Chemo- and Diastereoselective Synthesis of N-Propargyl Oxazolidines through a Copper-Catalyzed Domino A3 Reaction

Article abstract of DOI:10.1021/acs.joc.8b03244

Herein we describe a highly chemoselective A³-coupling/annulation of amino alcohols, formaldehyde, two kinds of aldehydes and alkynes, catalyzed by copper(II). This cascade reaction, employing readily available materials, provides a new and highly effective access to chiral N-propargyl oxazolidines with good diastereoselectivity (up to >20:1). In the case of ortho-substituted aromatic aldehydes, an intriguing steric effect is observed: a bulky group exhibits a remarkably adverse effect on the diastereoselectivity for the formation of the title molecule.

Full text of DOI:10.1021/acs.joc.8b03244

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Article
Chemo- and Diastereoselective Synthesis of N-Propargyl
Oxazolidines through a Copper-Catalyzed Domino A3 Reaction
Yazhen Zhang, Liliang Huang, Xiaoyang Li, Le Wang, and Huangdi Feng
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b03244 • Publication Date (Web): 22 Mar 2019
Downloaded from http://pubs.acs.org on March 22, 2019
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Chemo- and Diastereoselective Synthesis of N-Propargyl Oxazolidines
through a Copper-Catalyzed Domino A3 Reaction
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Yazhen Zhang,† Liliang Huang,† Xiaoyang Li, Le Wang, and Huangdi Feng*
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College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science,
333 Longteng Road, Shanghai, 201620, China; *E-mail: hdfeng@sues.edu.cn;
†These authors contributed equally
Graphical Abstract
O
R2
O
R1
Y
N
HCHO, R2 CHO
R3
N
R3
major
OH
X
R1
O
20 mol% CuCl2, DCE
X = I, Br
Y = C, N
NH2
R1
N
R3
Low diastereomeric ratio
excellent diastereoselective: dr > 20:1
minor
highly chemoselective: up 84% yield
broad substrate scope: 42 examples
ABSTRACT
Herein we describe a highly chemoselective A3-coupling/annulation of amino alcohols,
formaldehyde, two kinds of aldehydes and alkynes, catalyzed by a copper(II). This cascade
reaction, employing readily available materials, provides a new and highly effective access to
chiral N-propargyl oxazolidines with good diastereoselectivity (up to >20:1). In the case of
ortho-substituted aromatic aldehydes, an intriguing steric effect is observed: a bulky group
exhibits a remarkably adverse effect on the diastereoselectivity for the formation of the title
molecule.
INTRODUCTION
Chiral oxazolidine derivatives have gained considerable attention due to their broad biological
profiles in medicinal chemistry1, and wide utilities in chemical and material research.2 Among
them, the study of 1,3-oxazolidine compounds as a synthetic antibiotic3 or Ƙ opioid receptor
agonist4 is of growing interest, such as Quinocarcin, Malbracheamide B unit and SKY-146 (Fig
1).5 Meanwhile, these structural motifs are diffusely explored as chiral ligands,6 catalysts,7 and
chiral building blocks,8 exhibiting high enantioselectivity in asymmetric synthesis. Additionally,
some reactivity features of oxazolidine species have been reported in the literature, including
nucleophilic additions, ring-opening reactions, and ring expansions.9
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O
CO2H
Me
Me Me
MeO
N
BOM
H
N
O
Me
N
N
O
N
O
N
Cl
Me
H
Ph
H
O
OMe
O
OH
OH
Malbracheamide B unit
Quinocarcin
SYK-146
9
Figure 1. Several Pharmacologically Active Molecules with Oxazolidine Unit
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Notwithstanding the impressive scope of the oxazolidines, it does not fully exploit the synthetic
method for the construction of triple-bond-containing oxazolidines, e.g. N-propargyl
oxazolidines. Whereas the reactivity of C≡C triple bonds has gained tremendous popularity, the
corresponding N-propargyl oxazolidines should occupy an important position in synthetic
chemistry.10 Over the years, chiral amino alcohols have emerged as versatile substrates for the
synthesis of a wide range of chiral 1,3-oxazolidines involving the formation of the C-N and the
C-O bond.11 In addition, a few reports appeared on the generation of chiral propargylamines
while amino alcohols were used as chiral sources (Scheme 1a).12 Among these reports, most
synthetic strategies were based on chiral prolinols or 1,3-oxazolidines. However, the use of
chain 1,2-amino alcohols has scarcely been introduced, and chemo- and diastereocontrol
remains a challenging task. Recently, we have established a metal-free decarboxylation method
for the formation of N-propargyl oxazolidines via A3-coupling of formaldehyde, alkynes with in
situ generated 1,3-oxazolidines (Scheme 1b).13 Due to their important biological activities and
synthetic applications, we next sought to extend this system to the diastereodivergent synthesis
of chiral N-propargyl oxazolidines (Scheme 1c). To the best of our knowledge, the one step
coupling of amino alcohols with two different aldehydes and alkynes remains elusive in the
literature. In particular, two key challenges need to be addressed to achieve the efficient access
to target product 5. First, the diastereocontrolled generation of 2,4- or 2,5-disubstituted
oxazolidines is typically depending on the structure of the starting 1,2-amino alcohol,
N-unsubstituted substrates are relatively rarely reported and not amenable for
diastereoselectivity.14 Moreover, chemoselective methods for the preparation of the desired
product 5 are extremely difficult to perform, especially when two different aldehydes are
introduced.
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a) Classical approach
R
N
R1
OH
R3
O
N
R2Al
R1
NH
R
R1
R2
HO
HO
R3
R2
R
O
N
cat. Cu, Au, Sn
OH
+
R3
+
R3
N
R2
H
R2
H
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b) Our previous work
OH
O
N
CH2Cl2, 60 o
C
R1
R1
HCHO
R2
COOH
+
+
11 h
R2
NH2
O
O
N
c) This work (chemo-, diastereoselectivity)
R2
5
2
R1
4
R1
5-1
5
[ ]
[
]
N
R3
R3
HCHO, R2 CHO
major
OH
R3
undesired
O
R1
O
N
20 mol% CuCl2, DCE
NH2
R2
R1
R1
N
R3
R3
R2
R2
Scheme 1. Diastereoselective Access to Propargylamines and Oxazolidines from Amino Alcohols
RESULTS AND DISCUSSION
We launched our studies by examining the coupling of (R)-plenylglycinol 1a, formaldehyde
solution 2a, benzaldehyde 3a, and phenylacetylene 4a. To our delight, in the presence of 10
o
mol% CuBr2 at 80 C for 10 h, the target oxazolidine 5a was obtained in 52% yield with more
than 20:1 diastereomeric ratio (Table 1, entry 1). The structure and stereochemistry of 5a (R)
were confirmed by X-ray crystallographic analysis.15 Further optimization of the reaction
conditions, such as the ratio of the starting materials, the amount of catalysts, the kind of
solvent, and the temperature was performed (Table 1). Owing to homo-coupling 1,3-diyne was
detected as a byproduct. The amount of phenylacetylene 4a was tested to inhibit its formation,
and the title compound was delivered in 64% and 72% yield, respectively (entries 2 and 3). In
the investigation of the solvent effect, we found that 1,4-dioxane, toluene, and acetonitrile, as
well as solvent-free conditions, led to a negative effect on the yield, resulting in the generation
of byproduct 5-1 (entries 4-7). Next, various copper catalysts were evaluated. The lowest yield
of the product (34%) was observed when Cu(OAc)2 was introduced (entry 8). In addition, both
CuSO4 and CuI showed moderate efficiency while excellent stereoselectivity was obtained (dr >
20/1, entries 9 and 10). In the case of CuBr, CuCl, and CuCl2, there was an upward trend of the
yield (up to 82%), together with an excellent diastereoselectivity (entries 11-13). Notably,
reducing the amount of CuCl2 resulted in a decreased yield of the target product (entry 14).
Moreover, a slightly increased yield and excellent diastereoselectivity were achieved (84%, dr >
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20/1, entry 15) when using 20 mol% CuCl2. The reaction was also sensitive to the reaction
5
6
o
temperature, and a lower yield of the expected product was obtained at 100 C resulting in an
7
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increased amount of byproducts (entry 16). Although the reaction temperature at 60 °C still held
good diastereoselectivity, only a moderate yield was observed (entry 17). When the reaction
was carried out under microwave-irradiation for 30 min, a significantly lower yield of the
desired product was observed (entry 18).
