBPin as the
reductant, in one step, the tertiary allylic alcohol 2a was
achieved in 88% yield with 81:19 er under similar catalytic
conditions. (b) In Ni catalyzed tandem reductive cyclization
and cross-coupling, the initial results showed that the new
product 3u was obtained in 82% yield with 93:7 er when 1u
was coupled with PhB(OH)2 using tBuOH as the solvent.
These initial results are interesting and might expand its other
new research fields and need more detailed explorations in the
future.
To confirm our estimation, a stereochemical model was
developed for this enantioselective process based on the
proposed mechanism, and a React-IR experiment was set up
for monitoring the stoichiometric reaction procedure (Figure
3). A stoichiometric amount of Ni(cod)2 was mixed with
ligand (R)-AntPhos with stirring in dioxane at room
temperature; an absorption peak at 1392 cm−1 was monitored;
possibly, the Ni(0)−P bond asymmetric stretch indicated the
formation of Ni(0) species with phosphorus ligand (R)-
AntPhos, which is stage I. After the addition of N-1,6-alkynone
1a, the solution was turned dark brown quickly, the peak at
1708 cm−1 for ketone functional group appeared dramatically,
and then gradually decreased as 1a was consumed to the
Ni(II) metallacycle III; thus, a peak at 1350 cm−1 was found
and gradually increased at the same time and persisted until
the curve changed to flat in 1 h. Then, the reductant HSiEt3
was added; the peak 1708 and 1350 cm−1 was dropped quickly
afterward, while the peak of 2092 cm−1 showed the trends of
HSiEt3 absorption and was slowly consumed with the cyclized
tertiary allylic alcohol 2a produced.
With the successful development of this efficient nickel
catalyst, we are curious for its practicability of the reductive
coupling reaction. Under the optimized reaction conditions, a
gram-scale reductive coupling of 1a (2.00 g) was carried out in
dioxane/THF(1:1) at 0 °C for 48 h in the presence of 5 mol %
Ni(cod)2 and 5 mol % (R)-AntPhos using Et3SiH as the
reductant and then treated with TBAF to obtain the product
2a (1.99 g) in 99% yield, >99:1 E/Z and 99:1 er (Scheme 3).
There is no loss of its reactivity, stereoselectivity, and
enantioselectivity, which proved that this Ni-catalyzed stereo-
selectivity asymmetric reductive coupling reaction is practical
and efficient.
CONCLUSIONS
■
In summary, we have developed a highly efficient stereo-
selective asymmetric intramolecular reductive coupling of N-
1,6-alkynones catalyzed by a Ni(cod)2 with P-chiral mono-
phosphine ligand (R)-AntPhos with triethylsilane as the
reducing agent. Varieties of pyrrolidines bearing a chiral
tertiary allylic alcohol were synthesized in high yields (up to
99%), excellent stereoselectivity (>99:1 E/Z), and enantiose-
lectivity (>99:1 er). Totally, 35 substrates were affordable for
this process, and very broad substrate scope was realized.
Detailed mechanistic studies were investigated by the proposed
stereochemical model of catalytic cycle and React-IR analysis
of stoichiometric reaction with Ni(cod)2, (R)-AntPhos, and
other reactants. The results showed that the cycloaddition
stage Ni(II) metallacycle III is the enantioselective-determined
step, while ligand (R)-AntPhos played an important role for
providing a large π-conjugated system or steric interactions,
thus processing excellent stereoselectivity and enantioselectiv-
ity of the product. Control experiments were set up to confirm
our estimation of its mechanism. This method has been proved
to be a practical pathway for concise synthesis of pyrrolidines
with chiral tertiary alcohol as gram-scale preparation of the
pyrrolidine product was conducted to show the capability and
scalability of this methodology. Further discovery of new
reactions with (R)-AntPhos and N-1,6-alkynone indicated that
there are interesting potential for this type of couplings, new
Temporarily clarifying the mechanism of this nickel
catalyzed coupling reaction, the highly enantioselective trans-
formation with (R)-AntPhos promoted us to further explore
its other asymmetric coupling reactions. Surprisingly, two new
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Figure 3. React-IR of stoichiometric reaction.
1H decoupling. Multiplicities are abbreviated as follows: singlet (s),
doublet (d), triplet (t), quartet (q), doublet−doublet (dd), quintet
(quint), septet (sept), multiplet (m), and broad (br). MS was
measured on Agilent 5973N (EI) and Agilent 1100 Series LC/MSD
(ESI) mass spectrometers. HRMS was measured on Waters Xevo G2-
XS Q-TOF (TOF) mass spectrometers. Column chromatography was
performed with silica gel (200−300 mesh). HPLC analyses and
purifications were performed on a Thermo Fisher LC system with a
UV−vis detector using CHIRALCEL columns.
creative research fields may be explored in the future. P-chiral
ligand application to useful organic synthesis has proved to be
an effective strategy for developing practical asymmetric
transformations. The ligand applied in this study has high
potential for application in other coupling reactions. Further
exploration on a more practical catalyst system and develop-
ment of various efficient metal-catalyzed asymmetric reactions
are under investigation in our laboratory.
Synthesis of N-1,6-Alkynones 1a−1ai. The N-1,6-alkynones 1a−
1ai were synthesized according to the similar procedure17 published
by Tang et al. with slight adaptations.
EXPERIMENTAL SECTION
■
General Information and Materials. All reactions and
manipulations were performed in a nitrogen-filled glove box or
using standard Schlenk techniques, unless otherwise noted. All
anhydrous solvents were purchased from J&K Chemicals or Alfa
Chemicals Inc or used after standard purification procedures.
Ni(cod)2 was purchased from Strem Chemicals. Commercialized
reagents were used without further purifications. All air sensitive
ligands were stored in a nitrogen-filled glove box before use. Chiral
ligand intermediates were prepared according to our reported
procedures cod = 1,5-cyclooctadiene.
tert-Butyl Tosylcarbamate (S2). 4-Methylbenzenesulfonamide
(21.8 g, 127 mmol, 1.0 equiv), triethylamine (20 mL, 140 mmol,
1.1 equiv), and 4-dimethylaminopyridine (1.57 g, 12.7 mmol, 0.1
equiv) were dissolved in 150 mL of dichloromethane (DCM) and
stirred to obtain a suspension. Then, di(tert-butyl) carbonate was
dissolved in 250 mL of DCM and then slowly dropped into the
reaction system for 25 min and stirred for 2 h. The reaction was
quenched with 1 M HCl 250 mL, extracted with EtOAc, washed with
saturated brine, dried with anhydrous Na2SO4, filtered, and
concentrated under vacuum. The residue was recrystallized with n-
hexane/EtOAc (80:20) to afford S2 as a white solid (30.0 g, 87%).
1H, and 13C NMR data were recorded on a Bruker DRX500,
DRX400, and NMR spectrometer with CDCl3 or CD3OD as the
1
solvent. H chemical shifts were referenced to CDCl3 at 7.26 ppm.
13C chemical shifts were referenced to CDCl3 at 77.16 ppm and
obtained with 1H decoupling. 31P shifts were referenced to 85%
H3PO4 in D2O at 0.0 ppm as the external standard and obtained with
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S2: 1H NMR (500 MHz, CDCl3): δ 7.90 (d, J = 8.3 Hz, 2H), 7.34 (d,
J = 8.1 Hz, 2H), 7.19 (s, 1H), 2.45 (s, 3H), 1.38 (s, 9H).
1
The H NMR spectra are in agreement with those reported in the
literature.20
4-Methyl-N-(prop-2-ynyl)-benzenesulfonamide (S3). tert-Butyl
tosylcarbamate (35.4 g, 130.6 mmol, 1.0 equiv) and K2CO3 (27 g,
1b. The resulting residue was purified by column chromatography
(90:10, n-hexane/EtOAc) to give 1b (1.98 g, 95%) as a white powder.
1H NMR (500 MHz, CDCl3): δ 7.98 (d, J = 7.4 Hz, 2H), 7.81 (d, J =
8.2 Hz, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.7 Hz, 2H), 7.31
(d, J = 8.2 Hz, 2H), 7.08−6.89 (m, 4H), 4.80 (s, 2H), 4.48 (s, 2H),
2.40 (s, 3H), 2.31 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ
193.5, 143.8, 138.7, 136.1, 135.0, 133.8, 131.5, 129.7, 128.9, 128.8,
128.2, 127.7, 118.9, 86.4, 80.9, 51.9, 38.4, 21.5, 21.4. HRMS (ESI) m/
z: [M + Na]+ calcd for C25H23NO3SNa, 440.1296; found, 440.1322.
1c. The resulting residue was purified by column chromatography
(90:10, n-hexane/EtOAc) to give 1c (1.86 g, 86%) as a white powder.
195.8 mmol, 1.5 equiv) were dissolved in 100 mL dimethylformamide
(DMF) and stirred at rt for 4 h. Then, propargyl bromide (11.3 mL,
143.7 mmol, 1.1 equiv) was added to the above solution and stirred at
rt for 10 h. The reaction was quenched with water, extracted with
EtOAc, washed with saturated brine, dried with anhydrous Na2SO4,
filtered, and concentrated under vacuum. The residue was dissolved in
100 mL of DCM and 40 mL of CF3COOH and stirred at rt overnight.
The reaction was quenched with water, extracted with EtOAc, washed
with saturated brine, dried with anhydrous Na2SO4, filtered, and
concentrated under vacuum. The residue was recrystallized with n-
hexane/EtOAc (90:10) to afford S3 as a white solid (23.2 g, 85%). 1H
NMR (500 MHz, chloroform-d): δ 7.77 (d, J = 8.3 Hz, 2H), 7.34−
7.30 (m, 2H), 4.50 (s, 1H), 3.84 (dd, J = 6.0, 2.5 Hz, 2H), 2.44 (s,
3H), 2.11 (t, J = 2.5 Hz, 1H).
1H NMR (500 MHz, CDCl3): δ 8.02−7.98 (m, 2H), 7.84 (d, J = 8.3
Hz, 2H), 7.64−7.60 (m, 1H), 7.50 (t, J = 7.8 Hz, 2H), 7.33 (d, J = 8.1
Hz, 2H), 7.07 (q, J = 8.3 Hz, 4H), 4.83 (s, 2H), 4.51 (s, 2H), 2.63 (q,
J = 7.6 Hz, 2H), 2.42 (s, 3H), 1.22 (t, J = 7.6 Hz, 3H). 13C{1H} NMR
(126 MHz, CDCl3): δ 193.5, 189.8, 145.1, 143.7, 136.1, 135.0, 133.8,
131.6, 129.7, 128.8, 128.2, 127.7, 127.7, 119.2, 86.4, 80.9, 51.9, 38.4,
28.8, 21.5, 15.3. HRMS (ESI) m/z: [M + Na]+ calcd for
C26H25NO3SNa, 454.1453; found, 454.1452.
1
The H NMR spectra are in agreement with those reported in the
literature.20
4-Methyl-N-(2-oxo-2-phenylethyl)-N-(prop-2-ynyl)-
benzenesulfonamide (S4). To a solution of S3 (6.3 g, 30 mmol, 1.0
1d. The resulting residue was purified by column chromatography
(90:10, n-hexane/EtOAc) to give 1d (1.80 g, 81%) as a white powder.
equiv), 2-bromo-1-phenylethan-1-one (6.2 g, 31.5 mmol, 1.05 equiv),
and Bu4NI (1.108 g, 3 mmol, 0.1 equiv) in 60 mL of DMF at 0 °C
was added K2CO3 (6.2 g, 45 mmol, 1.5 equiv) and stirred at 0 °C for
1 h. Then, the reaction was quenched with water, extracted with
EtOAc, washed with saturated brine, dried with anhydrous Na2SO4,
filtered, and concentrated under vacuum. The residue was recrystal-
lized with n-hexane/EtOAc (90:10) to afford S4 as a white solid (8.55
g, 87%). 1H NMR (500 MHz, CDCl3): δ 7.97−7.92 (m, 2H), 7.77 (d,
J = 8.3 Hz, 2H), 7.61 (t, J = 7.4 Hz, 1H), 7.49 (t, J = 7.8 Hz, 2H),
7.32 (d, J = 8.2 Hz, 2H), 4.81 (s, 2H), 4.29 (d, J = 2.4 Hz, 2H), 2.44
(s, 3H), 2.11 (d, J = 2.5 Hz, 1H). The 1H NMR spectra are in
agreement with those reported in the literature.21
1H NMR (500 MHz, CDCl3): δ 7.99−7.95 (m, 2H), 7.81 (d, J = 8.3
Hz, 2H), 7.62−7.57 (m, 1H), 7.47 (t, J = 7.8 Hz, 2H), 7.30 (d, J = 8.1
Hz, 2H), 7.10−7.01 (m, 4H), 4.80 (s, 2H), 4.48 (s, 2H), 2.86 (p, J =
6.9 Hz, 1H), 2.39 (s, 3H), 1.21 (d, J = 6.9 Hz, 6H). 13C{1H} NMR
(126 MHz, CDCl3): δ 193.4, 149.7, 143.7, 136.1, 135.0, 133.8, 131.7,
129.7, 128.8, 128.2, 127.7, 126.3, 119.3, 86.5, 80.8, 51.9, 38.4, 34.0,
23.7, 21.5. HRMS (ESI) m/z: [M + Na]+ calcd for C27H27NO3SNa,
468.1609; found, 468.1609.
