Chemoselective P(NMe2)3-Mediated Reductive Epoxidation between Two Different Carbonyl Electrophiles: Synthesis of Highly Functionalized Unsymmetrical Epoxides

Article abstract of DOI:10.1021/acs.joc.8b00995

Herein, we report a chemoselective P(NMe₂)₃-mediated reductive epoxidation of α-dicarbonyl compounds such as isatins, α-keto esters, and α-diketones with aldehydes and ketones, leading to an efficient synthesis of a wide range of highly functionalized unsymmetrical epoxides in moderate to excellent yields and diastereoselectivities. The Kukhtin-Ramirez adduct, which is exclusively generated in situ from an α-dicarbonyl compound and P(NMe₂)₃, plays a key role in governing the chemoselectivity. It represents the first practical synthesis of unsymmetrical epoxides via direct reductive epoxidation of two different carbonyl electrophiles and also complements the existing methods of generating epoxides.

Full text of DOI:10.1021/acs.joc.8b00995

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Article
Chemoselective P(NMe2)3-Mediated Reductive Epoxidation
between Two Different Carbonyl Electrophiles: Synthesis
of Highly Functionalized Unsymmetrical Epoxides
Rong Zhou, Honghui Zhang, Jialin Liu, Rongfang Liu, Wen-Chao Gao, Yan Qiao, and Ruifeng Li
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00995 • Publication Date (Web): 05 Jun 2018
Downloaded from http://pubs.acs.org on June 5, 2018
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The Journal of Organic Chemistry
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Chemoselective P(NMe2)3-Mediated Reductive Epoxidation between Two Different
Carbonyl Electrophiles: Synthesis of Highly Functionalized Unsymmetrical
Epoxides
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Rong Zhou,*, † Honghui Zhang, † Jialin Liu,† Rongfang Liu,† Wen-Chao Gao,* ,† Yan Qiao,†† and
Ruifeng Li†
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† College of Chemistry and Chemical Engineering, Taiyuan University of Technology, Taiyuan, 030024,
P. R. China
†† The State Key Laboratory of Coal Conversion, Institute of Coal Chemistry, Chinese Academy of
Sciences, Taiyuan, 030001, P. R. China
Eꢀmail: zhourong@tyut.edu.cn; gaowenchao@tyut.edu.cn
TOC graphic
Abstract
Herein, we report a chemoselective P(NMe2)3ꢀmediated reductive epoxidation of αꢀdicarbonyl
compounds such as isatins, αꢀketo esters, and αꢀdiketones with aldehydes and ketones, leading to an
efficient synthesis of a wide range of highly functionalized unsymmetrical epoxides in moderate to
excellent yields and diastereoselectivities. The KukhtinꢀRamirez adduct, which is exclusively generated
in situ from αꢀdicarbonyl compound and P(NMe2)3, plays a key role in governing the chemoselectivity.
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It represents the first practical synthesis of unsymmetrical epoxides via direct reductive epoxidation of
two different carbonyl electrophiles and also complements the existing methods to epoxides.
Introduction
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Epoxides are highly important structural components in many naturally occurring and
pharmacologically active molecules, and also serve as versatile intermediates in organic synthesis.1
Intensive research efforts in the past several decades have led to the development of many efficient
strategies to this class of compounds.2ꢀ6 Among them, the alkene epoxidations such as Sharpless3 and
Shi4 epoxidations have been demonstrated to be powerful tools in both industrialꢀ and academicꢀscale
syntheses for olefinic substrates (Scheme 1, eq a). Furthermore, the cyclization of sulfur ylides5 or αꢀ
haloenolates6 with carbonyl compounds provides alternative valuable approaches to epoxides in an
oxidantꢀfree manner (Scheme 1, eq b and c). Despite the efficiency of the existing methods, there
remains significant room for the development of additional complementary epoxidation strategies,
especially aiming at synthesis of highly functionalized epoxides from readily available and bench stable
precursors under oxidantꢀfree conditions.
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Scheme 1. Different Epoxidation Methodologies
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The direct reductive epoxidation of two different carbonyl electrophiles such as aldehydes and ketones
represents a straightforward approach to epoxides from readily available starting material.7 However,
chemoselective epoxidation would be challenging due to the competing reactions between homoꢀ and
heteroꢀcoupling between the two carbonyls.7d To achieve a highly chemoselective epoxidation, a
reactive intermediate should be chemoselectively generated first from one carbonyl compound, and then
once generated it can directly couple with the other carbonyl molecule to deliver the epoxide product.
Keeping this in mind, we envisioned that a chemoselective reductive epoxidation of αꢀdicarbonyl
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compounds such as αꢀketo esters/amides, and αꢀdiketones with carbonyls including aldehydes and
ketones under the influence of trivalent phosphorus reagents would be feasible. It is well known that the
αꢀdicarbonyl compounds could readily undergo the KukhtinꢀRamirez addition with trivalent phosphorus
reagents to afford the reactive dipolar adducts.8 Our group and others have recently demonstrated in a
series of documents that the KukhtinꢀRamirez adducts could serve as a versatile C1 synthon in reactions
with both nucleophiles9 and electrophiles10,11 due to their dipolar structural properties. We therefore
proposed that the KukhtinꢀRamirez adduct would be selectively generated first from αꢀdicarbonyl
compound and trivalent phosphorus reagent even in the presence of carbonyls such as aldehydes or
ketones. This adduct would then proceed to trigger a dipolar epoxidation with the other carbonyl
molecule to afford the desired unsymmetrical epoxide product (Scheme 1, eq d). Herein we report a
chemoselective P(NMe2)3ꢀmediated reductive epoxidation of readily available αꢀdicarbonyl compounds
such as isatins, αꢀketo esters, and αꢀdiketones with aldehydes and ketones, leading to an efficient
synthesis of a wide range of highly functionalized unsymmetrical epoxides in moderate to excellent
yields and diastereoselectivities. It represents the first practical synthesis of unsymmetrical epoxides via
direct reductive epoxidation of two different carbonyl electrophiles and also complements the existing
methods to epoxides.7,12
Results and Discussion
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We commenced the proposed epoxidation by treating Nꢀmethyl isatin 1a with benzaldehyde 2a under
the predetermined conditions listed in Table 1. Delightfully, the expected spirooxindoleꢀepoxide 3aa
was exclusively afforded in 60% isolated yield and 88:12 diastereoselectivity with transꢀ3aa (the
functional groups with higher priority on the epoxide moiety such as the phenyl and the amide groups
are on the opposite side) being the major diastereomer, without formation of any homoꢀcoupling
byproducts (Table 1, entry 1). It therefore represents a highly chemoselective reductive epoxidation
between two different carbonyls and also provides a facile synthesis of multiꢀfunctionalized
unsymmetrical epoxides. The reaction conditions were subsequently surveyed to improve the reaction
efficiency. Among several common solvents such as CH2Cl2, CHCl3, toluene, THF, and acetonitrile
surveyed, CHCl3 was the optimal reaction medium, affording the product 3aa in 88% yield and 90:10
diastereoselectivity (entries 1ꢀ5). The influence of the trivalent phosphorus reagents was also
investigated. Replacement of P(NMe2)3 with P(OMe)3 resulted in decreased reactivity, whereas both
tributylphosphine and triphenylphosphine afforded no desired product (entries 6ꢀ8). Other substituents R
instead of methyl group on the nitrogen atom of the isatin 1 were examined as well. Both the yields and
diastereoselectivities decreased when either an allyl or a benzyl group was introduced to the nitrogen
atom (entries 9 and 10).