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Table 1: Optimization of Reaction Conditionsa
O
OH
O
O
Ph
catal., solvent
temp., 10 h
Ph
+
+
+
N
Ph
H
H
H
Ph
NH2
Ph
Ph
1a
2a
3a
4a
5a
entry
1d
2e
3
catalyst (mol%)
CuBr2 (10)
CuBr2 (10)
CuBr2 (10)
CuBr2 (10)
CuBr2 (10)
CuBr2 (10)
CuBr2 (10)
Cu(OAC)2 (10)
CuSO4 (10)
CuI (10)
solvent
DCE
temp.(oC)
80
yieldb (%)
52%
64%
72%
46%
51%
33%
45%
34%
60%
57%
66%
80%
82%
60%
84%
66%
49%
36%
drc
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
DCE
80
DCE
80
4
1,4-dioxane
toluence
CH3CN
--
80
5
80
6
80
7
80
8
DCE
80
9
DCE
80
10
11
12
13
14
15
16
17
18f
DCE
80
CuBr (10)
DCE
80
CuCl (10)
DCE
80
CuCl2 (10)
CuCl2 (5)
DCE
80
DCE
80
CuCl2 (20)
CuCl2 (20)
CuCl2 (20)
CuCl2 (20)
DCE
80
DCE
100
60
DCE
DCE
80
aReaction conditions: 1a (0.55 mmol), 2a (0.50 mmol), 3a (0.55 mmol) and 4a (0.40 mmol) in 1 mL of
b
c
1
solvent; Isolated yield; Diastereomeric ratios were determined by H NMR spectroscopy of the crude
reaction mixture; d0.7mmol 4a was used. e0.55 mmol 4a was used. fmicrowave irradiation for 30 min.
Having identified the optimal reaction conditions, we first examined the scope of his one-pot
transformation of amino alcohol 1 and alkyne 4 (Table 2). In general, various substituents
seemed to be well-tolerated, giving a variety of oxazolidines with a high diastereomeric ratio
and moderate to good yield. All chiral amino alcohols substituted with aryl, alkyl and diphenyl
worked well, and provided the corresponding products (5a-5f) with 53−84% yields and with
complete diastereoselectivity (diastereometric ratio >20/1) except for 5b (95/5 dr). Additionally,
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a range of phenylacetylenes with various functional groups, including electron-donating groups
(methoxyl, methyl, ethyl, t-butyl, phenyl) and electron-withdrawing groups (fluoro,
trifluoromethyl), could be readily converted into the oxazolidine-propargylamines 5g-5r in
good yields. Furthermore, alkyl substituted alkynes were suitable coupling partners for this
domino reaction, effectively leading to target products 5s-5u with excellent
diastereoselectivities. It was noteworthy that 3-chloropropyne also could be employed, and the
resulting product 5v was obtained in 42% yield with 90/10 dr.
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Table 2: Scope of the Amino Alcohols 1 and Alkynes 4a
OH
O
O
20 mol% CuCl2
R1
O
R3
R1
+
+
+
N
DCE
H
H
NH2
80 oC, 10-11h
R3
1
5
2a
3a
4
O
O
O
O
Ph
Ph
5c
N
N
N
N
Me
5d
Bn
Ph
Ph
, 68%, >20/1 dr
, 53%, >20/1 dr
5b
, 65%, 95/5 dr
5a
, 84%, >20/1 dr
O
N
O
N
O
O
Me
Ph
N
N
Ph
MeO
5e
5f
, 69%, >20/1 dr
, 81%, >20/1 dr
5h
, 79%, >20/1 dr
5g
, 65%, >20/1 dr
O
N
O
O
O
N
N
N
Ph
Ph
Ph
Ph
Me
Et
t-Bu
OMe
5i
, 70%, >20/1 dr
5j
, 71%, >20/1 dr
5k
5l
, 62 %, >20/1 dr
, 74%,>20/1 dr
O
N
O
N
O
N
O
F
N
Ph
Ph
Ph
Ph
Ph
Ph
F
F
5m
, 60%, >20/1 dr
5n
5o
5p
, 74%, >20/1 dr
, 76%, >20/1 dr
, 80%, >20/1 dr
O
O
O
N
O
N
F
F
N
N
Ph
CF3
Ph
Ph
5t
5q
, 69%, >20/1 dr
5r
, 73%, >20/1 dr
5s
, 71%, >20/1 dr
, 69%, >20/1 dr
O
O
N
N
Ph
5u,
Ph
Cl
5v,
50%, >20/1 dr
42%, 90/10 dr
aReaction conditions: CuCl2 (20 mol%), 1 (0.55 mmol), 2a (0.50 mmol), 3a (0.55 mmol) and 4 (0.40
o
mmol), in 1,2-dichloroethane (1.0 mL) at 80 C for 10-11 hours under oil bath; Isolated yield based
1
on alkyne. Diastereomeric ratios were determined by H NMR spectroscopy of the crude reaction
mixture.
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We then evaluated the scope of aldehyde 3 to enhance the applicability of the reaction (Table 3).
The reaction performed well for a diverse range of aryl-substituted substrates to afford the
desired products 5w-5ze with excellent diastereoselectivities and good yields. The electronic
variation of the aryl group was well-tolerated, ranging from electron-donating groups (methyl,
dimethyl) to electron-withdrawing groups (bromo, trifluoromethyl, fluoro, nitro). However, the
size of the substituent group on the ortho-position of the benzene ring showed a strong influence
on the diastereoselectivity. Attaching a bulky substituent (such as bromo) reduced the
diastereometric ratio dramatically. In addition, several heterocyclic aldehydes were found
suitable for this reaction. In these cases, the desired products 5zf-5zi were obtained in 59−66%
yields with high diastereomeric ratios. The effect of alkyl substituents (isobutyl, cyclohexyl, and
2-ethylbutyl) on the reactivity was investigated, but only 5zj was isolated in a yield of 75 %. In
other cases, the 4-phenyl-3-(3-phenylprop-2-yn-1-yl)oxazolidine was obtained as the main
byproduct.
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Table 3: Substrate Scope of the Aldehydes 3a
O
OH
R2
O
20 mol% CuCl2
R2
+
+
+
O
N
DCE
H
H
Ph
NH2
Ph
80 oC, 10-11h
1a
2a
3
4a
5
Me
Me
Me
O
O
O
O
N
N
N
N
Ph
Ph
5z
Ph
5w
Ph
5x
5y
, 67%, >20/1 dr
, 70%, >20/1 dr
, 65%, >20/1 dr
CF3
, 72%, >20/1 dr
Br
O
CF3
F
O
N
O
N
O
N
N
Ph
Ph
Ph
Ph
5zd
5zc
, 71%, >20/1 dr
5za
5zb
,69%, >20/1 dr
O
, 79%, 89/11 dr
,73%, >20/1 dr
O
NO2
O
N
O
N
N
N
N
N
N
Ph
Ph
Ph
Ph
5zh
5zf
5zg
5ze
, 63%, >20/1 dr
O
, 66%, >20/1 dr
, 59%, >20/1 dr
O
, 68%, >20/1 dr
O
O
N
O
N
N
N
Ph
Ph
5zl
Ph
5zj
Ph
5zi,
5zk
, trace
61%, >20/1 dr
, 75%, >20/1 dr
, trace
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aReaction conditions: CuCl2 (20 mol%), 1a (0.55 mmol), 2a (0.50 mmol), 3 (0.55 mmol) and 4a (0.40
o
mmol), in 1,2-dichloroethane (1.0 mL) at 80 C for 10-11h under oil bath; Isolated yield based on
alkyne. Diastereomeric ratios were determined by 1H NMR spectroscopy of the crude reaction mixture.
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To clearly illustrate steric effect of the ortho-substituents on the diastereoselectivity, a series of
ortho-substituted benzaldehydes were examined (Table 4). Increasing the steric bulk of the
halogen substituents (chloro, bromo, indo) resulted in reduced diastereoselectivity of the chiral
oxazolidine-propargylamine products 5za, 5zm-5zo. Meanwhile, the yield of products 5zn and
5zo was also decreased to 54% and 42% respectively. Notably, good yield and
diastereoselectivity of product 5zp were obtained, when 2,6-dichlorobenzaldehyde was treated
to amplify the steric hindrance. These results indicated that the atomic radius was part of the
key factors to affect the diastereomeric ratio in the process. Here, some substituents of
o-benzaldehyde, such as methyl, trifluoromethyl, and nitro were well tolerated to give the target
products with a satisfactory diastereomeric ratio, albeit with slightly reduced yield (5w, 5zq,
5zr, 5z). In addition, 2,4,6-trimethoxybenzaldehyde did not lead to the formation of product
(5zs) mainly giving the byproduct 4-phenyl-3-(3-phenylprop-2-yn-1-yl)oxazolidine.
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12
13
14
15
16
17
18
19
20
21
22
23
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25
26
27
28
29
30
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32
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34
35
36
37
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Table 4: Steric hindrance effect of the o-substituted aromatic aldehydesa
O
OH
O
20 mol% CuCl2
O
+
+
Ph
+
N
R
DCE
Ph
H
H
Ph
NH2
1a
R
80 oC, 10-11h
2a
3
4a
5
O
O
O
O
N
N
N
N
Cl
Br
I
N
Br
Ph
Ph
5zn
Ph
5zo
Ph
Ph
5zm
5za
, 75%, >20/1 dr
Cl
, 79%, 89/11 dr
, 54%, 56/44 dr
, 42%, 81/19 dr
Cl
O
O
O
O
N
N
H3C
N
F3C
Cl
N
O2N
Ph
5zp
Ph
5zq
Ph
5zr
, 72%, >20/1 dr
MeO
5w
, 50%, >20/1 dr
, 72%, >20/1 dr
CH3
, 46%, >20/1 dr
OMe
O
O
N
N
H3C
MeO
Ph
5zs
Ph
5z
, n.d.