4-Methyl-N-(2-oxo-2-phenylethyl)-N-(3-phenylprop-2-ynyl)-
benzene-sulfonamide. 1a is synthesized by Sonogashira reaction. S4
1e. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 1e (1.90 g, 90%) as a white powder.
(1.64 g, 5 mmol), PdCl2 (PPh3)2 (175 mg, 0.25 mmol, 5 mol %), and
CuI (48 mg, 0.25 mmol, 5 mol %) in a round-bottomed flask. Seal
with rubber triethylamine (20 mL) was added to the septum of the
flask, and then, iodobenzene (824 μL, 7.5 mmol) was added. The
reaction mixture was stirred under argon until the starting material
disappeared (TLC check, 6 h). The reaction mixture was cooled to
room temperature, neutralized with 1 M HCl, and the aqueous phase
was extracted with ethyl acetate (20 mL). The combined organic
phases were washed with water (40 mL), dried over Na2SO4, and
evaporated in vacuo. The resulting residue was purified by column
chromatography (90:10, n-hexane/EtOAc) to give 1a (1.93 g, 96%)
1H NMR (500 MHz, CDCl3): δ 7.98 (d, J = 7.4 Hz, 2H), 7.81 (d, J =
8.2 Hz, 2H), 7.60 (d, J = 7.5 Hz, 1H), 7.49 (t, J = 7.8 Hz, 2H), 7.31
(d, J = 8.1 Hz, 2H), 7.13−7.06 (m, 2H), 6.92 (t, J = 8.6 Hz, 2H), 4.81
(s, 2H), 4.46 (s, 2H), 2.40 (s, 3H). 13C{1H} NMR (126 MHz,
CDCl3): δ 193.4, 163.6, 161.58, 143.8, 136.1, 134.9, 133.9, 133.6,
133.5, 129.7, 128.9, 128.2, 127.8, 118.1, 118.1, 115.6, 115.4, 85.2,
81.4, 51.9, 38.3, 21.5. HRMS (ESI) m/z: [M + Na]+ calcd for
C24H20FNO3SNa, 444.1046; found, 444.1061.
1f. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 1f (1.97 g, 90%) as a white powder.
1
as a white powder. H NMR (500 MHz, CDCl3): δ 8.01−7.85 (m,
2H), 7.83 (d, J = 8.3 Hz, 2H), 7.61 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.7
Hz, 2H), 7.32−7.30 (m, 3H), 7.28 (t, J = 7.4 Hz, 2H), 7.23−7.12 (m,
1
2H), 4.84 (s, 2H), 4.52 (s, 2H), 2.41 (s, 3H). The H NMR spectra
are in agreement with those reported in the literature.17
Preparations of 1b−1t were carried out according to a similar
procedure of 1a from corresponding aryl iodides.
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1H NMR (500 MHz, CDCl3): δ 7.99−7.96 (m, 2H), 7.80 (d, J = 8.3
Hz, 2H), 7.63−7.59 (m, 1H), 7.50−7.47 (m, 2H), 7.32−7.29 (m,
2H), 7.21 (d, J = 8.6 Hz, 2H), 7.03 (d, J = 8.6 Hz, 2H), 4.80 (s, 2H),
4.47 (s, 2H), 2.40 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ
193.4, 143.8, 136.1, 134.9, 134.7, 133.9, 132.9, 129.7, 128.9, 128.5,
128.2, 127.8, 120.5, 85.1, 82.8, 52.0, 38.3, 21.6. HRMS (ESI) m/z: [M
+ Na]+ calcd for C24H20ClNO3SNa, 460.0750; found, 460.0751.
1g. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 1g (1.89 g, 87%) as a white powder.
1k. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 1k (1.64 g, 78%) as a white powder.
1H NMR (500 MHz, CDCl3): δ 8.00−7.97 (m, 2H), 7.81 (d, J = 8.3
Hz, 2H), 7.61 (t, J = 7.4 Hz, 1H), 7.49 (t, J = 7.8 Hz, 2H), 7.32 (d, J =
8.0 Hz, 2H), 7.19 (td, J = 8.0, 6.0 Hz, 1H), 6.99 (td, J = 8.4, 2.3 Hz,
1H), 6.90 (d, J = 7.7 Hz, 1H), 6.75−6.69 (m, 1H), 4.80 (s, 2H), 4.48
(s, 2H), 2.41 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 193.3,
163.1, 161.1, 144.0, 136.0, 134.9, 133.9, 129.8, 129.8, 128.9, 128.2,
127.8, 127.5, 127.4, 123.8, 123.8, 118.6, 118.4, 116.0, 115.9, 84.9,
82.7, 52.0, 38.2, 21.5. HRMS (ESI) m/z: [M + Na]+ calcd for
C24H20FNO3SNa, 444.1046; found, 444.1061.
1H NMR (500 MHz, CDCl3): δ 7.97 (d, J = 7.6 Hz, 2H), 7.81 (d, J =
8.2 Hz, 2H), 7.59 (t, J = 7.4 Hz, 1H), 7.47 (t, J = 7.9 Hz, 2H), 7.28 (s,
2H), 7.24 (d, J = 7.7 Hz, 1H), 7.02 (d, J = 7.5 Hz, 1H), 6.83−6.77
(m, 2H), 4.88 (s, 2H), 4.55 (s, 2H), 3.70 (s, 3H), 2.36 (s, 3H).
13C{1H} NMR (126 MHz, CDCl3): δ 193.5, 160.1, 143.6, 136.1,
135.1, 133.7, 133.4, 130.0, 129.6, 128.8, 128.1, 127.7, 120.2, 111.3,
110.4, 85.7, 82.9, 55.5, 51.8, 38.6, 21.5. HRMS (ESI) m/z: [M + Na]+
calcd for C25H23NO4SNa, 456.1245; found, 456.1263.
1l. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 1l (1.99 g, 92%) as a white powder.
1h. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 1h (1.70 g, 72%) as a white powder.
1H NMR (500 MHz, CDCl3): δ 7.98 (d, J = 7.4 Hz, 2H), 7.81 (d, J =
8.2 Hz, 2H), 7.59 (d, J = 7.4 Hz, 1H), 7.48 (t, J = 7.7 Hz, 2H), 7.31
(d, J = 8.1 Hz, 2H), 7.05 (d, J = 8.7 Hz, 2H), 6.75 (d, J = 8.7 Hz, 2H),
4.81 (s, 2H), 4.47 (s, 2H), 3.79 (s, 3H), 2.40 (s, 3H). 13C{1H} NMR
(126 MHz, CDCl3): δ 193.5, 159.8, 143.7, 136.1, 135.0, 133.8, 133.1,
129.7, 128.8, 128.2, 127.7, 114.1, 113.8, 86.2, 80.2, 55.3, 51.9, 38.4,
21.5. HRMS (ESI) m/z: [M + Na]+ calcd for C25H23NO4SNa,
456.1245; found, 456.1263.
1H NMR (500 MHz, CDCl3): δ 7.98 (d, J = 7.4 Hz, 2H), 7.81 (d, J =
8.2 Hz, 2H), 7.62 (t, J = 7.4 Hz, 1H), 7.52−7.46 (m, 4H), 7.31 (d, J =
8.2 Hz, 2H), 7.21 (d, J = 8.2 Hz, 2H), 4.82 (s, 2H), 4.50 (s, 2H), 2.39
(s, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 193.3, 143.9, 136.0,
134.8, 134.0, 131.9, 129.7, 128.9, 128.2, 127.8, 125.1, 125.1, 84.8,
84.4, 52.0, 38.2, 21.5. HRMS (ESI) m/z: [M + Na]+ calcd for
C25H20F3NO3SNa, 494.1014; found, 494.0950.
1m. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 1m (1.63 g, 69%) as a white
1i. The resulting residue was purified by column chromatography
(90:10, n-hexane/EtOAc) to give 1i (1.88 g, 90%) as a white powder.
1
powder. H NMR (500 MHz, CDCl3): δ 7.99 (dd, J = 8.3, 1.1 Hz,
2H), 7.82 (d, J = 8.3 Hz, 2H), 7.63−7.60 (m, 1H), 7.54−7.47 (m,
3H), 7.36 (d, J = 7.7 Hz, 1H), 7.34−7.30 (m, 4H), 4.80 (s, 2H), 4.50
(s, 2H), 2.38 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 193.3,
144.1, 136.0, 134.8, 134.7, 134.0, 130.9, 130.7, 129.7, 128.9, 128.8,
128.3, 128.2, 127.8, 125.1 (d, J = 3.8 Hz), 124.7, 122.9, 122.5, 84.6,
83.4, 52.0, 38.2, 21.4. HRMS (ESI) m/z: [M + Na]+ calcd for
C25H20F3NO3SNa, 494.1014; found, 494.0995.
1H NMR (500 MHz, CDCl3): δ 7.98 (d, J = 7.4 Hz, 2H), 7.81 (d, J =
8.2 Hz, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.7 Hz, 2H), 7.32
(d, J = 8.0 Hz, 2H), 7.13−7.07 (m, 2H), 6.91 (s, 2H), 4.81 (s, 2H),
4.48 (s, 2H), 2.40 (s, 3H), 2.27 (s, 3H). 13C{1H} NMR (126 MHz,
CDCl3): δ 193.4, 143.7, 137.8, 136.1, 135.0, 133.8, 132.2, 129.7,
129.4, 128.8, 128.7, 128.2, 128.1, 127.8, 121.8, 86.4, 81.2, 51.9, 38.3,
21.5, 21.2. HRMS (ESI) m/z: [M + Na]+ calcd for C25H23NO3SNa,
440.1296; found, 440.1322.
1n. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 1n (1.93 g, 88%) as a white powder.
1j. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 1j (2.01 g, 92%) as a white powder.
1H NMR (500 MHz, CDCl3): δ 7.97 (d, J = 7.2 Hz, 2H), 7.80 (d, J =
8.3 Hz, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.7 Hz, 2H), 7.31
(d, J = 7.3 Hz, 1H), 7.28 (s, 2H), 7.17 (ddt, J = 14.8, 13.6, 4.3 Hz,
3H), 4.90 (s, 2H), 4.57 (s, 2H), 2.33 (s, 3H). 13C{1H} NMR (126
MHz, CDCl3): δ 193.7, 144.2, 136.3, 136.1, 135.3, 134.2, 133.6,
130.1, 130.0, 129.5, 129.2, 128.5, 128.0, 126.7, 122.4, 87.4, 83.5, 52.2,
38.7, 21.8. HRMS (ESI) m/z: [M + Na]+ calcd for C24H20ClNO3SNa,
460.0750; found, 460.0707.
1o. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 1o (1.83 g, 87%) as a white powder.
1H NMR (500 MHz, CDCl3): δ 7.98 (d, J = 7.2 Hz, 2H), 7.80 (d, J =
8.3 Hz, 2H), 7.60 (d, J = 7.4 Hz, 1H), 7.48 (t, J = 7.8 Hz, 2H), 7.28
(d, J = 8.3 Hz, 3H), 7.12 (td, J = 7.4, 1.6 Hz, 1H), 7.03−6.97 (m,
2H), 4.84 (s, 2H), 4.54 (s, 2H), 2.34 (s, 3H). 13C{1H} NMR (126
1H NMR (500 MHz, CDCl3): δ 7.99 (d, J = 7.3 Hz, 2H), 7.81 (d, J =
8.1 Hz, 2H), 7.61 (d, J = 7.2 Hz, 1H), 7.49 (t, J = 7.7 Hz, 2H), 7.33
(d, J = 8.1 Hz, 2H), 7.25 (s, 1H), 7.16 (t, J = 7.9 Hz, 1H), 7.03−6.97
(m, 2H), 4.79 (s, 2H), 4.48 (s, 2H), 2.42 (s, 3H). 13C{1H} NMR
(126 MHz, CDCl3): δ 193.3, 144.0, 136.0, 134.9, 133.9, 131.5, 129.8,
129.7, 129.5, 128.9, 128.9, 128.2, 127.8, 123.7, 84.8, 82.9, 52.0, 38.2,
21.6. HRMS (ESI) m/z: [M + Na]+ calcd for C24H20ClNO3SNa,
460.0750; found, 460.0751.