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Table 1. Screening of the Reaction Conditionsa
entry
solvent
CH2Cl2
CHCl3
PR'3
yield (%)b
3aa, 60
3aa, 88
3aa, 56
drc
isatin 1
1a
1
2
3
P(NMe2)3
P(NMe2)3
P(NMe2)3
88:12
90:10
75:25
1a
Toluene
1a
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4
THF
P(NMe2)3
P(NMe2)3
P(OMe)3
PBu3
70:30
89:11
80:20
ꢀ
1a
1a
1a
1a
1a
1b
1c
3aa, 20
3aa, 36
3aa, 44
3aa, 0
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CH3CN
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
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PPh3
ꢀ
3aa, 0
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P(NMe2)3
P(NMe2)3
62:38
52:48
3ba, 51
3ca, 65
10
a Reaction conditions: isatin 1 (0.2 mmol), benzaldehyde 2a (0.24 mmol), PR'3 (0.22 mmol), and 4Å
molecular sieves in solvent (2.0 mL), ꢀ78 C to r.t., 12 h. The combined yields of two isolated
diastereomers based on 1. c Determined by 1H NMR assay of the crude mixture and referring to the ratio
of trans-3 versus cisꢀ3
o
b
Employing the optimal reaction conditions listed in Table 1, entry 2, the generality of the
epoxidations was investigated (Table 2). The isatins bearing different R1 group on the phenyl ring of the
oxindole framework were first examined. Both electronꢀdonating and electronꢀwithdrawing R1 groups
were well tolerated, readily affording the corresponding spiroꢀepoxides 3 with representative aldehyde
2a in moderate to good yields and diastereoselectivities (entries 1ꢀ9). Furthermore, substituted aldehydes
with different electronic and steric properties were investigated with representative isatin 1a. Aromatic
aldehydes bearing either electronꢀdonating or electronꢀwithdrawing aryl groups proceeded smoothly in
the epoxidation (entries 10ꢀ15). Notably, the stericꢀdemanding substrates such as aldehydes 2e and 2f
afforded the corresponding epoxides in higher diastereoselectivities without any loss in reactivity
(entries 13 and 14). Heteroaromatic aldehydes such as furylaldehyde, thienylaldehyde, and
pyridylaldehyde were readily accommodated as well (entries 16ꢀ20). An α,βꢀunsaturated aldehyde such
as (E)ꢀcinnamylaldehyde was also effective, affording the desired product in a moderate yield with a
good diastereoselectivity (entry 21). Aliphatic aldehydes such as propylaldehyde were applicable to this
protocol, giving the epoxide 3an in moderate yield and diastereoselectivity (entry 22).
Phenylpropioaldehyde 2o was also a feasible substrate, readily delivering its corresponding product 3ao
in good yield and moderate diastereoselectivity (entry 23).
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Gratifyingly, ketones such as ynones 4 were viable substrates in this epoxidation reaction, which
therefore afforded the desired epoxides bearing adjacent quaternary carbon stereocenters (Scheme 2).
However, efforts attempting to extend this methodology to other common ketones such as acetophenone
and 2ꢀbutanone gave negative results, and no reactions occurred. Furthermore, activated ketones such as
trifluoroacetophenone also failed to give the desired epoxide product. Fortunately, majority of the two
diastereomeric products listed in Table 2 and Scheme 2 were separable using column chromatography
isolations.
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Table 2. P(NMe2)3-Mediated Reductive Epoxidation of Isatins 1 and Aldehydes 2a
yield (%)b
3aa, 88
3da, 78
3ea, 58
3fa, 61
3ga, 67
3ha, 53
3ia, 56
3ja, 63
3ka, 59
3ab, 84
3ac, 85
3ad, 60
3ae, 82
3af, 78
3ag, 67
drc
R1 in 1
H (1a)
5ꢀMeO (1d)
5ꢀMe (1e)
4ꢀBr (1f)
5ꢀBr (1g)
6ꢀBr (1h)
4ꢀCl (1i)
5ꢀCl (1j)
5ꢀNO2 (1k)
1a
R2 in 2
entry
1
time (h)
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90:10
74:26
73:27
75:25
80:20
71:29
66:34
69:31
80:20
62:38
51:49
64:36
90:10
96:4
Ph (2a)
2
2a
3
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2a
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2a
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2a
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4ꢀMeOC6H4 (2b)
4ꢀMeC6H4 (2c)
4ꢀClC6H4 (2d)
2ꢀClC6H4 (2e)
2,4ꢀCl2C6H4 (2f)
4ꢀBrC6H4 (2g)
8
1a
12
7
1a
1a
7
1a
12
78:22
1a
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The Journal of Organic Chemistry
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86:14
75:25
60:40
95:5
1a
1a
1a
1a
1a
1a
1a
1a
2ꢀFuryl (2h)
3ah, 45
3ai, 53
3aj, 65
3ak, 98
3al, 43
3am, 48
3an, 67
3ao, 89
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2ꢀThienyl (2i)
2ꢀPyridyl (2j)
3ꢀPyridyl (2k)
4ꢀPyridyl (2l)
Eꢀcinnamyl (2m)
Et (2n)
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94:6
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90:10
74:26
60:40
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Phenylethynyl (2o)
a Reaction conditions: isatin 1 (0.2 mmol), aldehyde 2 (0.24 mmol), P(NMe2)3 (0.22 mmol), and 4Å
molecular sieves in CHCl3 (2.0 mL), ꢀ78 C to r.t. The combined yields of two isolated diastereomers
based on 1. Determined by H NMR assay of the crude mixture and referring to the ratio of trans-3
versus cisꢀ3.