, 67%, >20/1 dr
aReaction conditions: CuCl2 (20 mol%), 1a (0.55 mmol), 2a (0.5 mmol), 3 (0.55 mmol) and 4a (0.40 mmol),
in 1,2-dichloroethane (1.0 mL) at 80 oC for 10-11h under oil bath; Isolated yield based on alkyne.
1
Diastereomeric ratios were determined by H NMR spectroscopy of the crude reaction mixture; n.d. = not
detected.
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In order to better understand the process of the reaction, control experiments were performed.
(R)-3-benzyl-4-phenyloxazolidine A-1 and (R)-4-phenyloxazolidine A were prepared firstly,16
and both of them was subjected to the standard conditions. Not surprisingly, the desired product
5zt was obtained, which indicated that the C-O bond of oxazolidine ring could be cleaved by
copper-alkyne complex (Scheme 2a). However, no desired product 5zu was detected with 46%
recycling of starting material A (Scheme 2b). Interestingly, C-O bond of oxazolidine was
activated when benzaldehyde was introduced, and desired product 5a was observed (Scheme
2c). Based on control experiments and previous reports,12,14,17 a tentative mechanism is
proposed (Scheme 2d). Initially, oxazolidine A was in situ generated from the condensation of
amino alcohol 1 and formaldehyde. Then the intermediate A reacted with aldehyde 3, resulting
in the formation of a N-substituted oxazolidine B. Subsequently, treatment with copper-alkyne
complex, which could be obtained upon terminal alkyne activation by the copper(II) catalyst,
afforded the corresponding propargylamine species C with concomitant regeneration of the
copper catalyst. Finally, the intramolecular cyclization of intermediate C occurred to afford the
titled product 5 through intermediate D.
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Control Experiments:
OH
O
a)
b)
c)
standard conditions
Ph
+
Ph
N
N
Ph
Ph
5zt
Bn
Bn
A-1
4a
, 53%, >20/1 dr
(0.4 mmol)
(0.5 mmol)
OH
O
standard conditions
Ph
+
Ph
N
NH
Ph
H
Ph
5zu
A
4a
, n.d.
(0.4 mmol)
(0.5 mmol)
O
O
O
+
Ph
standard conditions
+
Ph
N
N
Ph
Ph
H
Ph
Ph
A
3a
4a
5a
, 48%, >20/1 dr
(0.5 mmol)
(0.5 mmol) (0.4 mmol)
d) Proposed Mechanism:
O
O
O
OH
O
R3
R3
H
R2
R1
A
H
N
N
R1
N
N
D
C
B
3
R1
OH
R1
OH
R3
H2O
R2
R2
R2
H2O
CuII
HCHO
+
O
N
R2
CuII
NH2
R1
R3
HO
R3
R1
5
4
1
Scheme 2. Control Experiments and Proposed Mechanism
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CONCLUSIONS
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In summary, we have developed a copper catalyzed A3-coupling/annulation of readily available
amino alcohols, formaldehyde, aldehydes and alkynes to form oxazolidine-propargylamines in
reasonable yields with good diastereoselectivities. Moreover, the steric effect on
diastereoselectivity was illustrated via evaluating the bulkiness of the ortho-substituent on the
aromatic aldehydes. This new activation method endures the dual challenge of chemoselectivity
and stereoselectivity, and has a wide range of substrate universality.
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EXPERIMENTAL SECTION
General Information. Unless otherwise noted, all commercial reagents were used directly as
purchased. All work-up and purification procedures were carried out with reagent-grade
solvents that had not been pre-dried under ambient atmosphere. Thin-layer chromatography
(TLC) was performed and Visualization of the compounds was accomplished with UV light
(254 nm) or iodine. Flash column chromatography was performed on silica gel (200–300 mesh).
1
All H and 13C NMR spectra were recorded on a Bruker Avance III instrument (400 MHz and
100 MHz, respectively). Chemical shifts (δ) are reported in ppm relative to the tetramethylsilane
1
(TMS) signal or residual protio solvent signal. Data for H NMR are recorded as follows:
chemical shift (δ, ppm), multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet or
unresolved, br = broad singlet, coupling constant(s) in Hz, integration). Data for 13C NMR is
reported in terms of chemical shift (δ, ppm). High resolution mass spectra were obtained on a
Waters GC-TOFMS mass spectrometer with an electron impact ionization (EI) probe. Optical
rotations were recorded on an Anton Paar MCP 5500 polarimeter. X-ray crystallographic
analyses were performed on an Bruker APEX-II CCD diffractometer. Melting Point: heating
rate: 2°C/min, the thermometer was corrected.
General Procedure for the Synthesis of N-Propargyl Oxazolidines. To a test tube equipped
with a magnetically stirred chip was added chiral hydroxylamine 1 (0.55 mmol), formaldehyde
solution 2a (0.50 mmol), another aldehyde 3 (0.55 mmol) and alkyne 4 (0.40 mmol) in
1,2-dichloroethane (1.0 mL). The catalyst CuCl2 (20% mmol) was added successively, and then
the tube was sealed. Finally, the reaction vessel was placed at 80 oC in oil bath for 10-11 hours.
After the reaction was completed, the resulting reaction suspension was directly loaded onto a
silicon gel column and flashed within 2-10% ethyl acetate in petroleum ether to afford the
desired product 5a–5zr as the oil or solid.
(2R,4R)-2,4-diphenyl-3-(3-phenylprop-2-yn-1-yl)oxazolidine (5a) The product 5a (113.9 mg,
84% yield, >20/1 dr) was obtained following the general procedure as a white solid; [α]D
=
25
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−65.2 (c 0.6, CHCl3); MP: 103–105 oC; 1H NMR (400 MHz, CDCl3) δ 7.67–7.63 (m, 2H), 7.56–
7.50 (m, 2H), 7.48–7.42 (m, 3H), 7.41–7.35 (m, 4H), 7.35–7.28 (m, 4H), 5.43 (s, 1H), 4.43–
4.32 (m, 2H), 4.04–3.94 (m, 1H), 3.52 (d, J = 18.0 Hz, 1H), 3.40 (d, J = 18.0 Hz, 1H); 13C{1H}
NMR (100 MHz, CDCl3) δ 139.0, 138.5, 131.9, 129.3, 128.8, 128.5, 128.4, 128.3, 128.2, 128.1,
128.1, 123.0, 94.7, 86.2, 83.0, 74.0, 64.4, 36.3; HRMS (EI) m/z calcd for C24H21NO[M]+
339.1603, found 339.1602.
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(2R,4R)-4-benzyl-2-phenyl-3-(3-phenylprop-2-yn-1-yl)oxazolidine (5b) The product 5b (91.8
mg, 65% yield, 95/5 dr) was obtained following the general procedure as a light yellow oil; 1H
NMR (400 MHz, CDCl3) δ 7.57–7.51 (m, 2H), 7.46–7.42 (m, 2H), 7.41–7.36 (m, 3H), 7.34–
7.29 (m, 5H), 7.28–7.20 (m, 3H), 5.27 (s, 1H), 4.01 (t, J = 7.5 Hz, 1H), 3.95–3.87 (m, 1H), 3.71
(d, J = 18.0 Hz, 1H), 3.67–3.57 (m, 1H), 3.45 (d, J = 18.0 Hz, 1H), 3.14–3.07 (m, 1H), 2.80–
2.72 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 139.0, 138.6, 131.7, 131.6, 129.1, 129.1,
128.5, 128.4, 128.3, 128.2, 128.0, 126.4, 123.0, 95.4, 85.8, 83.6, 71.5, 61.2, 39.3, 37.8, 29.7;
HRMS (EI) m/z calcd for C25H23NO[M]+ 353.1780, found 353.1785.
(2S,4S,5S)-2,4,5-triphenyl-3-(3-phenylprop-2-yn-1-yl)oxazolidine (5c) The product 5c (112.9
mg, 68% yield, >20/1 dr) was obtained following the general procedure as a light yellow solid;
MP: 94–96 oC; 1H NMR (400 MHz, CDCl3) δ 7.88–7.81 (m, 2H), 7.53–7.43 (m, 5H), 7.3–7.36
(m, 3H), 7.13–7.01 (m, 10H), 5.59 (s, 1H), 5.48 (d, J = 8.7 Hz, 1H), 4.78 (d, J = 8.7 Hz, 1H),
3.62–3.49 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 139.1, 137.6, 137.4, 131.8, 129.6,
128.9, 128.7, 128.4, 128.3, 127.7, 127.3, 127.3, 127.2, 127.0, 123.0, 94.2, 86.5, 82.9, 82.8, 68.8,
36.9; HRMS (EI) m/z calcd for C30H25NO[M]+ 415.1936, found 415.1938.
(2S,4S)-4-methyl-2-phenyl-3-(3-phenylprop-2-yn-1-yl)oxazolidine (5d) The product 5d (58.8
mg, 53% yield, >20/1 dr) was obtained following the general procedure as a light yellow oil; 1H
NMR (400 MHz, CDCl3) δ 7.53 (d, J = 7.7 Hz, 2H), 7.48–7.41 (m, 2H), 7.41–7.34 (m, 3H),
7.33–7.26 (m, 3H), 5.22 (s, 1H), 4.17 (t, J = 7.1 Hz, 1H), 3.79–3.70 (m, 2H), 3.49–3.36 (m, 2H),
1.23 (d, J = 6.0 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 139.2, 131.8, 129.1, 128.4, 128.3,
128.2, 128.0, 123.0, 94.9, 85.8, 83.1, 73.1, 55.0, 36.2, 15.8; HRMS (EI) m/z calcd for
C19H19NO[M]+ 277.1467, found 277.1471.