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133.9, 132.5, 129.8, 129.7, 128.8, 128.2, 128.1, 127.7, 127.5, 126.8,
121.9, 85.7, 51.9, 38.5, 21.6. HRMS (ESI) m/z: [M + Na]+ calcd for
C22H19NO3S2Na, 432.0704; found, 432.0679.
1t. The resulting residue was purified by column chromatography
(90:10, n-hexane/EtOAc) to give 1t (1.62 g, 79%)as a yellow powder.
MHz, CDCl3): δ 193.4, 163.7, 161.7, 143.8, 135.9, 135.0, 133.8,
133.4, 130.4, 130.3, 129.7, 128.8, 128.1, 127.7, 123.8, 123.8, 115.5,
115.3, 110.7, 110.6, 87.0, 79.8, 51.8, 38.4, 21.5. HRMS (ESI) m/z: [M
+ Na]+ calcd for C24H20FNO3SNa, 444.1046; found, 444.1061.
1p. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 1p (1.91 g, 88%) as a white powder.
1H NMR (500 MHz, CDCl3): δ 8.01−7.96 (m, 2H), 7.81 (d, J = 8.3
Hz, 2H), 7.60 (d, J = 7.4 Hz, 1H), 7.48 (t, J = 7.8 Hz, 2H), 7.31 (d, J
= 8.1 Hz, 2H), 7.21−7.14 (m, 2H), 6.82 (dd, J = 4.9, 1.2 Hz, 1H),
4.81 (s, 2H), 4.47 (s, 2H), 2.41 (s, 3H). 13C{1H} NMR (126 MHz,
CDCl3): δ 193.4, 143.8, 136.1, 135.0, 133.8, 129.7, 129.2, 128.8,
128.2, 127.8, 125.2, 121.1, 81.4, 81.3, 51.9, 38.3, 21.6. HRMS (ESI)
m/z: [M + Na]+ calcd for C22H19NO3S2Na, 432.0704; found,
432.0679.
Preparations of 1u−1ai were carried out according to a similar
procedure of 1a from corresponding 2-bromoaryl ethyl ketones.
1u. The resulting residue was purified by column chromatography
(90:10, n-hexane/EtOAc) to give 1u (1.82 g, 87%) as a white powder.
1H NMR (500 MHz, CDCl3): δ 7.98 (d, J = 7.2 Hz, 2H), 7.81 (d, J =
8.3 Hz, 2H), 7.60 (d, J = 7.4 Hz, 1H), 7.47 (d, J = 7.6 Hz, 2H), 7.32
(d, J = 8.1 Hz, 2H), 7.13 (d, J = 7.9 Hz, 1H), 6.83 (dd, J = 8.3, 2.5 Hz,
1H), 6.70 (d, J = 7.6 Hz, 1H), 6.65−6.60 (m, 1H), 4.81 (s, 2H), 4.49
(s, 2H), 3.75 (s, 3H), 2.40 (s, 3H). 13C{1H} NMR (126 MHz,
CDCl3): δ 193.4, 159.2, 136.1, 134.9, 133.9, 129.7, 129.2, 128.9,
128.2, 127.7, 124.1, 123.0, 116.9, 114.8, 86.1, 55.3, 51.9, 38.3, 21.5.
HRMS (ESI) m/z: [M + Na]+ calcd for C25H23NO4SNa, 456.1245;
found, 456.1219.
1q. The resulting residue was purified by column chromatography
(90:10, n-hexane/EtOAc) to give 1q (1.96 g, 91%) as a white powder.
1H NMR (500 MHz, CDCl3): δ 7.88 (d, J = 8.3 Hz, 2H), 7.81 (d, J =
8.3 Hz, 2H), 7.31−7.25 (m, 5H), 7.24−7.20 (m, 2H), 7.14−7.05 (m,
2H), 4.78 (s, 2H), 4.48 (s, 2H), 2.41 (s, 3H), 2.38 (s, 3H). 13C{1H}
NMR (126 MHz, CDCl3): δ 193.0, 144.8, 143.8, 136.1, 132.5, 131.6,
129.7, 129.5, 128.5, 128.3, 128.2, 127.7, 122.1, 86.2, 81.7, 51.8, 38.3,
21.8, 21.5. HRMS (ESI) m/z: [M + Na]+ calcd for C25H23NO3SNa,
440.1296; found, 440.1279.
1H NMR (500 MHz, CDCl3): δ 7.97 (dd, J = 8.4, 1.2 Hz, 2H), 7.81
(d, J = 8.3 Hz, 2H), 7.59 (s, 1H), 7.47 (t, J = 7.8 Hz, 2H), 7.31 (d, J =
7.9 Hz, 2H), 6.97 (s, 1H), 6.87 (s, 2H), 4.80 (s, 2H), 4.48 (s, 2H),
2.40 (s, 3H), 2.21 (s, 3H), 2.17 (s, 3H). 13C{1H} NMR (126 MHz,
CDCl3): δ 193.5, 143.7, 137.5, 136.5, 136.2, 135.0, 133.8, 132.7,
129.7, 129.5, 129.1, 128.8, 128.2, 127.8, 119.2, 86.6, 51.9, 38.4, 21.5,
19.7, 19.5. HRMS (ESI) m/z: [M + Na]+ calcd for C26H25NO3SNa,
454.1453; found, 454.1452.
1v. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 1v (1.73 g, 82%) as a white powder.
1r. The resulting residue was purified by column chromatography
(90:10, n-hexane/EtOAc) to give 1r (2.11 g, 88%) as a white powder.
1H NMR (500 MHz, CDCl3): δ 8.06−8.02 (m, 2H), 7.80 (d, J = 8.3
Hz, 2H), 7.31 (d, J = 8.0 Hz, 3H), 7.23 (dd, J = 8.1, 6.6 Hz, 2H), 7.15
(dd, J = 11.9, 5.4 Hz, 2H), 7.10 (dd, J = 8.3, 1.3 Hz, 2H), 4.74 (s,
2H), 4.45 (s, 2H), 2.39 (s, 3H). The 1H NMR spectra are in
agreement with those reported in the literature.17
1H NMR (500 MHz, CDCl3): δ 8.00 (d, J = 7.5 Hz, 2H), 7.84 (d, J =
8.2 Hz, 2H), 7.61 (t, J = 7.4 Hz, 1H), 7.54 (s, 2H), 7.47 (dq, J = 16.2,
7.8 Hz, 6H), 7.37 (d, J = 7.4 Hz, 1H), 7.33 (d, J = 8.1 Hz, 2H), 7.18
(d, J = 8.2 Hz, 2H), 4.84 (s, 2H), 4.52 (s, 2H), 2.40 (s, 3H). 13C{1H}
NMR (126 MHz, CDCl3): δ 193.4, 143.8, 141.4, 140.2, 136.1, 135.0,
133.8, 132.1, 129.7, 128.9, 128.9, 128.2, 127.8, 127.0, 126.8, 120.9,
86.1, 82.3, 51.9, 38.4, 21.6. HRMS (ESI) m/z: [M + Na]+ calcd for
C30H25NO3SNa, 502.1453; found, 502.1431.
1w. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 1w (1.47 g, 67%) as a white
1
powder. H NMR (500 MHz, CDCl3): δ 7.94 (d, J = 8.5 Hz, 2H),
1s. The resulting residue was purified by column chromatography
(90:10, n-hexane/EtOAc) to give 1s (1.66 g, 81%) as a yellow
7.80 (d, J = 8.2 Hz, 2H), 7.45 (d, J = 8.5 Hz, 2H), 7.31 (d, J = 8.2 Hz,
2H), 7.28 (d, J = 7.3 Hz, 1H), 7.23 (t, J = 7.4 Hz, 2H), 7.09 (d, J = 7.2
1
Hz, 2H), 4.74 (s, 2H), 4.45 (s, 2H), 2.39 (s, 3H). The H NMR
spectra are in agreement with those reported in the literature.17
1x. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 1x (1.95 g, 90%)as a white powder.
powder. 1H NMR (500 MHz, CDCl3): δ 7.99−7.96 (m, 2H), 7.81 (d,
J = 8.3 Hz, 2H), 7.61 (s, 1H), 7.49 (d, J = 7.9 Hz, 2H), 7.33 (d, J =
8.1 Hz, 2H), 7.20 (dd, J = 5.1, 1.0 Hz, 1H), 6.98−6.93 (m, 1H), 6.90
(dd, J = 5.1, 3.7 Hz, 1H), 4.79 (s, 2H), 4.52 (s, 2H), 2.42 (s, 3H).
13C{1H} NMR (126 MHz, CDCl3): δ 193.4, 143.9, 136.0, 134.9,
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1H NMR (500 MHz, CDCl3): δ 7.80 (d, J = 8.4 Hz, 3H), 7.52−7.48
(m, 1H), 7.29 (d, J = 8.0 Hz, 2H), 7.26−7.21 (m, 3H), 7.14−7.11 (m,
2H), 7.02 (dd, J = 11.0, 4.0 Hz, 1H), 6.97 (d, J = 8.4 Hz, 1H), 4.83 (s,
1
2H), 4.51 (s, 2H), 3.91 (s, 3H), 2.38 (s, 3H). The H NMR spectra
are in agreement with those reported in the literature.17
1y. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 1y (1.51 g, 64%) as a white powder.
1
3.88 (s, 3H), 2.38 (s, 3H). The H NMR spectra are in agreement
with those reported in the literature.17
1ad. The resulting residue was purified by column chromatography
(90:10, n-hexane/EtOAc) to give 1ad (1.96 g, 91%) as a white
1H NMR (500 MHz, CDCl3): δ 7.99 (dd, J = 8.3, 1.1 Hz, 2H), 7.82
(d, J = 8.3 Hz, 2H), 7.63−7.59 (m, 1H), 7.53 (d, J = 7.7 Hz, 1H),
7.49 (dd, J = 10.7, 4.8 Hz, 2H), 7.37 (t, J = 7.7 Hz, 1H), 7.34−7.29
1
powder. H NMR (500 MHz, CDCl3): δ 7.79 (d, J = 8.3 Hz, 2H),
1
(m, 4H), 4.80 (s, 2H), 4.50 (s, 2H), 2.38 (s, 3H). The H NMR
7.62 (d, J = 7.7 Hz, 1H), 7.32−7.21 (m, 5H), 7.13−7.08 (m, 2H),
7.06 (d, J = 8.6 Hz, 2H), 4.67 (s, 2H), 4.49 (s, 2H), 2.46 (s, 3H), 2.36
(d, J = 10.1 Hz, 6H). 13C{1H} NMR (126 MHz, CDCl3): δ 196.3,
143.7, 142.8, 139.3, 136.2, 133.1, 132.5, 131.6, 129.7, 128.8, 128.6,
128.2, 127.7, 126.4, 122.1, 86.2, 81.7, 53.4, 38.3, 21.5, 21.5, 21.3.
HRMS (ESI) m/z: [M + Na]+ calcd for C26H25NO3SNa, 454.1453;
found, 454.1452.
spectra are in agreement with those reported in the literature.17
1z. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 1z (1.52 g, 72%) as a white powder.
1ae. The resulting residue was purified by column chromatography
(90:10, n-hexane/EtOAc) to give 1ae (2.01 g, 84%) as a white
1H NMR (500 MHz, CDCl3): δ 7.80 (t, J = 8.4 Hz, 3H), 7.69−7.63
(m, 1H), 7.51−7.44 (m, 1H), 7.34−7.27 (m, 3H), 7.23 (t, J = 7.4 Hz,
3H), 7.13−7.08 (m, 2H), 4.76 (s, 2H), 4.47 (s, 2H), 2.39 (s, 3H).
13C{1H} NMR (126 MHz, CDCl3): δ 192.4, 163.8, 161.9, 144.0,
136.9, 135.8, 131.6, 130.6, 130.6, 129.8, 128.6, 128.2, 127.7, 124.0,
121.9, 121.0, 120.8, 115.1, 114.9, 86.4, 81.4, 52.1, 38.4, 21.5. HRMS
(ESI) m/z: [M + Na]+ calcd for C24H20FNO3SNa, 444.1046; found,
444.1061.