o
b
c
1
Scheme 2. P(NMe2)3-Mediated Reductive Epoxidation of Isatin 1a With Ynones 4
The scope of this epoxidation was further extended to other αꢀdicarbonyl compounds such as αꢀketo
esters and αꢀdiketones. Under the standard reaction conditions (Table 3), arylꢀsubstituted αꢀketo esters
6a-c bearing either electronꢀdonating or electronꢀwithdrawing aryl groups, and αꢀdiketones such as
benzil 6d and acenaphthoquinone 6e were all capable to afford their corresponding epoxides 7 with
representative aldehydes 2 in good to excellent yields with moderate to excellent diastereoselectivities
(entries 1ꢀ8).
Table 3. P(NMe2)3-Mediated Reductive Epoxidation of α-Keto Esters and α-Diketones 6 with
Aldehydes 2a
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entry
time (h)
yield (%)b
7aa, 71
7ac, 67
7ag, 72
7ak, 93
7bk, 92
7ck, 94
7dk, 88
7ek, 99
drc
R3, R4 in 6
R2 in 2
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7
80:20
71:29
90:10
82:18
71:29
68:32
51:49
98:2
Ph, OEt (6a)
Ph (2a)
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6a
4ꢀMeC6H4 (2c)
6a
4ꢀBrC6H4 (2g)
6a
3ꢀPyridyl (2k)
7
4ꢀMeC6H4, OEt (6b)
4ꢀBrC6H4, OEt (6c)
Ph, Ph (6d)
2k
2k
2k
2k
7
8
8
Acenaphthoquinone (6e)
a Reaction conditions: αꢀdicarbonyl compound 6 (0.2 mmol), aldehyde 2 (0.24 mmol), P(NMe2)3 (0.22
mmol), and 4Å molecular sieves in CHCl3 (2.0 mL), ꢀ78 oC to r.t. b The combined yields of two isolated
diastereomers based on 6. c Determined by 1H NMR assay of the crude mixture and referring to the ratio
of trans-7 versus cisꢀ7.
1
13
The structures of epoxides 3, 5, and 7 were identified by H, C NMR and HRMSꢀESI/MALDI
measurements. Representative compounds were further confirmed by NOESY (7ag and 7ck) and Xꢀray
crystallographic analyses (for crystal structure of 3af, see Supporting Information).
A proposed mechanism to account for the formation of epoxides is exemplified in Scheme 3 based on
the experimental results and the closely related reports from our group and others.10,11 Presumably, the
epoxidation is initiated with the in situ generation of the KukhtinꢀRamirez adduct I or II from αꢀ
dicarbonyl compound such as isatin 1a and hexamethylphosphorous triamide. Through its dipolar
structure II, the KukhtinꢀRamirez adduct then triggers a nucleophilic addition in a manner similar to
Aldol reaction to aldehyde such as 2a via two different modes, affording intermediate IIIa and IIIb,
respectively. Due to the possible π−π stacking interaction between the phenyl groups and less steric
hindrance between the small hydrogen and the bulky phosphonium moiety, the intermediate IIIa is
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predominantly generated, which then undergoes an intramolecular substitution similar to SN2 to finish
the ring closure, affording the major product transꢀ3aa and the phosphoric triamide byꢀproduct.10e,11b,c
On the other hand, ring closure of intermediate IIIb through the similar process provides the minor
product cisꢀ3aa. The chemoselectivity of this epoxidation was attributed by the exclusive Kukhtinꢀ
Ramirez addition of hexamethylphosphorous triamide to αꢀdicarbonyl compound such as 1a among the
two carbonyl electrophiles such as 1a and 2a.
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Scheme 3. A Proposed Mechanism for the Formation of Epoxide
R'
R'
R'
PR'3
O
O
O
O
P
PR'3
O
O
R' = NMe2
N
N
N
Me
1a
Me
I
II
Me
Ph
O
N
PR'3
R'3P=O
H
O
trans-3aa
major
O
ring
closure
IIIa
O
2a
Ph
Me
nucleophilic
addn.
H
O
R'3P=O
PR'3
Ph
cis-3aa
minor
O
ring
closure
N
Me
O
IIIb
Conclusion
In summary, a chemoselective P(NMe2)3ꢀmediated reductive epoxidation of αꢀdicarbonyl compounds
such as isatins, αꢀketo esters, and αꢀdiketones with aldehydes and ketones has been developed, which
provides an efficient synthesis of highly functionalized unsymmetrical epoxides in moderate to excellent
yields and diastereoselectivities. The chemoselectivity of this epoxidation originates from the exclusive
KukhtinꢀRamirez addition of αꢀdicarbonyl compounds with trivalent phosphorus reagents. It represents
the first practical synthesis of unsymmetrical epoxides via direct reductive epoxidation of two different
carbonyl electrophiles. The reaction benefits from its broad substrates scope, mild and oxidantꢀfree
conditions, readily available and bench stable starting material, and also complements the existing
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approaches to epoxides. Future efforts in our laboratory will be directed toward further expanding this
methodology to other more challenging substrates, and the relevant results will be reported in due course.
Experimental Section
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Unless otherwise noted, all reactions were carried out in nitrogen atmosphere under anhydrous
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1
13
conditions. All solvents were purified according to standard procedures. H and C NMR spectra were
recorded in CDCl3 with tetramethylsilane (TMS) as the internal standard. HRMS spectra were acquired
in the ESI mode with the mass analyzer of TOF used. Column chromatography was performed on silica
gel (200 ∼ 300 mesh) using a mixture of petroleum ether/ethyl acetate as eluant. Isatins 1,13 and arylꢀ
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substituted αꢀketo esters 614 were prepared according to the reported procedures.