(2S,4S)-4-isopropyl-2-phenyl-3-(3-phenylprop-2-yn-1-yl)oxazolidine (5e) The product 5e
(84.2 mg, 69% yield, >20/1 dr) was obtained following the general procedure as a light yellow
oil; 1H NMR (400 MHz, CDCl3) δ 7.58–7.51 (m, 2H), 7.46–7.41 (m, 2H), 7.40–7.34 (m, 3H),
7.34–7.27 (m, 3H), 5.30 (s, 1H), 4.01 (t, J = 7.9 Hz, 1H), 3.95 (m, 1H), 3.73 (d, J = 17.9 Hz,
1H), 3.46 (d, J = 17.9 Hz, 1H), 3.26–3.17 (m, 1H), 1.91 (m, 1H), 1.03–0.96 (m, 6H); 13C{1H}
NMR (100 MHz, CDCl3) δ 139.3, 131.7, 128.9, 128.3, 128.1, 128.0, 123.1, 95.4, 85.5, 84.3,
68.0, 65.1, 38.8, 29.7, 19.7, 17.0, 1.0; HRMS (EI) m/z calcd for C21H23NO[M]+ 305.1780, found
305.1783.
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(2S,4S)-2,4-diphenyl-3-(3-phenylprop-2-yn-1-yl)oxazolidine (5f) The product 5f (109.9 mg,
81% yield, >20/1 dr) was obtained following the general procedure as a white solid; [α]D
=
25
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68.4 (c 0.6, CHCl3); MP: 104–106 oC; 1H NMR (400 MHz, CDCl3) δ 7.68–7.62 (m, 2H), 7.56–
7.50 (m, 2H), 7.47–7.41 (m, 3H), 7.41–7.35 (m, 4H), 7.34–7.28 (m, 4H), 5.43 (s, 1H), 4.45–
4.30 (m, 2H), 4.03–3.95 (m, 1H), 3.52 (d, J = 18.0 Hz, 1H), 3.40 (d, J = 18.0 Hz, 1H); 13C{1H}
NMR (100 MHz, CDCl3) δ 139.0, 138.5, 131.9, 129.3, 128.8, 128.5, 128.4, 128.3, 128.2, 128.1,
128.1, 123.0, 94.7, 86.2, 83.0, 74.0, 36.3; HRMS (EI) m/z calcd for C24H21NO[M]+ 339.1603,
found 339.1604.
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(2R,4R)-3-(3-(2-methoxyphenyl)prop-2-yn-1-yl)-2,4-diphenyloxazolidine (5g) The product
5g (95.9 mg, 65% yield, >20/1 dr) was obtained following the general procedure as a yellow oil;
1H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 7.7 Hz, 2H), 7.54 (d, J = 7.8 Hz, 2H), 7.46–7.35 (m,
6H), 7.33–7.25 (m, 2H), 6.95–6.87 (m, 2H), 5.48 (s, 1H), 4.48 (t, J = 8.0 Hz, 1H), 4.35 (t, J =
7.5 Hz, 1H), 4.00 (t, J = 8.0 Hz, 1H), 3.91 (s, 3H), 3.55 (d, J = 18.0 Hz, 1H), 3.43 (d, J = 18.0
Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 160.3, 139.0, 138.7, 133.6, 129.6, 129.2, 128.7,
128.4, 128.2, 128.1, 128.0, 120.4, 110.7, 94.5, 87.2, 82.4, 73.9, 64.1, 55.8, 36.4, 29.7; HRMS
(EI) m/z calcd for C25H23NO2[M]+ 369.1729, found 369.1734.
(2R,4R)-2,4-diphenyl-3-(3-(m-tolyl)prop-2-yn-1-yl)oxazolidine (5h) The product 5h (111.6
mg, 79% yield, >20/1 dr) was obtained following the general procedure as a light yellow oil; 1H
NMR (400 MHz, CDCl3) δ 7.74–7.69 (m, 2H), 7.60 (d, J = 7.1 Hz, 2H), 7.52–7.41 (m, 5H),
7.38 (t, J = 7.3 Hz, 1H), 7.34–7.24 (m, 3H), 7.20 (d, J = 7.3 Hz, 1H), 5.49 (s, 1H), 4.50–4.39
(m, 2H), 4.06 (t, J = 7.7 Hz, 1H), 3.57 (d, J = 18.0 Hz, 1H), 3.46 (d, J = 18.0 Hz, 1H), 2.41 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ 139.0, 138.5, 138.1, 134.5, 132.4, 129.8, 129.3, 129.1,
128.9, 128.8, 128.5, 128.3, 128.2, 128.1, 122.8, 94.7, 86.4, 82.5, 74.0, 64.4, 36.2, 21.3;HRMS
(EI) m/z calcd for C25H23NO[M]+ 353.1780, found 353.1768.
(2R,4R)-2,4-diphenyl-3-(3-(p-tolyl)prop-2-yn-1-yl)oxazolidine (5i) The product 5i (101.7 mg,
1
70% yield, >20/1 dr) was obtained following the general procedure as a light yellow oil; H
NMR (400 MHz, CDCl3) δ 7.67–7.63 (m, 2H), 7.57–7.50 (m, 2H), 7.45–7.37 (m, 5H), 7.35–
7.29 (m, 3H), 7.13 (d, J = 7.8 Hz, 2H), 5.42 (s, 1H), 4.43–4.32 (m, 2H), 4.03–3.95 (m, 1H), 3.51
(d, J = 17.9 Hz, 1H), 3.39 (d, J = 17.9 Hz, 1H) , 2.36 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3)
δ 139.0, 138.5, 138.3, 131.7, 129.7, 129.2, 129.1, 129.0, 128.7, 128.5, 128.2, 128.1, 119.9, 94.7,
86.2, 82.1, 73.9, 64.3, 36.2, 21.4; HRMS (EI) m/z calcd for C25H23NO[M]+ 353.1780, found
353.1781.
(2R,4R)-3-(3-(4-ethylphenyl)prop-2-yn-1-yl)-2,4-diphenyloxazolidine (5j) The product 5j
(104.3 mg, 71% yield, >20/1 dr) was obtained following the general procedure as a yellow oil;
1H NMR (400 MHz, CDCl3) δ 7.67–7.62 (m, 2H), 7.55–7.50 (m, 2H), 7.44–7.34 (m, 7H), 7.33–
7.28 (m, 1H), 7.15 (d, J = 8.1 Hz, 2H), 5.42 (s, 1H), 4.41 (t, J = 7.9 Hz, 1H), 4.34 (t, J = 7.4 Hz,
1H), 4.02–3.95 (m, 1H), 3.51 (d, J = 17.9 Hz, 1H), 3.39 (d, J = 17.9 Hz, 1H), 2.68–2.60 (m,
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2H), 1.23 (t, J = 7.6 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.7, 139.1, 138.6, 131.8,
129.3, 128.8, 128.5, 128.2, 128.1, 127.9, 127.8, 120.2, 94.7, 86.3, 82.2, 74.0, 64.4, 36.3, 28.9,
15.4; HRMS (EI) m/z calcd for C26H25NO[M]+ 367.1936, found 367.1939.
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(2R,4R)-3-(3-(4-(tert-butyl)phenyl)prop-2-yn-1-yl)-2,4-diphenyloxazolidine
(5k)
The
product 5k (116.9 mg, 74% yield, >20/1 dr) was obtained following the general procedure as a
yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.68–7.62 (m, 2H), 7.56–7.49 (m, 2H), 7.44–7.37 (m,
6H), 7.36 (s, 2H), 7.34–7.26 (m, 2H), 5.42 (s, 1H), 4.41 (t, J = 7.9 Hz, 1H), 4.34 (t, J = 7.4 Hz,
1H), 4.03–3.94 (m, 1H), 3.51 (d, J = 18.0 Hz, 1H), 3.39 (d, J = 18.0 Hz, 1H), 1.32 (s, 9H);
13C{1H} NMR (100 MHz, CDCl3) δ 151.6, 139.1, 138.6, 134.4, 131.6, 129.8, 129.3, 128.8,
128.5, 128.2, 128.1, 125.4, 120.1, 94.7, 86.3, 82.2, 64.4, 36.3, 34.8, 31.2; HRMS (EI) m/z calcd
for C28H29NO[M]+ 395.2249, found 395.2251.