1
powder. H NMR (500 MHz, CDCl3): δ 8.06 (d, J = 8.4 Hz, 2H),
7.83 (d, J = 8.2 Hz, 2H), 7.70 (d, J = 8.4 Hz, 2H), 7.63−7.58 (m,
2H), 7.48 (t, J = 7.5 Hz, 2H), 7.41 (t, J = 7.3 Hz, 1H), 7.32 (d, J = 8.1
Hz, 2H), 7.27 (d, J = 2.4 Hz, 1H), 7.22 (t, J = 7.4 Hz, 2H), 7.13−7.08
(m, 2H), 4.83 (s, 2H), 4.50 (s, 2H), 2.39 (s, 3H). 13C{1H} NMR
(126 MHz, CDCl3): δ 193.0, 146.5, 143.8, 139.7, 136.0, 133.6, 131.6,
129.7, 129.0, 128.8, 128.6, 128.4, 128.2, 127.8, 127.5, 127.3, 122.0,
86.3, 81.6, 52.0, 38.4, 21.5. HRMS (ESI) m/z: [M + Na]+ calcd for
C30H25NO3SNa, 502.1453; found, 502.1476.
1aa. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 1aa (1.90 g, 87%) as a white
1af. The resulting residue was purified by column chromatography
(90:10, n-hexane/EtOAc) to give 1af (1.86 g, 82%) as a white
1
powder. H NMR (500 MHz, CDCl3): δ 7.94 (t, J = 1.8 Hz, 1H),
7.89−7.87 (m, 1H), 7.80 (d, J = 8.3 Hz, 2H), 7.58−7.56 (m, 1H),
7.42 (d, J = 7.9 Hz, 1H), 7.35−7.30 (m, 3H), 7.25−7.21 (m, 2H),
7.13−7.10 (m, 2H), 4.75 (s, 2H), 4.47 (s, 2H), 2.40 (s, 3H). 13C{1H}
NMR (126 MHz, CDCl3): δ 192.4, 144.0, 136.4, 135.8, 135.2, 133.7,
131.6, 130.2, 129.8, 128.7, 128.2, 128.2, 127.7, 126.3, 121.9, 86.4,
81.4, 52.1, 38.4, 21.5. HRMS (ESI) m/z: [M + Na]+ calcd for
C24H20ClNO3SNa, 460.0750; found, 460.0751.
1
powder. H NMR (500 MHz, CDCl3): δ 8.53 (s, 1H), 8.01 (dd, J =
8.6, 1.7 Hz, 1H), 7.96 (d, J = 8.1 Hz, 1H), 7.89 (dd, J = 13.3, 8.4 Hz,
2H), 7.84 (d, J = 8.3 Hz, 2H), 7.65−7.59 (m, 1H), 7.58−7.54 (m,
1H), 7.32 (d, J = 8.0 Hz, 2H), 7.27 (s, 1H), 7.23−7.18 (m, 2H),
7.13−7.09 (m, 2H), 4.94 (s, 2H), 4.52 (s, 2H), 2.40 (s, 3H). 13C{1H}
NMR (126 MHz, CDCl3): δ 193.4, 143.8, 136.1, 135.9, 132.4, 132.3,
131.7, 130.1, 129.7, 129.7, 128.9, 128.8, 128.6, 128.2, 127.9, 127.7,
127.0, 123.6, 122.0, 86.3, 81.7, 52.0, 38.4, 21.5. HRMS (ESI) m/z: [M
+ Na]+ calcd for C28H23NO3SNa, 476.1296; found, 476.1296.
1ag. The resulting residue was purified by column chromatography
(90:10, n-hexane/EtOAc) to give 1ag (1.51 g, 79%) as a white
1ab. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 1ab (1.95 g, 90%) as a white
1
powder. H NMR (500 MHz, CDCl3): δ 7.81 (d, J = 8.3 Hz, 2H),
7.56 (d, J = 7.7 Hz, 1H), 7.51−7.50 (m, 1H), 7.37 (d, J = 7.9 Hz,
1H), 7.31 (d, J = 8.1 Hz, 2H), 7.25−7.20 (m, 3H), 7.14 (dd, J = 8.2,
2.0 Hz, 1H), 7.12−7.09 (m, 2H), 4.79 (s, 2H), 4.48 (s, 2H), 3.85 (s,
3H), 2.39 (s, 3H). The 1H NMR spectra are in agreement with those
reported in the literature.17
1
powder. H NMR (500 MHz, CDCl3): δ 7.76 (d, J = 8.3 Hz, 2H),
1ac. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 1ac (1.88 g, 87%) as a white
7.29 (d, J = 8.6 Hz, 3H), 7.24 (d, J = 1.6 Hz, 2H), 7.16−7.13 (m,
1
2H), 4.44 (s, 2H), 4.40 (s, 2H), 2.39 (s, 3H), 1.18 (s, 9H). The H
powder. H NMR (500 MHz, CDCl3): δ 7.98 (d, J = 8.9 Hz, 2H),
NMR spectra are in agreement with those reported in the literature.17
1ah. The resulting residue was purified by column chromatography
(90:10, n-hexane/EtOAc) to give 1ah (1.41 g, 77%) as a white
1
7.81 (d, J = 8.3 Hz, 2H), 7.33−7.26 (m, 3H), 7.25−7.19 (m, 2H),
7.13−7.08 (m, 2H), 6.97−6.92 (m, 2H), 4.75 (s, 2H), 4.47 (s, 2H),
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1
(s, 1H). The H NMR spectra are in agreement with those reported
in the literature.17
2b. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 2b (80.6 mg, 96%) as a yellow oil,
99:1 er. [α]2D5 −18.1 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 1
mL/min, hexanes/isopropanol: 15/85, 254 nm, 8.23 min (S), 15.80
1
powder. H NMR (500 MHz, CDCl3): δ 7.77 (d, J = 8.3 Hz, 2H),
7.30−7.23 (m, 5H), 7.14−7.10 (m, 2H), 4.41 (s, 2H), 4.23 (s, 2H),
2.36 (s, 3H), 2.21 (ddd, J = 12.4, 7.9, 4.5 Hz, 1H), 1.08 (p, J = 3.7 Hz,
2H), 0.96 (dq, J = 7.4, 3.7 Hz, 2H). 13C{1H} NMR (126 MHz,
CDCl3): δ 205.3, 143.9, 135.7, 131.6, 129.7, 128.6, 128.2, 127.7,
122.0, 86.2, 81.3, 55.6, 38.8, 21.5, 17.9, 11.8. HRMS (ESI) m/z: [M +
Na]+ calcd for C21H21NO3SNa, 390.1140; found, 390.1127.
1
min (R). H NMR (500 MHz, CDCl3): δ 7.76 (d, J = 6.6 Hz, 2H),
7.51−7.44 (m, 2H), 7.41−7.29 (m, 5H), 7.28 (d, J = 5.6 Hz, 1H),
7.11 (d, J = 6.1 Hz, 1H), 6.97 (d, J = 9.0 Hz, 2H), 6.28 (t, J = 2.0 Hz,
1H), 4.54 (dd, J = 12.0, 2.0 Hz, 1H), 4.29 (dd, J = 12.0, 2.0 Hz, 1H),
3.60 (dd, J = 20.1, 8.3 Hz, 2H), 2.46 (s, 4H), 2.36 (s, 3H). 13C{1H}
NMR (126 MHz, CDCl3): δ 143.9, 142.3, 141.5, 138.3, 135.5, 133.0,
129.8, 129.5, 128.8, 128.6, 128.3, 127.9, 127.9, 126.7, 126.2, 125.5,
82.0, 61.4, 50.6, 21.6, 21.5. HRMS (ESI) m/z: [M + Na]+ calcd for
C25H25NO3SNa, 442.1453; found, 442.1470.
1ai. The resulting residue was purified by column chromatography
(90:10, n-hexane/EtOAc) to give 1ai (1.94 g, 84%) as a white
2c. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 2c (78.0 mg, 90%) as a white solid,
99:1 er. [α]2D5 −29.3 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
mL/min, hexanes/isopropanol: 20/80, 254 nm, 6.58 min (R), 13.86
1
min (S). H NMR (500 MHz, CDCl3): δ 7.74 (d, J = 8.2 Hz, 2H),
1
7.47−7.42 (m, 2H), 7.37−7.28 (m, 5H), 7.18 (d, J = 8.1 Hz, 2H),
7.06 (d, J = 8.1 Hz, 2H), 6.25 (s, 1H), 4.51 (dd, J = 14.9, 2.4 Hz, 1H),
4.26 (dd, J = 14.9, 2.5 Hz, 1H), 3.60 (d, J = 10.4 Hz, 1H), 3.53 (d, J =
10.4 Hz, 1H), 2.64 (q, J = 7.6 Hz, 2H), 2.43 (s, 3H), 2.37 (s, 1H),
1.23 (t, J = 7.6 Hz, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 144.3,
143.9, 141.5, 133.0, 129.8, 128.6, 128.3, 128.2, 127.9, 126.5, 126.3,
82.1, 61.5, 50.7, 28.6, 21.6, 15.5. HRMS (ESI) m/z: [M + Na]+ calcd
for C26H27NO3SNa, 456.1609; found, 456.1525.
powder. H NMR (500 MHz, CDCl3): δ 7.75 (d, J = 8.3 Hz, 2H),
7.32−7.25 (m, 4H), 7.24 (t, J = 1.7 Hz, 1H), 7.18−7.13 (m, 2H),
4.43 (s, 2H), 4.36 (s, 2H), 2.38 (s, 3H), 2.03 (s, 3H), 1.84 (d, J = 2.5
Hz, 6H), 1.74 (d, J = 12.4 Hz, 3H), 1.67 (d, J = 11.5 Hz, 3H).
13C{1H} NMR (126 MHz, CDCl3): δ 208.4, 143.6, 136.4, 131.6,
129.6, 128.6, 128.2, 127.6, 122.2, 100.0, 85.9, 81.9, 49.5, 45.9, 38.1,
37.8, 36.4, 27.8, 21.5. HRMS (ESI) m/z: [M + Na]+ calcd for
C28H31NO3SNa, 484.1922; found, 484.1927.
General Procedure of Nickel-Catalyzed Intramolecular
Reductive Coupling of N-1,6-Alkynones. General Procedure
for Asymmetric Synthesis. In glove box, Ni(cod)2 (2.8 mg, 0.010
mmol, 5 mol %), (R)-AntPhos (3.7 mg, 0.010 mmol, 5 mol %), and
dioxane/THF (1:1, 0.5 mL) were added to a 5 mL screw-cap vial
equipped with a magnetic stirring bar. Then, substrate 1 (0.20 mmol,
1.00 equiv) was added followed by Et3SiH (93 μL, 0.60 mmol, 3.00
equiv) in one portion. The vial was closed with a screw-cap, and the
resulting mixture was stirred at 0 °C for 24 h, and then quenched with
saturated NaHCO3 solution, extracted with EtOAc, washed with
saturated brine, dried over anhydrous sodium sulfate, filtered, and
concentrated under vacuum. After desilylation with TBAF in THF,
the reaction was quenched with saturated NH4Cl solution, extracted
with EtOAc, washed with brine, dried over anhydrous sodium sulfate,
filtered, and concentrated under vacuum. The residue was purified by
column chromatography to afford chiral compound 2.
General Procedure for Preparing the Racemic Product. In the
glove box, Ni(cod)2 (2.8 mg, 0.010 mmol, 5 mol %), PPh3 (2.6 mg,
0.010 mmol, 5 mol %), and dioxane (0.5 mL) were added to a 5 mL
screw-cap vial equipped with a magnetic stirring bar. Then, substrate
1 (0.20 mmol, 1.00 equiv) was added followed by Et3SiH (93 μL, 0.60
mmol, 3.00 equiv) in one portion. The vial was closed with a screw
cap, and the resulting mixture was stirred at 25 °C for 24 h and then
quenched with saturated NaHCO3 solution, extracted with EtOAc,
washed with saturated brine, dried over anhydrous sodium sulfate,
filtered, and concentrated under vacuum. After desilylation with
TBAF in THF, the reaction was quenched with saturated NH4Cl
solution, extracted with EtOAc, washed with brine, dried over
anhydrous sodium sulfate, filtered, and concentrated under vacuum.
The residue was purified by column chromatography to afford
racemic compound 2.