General Procedure for the Chemoselective Epoxidation of α-Dicarbonyl Compounds 1 or 6 with
o
Aldehyde 2 or Ynone 4: Under a N2 atmosphere and at ꢀ78 C, P(NMe2)3 (40 ꢀL, 0.22 mmol) in
chloroform (0.5 mL) was added dropwise to a mixture of αꢀdicarbonyl compound 1 or 5 (0.2 mmol),
aldehyde 2 or ynone 4 (0.24 mmol), and 4Å molecular (150 mg) in chloroform (1.5 mL) by means of
syringe. The resulting reaction mixture was then slowly warmed up to room temperature and stirred at rt
for a time indicated in Table 2, 3 or Scheme 2. The solvent was removed on a rotary evaporator under
reduced pressure and the residue was subjected to column chromatographic isolation on silica gel by
gradient elution using petroleum ether /ethyl acetate (20:1 ∼ 3:1) to give the epoxide 3, 5 or 7.
1-Methyl-3'-phenylspiro[indoline-3,2'-oxiran]-2-one (3aa). Table 1, entry 2; prepared according to
the typical procedure, NꢀMethyl isatin 1a (32 mg, 0.2 mmol) and aldehyde 2a (25 mg, 0.24 mmol) were
employed to give 3aa as two separable diastereomers (combined yields 88%, dr 90:10). The major
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isomer transꢀ3aa (40 mg, 79%), a white solid; mp: 158ꢀ159 C; H NMR (400 MHz, CDCl3) δ 7.48 –
7.34 (m, 5H), 7.27 (dt, J = 7.8, 1.6 Hz, 1H), 6.87 (d, J = 7.8 Hz, 1H), 6.76 (t, J = 7.6 Hz, 1H), 6.47 (dd,
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J = 7.5, 0.6 Hz, 1H), 4.83 (s, 1H), 3.29 (s, 3H); C NMR (101 MHz, CDCl3) δ 171.7, 145.2, 133.1,
130.1, 128.6, 128.4, 126.6, 123.6, 122.4, 120.8, 108.7, 65.0, 61.5, 26.6. the minor isomer cisꢀ3aa (4 mg,
9%), a white solid; 1H NMR (400 MHz, CDCl3) δ 7.63 – 7.57 (m, 2H), 7.43 – 7.34 (m, 4H), 7.25 – 7.21
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(m, 1H), 7.16 – 7.09 (m, 1H), 6.89 (d, J = 7.8 Hz, 1H), 4.67 (s, 1H), 3.15 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 169.8, 144.6, 131.7, 130.2, 128.8, 127.7, 127.4, 123.6, 122.6, 121.6, 108.6, 67.5, 61.9, 26.5;
HRMS−ESI ([M + H]+) Calcd for C16H14NO2 252.1019, found 252.1017.
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Allyl-3'-phenylspiro[indoline-3,2'-oxiran]-2-one (3ba). Table 1, entry 9; prepared according to the
typical procedure, Nꢀallylic isatin 1b (37 mg, 0.2 mmol) and aldehyde 2a (25 mg, 0.24 mmol) were
employed to give 3ba as two separable diastereomers (combined yields 51%, dr 62:38). The major
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isomer transꢀ3ba (18 mg, 33%), a yellow colloid; H NMR (400 MHz, CDCl3) δ 7.50 – 7.33 (m, 5H),
7.23 (dd, J = 7.8, 1.2 Hz, 1H), 6.89 (t, J = 9.8 Hz, 1H), 6.76 (td, J = 7.6, 0.7 Hz, 1H), 6.48 (dd, J = 7.5,
0.6 Hz, 1H), 5.88 (ddt, J = 17.1, 10.5, 5.4 Hz, 1H), 5.36 – 5.22 (m, 2H), 4.85 (s, 1H), 4.54 – 4.35 (m,
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2H); C NMR (101 MHz, CDCl3) δ 171.4, 144.4, 133.1, 131.1, 130.0, 128.7, 128.4, 126.7, 123.7,
122.4, 120.9, 118.1, 109.5, 65.1, 61.5, 42.9. The minor isomer cisꢀ3ba (10 mg, 18%), a pale yellow
solid; mp: 156ꢀ158 oC; 1H NMR (400 MHz, CDCl3) δ 7.60 (t, J = 6.8 Hz, 2H), 7.44 – 7.30 (m, 4H), 7.23
(d, J = 11.2 Hz, 1H), 7.12 (t, J = 7.5 Hz, 1H), 6.90 (d, J = 7.8 Hz, 1H), 5.89 – 5.70 (m, 1H), 5.28 – 5.16
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(m, 2H), 4.69 (s, 1H), 4.27 (d, J = 5.4 Hz, 2H); C NMR (101 MHz, CDCl3) δ 169.6, 143.8, 131.7,
131.2, 130.1, 128.8, 127.7, 127.4, 123.6, 122.6, 121.7, 118.0, 109.5, 67.6, 61.8, 42.7. HRMS−ESI ([M +
H]+) Calcd for C18H16NO2 278.1176, found 278.1180.
Benzyl-3'-phenylspiro[indoline-3,2'-oxiran]-2-one (3ca). Table 1, entry 10; prepared according to the
typical procedure, Nꢀbenzylic isatin 1c (47 mg, 0.2 mmol) and aldehyde 2a (25 mg, 0.24 mmol) were
employed to give 3ca as two separable diastereomers (combined yields 65%, dr 52:48). The major
isomer transꢀ3ca (22 mg, 34%), a white solid; mp: 140ꢀ142 oC; 1H NMR (400 MHz, CDCl3) δ 7.48 (dd,
J = 7.7, 1.1 Hz, 2H), 7.45 – 7.36 (m, 4H), 7.35 – 7.24 (m, 4H), 7.15 (td, J = 7.8, 1.1 Hz, 1H), 6.79 – 6.68
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(m, 2H), 6.47 (d, J = 7.4 Hz, 1H), 5.06 – 4.93 (m, 2H), 4.90 (s, 1H); C NMR (101 MHz, CDCl3) δ
171.8, 144.4, 135.3, 133.1, 130.1, 128.9, 128.7, 128.4, 127.8, 127.4, 126.7, 123.7, 122.5, 120.9, 109.6,
65.2, 61.5, 44.3. The minor isomer cisꢀ3ca (20 mg, 31%), a pale yellow solid; mp: 151ꢀ153 oC; 1H NMR
(400 MHz, CDCl3)δ 7.63 (d, J = 7.7 Hz, 2H), 7.45 – 7.34 (m, 3H), 7.32 – 7.23 (m, 7H), 7.08 (t, J = 7.5
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Hz, 1H), 6.79 (d, J = 7.8 Hz, 1H), 4.92 (d, J = 15.6 Hz, 1H), 4.75 (d, J = 15.6 Hz, 1H), 4.71 (s, 1H); C
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NMR (101 MHz, CDCl3) δ 170.0, 143.7, 135.4, 131.7, 130.1, 128.9, 128.8, 127.8, 127.7, 127.5, 127.4,
122.7, 121.7, 109.6, 67.7, 61.9, 44.1. HRMS−ESI ([M + H]+) Calcd for C22H18NO2 328.1332, found
328.1342.