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(2R,4R)-3-(3-(4-methoxyphenyl)prop-2-yn-1-yl)-2,4-diphenyloxazolidine (5l) The product 5l
(96.0 mg, 62% yield, >20/1 dr) was obtained following the general procedure as a colourless oil;
1H NMR (400 MHz, CDCl3) δ 7.67–7.62 (m, 2H), 7.58–7.51 (m, 2H), 7.46–7.35 (m, 7H), 7.34–
7.29 (m, 1H), 6.88–6.83 (m, 2H), 5.42 (s, 1H), 4.43–4.32 (m, 2H), 4.02–3.95 (m, 1H), 3.82 (s,
3H), 3.50 (d, J = 17.9 Hz, 1H), 3.39 (d, J = 17.9 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ
159.6, 139.1, 138.6, 133.2, 129.2, 128.7, 128.4, 128.1, 128.0, 115.2, 114.0, 94.7, 86.0, 81.4,
73.9, 64.3, 55.3, 36.3; HRMS (EI) m/z calcd for C25H23NO2[M]+ 369.1729, found 369.1730.
(2R,4R)-3-(3-([1,1'-biphenyl]-4-yl)prop-2-yn-1-yl)-2,4-diphenyloxazolidine
(5m)
The
product 5m (99.6 mg, 60% yield, >20/1 dr) was obtained following the general procedure as a
light yellow solid; MP: 92–94 oC; 1H NMR (400 MHz, CDCl3) δ 7.70–7.65 (m, 2H), 7.64–7.50
(m, 8H), 7.49–7.30 (m, 9H), 5.45 (s, 1H), 4.46–4.34 (m, 2H), 4.05–3.95 (m, 1H), 3.55 (d, J =
18.0 Hz, 1H), 3.44 (d, J = 18.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 141.1 140.4,
139.0, 138.5, 132.2, 129.3, 128.9, 128.7, 128.5, 128.2, 128.1, 127.7, 127.0, 121.9, 94.8, 86.0,
83.6, 74.0, 64.4, 36.4; HRMS (EI) m/z calcd for C30H25NO[M]+ 415.1936, found 415.1930.
(2R,4R)-3-(3-(2-fluorophenyl)prop-2-yn-1-yl)-2,4-diphenyloxazolidine (5n) The product 5n
(108.6 mg, 76% yield, >20/1 dr) was obtained following the general procedure as a yellow oil;
1H NMR (400 MHz, CDCl3) δ 7.68–7.62 (m, 2H), 7.54 (d, J = 7.1 Hz, 2H), 7.46–7.35 (m, 6H),
7.34–7.26 (m, 2H), 7.13–7.05 (m, 2H), 5.43 (s, 1H), 4.43 (t, J = 7.9 Hz, 1H), 4.36 (t, J = 7.4 Hz,
1H), 4.00 (t, J = 7.9 Hz, 1H), 3.54 (d, J = 18.1 Hz, 1H), 3.42 (d, J = 18.1 Hz, 1H); 13C{1H}
NMR (100 MHz, CDCl3) δ 164.3, 161.8, 138.9, 138.5, 133.6, 130.0, 129.9, 129.3, 128.8, 128.5,
128.2, 128.1, 123.9, 115.6, 115.4, 111.7, 111.5, 94.6, 88.5, 79.5, 73.9, 64.3, 36.3; HRMS (EI)
m/z calcd for C24H20FNO[M]+ 357.1529, found 357.1523.
(2R,4R)-3-(3-(3-fluorophenyl)prop-2-yn-1-yl)-2,4-diphenyloxazolidine (5o) The product 5o
(114.3 mg, 80% yield, >20/1 dr) was obtained following the general procedure as a light yellow
oil; 1H NMR (400 MHz, CDCl3) δ 7.72–7.61 (m, 2H), 7.52–7.49 (m, 2H), 7.45–7.36 (m, 5H),
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7.35–7.29 (m, 1H), 7.28–7.23 (m, 1H), 7.22–7.17 (m, 1H), 7.14–7.08 (m, 1H), 7.05–6.97 (m,
1H), 5.39 (s, 1H), 4.40–4.31 (m, 2H), 4.08–3.90 (m, 1H), 3.51 (d, J = 18.0 Hz, 1H), 3.39 (d, J =
18.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 163.7, 161.2, 138.9, 138.4, 130.0, 129.9,
129.4, 128.8, 128.5, 128.2, 128.1, 127.7, 124.9, 124.8, 118.8, 118.5, 115.7, 115.5, 94.8, 85.0,
84.2, 74.0, 64.6, 36.3; HRMS (EI) m/z calcd for C24H20FNO[M]+ 357.1529, found 357.1536.
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(2R,4R)-3-(3-(4-fluorophenyl)prop-2-yn-1-yl)-2,4-diphenyloxazolidine (5p) The product 5p
(105.7 mg, 74% yield, >20/1 dr) was obtained following the general procedure as a light yellow
oil; 1H NMR (400 MHz, CDCl3) δ 7.75–7.68 (m, 2H), 7.65–7.56 (m, 2H), 7.52–7.43 (m, 7H),
7.42–7.36 (m, 1H), 7.11–7.04 (t, J = 8.7 Hz, 2H), 5.47 (s, 1H), 4.49–4.37 (m, 2H), 4.06 (t, J =
6.4 Hz, 1H), 3.58 (d, J = 17.9 Hz, 1H), 3.46 (d, J = 17.9 Hz, 1H); 13C{1H} NMR (100 MHz,
CDCl3) δ 163.8, 161.3, 139.0, 138.5, 133.7, 133.7, 129.3, 128.8, 128.5, 128.2, 128.0, 119.1,
115.7, 115.5, 94.8, 85.1, 82.8, 74.0, 64.6, 36.3; HRMS (EI) m/z calcd for C24H20FNO[M]+
357.1529, found 357.1532.
(2R,4R)-2,4-diphenyl-3-(3-(4-(trifluoromethyl)phenyl)prop-2-yn-1-yl)oxazolidine (5q) The
product 5q (115.6 mg, 69% yield, >20/1 dr) was obtained following the general procedure as a
colourless oil; 1H NMR (400 MHz, CDCl3) δ 7.74–7.68 (m, 2H), 7.65–7.54 (m, 6H), 7.52–7.42
(m, 5H), 7.41–7.35 (t, J = 7.2 Hz, 1H), 5.45 (s, 1H), 4.46–4.36 (m, 2H), 4.05 (t, J = 11.1 Hz,
1H), 3.60 (d, J = 18.0 Hz, 1H), 3.48 (d, J = 18.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ
138.9, 138.3, 134.4, 132.0, 129.4, 128.8, 128.5, 128.2, 128.1, 128.0, 126.8, 125.3, 125.2, 94.9,
85.9, 84.9, 74.0, 36.4. HRMS (EI) m/z calcd for C25H20F3NO[M]+ 407.1497, found 407.1490.
(2R,4R)-3-(3-(3,5-difluorophenyl)prop-2-yn-1-yl)-2,4-diphenyloxazolidine (5r) The product
5r (109.5 mg, 73% yield, >20/1 dr) was obtained following the general procedure as a yellow
oil; 1H NMR (400 MHz, CDCl3) δ 7.72–7.66 (m, 2H), 7.62–7.54 (m, 2H), 7.51–7.42 (m, 5H),
7.41–7.33 (m, 1H), 7.01–6.91 (m, 2H), 6.87–6.80 (m, 1H), 5.40 (s, 1H), 4.45–4.33 (m, 2H),
4.04 (t, J = 6.5 Hz, 1H), 3.57 (d, J = 18.0 Hz, 1H), 3.45 (d, J = 18.0 Hz, 1H); 13C{1H} NMR
(100 MHz, CDCl3) δ 164.0, 163.9, 161.5, 161.4, 138.8, 138.3, 129.4, 128.8, 128.5, 128.2, 128.1,
128.1, 128.0, 125.6, 114.9, 114.6, 104.7, 104.4, 104.2, 94.9, 85.5, 84.0, 74.0, 64.7, 36.4; HRMS
(EI) m/z calcd for C24H19F2NO[M]+ 375.1435, found 375.1437.
(2R,4R)-3-(3-cyclopropylprop-2-yn-1-yl)-2,4-diphenyloxazolidine (5s) The product 5s (86.1
mg, 71% yield, >20/1 dr) was obtained following the general procedure as a light yellow oil; 1H
NMR (400 MHz, CDCl3) δ 7.69–7.61 (m, 2H), 7.59–7.50 (m, 2H), 7.49–7.38 (m, 5H), 7.38–
7.30 (m, 1H), 5.35 (s, 1H), 4.43–4.28 (m, 2H), 4.04–3.95 (m, 1H), 3.29 (d, J = 17.7, 1.8 Hz,
1H), 3.17 (d, J = 17.7, 1.7 Hz, 1H), 1.31–1.27 (m, 1H), 0.87–0.78 (m, 2H), 0.74–0.63 (m, 2H);
13C{1H} NMR (100 MHz, CDCl3) δ 139.3, 138.7, 129.1, 128.7, 128.4, 128.1, 128.0, 94.6, 89.6,
73.9, 68.4, 64.2, 35.9, 8.4, 1.1, -0.5; HRMS (EI) m/z calcd for C21H21NO[M]+ 303.1623, found
303.1620.