2d. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 2d (70.7 mg, 79%) as a colorless oil,
96:4 er. [α]2D5 −54.9 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
mL/min, hexanes/isopropanol: 15/85, 254 nm, 5.03 min (S), 9.24
1
min (R). H NMR (500 MHz, CDCl3): δ 7.74 (d, J = 8.3 Hz, 2H),
7.48−7.43 (m, 2H), 7.36−7.28 (m, 5H), 7.22 (d, J = 8.3 Hz, 2H),
7.08 (d, J = 8.2 Hz, 2H), 6.26 (t, J = 2.6 Hz, 1H), 4.39 (ddd, J =
128.8, 14.9, 2.6 Hz, 2H), 3.64−3.49 (m, 2H), 2.91 (p, J = 6.9 Hz,
1H), 2.43 (s, 3H), 2.36 (s, 1H), 1.25 (d, J = 6.9 Hz, 6H). 13C{1H}
NMR (126 MHz, CDCl3): δ 149.0, 143.9, 141.6, 133.1, 133.0, 129.8,
128.6, 128.3, 127.9, 127.8, 126.8, 126.5, 126.3, 82.1, 61.6, 50.7, 33.9,
23.9, 21.6. HRMS (ESI) m/z: [M + Na]+ calcd for C27H29NO3SNa,
470.1766; found, 479.1767.
2e. The resulting residue was purified by column chromatography
(80:20, n-hexane/EtOAc) to give 2e (70.3 mg, 83%) as a white solid,
95:5 er. [α]2D5 −36.6 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 1
mL/min, hexanes/isopropanol: 20/80, 254 nm, 10.41 min (S), 13.87
1
min (R). H NMR (500 MHz, CDCl3): δ 7.73 (d, J = 5.7 Hz, 2H),
7.50−7.28 (m, 7H), 7.17−6.95 (m, 4H), 6.25 (s, 1H), 4.46 (d, J =
11.7 Hz, 1H), 4.22 (d, J = 11.7 Hz, 1H), 3.57 (q, J = 8.0 Hz, 2H),
2.43 (s, 4H). 13C{1H} NMR (126 MHz, CDCl3): δ 144.0, 142.2,
141.3, 132.9, 130.3, 130.2, 129.9, 128.4, 127.9, 126.2, 125.4, 115.8,
115.6, 81.9, 61.4, 50.5, 21.6. HRMS (ESI) m/z: [M + Na]+ calcd for
C24H22FNO3SNa, 446.1202; found, 446.1214.
2f. The resulting residue was purified by column chromatography
(80:20, n-hexane/EtOAc) to give 2f (77.3 mg, 88%) as a colorless oil,
99:1 er, [α]2D5 −32.25 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
mL/min, hexanes/isopropanol: 15/85, 254 nm, 6.90 min (S), 12.03
2a. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 2a (80.3 mg, 99%) as a white solid,
99:1 er. [α]2D5 −22.0 (c 1.0, CH2Cl2); enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 1
mL/min, hexanes/isopropanol: 15/85, 254 nm, 7.08 min (S), 8.11
1
min (R). H NMR (500 MHz, CDCl3): δ 7.74 (d, J = 6.6 Hz, 2H),
7.47−7.43 (m, 2H), 7.37−7.30 (m, 7H), 7.07 (d, J = 6.8 Hz, 2H),
6.25 (t, J = 2.5 Hz, 1H), 4.46 (dd, J = 12.0, 2.0 Hz, 1H), 4.22 (dd, J =
12.0, 2.0 Hz, 1H), 3.58 (d, J = 0.9 Hz, 2H), 2.44 (s, 3H), 2.32 (s, 1H).
13C{1H} NMR (126 MHz, CDCl3): δ 144.1, 143.2, 141.2, 134.0,
133.8, 132.9, 129.9, 129.8, 128.9, 128.4, 128.0, 127.9, 126.1, 125.3,
81.9, 61.3, 50.5, 21.6. HRMS (ESI) m/z: [M + Na]+ calcd for
C24H22ClNO3SNa, 462.0907; found, 462.0866.
1
min (R). H NMR (500 MHz, CDCl3): δ 7.74 (d, J = 6.6 Hz, 2H),
7.50−7.43 (m, 2H), 7.38−7.26 (m, 8H), 7.15 (d, J = 5.9 Hz, 2H),
6.30 (t, J = 2.0 Hz, 1H), 4.52 (dd, J = 12.0, 2.0 Hz, 1H), 4.27 (dd, J =
12.0, 2.0 Hz, 1H), 3.58 (dd, J = 19.0, 8.3 Hz, 2H), 2.44 (s, 3H), 2.39
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2g. The resulting residue was purified by column chromatography
(80:20, n-hexane/EtOAc) to give 2g (83.6 mg, 96%) as a white solid,
99:1 er. [α]2D5 −36.1 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
mL/min, hexanes/isopropanol: 20/80, 254 nm, 7.93 min (S), 20.91
99:1 er. [α]2D5 −22.6 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 1
mL/min, hexanes/isopropanol: 15/85, 254 nm, 6.27 min (S), 7.60
1
min (R). H NMR (500 MHz, CDCl3): δ 7.73 (d, J = 8.3 Hz, 2H),
7.47−7.44 (m, 2H), 7.37−7.26 (m, 6H), 6.82 (dd, J = 8.1, 2.2 Hz,
1H), 6.74 (d, J = 7.7 Hz, 1H), 6.67−6.62 (m, 1H), 6.26 (t, J = 2.5 Hz,
1H), 4.49 (dd, J = 15.0, 2.5 Hz, 1H), 4.25 (dd, J = 15.0, 2.6 Hz, 1H),
3.79 (s, 3H), 3.61−3.53 (m, 2H), 2.43 (s, 3H), 2.39 (s, 1H). 13C{1H}
NMR (126 MHz, CDCl3): δ 159.7, 144.0, 142.9, 141.4, 136.9, 132.9,
129.8, 129.7, 128.4, 127.9, 127.8, 126.5, 126.2, 120.8, 114.5, 113.3,
82.0, 61.4, 55.3, 50.6, 21.6. HRMS (ESI) m/z: [M + Na]+ calcd for
C25H25NO4SNa, 458.1402; found, 458.1379.
1
min (R). H NMR (500 MHz, CDCl3): δ 7.74 (d, J = 6.6 Hz, 2H),
7.45 (dd, J = 6.5, 1.0 Hz, 2H), 7.35−7.29 (m, 5H), 7.07 (d, J = 7.0
Hz, 2H), 6.88−6.85 (m, 2H), 6.21 (t, J = 2.0 Hz, 1H), 4.49 (dd, J =
11.8, 2.0 Hz, 1H), 4.24 (dd, J = 11.8, 2.0 Hz, 1H), 3.81 (s, 3H), 3.60
(d, J = 8.3 Hz, 1H), 3.52 (d, J = 8.3 Hz, 1H), 2.47 (s, 1H), 2.42 (s.
3H). 13C{1H} NMR (126 MHz, CDCl3): δ 159.3, 143.9, 141.6, 140.1,
133.0, 130.0, 129.8, 128.3, 127.9, 127.8, 126.3, 126.1, 114.1, 82.1,
61.6, 55.3, 50.7, 21.6. HRMS (ESI) m/z: [M + Na]+ calcd for
C25H25NO4SNa, 458.1402; found, 458.1423.
2m. The resulting residue was purified by column chromatography
(80:20, n-hexane/EtOAc) to give 2m (68.1 mg, 72%) as a white solid,
97:3 er. [α]2D5 −18.6 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
mL/min, hexanes/isopropanol: 15/85, 254 nm, 4.10 min (S), 4.77
2h. The resulting residue was purified by column chromatography
(80:20, n-hexane/EtOAc) to give 2h (74.7 mg, 79%) as a yellow oil,
98:2 er. [α]2D5 −6.4 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
mL/min, hexanes/isopropanol: 15/85, 254 nm, 5.03 min (S), 9.24
1
min (R). H NMR (500 MHz, CDCl3): δ 7.74 (d, J = 8.2 Hz, 2H),
7.54−7.44 (m, 4H), 7.40−7.30 (m, 7H), 6.34 (t, J = 2.4 Hz, 1H),
4.47 (dd, J = 15.1, 2.4 Hz, 1H), 4.24 (dd, J = 15.1, 2.5 Hz, 1H), 3.60
(s, 2H), 2.44 (s, 3H), 2.43 (s, 1H). 13C{1H} NMR (126 MHz,
CDCl3): δ 144.7, 144.1, 141.0, 136.3, 132.8, 131.1, 129.9, 129.2,
128.5, 128.1, 127.9, 126.1, 125.5, 125.1, 124.5, 81.8, 61.2, 50.3, 21.6.
HRMS (ESI) m/z: [M + Na]+ calcd for C25H22F3NO3SNa, 496.1170;
found, 496.1157.
1
min (R). H NMR (500 MHz, CDCl3): δ 7.74 (d, J = 8.3 Hz, 2H),
7.60 (d, J = 8.2 Hz, 2H), 7.49−7.43 (m, 2H), 7.39−7.31 (m, 5H),
7.24 (d, J = 8.2 Hz, 2H), 6.35 (s, 1H), 4.48 (dd, J = 15.1, 2.5 Hz, 1H),
4.25 (dd, J = 15.2, 2.6 Hz, 1H), 3.60 (d, J = 2.1 Hz, 2H), 2.44 (s, 3H),
2.42 (s, H). 13C{1H} NMR (126 MHz, CDCl3): δ 145.3, 144.1,
141.1, 139.0, 132.8, 129.9, 128.7, 128.5, 128.1, 127.9, 126.1, 125.6,
125.1 (d, J = 3.8 Hz), 81.9, 61.2, 50.4, 21.6. HRMS (ESI) m/z: [M +
Na]+ calcd for C25H22F3NO3SNa, 496.1170; found, 496.1157.
2i. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 2i (80.5 mg, 96%) as a white solid,
98:2 er, [α]2D5 −16.2 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 1
mL/min, hexanes/isopropanol: 15/85, 254 nm, 5.68 min (S), 6.47
2n. The resulting residue was purified by column chromatography
(80:20, n-hexane/EtOAc) to give 2n (63.3 mg, 72%) as a yellow oil,
92:8 er. [α]2D5 −12.9 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 1
mL/min, hexanes/isopropanol: 15/85, 254 nm, 4.74 min (S), 6.96
1
min (R). H NMR (500 MHz, CDCl3): δ 7.69 (d, J = 6.5 Hz, 2H),
7.48 (d, J = 5.9 Hz, 2H), 7.38−7.22 (m, 8H), 7.15 (d, J = 5.9 Hz,
1H), 6.56 (t, J = 2.1 Hz, 1H), 4.38 (dd, J = 12.0, 1.8 Hz, 1H), 4.13
(dd, J = 11.1, 1.8 Hz, 1H), 3.66−3.57 (m, 2H), 2.43 (s, 3H), 2.39 (s,
1H). 13C{1H} NMR (126 MHz, CDCl3): δ 144.8, 144.0, 140.9, 133.9,
133.8, 133.1, 129.8, 129.7, 129.2, 129.1, 128.4, 128.0, 127.8, 126.9,
126.2, 123.4, 81.6, 61.5, 50.0, 21.6. HRMS (ESI) m/z: [M + Na]+
calcd for C24H22ClNO3SNa, 462.0907; found, 462.0910.
1
min (R). H NMR (500 MHz, CDCl3): δ 7.74 (d, J = 8.3 Hz, 2H),
7.47−7.42 (m, 2H), 7.39−7.28 (m, 5H), 7.15 (d, J = 8.0 Hz, 2H),
7.03 (d, J = 6.5 Hz, 2H), 6.25 (t, J = 1.9 Hz, 1H), 4.50 (dd, J = 11.9,
1.9 Hz, 1H), 4.26 (dd, J = 11.9, 2.0 Hz, 1H), 3.60 (d, J = 8.3 Hz, 1H),
3.54 (d, J = 8.3 Hz, 1H), 2.45 (s, 4H), 2.37 (s, 3H). 13C{1H} NMR
(126 MHz, CDCl3): δ 143.9, 141.6, 141.5, 138.0, 133.0, 132.7, 129.8,
129.4, 128.5, 128.3, 127.9, 127.8, 126.4, 126.3, 82.0, 61.5, 50.7, 21.6,
21.2. HRMS (ESI) m/z: [M + Na]+ calcd for C25H25NO3SNa,
442.1453; found, 442.1427.