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5-Methoxy-1-methyl-3'-phenylspiro[indoline-3,2'-oxiran]-2-one (3da). Table 2, entry 2; prepared
according to the typical procedure, isatin 1d (38 mg,0.2 mmol) and aldehyde 2a (25 mg, 0.24 mmol)
were employed to give 3da as two separable diastereomers (combined yields 78%, dr 74:26). The major
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isomer transꢀ3da (34 mg, 60%), a white solid; mp: 155ꢀ157 C; H NMR (400 MHz, CDCl3) δ 7.63 –
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7.30 (m, 5H), 6.89 – 6.64 (m, 2H), 6.04 (d, J = 2.3 Hz, 1H), 4.83 (s, 1H), 3.47 (s, 3H), 3.27 (s, 3H); C
NMR (101 MHz, CDCl3) δ 171.3, 155.4, 138.5, 133.2, 128.6, 128.4, 126.7, 122.0, 115.1, 110.3, 109.0,
64.9, 61.6, 55.4, 26.7. The minor isomer cisꢀ3da (10 mg, 18%), a white solid; mp: 167ꢀ169 oC; 1H NMR
(400 MHz, CDCl3) δ 7.53 (dt, J = 3.7, 2.1 Hz, 2H), 7.39 – 7.24 (m, 3H), 6.84 (dd, J = 8.5, 2.6 Hz, 1H),
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6.77 (d, J = 2.5 Hz, 1H), 6.72 (d, J = 8.5 Hz, 1H), 4.56 (s, 1H), 3.76 (s, 3H), 3.05 (s, 3H); C NMR
(101 MHz, CDCl3) δ 169.6, 156.1, 138.0, 131.7, 128.8, 127.7, 127.4, 124.8, 114.9, 109.1, 108.6, 67.6,
62.1, 55.9, 26.6. HRMS−ESI ([M + H]+) Calcd for C17H16NO3 282.1125, found 282.1137.
1,5-Dimethyl-3'-phenylspiro[indoline-3,2'-oxiran]-2-one (3ea). Table 2, entry 3; prepared according
to the typical procedure, isatin 1e (35mg, 0.2 mmol) and aldehyde 2a (25 mg, 0.24 mmol) were
employed to give 3ea as two separable diastereomers (combined yields 58%, dr 73:27). The major
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isomer transꢀ3ea (24 mg, 46%), a white solid; mp: 172ꢀ173 C; H NMR (400 MHz, CDCl3) δ 7.51 –
7.33 (m, 5H), 7.06 (dd, J = 7.9, 0.8 Hz, 1H), 6.75 (d, J = 7.9 Hz, 1H), 6.40 – 6.13 (m, 1H), 4.81 (s, 1H),
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3.27 (s, 3H), 2.06 (s, 3H); C NMR (101 MHz, CDCl3) δ 171.6, 142.8, 133.2, 131.9, 130.3, 128.6,
128.3, 126.7, 124.5, 120.8, 108.3, 64.9, 61.6, 26.6, 20.9. The minor isomer cisꢀ3ea (7 mg, 12%), a white
solid; mp: 179ꢀ181 oC; 1H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 7.1 Hz, 2H), 7.37 (dt, J = 8.5, 6.9 Hz,
3H), 7.19 (dd, J = 7.9, 0.6 Hz, 1H), 7.06 (s, 1H), 6.78 (d, J = 7.9 Hz, 1H), 4.64 (s, 1H), 3.13 (s, 3H),
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2.38 (s, 3H); C NMR (101 MHz, CDCl3) δ 169.8, 142.2, 132.3, 131.8, 130.4, 128.77, 127.7, 127.4,
123.6, 122.3, 108.3, 67.4, 62.0, 26.5, 21.0. HRMS−ESI ([M + H]+) Calcd for C17H16NO2 266.1176,
found 266.1187.
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4-Bromo-1-methyl-3'-phenylspiro[indoline-3,2'-oxiran]-2-one (3fa). Table 2, entry 4; prepared
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according to the typical procedure, isatin 1f (48 mg, 0.2 mmol) and aldehyde 2a (25 mg, 0.24 mmol)
were employed to give 3fa as two separable diastereomers (combined yields 61%, dr 75:25). The major
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isomer transꢀ3fa (30 mg, 46%), a white solid; mp: 165ꢀ167 C; H NMR (400 MHz, CDCl3) δ 7.39 –
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7.25 (m, 5H), 7.16 (t, J = 8.0 Hz, 1H), 7.02 (d, J = 8.2 Hz, 1H), 6.88 (d, J = 7.8 Hz, 1H), 4.74 (s, 1H),
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3.32 (s, 3H); C NMR (101 MHz, CDCl3) δ 171.9, 146.9, 130.9, 128.7, 128.3, 128.2, 127.8, 119.7,
o
119.6, 107.6, 66.4, 62.4, 26.9. The minor isomer cisꢀ3fa (10mg, 15%), a white solid; mp: 175ꢀ177 C;
1H NMR (400 MHz, CDCl3) δ 7.60 (dd, J = 7.9, 1.2 Hz, 2H), 7.44 – 7.31 (m, 3H), 7.24 – 7.18 (m, 2H),
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6.93 – 6.78 (m, 1H), 5.49 (s, 1H), 3.12 (s, 3H); C NMR (101 MHz, CDCl3) δ 169.1, 146.6, 131.3,
131.1, 128.7, 127.6, 127.6, 127.2, 120.9, 117.7, 107.7, 62.6, 62.1, 26.6. HRMS−ESI ([M + H]+) Calcd
for C16H13BrNO2 330.0124, found 330.0135.