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(2R,4R)-3-(4,4-dimethylpent-2-yn-1-yl)-2,4-diphenyloxazolidine (5t) The product 5t (88.1
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mg, 69% yield, >20/1 dr) was obtained following the general procedure as a yellow oil; H
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NMR (400 MHz, CDCl3) δ 7.67–7.61 (m, 2H), 7.56–7.50 (m, 2H), 7.48–7.39 (m, 5H), 7.37–
7.32 (m, 1H), 5.34 (s, 1H), 4.38–4.28 (m, 2H), 4.04–3.95 (m, 1H), 3.30 (d, J = 17.6 Hz, 1H),
3.18 (d, J = 17.6 Hz, 1H), 1.30 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 139.2, 138.7, 129.1,
128.6, 128.4, 128.1, 128.0, 127.9, 95.1, 94.5, 73.9, 71.3, 64.1, 35.7, 31.3, 27.6; HRMS (EI) m/z
calcd for C22H25NO[M]+ 319.1933, found 319.1929.
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(2R,4R)-3-(hept-2-yn-1-yl)-2,4-diphenyloxazolidine (5u) The product 5u (63.8 mg, 50%
yield, >20/1 dr) was obtained following the general procedure as a colourless oil; 1H NMR (400
MHz, CDCl3) δ 7.67–7.61 (m, 2H), 7.56–7.50 (m, 2H), 7.47–7.38 (m, 5H), 7.36–7.31 (m, 1H),
5.36 (s, 1H), 4.40–4.31 (m, 2H), 4.03–3.95 (m, 1H), 3.34–3.26 (m, 1H), 3.22–3.14 (m, 1H),
2.31–2.19 (m, 2H), 1.61–1.45 (m, 4H), 0.99 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 139.2, 138.6, 129.2, 128.7, 128.4, 128.1, 128.1, 128.0, 127.7, 94.5, 86.4, 85.9, 73.9,
72.9, 64.0, 35.6, 31.1, 22.0, 18.4, 13.7; HRMS (EI) m/z calcd for C22H25NO[M]+ 319.1936,
found 319.1936.
(2R,4R)-3-(4-chlorobut-2-yn-1-yl)-2,4-diphenyloxazolidine (5v) The product 5v (52.3 mg,
42% yield, 90/10 dr) was obtained following the general procedure as a colourless oil; 1H NMR
(400 MHz, CDCl3) δ 7.72–7.62 (m, 2H), 7.58–7.51 (m, 2H), 7.49–7.39 (m, 5H), 7.39–7.32 (m,
1H), 5.34 (s, 1H), 4.41–4.30 (m, 2H), 4.22 (s, 2H), 4.01 (t, J = 7.6 Hz, 1H), 3.39 (d, J = 18.0 Hz,
1H), 3.26 (d, J = 18.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 138.9, 138.3, 129.3, 128.8,
128.5, 128.2, 128.1, 128.0, 126.8, 94.6, 79.0, 76.7, 73.9, 64.3, 35.7, 31.5; HRMS (EI) m/z calcd
for C19H18ClNO[M]+ 311.1077, found 311.1079.
(2R,4R)-4-phenyl-3-(3-phenylprop-2-yn-1-yl)-2-(o-tolyl)oxazolidine (5w) The product 5w
(101.7 mg, 72% yield, >20/1 dr) was obtained following the general procedure as a light yellow
oil; 1H NMR (400 MHz, CDCl3) δ 7.64–7.54 (m, 2H), 7.52–7.46 (m, 4H), 7.45–7.40 (m, 2H),
7.39–7.31 (m, 5H), 7.26–7.22 (m, 1H), 5.42 (s, 1H), 4.47–4.36 (m, 2H), 4.07–3.99 (m, 1H),
3.56 (d, J = 18.0 Hz, 1H), 3.45 (d, J = 17.9 Hz, 1H), 2.45 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 138.8, 138.5, 138.2, 131.8, 130.1, 128.7, 128.7, 128.4, 128.3, 128.2, 128.1, 125.3,
123.0, 94.7, 86.2, 82.9, 73.9, 64.3, 36.2, 21.5; HRMS (EI) m/z calcd for C25H23NO[M]+
353.1780, found 353.1773.
(2R,4R)-4-phenyl-3-(3-phenylprop-2-yn-1-yl)-2-(m-tolyl)oxazolidine (5x) The product 5x
(91.8 mg, 65% yield, >20/1 dr) was obtained following the general procedure as a light yellow
oil; 1H NMR (400 MHz, CDCl3) δ 7.64–7.56 (m, 2H), 7.54–7.47 (m, 4H), 7.47–7.42 (m, 2H),
7.41–7.34 (m, 5H), 7.30–7.22 (m, 1H), 5.44 (s, 1H), 4.48–4.37 (m, 2H), 4.08–3.99 (m, 1H),
3.57 (d, J = 18.0 Hz, 1H), 3.47 (d, J = 18.0 Hz, 1H), 2.46 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 138.9, 138.5, 138.2, 131.8, 130.1, 128.7, 128.7, 128.3, 128.2, 128.1, 125.3, 123.1,
94.8, 86.2, 83.0, 73.9, 64.4, 36.3, 21.5;HRMS (EI) m/z calcd for C25H23NO[M]+ 353.1780,
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found 353.1782.
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(2R,4R)-4-phenyl-3-(3-phenylprop-2-yn-1-yl)-2-(p-tolyl)oxazolidine (5y) The product 5y
(98.8 mg, 70% yield, >20/1 dr) was obtained following the general procedure as a colourless oil;
1H NMR (400 MHz, CDCl3) δ 7.62–7.54 (m, 4H), 7.53–7.46 (m, 2H), 7.43–7.40 (m, 2H), 7.39–
7.34 (m, 4H), 7.27 (d, J = 8.5 Hz, 2H), 5.43 (s, 1H), 4.46–4.35 (m, 2H), 4.02 (t, J = 7.6 Hz, 1H),
3.55 (d, J = 17.9 Hz, 1H), 3.44 (d, J = 17.9 Hz, 1H), 2.42 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 139.1, 138.6, 136.0, 131.8, 129.2, 128.7, 128.3, 128.2, 128.1, 128.1, 123.1, 94.6, 86.1,
83.0, 73.9, 64.4, 36.3, 21.3; HRMS (EI) m/z calcd for C25H23NO[M]+ 353.1780, found
353.1780.
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(2R,4R)-2-(2,5-dimethylphenyl)-4-phenyl-3-(3-phenylprop-2-yn-1-yl)oxazolidine (5z) The
product 5z (98.4 mg, 67% yield, >20/1 dr) was obtained following the general procedure as a
yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.63–7.57 (m, 3H), 7.52–7.43 (m, 4H), 7.41–7.35 (m,
4H), 7.13 (d, J = 1.0 Hz, 2H), 5.71 (s, 1H), 4.48–4.37 (m, 2H), 4.08–3.97 (m, 1H), 3.58 (d, J =
17.9 Hz, 1H), 3.46 (d, J = 17.9 Hz, 1H), 2.59 (s, 3H), 2.43 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 138.5, 135.6, 135.5, 134.9, 131.8, 130.7, 129.6, 129.0, 128.8, 128.4, 128.2, 128.1,
128.1, 123.1, 92.2, 86.2, 83.1, 73.6, 64.4, 36.2, 21.2, 18.7; HRMS (EI) m/z calcd for
C26H25NO[M]+ 367.1936, found 367.1938.
(2R,4R)-2-(2-bromophenyl)-4-phenyl-3-(3-phenylprop-2-yn-1-yl)oxazolidine (5za) The
product 5za (131.8 mg, 79% yield, 89/11 dr) was obtained following the general procedure as a
white solid; MP: 117–119 oC; 1H NMR (400 MHz, CDCl3) δ 7.96–7.91 (m, 1H), 7.66–7.56 (m,
3H), 7.51–7.41 (m, 5H), 7.41–7.33 (m, 4H), 7.30–7.24 (m, 1H), 5.98 (s, 1H), 4.55–4.45 (m,
1H), 4.40 (t, J = 7.4 Hz, 1H), 4.05–3.98 (m, 1H), 3.59 (d, J = 17.9 Hz, 1H), 3.49 (d, J = 17.9 Hz,
1H); 13C{1H} NMR (100 MHz, CDCl3) δ 138.1, 137.8, 133.0, 131.8, 130.5, 130.1, 128.8, 128.3,
128.2, 128.2, 128.1, 127.7, 124.8, 123.0, 93.0, 86.2, 83.1, 73.9, 64.6, 36.6; HRMS (EI) m/z
calcd for C24H20BrNO[M]+ 417.0728, found 417.0734.
(2R,4R)-4-phenyl-3-(3-phenylprop-2-yn-1-yl)-2-(3-(trifluoromethyl)phenyl)oxazolidine
(5zb) The product 5zb (118.9 mg, 73% yield, >20/1 dr) was obtained following the general
procedure as a light yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.95 (s, 1H), 7.87 (d, J = 7.7 Hz,
1H), 7.70 (d, J = 7.8 Hz, 1H), 7.61–7.55 (m, 3H), 7.51–7.42 (m, 4H), 7.40–7.33 (m, 4H), 5.52
(s, 1H), 4.49–4.38 (m, 2H), 4.08–4.00 (m, 1H), 3.59 (d, J = 18.0 Hz, 1H), 3.43 (d, J = 18.0 Hz,
1H); 13C{1H} NMR (100 MHz, CDCl3) δ 140.4, 137.9, 131.8, 131.6, 128.9, 128.8, 128.4, 128.3,
128.0, 126.1, 126.1, 125.0, 124.9, 122.8, 94.0, 86.4, 82.5, 74.0, 64.6, 36.4; HRMS (EI) m/z
calcd for C25H20F3NO[M]+ 407.1497, found 407.1498.