2o. The resulting residue was purified by column chromatography
(80:20, n-hexane/EtOAc) to give 2o (65.2 mg, 77%) as a white solid,
>99:1 er. [α]2D5 −21.1 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 1
mL/min, hexanes/isopropanol: 15/85, 254 nm, 5.26 min (S), 6.57
2j. The resulting residue was purified by column chromatography
(80:20, n-hexane/EtOAc) to give 2j (75.7 mg, 86%) as a white solid,
98:2 er. [α]2D5 −16.5 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 1
mL/min, hexanes/isopropanol: 15/85, 254 nm, 5.39 min (S), 6.25
1
min (R). H NMR (500 MHz, CDCl3): δ 7.69 (d, J = 8.1 Hz, 2H),
7.45 (d, J = 7.3 Hz, 2H), 7.34−7.27 (m, 5H), 7.16−7.10 (m, 2H),
7.05−6.98 (m, 1H), 6.46 (d, J = 2.6 Hz, 1H), 4.37 (dd, J = 15.1, 1.9
Hz, 1H), 4.17 (dd, J = 15.0, 2.0 Hz, 1H), 3.62−3.56 (m, 2H), 2.62−
2.49 (m, 1H), 2.41 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ
161.0, 159.1, 144.8, 144.0, 141.3, 132.9, 129.8, 129.7, 129.7, 129.2,
129.1, 128.4, 128.0, 127.8, 126.1, 124.2, 124.1, 123.5, 123.4, 118.8,
115.8, 115.6, 81.7, 61.4, 50.5, 50.4, 21.6. HRMS (ESI) m/z: [M +
Na]+ calcd for C24H22FNO3SNa, 446.1202; found, 446.1171.
1
min (R). H NMR (500 MHz, CDCl3): δ 7.69 (d, J = 8.1 Hz, 2H),
7.48 (d, J = 7.4 Hz, 2H), 7.40−7.27 (m, 6H), 7.29−7.20 (m, 2H),
7.15 (d, J = 7.4 Hz, 1H), 6.56 (s, 1H), 4.38 (dd, J = 14.9, 2.2 Hz, 1H),
4.14 (d, J = 2.3 Hz, 1H), 3.72−3.46 (m, 2H), 2.43 (s, 3H), 2.39 (s,
1H). 13C{1H} NMR (126 MHz, CDCl3): δ 143.9, 143.1, 140.0, 133.1,
132.9, 132.2, 129.0, 128.9, 128.3, 128.2, 127.5, 127.2, 126.9, 126.0,
125.4, 122.6, 80.8, 60.6, 59.6, 49.1, 20.7. HRMS (ESI) m/z: [M +
Na]+ calcd for C24H22ClNO3SNa, 462.0907; found, 462.0910.
2k. The resulting residue was purified by column chromatography
(80:20, n-hexane/EtOAc) to give 2k (81.3 mg, 96%) as a yellow oil,
99:1 er. [α]2D5 −6.8 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 1
mL/min, hexanes/isopropanol: 25/75, 254 nm, 10.77 min (S), 11.82
min (R). 1H NMR (500 MHz, CDCl3): δ 7.77−7.65 (m, 2H), 7.50−
7.41 (m, 2H), 7.38−7.26 (m, 6H), 6.96 (td, J = 6.7, 2.0 Hz, 1H), 6.91
(dd, J = 6.2, 1.2 Hz, 1H), 6.82 (dt, J = 8.0, 1.7 Hz, 1H), 6.26 (t, J =
2.1 Hz, 1H), 4.34 (ddd, J = 94.0, 12.1, 2.1 Hz, 2H), 3.58 (d, J = 1.7
Hz, 2H), 2.58 (s, 1H), 2.43 (s, 3H). 13C{1H} NMR (126 MHz,
CDCl3): δ 163.8, 61.8, 144.1, 144.0, 141.3, 137.8, 137.7, 132.8, 130.2,
130.1, 129.9, 128.4, 128.0, 127.9, 126.1, 125.4, 124.3, 115.3, 115.1,
114.9, 114.7, 81.9, 61.3, 50.5, 21.6. HRMS (ESI) m/z: [M + Na]+
calcd for C24H22FNO3SNa, 446.1202; found, 446.1171.
2p. The resulting residue was purified by column chromatography
(80:20, n-hexane/EtOAc) to give 2p (83.6 mg, 96%) as a white solid,
>99:1 er. [α]2D5 −9.6 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 1
mL/min, hexanes/isopropanol: 15/85, 254 nm, 6.78 min (S), 8.39
1
min (R). H NMR (500 MHz, CDCl3): δ 7.71 (d, J = 6.6 Hz, 2H),
7.51−7.46 (m, 2H), 7.36−7.26 (m, 6H), 7.08 (dd, J = 6.1, 1.1 Hz,
1H), 6.96 (t, J = 6.0 Hz, 1H), 6.85 (d, J = 6.6 Hz, 1H), 6.64 (t, J = 2.0
Hz, 1H), 4.37 (dd, J = 11.9, 1.9 Hz, 1H), 4.20 (dd, J = 11.9, 2.1 Hz,
1H), 3.74 (s, 3H), 3.63−3.53 (m, 2H), 2.43 (s, 3H), 2.36 (s, 1H).
13C{1H} NMR (126 MHz, CDCl3): δ 157.0, 143.8, 142.3, 141.8,
133.1, 129.8, 129.4, 128.7, 128.3, 127.8, 127.8, 126.2, 124.6, 121.4,
120.5, 110.7, 81.7, 61.5, 55.4, 50.6, 21.6. HRMS (ESI) m/z: [M +
Na]+ calcd for C25H25NO4SNa, 458.1402; found, 458.1379.
2q. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 2q (79.7 mg, 92%) as a white solid,
95:5 er. [α]2D5 −24.0 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
2l. The resulting residue was purified by column chromatography
(80:20, n-hexane/EtOAc) to give 2l (83.6 mg, 96%) as a yellow oil,
5177
https://doi.org/10.1021/acs.joc.1c00079
J. Org. Chem. 2021, 86, 5166−5182

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
mL/min, hexanes/isopropanol: 15/85, 254 nm, 12.03 min (S), 14.69
min (R). H NMR (500 MHz, CDCl3): δ 7.74 (d, J = 8.2 Hz, 2H),
mL/min, hexanes/isopropanol: 15/85, 254 nm, 5.25 min (S), 5.58
min (R). H NMR (500 MHz, CDCl3): δ 7.73 (d, J = 6.6 Hz, 2H),
1
1
7.50−7.40 (m, 2H), 7.38−7.27 (m, 5H), 7.12 (d, J = 8.2 Hz, 1H),
6.89 (d, J = 6.6 Hz, 2H), 6.22 (t, J = 2.3 Hz, 1H), 4.52 (dd, J = 14.9,
2.4 Hz, 1H), 4.26 (dd, J = 14.9, 2.4 Hz, 1H), 3.60 (d, J = 10.4 Hz,
1H), 3.53 (d, J = 10.4 Hz, 1H), 2.43 (s, 3H), 2.41 (s, 1H), 2.25 (d, J =
7.3 Hz, 6H). 13C{1H} NMR (126 MHz, CDCl3): δ 143.9, 141.6,
141.3, 136.9, 136.7, 133.2, 133.0, 130.1, 130.0, 129.8, 128.3, 127.9,
127.8, 126.6, 126.3, 125.8, 82.1, 61.5, 50.6, 21.6, 19.8, 19.6. HRMS
(ESI) m/z: [M + Na]+ calcd for C26H27NO3SNa, 456.1609; found,
456.1525.
7.46−7.39 (m, 2H), 7.39−7.26 (m, 5H), 7.14 (d, J = 6.0 Hz, 2H),
7.01 (t, J = 6.9 Hz, 2H), 6.28 (t, J = 1.8 Hz, 1H), 4.49 (dd, J = 12.0,
1.9 Hz, 1H), 4.25 (dd, J = 12.0, 2.0 Hz, 1H), 3.58 (d, J = 8.3 Hz, 1H),
3.50 (d, J = 8.3 Hz, 1H), 2.43 (s, 4H). 13C{1H} NMR (126 MHz,
CDCl3): δ 161.4, 144.1, 142.3, 137.3, 135.4, 132.9, 129.9, 128.7,
128.6, 128.1, 128.0, 127.8, 126.7, 115.3, 115.1, 81.6, 61.4, 50.6, 21.6.
HRMS (ESI) m/z: [M + Na]+ calcd for C24H22FNO3SNa, 446.1202;
found, 446.1171.
2w. The resulting residue was purified by column chromatography
(80:20, n-hexane/EtOAc) to give 2w (72.1 mg, 82%) as a colorless
oil, >99:1 er, [α]2D5 −25.06 (c 1.0, CH2Cl2); the enantiomeric ratio
was determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate:
0.5 mL/min, hexanes/isopropanol: 30/70, 254 nm, 6.07 min (S), 6.44
2r. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 2r (70.3 mg, 73%) as a white solid,
98:2 er. [α]2D5 −38.7 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
mL/min, hexanes/isopropanol: 15/85, 254 nm, 9.66 min (R), 11.88
1
min (R). H NMR (500 MHz, CDCl3): δ 7.73 (d, J = 8.2 Hz, 2H),
1
min (S). H NMR (500 MHz, CDCl3): δ 7.76 (d, J = 6.6 Hz, 2H),
7.42−7.27 (m, 9H), 7.14 (d, J = 7.4 Hz, 2H), 6.27 (t, J = 2.5 Hz, 1H),
4.51 (dd, J = 15.1, 2.5 Hz, 1H), 4.25 (dd, J = 15.1, 2.6 Hz, 1H), 3.59
(d, J = 10.5 Hz, 1H), 3.49 (d, J = 10.5 Hz, 1H), 2.44 (s, 3H), 2.34 (s,
1H). 13C{1H} NMR (126 MHz, CDCl3): δ 144.1, 142.2, 140.0, 135.3,
133.9, 132.9, 129.9, 128.8, 128.6, 128.5, 128.1, 127.9, 127.7, 126.9,
81.7, 61.5, 50.6, 21.6. HRMS (ESI) m/z: [M + Na]+ calcd for
C24H22ClNO3SNa, 462.0907; found, 462.0866.
7.59 (dd, J = 6.5, 1.4 Hz, 4H), 7.51−7.41 (m, 4H), 7.41−7.30 (m,
6H), 7.22 (d, J = 6.6 Hz, 2H), 6.33 (t, J = 2.1 Hz, 1H), 4.56 (dd, J =
12.0, 1.9 Hz, 1H), 4.31 (dd, J = 12.0, 2.0 Hz, 1H), 3.65−3.52 (m,
2H), 2.43 (s, 3H), 2.40 (s, 1H). 13C{1H} NMR (126 MHz, CDCl3):
δ 144.0, 142.6, 141.4, 140.7, 140.2, 134.5, 133.0, 129.9, 129.0, 128.9,
128.4, 127.9, 127.8, 127.6, 127.3, 127.0, 126.2, 126.1, 82.0, 61.5, 50.7,
21.6. HRMS (ESI) m/z: [M + Na]+ calcd for C30H27NO3SNa,
504.1609; found, 504.1618.
2x. The resulting residue was purified by column chromatography
(80:20, n-hexane/EtOAc) to give 2x (81.8 mg, 94%) as a white solid,
99:1 er, [α]2D5 −36.32 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
mL/min, hexanes/isopropanol: 25/75, 254 nm, 16.85 min (R), 21.99
2s. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 2s (71.5 mg, 87%) as a white solid,
99:1 er. [α]2D5 −18.8 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
mL/min, hexanes/isopropanol: 15/85, 254 nm, 5.35 min (R), 6.22
1
min (S). H NMR (500 MHz, CDCl3): δ 7.68 (d, J = 6.6 Hz, 2H),
7.39−7.32 (m, 3H), 7.31−7.24 (m, 4H), 7.19 (d, J = 5.6 Hz, 2H),
6.97−6.83 (m, 2H), 6.43 (t, J = 2.1 Hz, 1H), 4.41−4.27 (m, 2H),
3.91 (d, J = 7.7 Hz, 1H), 3.83 (s, 1H), 3.70 (s, 3H), 3.37 (d, J = 7.7
Hz, 1H), 2.40 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 156.0,
143.6, 141.3, 136.0, 132.6, 130.8, 129.6, 129.3, 128.6, 128.5, 127.9,
127.8, 127.6, 125.3, 120.9, 111.1, 80.9, 59.6, 55.2, 50.9, 21.5. HRMS
(ESI) m/z: [M + Na]+ calcd for C25H25NO4SNa, 458.1402; found,
458.1379.