5-Bromo-1-methyl-3'-phenylspiro[indoline-3,2'-oxiran]-2-one (3ga). Table 2, entry 5; prepared
according to the typical procedure, isatin 1g (48 mg, 0.2 mmol) and aldehyde 2a (25 mg, 0.24 mmol)
were employed to give 3ga as two separable diastereomers (combined yields 67%, dr 80:20). The major
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isomer transꢀ3ga (36 mg, 55%), a white solid; mp: 177ꢀ179 C; H NMR (400 MHz, CDCl3) δ 7.46 –
7.39 (m, 5H), 7.38 (d, J = 2.0 Hz, 1H), 6.74 (d, J = 8.3 Hz, 1H), 6.55 (d, J = 2.0 Hz, 1H), 4.83 (s, 1H),
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3.28 (s, 3H); C NMR (101 MHz, CDCl3) δ 171.1, 144.2, 132.9, 132.6, 129.0, 128.6, 126.7, 126.6,
123.0, 115.1, 109.9, 65.3, 61.2, 26.7. The minor isomer cisꢀ3ga (8 mg, 12%), a white solid; mp: 168ꢀ
170 oC; 1H NMR (400 MHz, CDCl3) δ 7.51 (dd, J = 7.7, 1.6 Hz, 2H), 7.35 – 7.26 (m, 3H), 7.19 (dd, J =
7.9, 1.6 Hz, 1H), 7.01 (d, J = 7.9 Hz, 1H), 6.97 (d, J = 1.6 Hz, 1H), 4.58 (s, 1H), 3.05 (s, 3H); 13C NMR
(101 MHz, CDCl3) δ 169.6, 145.7, 131.3, 128.9, 127.7, 127.4, 125.4, 123.9, 122.8, 122.5, 112.2, 67.5,
61.6, 26.6. HRMS−ESI ([M + H]+) Calcd for C16H13BrNO2 330.0124, found 330.0131.
6-Bromo-1-methyl-3'-phenylspiro[indoline-3,2'-oxiran]ꢀ2-one (3ha). Table 2, entry 6; prepared
according to the typical procedure, isatin 1h (48 mg, 0.2 mmol) and aldehyde 2a (25 mg, 0.24 mmol)
were employed to give 3ha as two separable diastereomers (combined yields 53%, dr 71:29). The major
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isomer transꢀ3ha (26 mg, 39%), a pale yellow solid; mp: 163ꢀ165 C; H NMR (400 MHz, CDCl3) δ
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7.59 (dd, J = 7.9, 1.5 Hz, 2H), 7.43 – 7.32 (m, 3H), 7.28 – 7.26 (m, 1H), 7.09 (d, J = 7.9 Hz, 1H), 7.05
(d, J = 1.6 Hz, 1H), 4.65 (s, 1H), 3.13 (s, 3H); 13C NMR (101 MHz, CDCl3)δ 169.6, 145.8, 131.3, 128.9,
127.8, 127.4, 125.4, 123.9, 122.8, 122.5, 112.2, 67.6, 61.6, 26.6. The minor isomer cisꢀ3ha (9 mg,
14%), a pale yellow solid; mp: 168ꢀ170 oC;1H NMR (400 MHz, CDCl3) δ 7.50 – 7.32 (m, 5H), 7.02 (d,
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J = 1.5 Hz, 1H), 6.90 (dd, J = 8.0, 1.5 Hz, 1H), 6.29 (d, J = 8.0 Hz, 1H), 4.82 (s, 1H), 3.28 (s, 3H); C
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NMR (101 MHz, CDCl3) δ 171.5, 146.4, 132.9, 128.9, 128.5, 126.6, 125.3, 124.7, 124.2, 119.9, 112.2,
65.1, 61.3, 26.8. HRMS−ESI ([M + H]+) Calcd for C16H13BrNO2 330.0124, found 330.0130.
4-Chloro-1-methyl-3'-phenylspiro[indoline-3,2'-oxiran]-2-one (3ia). Table 2, entry 7; prepared
according to the typical procedure, isatin 1i (39mg, 0.2 mmol) and aldehyde 2a (25 mg, 0.24 mmol)
were employed to give 3ia as two separable diastereomers (combined yields 56%, dr 66:34). The major
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isomer transꢀ3ia (21 mg, 37%), a white solid; mp: 165ꢀ167 C; H NMR (400 MHz, CDCl3) δ 7.36 –
7.29 (m, 4H), 7.24 (dd, J = 13.9, 5.9 Hz, 2H), 6.82 (dd, J = 8.0, 4.5 Hz, 2H), 4.75 (s, 1H), 3.32 (s, 3H);
13C NMR (101 MHz, CDCl3) δ 171.8, 146.9, 134.0, 131.9, 130.9, 128.6, 128.2, 127.5, 124.9, 117.7,
o
107.1, 66.3, 62.4, 26.9. The minor isomer cisꢀ3ia (11 mg, 19%), a pale yellow solid; mp: 173ꢀ175 C;
1H NMR (400 MHz, CDCl3) δ 7.69 – 7.52 (m, 2H), 7.46 – 7.27 (m, 4H), 7.04 (dd, J = 8.3, 0.7 Hz, 1H),
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6.79 (dd, J = 7.8, 0.6 Hz, 1H), 5.43 (s, 1H), 3.13 (s, 3H); C NMR (101 MHz, CDCl3) δ 169.1, 146.4,
131.3, 131.0, 130.3, 128.7, 127.6, 127.6, 124.1, 119.3, 107.1, 62.4, 62.3, 26.7. HRMS−ESI ([M + H]+)
Calcd for C16H13ClNO2 286.0629, found 286.0639.