(2R,4R)-4-phenyl-3-(3-phenylprop-2-yn-1-yl)-2-(4-(trifluoromethyl)phenyl)oxazolidine
(5zc) The product 5zc (112.4 mg, 69% yield, >20/1 dr) was obtained following the general
procedure as a colourless oil; 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 8.1 Hz, 2H), 7.73 (d, J
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= 8.1 Hz, 2H), 7.57 (d, J = 7.0 Hz, 2H), 7.50–7.41 (m, 4H), 7.41–7.34 (m, 4H), 5.52 (s, 1H),
4.50–4.39 (m, 2H), 4.04 (t, J = 7.2 Hz, 1H), 3.59 (d, J = 18.0 Hz, 1H), 3.43 (d, J = 18.0 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 143.3, 138.0, 131.8, 128.8, 128.5, 128.4, 128.3, 128.0,
125.5, 125.4, 122.8, 94.0, 86.4, 82.6, 74.1, 64.7, 36.5; HRMS (EI) m/z calcd for
C25H20F3NO[M]+ 407.1497, found 407.1497.
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(2R,4R)-2-(4-fluorophenyl)-4-phenyl-3-(3-phenylprop-2-yn-1-yl)oxazolidine (5zd) The
product 5zd (101.4 mg, 71% yield, >20/1 dr) was obtained following the general procedure as a
colourless oil; 1H NMR (400 MHz, CDCl3) δ 7.74–7.67 (m, 2H), 7.60 (d, J = 7.2 Hz, 2H), 7.57–
7.50 (m, 2H), 7.46 (t, J = 7.3 Hz, 2H), 7.42–7.36 (m, 4H), 7.18 (t, J = 8.7 Hz, 2H), 5.48 (s, 1H),
4.51–4.39 (m, 2H), 4.05 (t, J = 7.7 Hz, 1H), 3.59 (d, J = 18.0 Hz, 1H), 3.44 (d, J = 18.0 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 164.7, 162.3, 138.4, 134.9, 131.8, 130.1, 130.0, 128.8,
128.4, 128.2, 128.1, 123.0, 115.6, 115.3, 94.1, 86.3, 82.8, 73.9, 64.4, 36.2; HRMS (EI) m/z
calcd for C24H20FNO[M]+ 357.1529, found 357.1531.
(2R,4R)-2-(4-nitrophenyl)-4-phenyl-3-(3-phenylprop-2-yn-1-yl)oxazolidine
(5ze)
The
product 5ze (104.5 mg, 68% yield, >20/1 dr) was obtained following the general procedure as a
o
light yellow solid; MP: 114–116 C; 1H NMR (400 MHz, CDCl3) δ 8.31 (d, J = 8.4 Hz, 2H),
7.85 (d, J = 8.3 Hz, 2H), 7.53 (d, J = 7.3 Hz, 2H), 7.48–7.41 (m, 4H), 7.37 (s, 4H), 5.54 (s, 1H),
4.53–4.35 (m, 2H), 4.08–3.99 (m, 1H), 3.59 (d, J = 18.1 Hz, 1H), 3.41 (d, J = 18.0 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 148.6, 146.5, 137.5, 131.7, 129.0, 128.8, 128.4, 128.4,
127.9, 123.7, 122.6, 93.4, 86.5, 82.2, 74.1, 64.7, 36.5; HRMS (EI) m/z calcd for
C24H20N2O3[M]+ 384.1474, found 384.1478.
(2R,4R)-4-phenyl-3-(3-phenylprop-2-yn-1-yl)-2-(pyridin-2-yl)oxazolidine (5zf) The product
5zf (85.7 mg, 63% yield, >20/1 dr) was obtained following the general procedure as a yellow
oil; 1H NMR (400 MHz, CDCl3) δ 8.68–8.64 (m, 1H), 7.85–7.80 (m, 2H), 7.60–7.51 (m, 2H),
7.48–7.38 (m, 4H), 7.38–7.29 (m, 5H), 5.59 (s, 1H), 4.55–4.47 (m, 1H), 4.44 (t, J = 7.3 Hz, 1H),
4.10–4.01 (m, 1H), 3.70 (d, J = 17.8 Hz, 1H), 3.61 (d, J = 17.8 Hz, 1H); 13C{1H} NMR (100
MHz, CDCl3) δ 159.7, 149.0, 138.2, 138.2, 136.9, 131.9, 128.7, 128.2, 128.1, 128.1, 128.0,
123.6, 123.0, 121.5, 95.0, 86.1, 83.2, 74.3, 64.9, 37.1; HRMS (EI) m/z calcd for C23H20N2O[M]+
340.1576, found 340.1574.
(2R,4R)-4-phenyl-3-(3-phenylprop-2-yn-1-yl)-2-(pyridin-3-yl)oxazolidine (5zg) The product
5zg (89.8 mg, 66% yield, >20/1 dr) was obtained following the general procedure as a light
yellow oil; 1H NMR (400 MHz, CDCl3) δ 8.88 (d, J = 1.6 Hz, 1H), 8.70–8.65 (m, 1H), 8.04–
7.98 (m, 1H), 7.61–7.52 (m, 2H), 7.50–7.34 (m, 9H), 5.50 (s, 1H), 4.47–4.36 (m, 2H), 4.06–
3.98 (m, 1H), 3.58 (d, J = 18.0 Hz, 1H), 3.41 (d, J = 18.0 Hz, 1H); 13C{1H} NMR (100 MHz,
CDCl3) δ 150.6, 149.9, 137.9, 135.8, 134.7, 131.8, 128.8, 128.3, 128.3, 127.9, 123.6, 122.7,
92.8, 86.5, 82.4, 74.0, 64.6, 36.4; HRMS (EI) m/z calcd for C23H20N2O[M]+ 340.1576, found
340.1573.
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(2R,4R)-4-phenyl-3-(3-phenylprop-2-yn-1-yl)-2-(pyridin-4-yl)oxazolidine (5zh) The product
5zh (80.3 mg, 59% yield, >20/1 dr) was obtained following the general procedure as a yellow
oil; 1H NMR (400 MHz, CDCl3) δ 8.71 (d, J = 5.9 Hz, 2H), 7.62–7.57 (m, 2H), 7.56–7.50 (m,
2H), 7.49–7.34 (m, 8H), 5.46 (s, 1H), 4.50–4.37 (m, 2H), 4.03–3.96 (m, 1H), 3.59 (d, J = 18.0
Hz, 1H), 3.45 (d, J = 18.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 161.6, 150.1, 148.2,
137.7, 131.8, 128.8, 128.4, 128.3, 127.9, 122.8, 93.2, 86.5, 82.4, 74.2, 64.8, 36.7; HRMS (EI)
m/z calcd for C23H20N2O[M]+ 340.1576, found 340.1576.
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(2R,4R)-2-(furan-2-yl)-4-phenyl-3-(3-phenylprop-2-yn-1-yl)oxazolidine (5zi) The product
5zi (80.3 mg, 61% yield, >20/1 dr) was obtained following the general procedure as a colourless
oil; 1H NMR (400 MHz, CDCl3) δ 7.61–7.53 (m, 3H), 7.50–7.46 (m, 2H), 7.45–7.40 (m, 2H),
7.38–7.34 (m, 4H), 6.65 (d, J = 3.1 Hz, 1H), 6.46–6.42 (m, 1H), 5.63 (s, 1H), 4.44–4.38 (m,
1H), 4.33 (t, J = 7.2 Hz, 1H), 4.01–3.95 (m, 1H), 3.64 (s, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ 152.5, 143.4, 137.9, 131.8, 128.7, 128.3, 128.3, 128.1, 128.0, 122.9, 110.2, 109.3,
88.1, 86.2, 82.9, 7, 73.6, 64.5, 37.2; HRMS (EI) m/z calcd for C22H19NO2[M]+ 329.1416, found
329.1410.
(2R,4R)-2-isopropyl-4-phenyl-3-(3-phenylprop-2-yn-1-yl)oxazolidine (5zj) The product 5zj
(95.2 mg, 75% yield, >20/1 dr) was obtained following the general procedure as a light yellow
oil; 1H NMR (400 MHz, CDCl3) δ 7.54–7.46 (m, 4H), 7.44–7.31 (m, 6H), 4.56 (s, 1H), 4.37–
4.28 (m, 1H), 4.25 (t, J = 7.2 Hz, 1H), 3.78–3.70 (m, 1H), 3.63 (t, J = 14.3 Hz, 2H), 2.10–1.91
(m, 1H), 1.17–1.09 (m, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 139.0, 131.8, 128.6, 128.3,
128.2, 127.9, 123.1, 97.4, 85.7, 83.6, 73.7, 65.2, 37.8, 31.1, 29.7, 18.8, 15.3; HRMS (EI) m/z
calcd for C21H23NO[M]+ 305.1780, found 305.1776.