1
min (S). H NMR (500 MHz, CDCl3): δ 7.75 (d, J = 6.5 Hz, 2H),
7.45 (d, J = 5.9 Hz, 2H), 7.38−7.27 (m, 6H), 7.08 (s, 1H), 6.97 (d, J
= 4.0 Hz, 1H), 6.29 (t, J = 2.1 Hz, 1H), 4.47 (dd, J = 11.9, 1.7 Hz,
1H), 4.21 (dd, J = 11.9, 1.8 Hz, 1H), 3.62 (d, J = 8.3 Hz, 1H), 3.53
(d, J = 8.3 Hz, 1H), 2.48 (s, 1H), 2.43 (s, 3H). 13C{1H} NMR (126
MHz, CDCl3): δ 144.0, 141.4, 137.2, 132.8, 129.9, 128.3, 127.9,
127.6, 126.2, 126.1, 124.4, 120.4, 81.8, 61.9, 50.9, 21.6. HRMS (ESI)
m/z: [M + Na]+ calcd for C22H21NO3S2Na, 434.0861; found,
434.0855.
2y. The resulting residue was purified by column chromatography
(80:20, n-hexane/EtOAc) to give 2y (89.9 mg, 95%) as a yellow oil,
>99:1 er, [α]2D5 −18.19 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
mL/min, hexanes/isopropanol: 30/70, 254 nm, 4.56 min (S), 4.99
2t. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 2t (66.6 mg, 81%) as a colorless oil,
99:1 er. [α]2D5 −18.0 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
mL/min, hexanes/isopropanol: 15/85, 254 nm, 4.88 min (R), 6.16
1
min (R). H NMR (500 MHz, CDCl3): δ 7.73 (d, J = 8.1 Hz, 2H),
7.59 (s, 4H), 7.32 (ddt, J = 23.3, 14.6, 7.4 Hz, 5H), 7.14 (d, J = 7.6
Hz, 2H), 6.26 (t, J = 2.1 Hz, 1H), 4.53 (dd, J = 15.1, 2.3 Hz, 1H),
4.27 (dd, J = 15.1, 2.4 Hz, 1H), 3.62 (d, J = 10.5 Hz, 1H), 3.51 (d, J =
10.5 Hz, 1H), 2.59 (s, 1H), 2.44 (s, 3H). 13C{1H} NMR (126 MHz,
CDCl3): δ 145.7, 144.2, 142.2, 135.2, 132.7, 129.9, 128.8, 128.6,
128.2, 127.9, 127.2, 126.7, 125.3 (d, J = 3.8 Hz), 125.2, 81.7, 61.6,
50.7, 21.6. HRMS (ESI) m/z: [M + Na]+ calcd for C25H22F3NO3SNa,
496.1170; found, 496.1157.
1
min (S). H NMR (500 MHz, CDCl3): δ 7.76 (d, J = 8.2 Hz, 2H),
7.47−7.42 (m, 2H), 7.39−7.29 (m, 6H), 7.06−6.96 (m, 1H), 6.89 (d,
J = 3.4 Hz, 1H), 6.45 (t, J = 2.5 Hz, 1H), 4.48 (dd, J = 15.5, 2.4 Hz,
1H), 4.19 (dd, J = 15.5, 2.5 Hz, 1H), 3.63 (d, J = 10.3 Hz, 1H), 3.52
(d, J = 10.3 Hz, 1H), 2.46 (s, 1H), 2.44 (s, 3H). 13C{1H} NMR (126
MHz, CDCl3): δ 144.0, 141.2, 140.5, 139.3, 132.6, 129.9, 128.4,
128.2, 128.0, 127.9, 127.6, 127.1, 126.2, 119.5, 81.8, 62.2, 51.0, 21.6.
HRMS (ESI) m/z: [M + Na]+ calcd for C22H21NO3S2Na, 434.0861;
found, 434.0855.
2z. The resulting residue was purified by column chromatography
(80:20, n-hexane/EtOAc) to give 2z (73.7 mg, 87%) as a colorless oil,
>99:1 er. [α]2D5 −11.1 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
mL/min, hexanes/isopropanol: 15/85, 254 nm, 5.23 min (S), 6.70
2u. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 2u (77.2 mg, 92%) as a colorless oil,
>99:1 er, [α]2D5 −24.3 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
mL/min, hexanes/isopropanol: 15/85, 254 nm, 10.80 min (S),12.22
1
min (R). H NMR (500 MHz, CDCl3): δ 7.74 (d, J = 6.6 Hz, 2H),
7.38−7.19 (m, 8H), 7.14 (d, J = 6.0 Hz, 2H), 7.05−6.92 (m, 1H),
6.28 (t, J = 1.9 Hz, 1H), 4.51 (dd, J = 12.0, 1.9 Hz, 1H), 4.25 (dd, J =
12.0, 2.0 Hz, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.50 (d, J = 8.4 Hz, 1H),
2.44 (s, 4H). 13C{1H} NMR (126 MHz, CDCl3): δ 144.1, 142.1,
135.3, 132.8, 130.0, 129.9, 128.7, 128.6, 128.1, 127.9, 127.0, 21.9,
114.9, 114.7, 113.7, 113.5, 100.00, 81.7, 61.5, 50.6, 21.6. HRMS (ESI)
m/z: [M + Na]+ calcd for C24H22FNO3SNa, 446.1202; found,
446.1171.
2aa. The resulting residue was purified by column chromatography
(80:20, n-hexane/EtOAc) to give 2aa (68.6 mg, 78%) as a white solid,
99:1 er, [α]2D5 −53.0 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
mL/min, hexanes/isopropanol: 15/85, 254 nm, 6.60 min (S), 7.50
1
min (R). H NMR (500 MHz, CDCl3): δ 7.72 (d, J = 6.6 Hz, 2H),
7.37−7.24 (m, 7H), 7.18−7.09 (m, 4H), 6.29 (t, J = 1.9 Hz, 1H),
4.48 (dd, J = 12.0, 1.9 Hz, 1H), 4.25 (dd, J = 12.0, 2.0 Hz, 1H), 3.59−
3.50 (m, 2H), 2.43 (s, 1H), 2.42 (s, 3H), 2.35 (s, 3H). 13C{1H} NMR
(126 MHz, CDCl3): δ 143.9, 142.5, 138.5, 137.7, 135.6, 133.0, 129.8,
129.1, 128.7, 128.6, 127.9, 127.8, 126.3, 126.2, 81.9, 61.3, 50.6, 21.6.
HRMS (ESI) m/z: [M + Na]+ calcd for C25H25NO3SNa, 442.1453;
found, 442.1427.
2v. The resulting residue was purified by column chromatography
(80:20, n-hexane/EtOAc) to give 2v (78.0 mg, 92%) as a colorless oil,
> 99:1 er. [α]2D5 −23.7 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
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1
min (R). H NMR (500 MHz, CDCl3): δ 7.73 (d, J = 8.2 Hz, 2H),
7.76 (m, 3H), 7.74 (d, J = 6.6 Hz, 2H), 7.54−7.45 (m, 2H), 7.43−
7.32 (m, 3H), 7.32−7.25 (m, 3H), 7.15 (d, J = 5.9 Hz, 2H), 6.31 (t, J
= 1.9 Hz, 1H), 4.59 (dd, J = 12.0, 2.0 Hz, 1H), 4.33 (dd, J = 12.0, 2.0
Hz, 1H), 3.73−3.62 (m, 2H), 2.50 (s, 1H), 2.40 (s, 3H). 13C{1H}
NMR (126 MHz, CDCl3): δ 144.0, 142.5, 138.6, 135.5, 133.1, 132.9,
132.8, 129.8, 128.7, 128.6, 128.3, 128.2, 128.0, 127.8, 127.5, 126.9,
126.5, 126.4, 125.4, 124.2, 82.3, 61.3, 50.7, 21.6. HRMS (ESI) m/z:
[M + Na]+ calcd for C28H25NO3SNa, 478.1453; found, 478.1447.
2ag. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 2ag (60.9 mg, 79%) as a white solid,
98:2 er. [α]2D5 +7.2 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
mL/min, hexanes/isopropanol: 15/85, 254 nm, 5.50 min (S), 5.95
7.46 (s, 1H), 7.37−7.25 (m, 8H), 7.14 (d, J = 7.6 Hz, 2H), 6.28 (t, J =
2.6 Hz, 1H), 4.51 (dd, J = 15.0, 2.3 Hz, 1H), 4.25 (dd, J = 15.0, 2.4
Hz, 1H), 3.60 (d, J = 10.5 Hz, 1H), 3.49 (d, J = 10.5 Hz, 1H), 2.53 (s,
1H), 2.43 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 144.1,
143.8, 142.1, 135.3, 134.4, 132.8, 129.9, 129.7, 128.7, 128.6, 128.1,
128.0, 127.8, 127.0, 126.5, 124.5, 81.6, 61.5, 50.6, 21.6. HRMS (ESI)
m/z: [M + Na]+ calcd for C24H22ClNO3SNa, 462.0907; found,
462.0910.
2ab. The resulting residue was purified by column chromatography
(80:20, n-hexane/EtOAc) to give 2ab (74.1 mg, 85%) as a yellow oil,
98:2 er. [α]2D5 −32.1 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
mL/min, hexanes/isopropanol: 25/75, 254 nm, 10.88 min (R), 13.37
1
min (R). H NMR (500 MHz, CDCl3): δ 7.68 (d, J = 8.1 Hz, 2H),
1
min (S). H NMR (500 MHz, CDCl3): δ 7.76 (d, J = 8.3 Hz, 2H),
7.37 (d, J = 7.6 Hz, 2H), 7.29 (d, J = 8.0 Hz, 3H), 7.17 (d, J = 7.5 Hz,
2H), 6.55 (t, J = 2.5 Hz, 1H), 4.25 (dd, J = 14.8, 2.4 Hz, 1H), 4.16−
4.09 (m, 1H), 3.91 (d, J = 10.4 Hz, 1H), 2.89 (d, J = 10.4 Hz, 1H),
2.40 (s, 3H), 1.67 (s, 1H), 1.02 (s, 9H). 13C{1H} NMR (126 MHz,
CDCl3): δ 143.8, 140.8, 135.7, 133.0, 129.8, 128.7, 128.6, 127.7,
127.6, 126.7, 84.3, 55.9, 51.5, 38.2, 25.1, 21.5. HRMS (ESI) m/z: [M
+ Na]+ calcd for C22H27NO3SNa, 408.1609; found, 408.1611.
2ah. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 2ah (59.8 mg, 81%) as a colorless
oil, 99:1 er. [α]2D5 −12.0 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
mL/min, hexanes/isopropanol: 20/80, 254 nm, 9.56 min (S), 12.06
min (R). 1H NMR (500 MHz, CDCl3): δ 7.82−7.66 (m, 2H), 7.36 (t,
J = 7.6 Hz, 2H), 7.34−7.26 (m, 3H), 7.18 (dd, J = 7.2, 1.6 Hz, 2H),
6.61 (t, J = 2.6 Hz, 1H), 4.35−4.14 (m, 2H), 3.34 (d, J = 9.9 Hz, 1H),
3.20 (d, J = 9.9 Hz, 1H), 2.41 (s, 3H), 1.70 (s, 1H), 1.06 (tt, J = 8.2,
5.3 Hz, 1H), 0.59−0.39 (m, 4H). 13C{1H} NMR (126 MHz, CDCl3):
δ 143.8, 140.9, 135.7, 132.9, 129.8, 128.7, 128.6, 127.8, 127.7, 124.2,
78.5, 58.6, 50.6, 21.5, 17.9, 1.2, 0.2. HRMS (ESI) m/z: [M + Na]+
calcd for C21H23NO3SNa, 392.1296; found, 392.1313.
7.41−7.27 (m, 6H), 7.17 (d, J = 7.4 Hz, 2H), 7.11−7.07 (m, 1H),
7.04−6.98 (m, 1H), 6.91−6.84 (m, 1H), 6.34 (t, J = 2.7 Hz, 1H),
4.53 (dd, J = 14.9, 2.4 Hz, 1H), 4.28 (dd, J = 14.9, 2.5 Hz, 1H), 3.83
(s, 3H), 3.63 (d, J = 10.4 Hz, 1H), 3.57 (d, J = 10.4 Hz, 1H), 2.46 (s,
4H). 13C{1H} NMR (126 MHz, CDCl3): δ 159.6, 143.9, 143.2, 142.4,
135.6, 133.0, 129.8, 129.4, 128.7, 128.6, 127.9, 127.8, 126.6, 118.6,
113.1, 112.3, 82.0, 61.5, 55.3, 50.6, 21.6. HRMS (ESI) m/z: [M +
Na]+ calcd for C25H25NO4SNa, 458.1402; found, 458.1379.