5-Chloro-1-methyl-3'-phenylspiro[indoline-3,2'-oxiran]-2-one (3ja). Table 2; entry 8; prepared
according to the typical procedure, isatin 1j (39 mg, 0.2 mmol) and aldehyde 2a (25 mg, 0.24 mmol)
were employed to give 3ja as two separable diastereomers (combined yields 63%, dr 69:31). The major
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isomer transꢀ3ja (25 mg, 44%), a white solid; mp: 188ꢀ189 C; H NMR (400 MHz, CDCl3) δ 7.51 –
7.34 (m, 5H), 7.24 (dd, J = 8.3, 2.1 Hz, 1H), 6.78 (d, J = 8.3 Hz, 1H), 6.42 (d, J = 2.1 Hz, 1H), 4.83 (s,
1H), 3.28 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 171.2, 143.7, 132.6, 129.9, 129.0, 128.6, 127.9, 126.5,
124.0, 122.6, 109.5, 65.2, 61.2, 26.7. The minor isomer cisꢀ3ja (11 mg, 19%), a white solid; mp: 180ꢀ
o
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182 C; H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 7.3 Hz, 2H), 7.49 – 7.31 (m, 4H), 7.21 (d, J = 1.3
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Hz, 1H), 6.82 (d, J = 8.3 Hz, 1H), 4.65 (s, 1H), 3.14 (d, J = 0.7 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ
169.4, 143.0, 131.2, 130.0, 129.0, 128.2, 127.8, 127.4, 125.3, 122.1, 109.5, 67.7, 61.6, 26.6. HRMS−ESI
([M + H]+) Calcd for C16H13ClNO2 286.0629, found 286.0636.
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1-Methyl-5-nitro-3'-phenylspiro[indoline-3,2'-oxiran]-2-one (3ka). Table 2, entry 9; prepared
according to the typical procedure, isatin 1k (41 mg, 0.2 mmol) and aldehyde 2a (25 mg, 0.24 mmol)
were employed to give 3ka as two separable diastereomers (combined yields 64%, dr 80:20). The major
isomer transꢀ3ka (28 mg, 47%), a white solid; mp: 180ꢀ181 oC; 1H NMR (400 MHz, CDCl3) δ 8.37 (dd,
J = 8.6, 2.3 Hz, 1H), 8.14 (d, J = 2.2 Hz, 1H), 7.65 – 7.48 (m, 2H), 7.46 – 7.37 (m, 3H), 6.99 (d, J = 8.6
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Hz, 1H), 4.79 (s, 1H), 3.23 (s, 3H); C NMR (101 MHz, CDCl3) δ 169.8, 149.7, 143.5, 130.5, 129.3,
127.9, 127.5, 127.0, 124.5, 117.7, 108.3, 68.0, 61.2, 27.0. The minor isomer cisꢀ3ka (10 mg, 17%), a
white solid; mp: 189ꢀ190 oC; 1H NMR (400 MHz, CDCl3) δ 8.37 (dd, J = 8.6, 2.3 Hz, 1H), 8.13 (d, J =
2.2 Hz, 1H), 7.60 (dd, J = 7.6, 1.8 Hz, 2H), 7.46 – 7.37 (m, 3H), 6.99 (d, J = 8.6 Hz, 1H), 4.79 (s, 1H),
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3.23 (s, 3H); C NMR (101 MHz, CDCl3) δ 169.8, 149.7, 143.5, 130.5, 129.3, 127.9, 127.5, 127.0,
124.5, 117.6, 108.3, 100.0, 68.0, 61.2, 27.0. HRMS−ESI ([M + H]+) Calcd for C16H13N2O4 297.0870,
found 297.0879.
3'-(4-Methoxyphenyl)-1-methylspiro[indoline-3,2'-oxiran]-2-one (3ab). Table 2, entry 10; prepared
according to the typical procedure, isatin 1a (32 mg, 0.2 mmol) and aldehyde 2b (33 mg, 0.24 mmol)
were employed to give 3ab as two separable diastereomers (combined yields 84%, dr 62:38). The major
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isomer transꢀ3ab (29 mg, 52%), a white solid; mp: 148ꢀ150 C; 1H NMR (400 MHz, CDCl3) δ 7.55 (d,
J = 8.8 Hz, 2H), 7.38 (td, J = 7.7, 1.3 Hz, 1H), 7.22 (dd, J = 7.4, 0.8 Hz, 1H), 7.12 (td, J = 7.6, 0.8 Hz,
1H), 6.94 – 6.87 (m, 3H), 4.62 (s, 1H), 3.81 (s, 3H), 3.15 (s, 3H);13C NMR (101 MHz, CDCl3) δ 170.1,
159.9, 144.4, 130.0, 128.8, 123.7, 123.5, 122.5, 121.4, 113.1, 108.5, 67.6, 62.0, 55.2, 26.4. The minor
isomer cisꢀ3ab (18 mg, 32%), a white solid; mp: 164ꢀ166 oC; 1H NMR (400 MHz, CDCl3) δ 7.57 – 7.50
(m, 2H), 7.38 (td, J = 7.8, 1.3 Hz, 1H), 7.22 (dd, J = 7.4, 0.7 Hz, 1H), 7.11 (td, J = 7.6, 0.8 Hz, 1H), 6.99
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– 6.85 (m, 3H), 4.61 (s, 1H), 3.81 (s, 3H), 3.15 (s, 3H); C NMR (101 MHz, CDCl3) δ 170.1, 159.9,
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144.4, 130.0, 128.8, 123.7, 123.6, 122.5, 121.4, 113.1, 108.5, 67.6, 62.0, 55.2, 26.4. HRMS−ESI ([M +
H]+) Calcd for C17H16NO3 282.1125, found 282.1125.