(2R,4R)-2-(2-chlorophenyl)-4-phenyl-3-(3-phenylprop-2-yn-1-yl)oxazolidine (5zm) The
product 5zm (111.9 mg, 75% yield, >20/1 dr) was obtained following the general procedure as a
white solid; MP: 119–121 oC; 1H NMR (400 MHz, CDCl3) δ 7.96–7.91 (m, 1H), 7.64–7.54 (m,
2H), 7.48–7.41 (m, 5H), 7.41–7.31 (m, 6H), 6.03 (s, 1H), 4.52–4.44 (m, 1H), 4.40 (t, J = 7.4 Hz,
1H), 4.06–3.96 (m, 1H), 3.59 (d, J = 17.9 Hz, 1H), 3.50 (d, J = 17.9 Hz, 1H); 13C{1H} NMR
(100 MHz, CDCl3) δ 138.1, 136.3, 135.0, 131.8, 130.1, 129.8, 129.7, 128.8, 128.3, 128.2, 128.2,
128.1, 127.1, 123.0, 90.8, 86.2, 83.0, 73.9, 64.6, 36.6; HRMS (EI) m/z calcd for
C24H20ClNO[M]+ 373.1233, found 373.1234.
(2R,4R)-2-(2-bromopyridin-3-yl)-4-phenyl-3-(3-phenylprop-2-yn-1-yl)oxazolidine
(5zn)
The product 5zn (90.3 mg, 54% yield, 56/44 dr) was obtained following the general procedure
as a white solid; MP: 111–113 oC; 1H NMR (400 MHz, CDCl3) δ 8.46–8.40 (m, 1H), 8.29–8.20
(m, 1H), 7.56 (d, J = 7.8 Hz, 2H), 7.48–7.42 (m, 4H), 7.41–7.32 (m, 5H), 5.92 (s, 1H), 4.53–
4.44 (m, 1H), 4.41 (t, J = 7.4 Hz, 1H), 4.00 (t, J = 8.1 Hz, 1H), 3.59 (d, J = 17.8 Hz, 1H), 3.49
(d, J = 17.8 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 151.7, 150.6, 150.0, 144.1, 138.9,
138.7, 137.7, 135.7, 133.5, 131.8, 128.9, 128.4, 128.0, 123.3, 123.0, 122.8, 92.5, 90.7, 86.5,
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82.7, 74.0, 64.8, 36.9; HRMS (EI) m/z calcd for C23H19BrN2O[M]+ 418.0681, found 418.0682.
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(2R,4R)-2-(2-iodophenyl)-4-phenyl-3-(3-phenylprop-2-yn-1-yl)oxazolidine
(5zo)
The
product 5zo (78.1 mg, 42% yield, 81/19 dr) was obtained following the general procedure as a
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white solid; MP: 98–100 C; 1H NMR (400 MHz, CDCl3) δ 7.94–7.86 (m, 2H), 7.65–7.55 (m,
2H), 7.52–7.41 (m, 5H), 7.40–7.32 (m, 4H), 7.15–7.08 (m, 1H), 5.78 (s, 1H), 4.54–4.45 (m,
1H), 4.39 (t, J = 7.4 Hz, 1H), 4.05–3.96 (m, 1H), 3.58 (d, J = 17.9 Hz, 1H), 3.47 (d, J = 17.9 Hz,
1H); 13C{1H} NMR (100 MHz, CDCl3) δ 140.2, 139.7, 138.0, 131.8, 130.9, 129.9, 128.7, 128.5,
128.2, 128.2, 128.2, 128.0, 123.0, 99.7, 97.3, 90.7, 86.3, 83.0, 73.8, 64.4, 36.5; HRMS (EI) m/z
calcd for C24H20INO[M]+ 465.0590, found 465.0590.
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(2R,4R)-2-(2,6-dichlorophenyl)-4-phenyl-3-(3-phenylprop-2-yn-1-yl)oxazolidine (5zp) The
product 5zp (117.2 mg, 72% yield, >20/1 dr) was obtained following the general procedure as a
o
white solid; MP: 99–101 C; 1H NMR (400 MHz, CDCl3) δ 7.67–7.59 (m, 2H), 7.51–7.44 (m,
2H), 7.42–7.39 (m, 3H), 7.38–7.34 (m, 5H), 7.29–7.21 (m, 1H), 6.37 (s, 1H), 4.49–4.38 (m,
2H), 4.24–4.19 (m, 1H), 3.52 (d, J = 17.9 Hz, 1H), 3.41 (d, J = 17.9 Hz, 1H); 13C{1H} NMR
(100 MHz, CDCl3) δ 137.2, 136.8, 133.5, 132.3, 131.8, 130.2, 129.7, 129.6, 128.7, 128.3, 128.2,
128.2, 123.0, 91.1, 86.2, 82.9, 74.0, 65.1, 36.2; HRMS (EI) m/z calcd for C24H19Cl2NO[M]+
407.0844, found 407.0848.
(2R,4R)-4-phenyl-3-(3-phenylprop-2-yn-1-yl)-2-(2-(trifluoromethyl)phenyl)oxazolidine
(5zq) The product 5zq (74.9 mg, 46% yield, >20/1 dr) was obtained following the general
procedure as a white solid; MP: 104–106 oC; 1H NMR (400 MHz, CDCl3) δ 8.30 (d, J = 7.8 Hz,
1H), 7.77–7.69 (m, 2H), 7.62 (d, J = 7.1 Hz, 2H), 7.53 (t, J = 7.6 Hz, 1H), 7.49–7.43 (m, 4H),
7.43–7.33 (m, 4H), 5.94 (s, 1H), 4.55–4.46 (m, 1H), 4.41 (t, J = 7.5 Hz, 1H), 4.08–4.00 (m, 1H),
3.58 (d, J = 17.9 Hz, 1H), 3.43 (d, J = 17.9 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 138.1,
138.0, 132.3, 131.8, 130.0, 129.1, 128.8, 128.2, 128.2, 128.0, 125.5, 125.4, 122.9, 89.4, 89.3,
86.1, 82.4, 74.0, 64.3, 36.3; HRMS (EI) m/z calcd for C25H20F3NO[M]+ 407.1497, found
407.1499.
((2R,4R)-2-(5-chloro-2-nitrophenyl)-4-phenyl-3-(3-phenylprop-2-yn-1-yl)oxazoledine (5zr)
The product 5zr (88.6 mg, 50% yield, >20/1 dr) was obtained following the general procedure
as a light yellow oil; 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 2.4 Hz, 1H), 7.85 (d, J = 8.6 Hz,
1H), 7.56–7.51 (m, 2H), 7.51–7.37 (m, 6H), 7.36–7.30 (m, 3H), 6.10 (s, 1H), 4.52–4.42 (m,
1H), 4.37 (t, J = 7.4 Hz, 1H), 3.96–3.88 (m, 1H), 3.64 (d, J = 17.8 Hz, 1H), 3.56 (d, J = 17.8 Hz,
1H); 13C{1H} NMR (100 MHz, CDCl3) δ 148.7, 139.2, 137.3, 136.4, 131.9, 130.2, 129.8, 128.9,
128.4, 128.3, 127.9, 125.8, 122.6, 89.3, 86.6, 82.5, 73.7, 65.3, 37.9; HRMS (EI) m/z calcd for
C24H19ClN2O3[M]+ 418.1084, found 418.1089.
(R)-2-(benzyl(3-phenylprop-2-yn-1-yl)amino)-2-phenylethan-1-ol (5zt) The product 5zt
(72.2 mg, 53% yield, >20/1 dr) was obtained following the general procedure as a light yellow
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oil; 1H NMR (400 MHz, CDCl3) δ 7.53 – 7.29 (m, 15H), 4.19 – 4.07 (m, 2H), 4.01 – 3.90 (m,
2H), 3.69 (d, J = 17.5 Hz, 1H), 3.55 (d, J = 13.3 Hz, 1H), 3.45 (d, J = 17.5 Hz, 1H), 2.51 (s,
1H); 13C{1H} NMR (100 MHz, CDCl3) δ 138.7, 138.2, 131.8, 129.0, 128.9, 128.6, 128.5, 128.3,
128.1, 128.0, 127.3, 123.2, 85.7, 84.9, 66.6, 62.7, 54.4, 39.9.; HRMS (EI) m/z calcd for
C24H23NO[M]+ 341.1776, found 341.1779.
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ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI:
NMR spectra for compounds 5a−5zj, 5zm−5zr (PDF)
AUTHOR INFORMATION
Corresponding Authors
*E-mail: hdfeng@sues.edu.cn.
ORCID
Huangdi Feng: 0000-0002-5500-8283
Notes
The authors declare no competing financial interest.
ACKNOWLEDGEMENTS
The authors thank Prof. Dr Erik Van der Eycken at the University of Leuven (KU Leuven) for
revising the English. This work was supported by Shanghai University of Engineering Science
and the Innovation Research Projects (nhrc-2015-15, 201810856017, cs1704006). We are
grateful to the China Postdoctoral Science Foundation (2016M601681), and the Opening Project
of Shanghai Key Laboratory of Chemical Biology for financial support.
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(15) CCDC 1886402 contains the supplementary crystallographic data for compound 5a. The
data can be obtained free of charge from The Cambridge Crystallographic Data Centre.
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