2ac. The resulting residue was purified by column chromatography
(80:20, n-hexane/EtOAc) to give 2ac (55.7 mg, 64%) as a white solid,
98:2 er, [α]2D5 −19.33 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
mL/min, hexanes/isopropanol: 25/75, 254 nm, 10.88 min (R), 13.37
1
min (S). H NMR (500 MHz, CDCl3): δ 7.73 (d, J = 6.6 Hz, 2H),
7.41−7.26 (m, 7H), 7.14 (d, J = 5.9 Hz, 2H), 6.89−6.78 (m, 2H),
6.31 (t, J = 2.1 Hz, 1H), 4.48 (dd, J = 12.0, 2.0 Hz, 1H), 4.25 (dd, J =
12.0, 2.0 Hz, 1H), 3.81 (s, 3H), 3.55 (d, J = 1.6 Hz, 2H), 2.42 (s, 3H),
2.36 (s, 1H). 13C{1H} NMR (126 MHz, CDCl3): δ 159.3, 143.9,
142.5, 135.6, 133.4, 129.8, 128.7, 128.6, 127.9, 127.8, 127.5, 126.2,
113.7, 100.0, 81.7, 61.2, 60.4, 55.3, 50.5, 21.6. HRMS (ESI) m/z: [M
+ Na]+ calcd for C25H25NO4SNa, 458.1402; found, 458.1379.
2ad. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 2ad (71.1 mg, 82%) as a colorless
oil, >99:1 er. [α]2D5 −60.67 (c 1.0, CH2Cl2); the enantiomeric ratio
was determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate:
0.5 mL/min, hexanes/isopropanol: 15/85, 254 nm, 3.87 min (R),
2ai. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 2ai (70.4 mg, 76%) as a white solid,
99:1 er, [α]2D5 −11.2 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
mL/min, hexanes/isopropanol: 20/80, 254 nm, 6.26 min (R), 6.85
1
min (S). H NMR (500 MHz, CDCl3): δ 7.69 (d, J = 7.7 Hz, 2H),
7.38 (d, J = 7.3 Hz, 2H), 7.29 (d, J = 7.1 Hz, 3H), 7.19 (d, J = 7.2 Hz,
2H), 6.47 (s, 1H), 4.24 (d, J = 14.8 Hz, 1H), 4.11 (d, J = 14.6 Hz,
1H), 3.99 (d, J = 10.3 Hz, 1H), 2.80 (d, J = 10.3 Hz, 1H), 2.40 (s,
3H), 1.97 (s, 3H), 1.73−1.54 (m, 13H). 13C{1H} NMR (126 MHz,
CDCl3): δ 143.7, 139.9, 135.6, 133.0, 129.8, 128.7, 128.6, 127.7,
127.1, 84.2, 54.6, 51.5, 39.6, 36.8, 35.9, 28.3, 21.5. HRMS (ESI) m/z:
[M + Na]+ calcd for C28H33NO3SNa, 486.2079; found, 486.2066.
Discovered New Asymmetric Couplings with (R)-AntPhos
and N-Alkynone. Synthetic Procedure (Scheme 4a). In a glove box,
Ni(cod)2 (2.8 mg, 0.010 mmol, 5 mol %), (R)-AntPhos (3.7 mg,
0.010 mmol, 5 mol %), and dioxane (0.5 mL) were added to a 5 mL
screw-cap vial equipped with a magnetic stirring bar. Substrate 1a
(83.4 mg, 0.20 mmol, 1.00 equiv) and pinacolborane (HBPin, 73.1,
0.60 mmol, 3.00 equiv) were added to the solution in one portion.
The vial was capped with a screw cap, and the resulting mixture was
stirred at 70 °C for 24 h, quenched with saturated NaHCO3 solution,
extracted with EtOAc, washed with saturated brine, dried over
anhydrous sodium sulfate, filtered, and concentrated under vacuum.
The residue was purified by column chromatography to obtain
compound 2a.
2a. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 2a (71.4 mg, 88%) as a white solid,
81:19 er. [α]2D5 −22.0 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
mL/min, hexanes/isopropanol: 15/85, 254 nm, 12.58 min (S), 15.07
min (R). All other physical and spectroscopic data of this compound
were identical to those mentioned above for compound 2a.
Synthetic Procedure (Scheme 4b). In the glove box, Ni(cod)2 (2.8
mg, 0.010 mmol, 5 mol %), (R)-AntPhos (3.7 mg, 0.010 mmol, 5 mol
%) and dioxane (0.5 mL) were added to a 5 mL screw-cap vial
1
4.87 min (S). H NMR (500 MHz, CDCl3): δ 7.72 (d, J = 8.2 Hz,
2H), 7.55 (d, J = 7.9 Hz, 1H), 7.36 (t, J = 7.6 Hz, 2H), 7.29 (d, J = 8.3
Hz, 3H), 7.15 (d, J = 7.4 Hz, 2H), 7.06−6.91 (m, 2H), 6.23 (t, J = 2.4
Hz, 1H), 4.57 (d, J = 2.4 Hz, 1H), 4.34 (d, J = 2.5 Hz, 1H), 3.65−
3.53 (m, 2H), 2.42 (s, 3H), 2.31 (s, 3H), 2.24 (s, 1H), 2.04 (s, 3H).
13C{1H} NMR (126 MHz, CDCl3): δ 143.8, 142.5, 137.9, 136.0,
135.7, 135.1, 133.1, 133.0, 129.7, 128.7, 128.5, 127.9, 127.8, 127.3,
126.4, 125.6, 82.6, 59.7, 50.6, 21.6, 21.3, 20.8. HRMS (ESI) m/z: [M
+ Na]+ calcd for C26H27NO3SNa, 456.1609; found, 456.1569.
2ae. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 2ae (58.7 mg, 61%) as a white solid,
99:1 er. [α]2D5 −0.77 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
mL/min, hexanes/isopropanol: 15/85, 254 nm, 9.56 min (R), 11.36
1
min (S). H NMR (500 MHz, CDCl3): δ 7.75 (d, J = 8.2 Hz, 2H),
7.62−7.50 (m, 6H), 7.45 (t, J = 7.6 Hz, 2H), 7.36 (t, J = 7.7 Hz, 3H),
7.30 (dd, J = 13.1, 7.8 Hz, 3H), 7.17 (d, J = 7.5 Hz, 2H), 6.37 (t, J =
2.3 Hz, 1H), 4.53 (dd, J = 15.0, 2.4 Hz, 1H), 4.30 (dd, J = 15.0, 2.5
Hz, 1H), 3.67−3.57 (m, 2H), 2.54 (s, 1H), 2.41 (s, 3H). 13C{1H}
NMR (126 MHz, CDCl3): δ 144.0, 142.4, 140.8, 140.5, 140.5, 135.6,
132.9, 129.9, 128.9, 128.7, 128.6, 128.0, 127.9, 127.5, 127.1, 127.0,
126.7, 126.6, 81.9, 61.4, 50.6, 21.6. HRMS (ESI) m/z: [M + Na]+
calcd for C30H27NO3SNa, 504.1609; found, 504.1618.
2af. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 2af (79.1 mg, 87%) as a white solid,
99:1 er. [α]2D5 −43.36 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
mL/min, hexanes/isopropanol: 15/85, 254 nm, 8.44 min (S), 19.25
min (R). 1H NMR (500 MHz, CDCl3): δ 8.08−7.99 (m, 1H), 7.90−
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Article
equipped with a magnetic stirring bar. Substrate 1u (83.4 mg 0.20
mmol, 1.00 equiv), phenylboronic acid [PhB(OH)2, 73.1 mg, 0.60
mmol, 3.00 equiv], and tert-butanol (tBuOH, 0.1 mL) were added to
the solution in one portion. The vial was capped with a screw cap, and
the resulting mixture was stirred at 70 °C for 24 h, quenched with
saturated NaHCO3 solution, extracted with EtOAc, washed with
saturated brine, dried over anhydrous sodium sulfate, filtered, and
concentrated under vacuum. The residue was purified by column
chromatography to obtain compound 3u.
Author Contributions
§W.C. and Y.C. contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support for this work was provided by the National
Natural Science Foundation of China (22061032), the Natural
Science Foundation of Inner Mongolia (2020MS02022), the
Science and Technology Program of Inner Mongolia
(2020GG0134), the Opening-fund from State Key Laboratory
of Bio-organic and Natural Products Chemistry of SIOC
(21300-5206002), the “JUN-MA” High-level Talents Program
of Inner Mongolia University (21300-5185121), the “Grass-
land Talents” Program of Inner Mongolia (12000-12102414),
and the High-level Recruit Program of Inner Mongolia
(12000-13000603). Innovation fund from Inner Mongolia
University to W.C. and W.J. is acknowledged. We are grateful
to Prof. Shufeng Chen and Dr. He Meng (Inner Mongolia
University) for NMR assistance, Prof. Hao Zhang and Dr. Li
Ling (Inner Mongolia University) for HRMS assistance, and
Mettler Toledo for the ReactIR Instrument.
3u. The resulting residue was purified by column chromatography
(85:15, n-hexane/EtOAc) to give 3u (83.2 mg, 82%) as a colorless oil,
93:7 er. [α]2D5 −12.12 (c 1.0, CH2Cl2); the enantiomeric ratio was
determined by chiral HPLC. Chiralpark AD-H, 25 °C, flow rate: 0.5
mL/min, hexanes/isopropanol: 15/85, 254 nm, 8.88 min (S), 17.36
1
min (R). H NMR (500 MHz, CDCl3): δ 7.71 (d, J = 8.2 Hz, 2H),
7.38 (d, J = 8.0 Hz, 2H), 7.30 (t, J = 7.5 Hz, 2H), 7.24 (d, J = 7.4 Hz,
1H), 7.11−6.85 (m, 8H), 6.75−6.70 (m, 2H), 6.64 (d, J = 8.1 Hz,
1H), 6.58 (t, J = 7.3 Hz, 1H), 4.23 (d, J = 13.9 Hz, 1H), 4.03 (d, J =
14.0 Hz, 1H), 3.52 (d, J = 10.0 Hz, 1H), 3.50 (s, 3H), 3.46 (d, J =
10.0 Hz, 1H), 2.93 (s, 1H), 2.48 (s, 3H). 13C{1H} NMR (126 MHz,
CDCl3): δ 154.9, 143.7, 141.8, 140.5, 139.2, 137.7, 131.9, 130.2,
129.5, 128.5, 128.5, 128.4, 128.2, 127.7, 127.4, 127.3, 126.8, 126.6,
120.4, 110.1, 79.4, 62.2, 54.6, 53.2, 21.6. HRMS (ESI) m/z: [M +
Na]+ calcd for C31H29NO4SNa, 534.1715; found, 534.1722.
ASSOCIATED CONTENT
■
sı
* Supporting Information
REFERENCES
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Guodu Liu − Inner Mongolia Key Laboratory of Fine Organic
Synthesis, College of Chemistry and Chemical Engineering,
Inner Mongolia University, Hohhot 010021, China; State
Key Laboratory of Bio-Organic and Natural Products
Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, Shanghai 200032, China; orcid.org/
0000-0002-1249-0313; Email: guoduliu@imu.edu.cn
Authors
Wanjun Chen − Inner Mongolia Key Laboratory of Fine
Organic Synthesis, College of Chemistry and Chemical
Engineering, Inner Mongolia University, Hohhot 010021,
China
Yaping Cheng − Inner Mongolia Key Laboratory of Fine
Organic Synthesis, College of Chemistry and Chemical
Engineering, Inner Mongolia University, Hohhot 010021,
China
Tao Zhang − Inner Mongolia Key Laboratory of Fine Organic
Synthesis, College of Chemistry and Chemical Engineering,
Inner Mongolia University, Hohhot 010021, China
Yu Mu − Inner Mongolia Key Laboratory of Fine Organic
Synthesis, College of Chemistry and Chemical Engineering,
Inner Mongolia University, Hohhot 010021, China
Wenqi Jia − Inner Mongolia Key Laboratory of Fine Organic
Synthesis, College of Chemistry and Chemical Engineering,
Inner Mongolia University, Hohhot 010021, China
Complete contact information is available at:
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https://doi.org/10.1021/acs.joc.1c00079
J. Org. Chem. 2021, 86, 5166−5182

The Journal of Organic Chemistry
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Article
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