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1-Methyl-3'-(p-tolyl)spiro[indoline-3,2'-oxiran]-2-one (3ac). Table 2, entry 11; prepared according to
the typical procedure, isatin 1a (32 mg, 0.2 mmol) and aldehyde 2c (29 mg, 0.24 mmol) were employed
to give 3ac as two separable diastereomers (combined yields 85%, dr 51:49). The major isomer transꢀ
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3ac (22 mg, 43%), a white solid; mp: 159ꢀ160 C; H NMR (400 MHz, CDCl3) δ 7.33 (d, J = 8.0 Hz,
2H), 7.27 (td, J = 7.8, 1.3 Hz, 1H), 7.21 (d, J = 7.9 Hz, 2H), 6.86 (d, J = 7.8 Hz, 1H), 6.78 (td, J = 7.6,
0.9 Hz, 1H), 6.51 (dd, J = 7.5, 0.7 Hz, 1H), 4.79 (s, 1H), 3.29 (s, 3H), 2.38 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 171.8, 145.1, 138.5, 130.1, 130.0, 129.1, 126.6, 123.7, 122.4, 121.0, 108.5, 65.1, 61.6, 26.6,
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21.29. The minor isomer cisꢀ3ac (21 mg, 42%), a white solid; mp: 167ꢀ168 C; H NMR (400 MHz,
CDCl3) δ 7.49 (d, J = 8.1 Hz, 2H), 7.38 (ddd, J = 7.7, 6.1, 1.3 Hz, 1H), 7.21 (dd, J = 9.4, 4.4 Hz, 3H),
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7.13 – 7.08 (m, 1H), 6.89 (d, J = 7.8 Hz, 1H), 4.64 (s, 1H), 3.14 (s, 3H), 2.35 (s, 3H); C NMR (101
MHz, CDCl3) δ 169.9, 144.5, 138.5, 130.0, 128.6, 128.4, 127.3, 123.7, 122.5, 121.5, 108.5, 67.6, 61.9,
26.4, 21.35. HRMS−ESI ([M + H]+) Calcd for C17H16NO2 266.1176, found 266.1188.
3'-(4-Chlorophenyl)-1-methylspiro[indoline-3,2'-oxiran]-2-one (3ad). Table 2, entry 12; prepared
according to the typical procedure, isatin 1a (32 mg, 0.2 mmol) and aldehyde 2d (34 mg, 0.24 mmol)
were employed to give 3ad as two separable diastereomers (combined yields 60%, dr 64:36). The major
isomer transꢀ3ad (21 mg, 38%), a white solid; mp: 162ꢀ164 C; 1H NMR (400 MHz, CDCl3) δ 7.40 (d,
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J = 9.3 Hz, 4H), 7.29 (td, J = 7.8, 1.1 Hz, 1H), 6.88 (d, J = 7.8 Hz, 1H), 6.80 (t, J = 7.6 Hz, 1H), 6.45 (d,
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J = 7.3 Hz, 1H), 4.77 (s, 1H), 3.29 (s, 3H); C NMR (101 MHz, CDCl3) δ 171.3, 145.2, 134.5, 131.7,
130.3, 128.7, 128.1, 123.4, 122.5, 120.4, 108.7, 64.3, 61.5, 26.6. The minor isomer cisꢀ3ad (12 mg,
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22%), a white solid; mp: 175ꢀ177 C; H NMR (400 MHz, CDCl3) δ 7.55 (d, J = 8.4 Hz, 2H), 7.44 –
7.33 (m, 3H), 7.23 (d, J = 7.3 Hz, 1H), 7.13 (t, J = 7.5 Hz, 1H), 6.91 (d, J = 7.8 Hz, 1H), 4.63 (s, 1H),
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3.16 (s, 3H); C NMR (101 MHz, CDCl3) δ 169.7, 144.5, 134.7, 130.3, 130.2, 128.8, 128.0, 123.2,
122.7, 121.6, 108.7, 66.8, 61.9, 26.5. HRMS−ESI ([M + H]+) Calcd for C16H13ClNO2 286.0629, found
286.0633.
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3'-(2-Chlorophenyl)-1-methylspiro[indoline-3,2'-oxiran]-2-one (3ae). Table 2, entry 13; prepared
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according to the typical procedure,isatin 1a (32 mg, 0.2 mmol) and aldehyde 2e (34 mg, 0.24 mmol)
were employed to give 3ae as two separable diastereomers (combined yields 82%, dr 90:10). The major
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isomer transꢀ3ae (42 mg, 74%), a pale red solid; mp: 166ꢀ168 oC; H NMR (400 MHz, CDCl3) δ 7.72
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(d, J = 7.3 Hz, 1H), 7.45 – 7.25 (m, 4H), 6.87 (d, J = 7.8 Hz, 1H), 6.73 (t, J = 7.6 Hz, 1H), 6.22 (d, J =
7.5 Hz, 1H), 4.81 (s, 1H), 3.31 (s, 3H);13C NMR (101 MHz, CDCl3) δ 171.2, 145.2, 133.2, 131.8, 130.2,
129.9, 129.1, 128.2, 126.7, 122.8, 122.4, 120.5, 108.6, 63.5, 61.3, 26.7; HRMS−ESI ([M + H]+) Calcd
for C16H13ClNO2 286.0629, found 286.0628.
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3'-(2,4-Dichlorophenyl)-1-methylspiro[indoline-3,2'-oxiran]-2-one (3af). Table 2, entry 14; prepared
according to the typical procedure, isatin 1a (32 mg, 0.2 mmol) and aldehyde 2f (35 mg, 0.24 mmol)
were employed to give 3af (combined yields 78%, dr 96:4). The major isomer transꢀ3af (47 mg, 76%), a
white solid; mp: 171ꢀ173 oC; 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 8.3 Hz, 1H), 7.41 (dd, J = 8.3,
1.6 Hz, 1H), 7.35 – 7.26 (m, 2H), 6.89 (d, J = 7.9 Hz, 1H), 6.78 (t, J = 7.6 Hz, 1H), 6.24 (d, J = 7.5 Hz,
1H), 4.76 (s, 1H), 3.31 (s, 3H); 13CNMR (101 MHz, CDCl3) δ 170.9, 145.2, 135.2, 134.0, 130.6, 130.4,
129.2, 129.1, 127.2, 122.7, 122.5, 120.2, 108.8, 63.1, 61.3, 26.7; HRMS−ESI ([M + H]+) Calcd for
C16H12Cl2NO2 320.0240, found 320.0246 .
3'-(4-Bromophenyl)-1-methylspiro[indoline-3,2'-oxiran]-2-one (3ag). Table 2, entry 15; prepared
according to the typical procedure, isatin 1a (32 mg, 0.2 mmol) and aldehyde 2g (44 mg, 0.24 mmol)
were employed to give 3ag as two separable diastereomers (combined yields 67%, dr 78:22). The major
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isomer transꢀ3ag (32 mg, 51%), a white solid; mp: 158ꢀ160 C; 1H NMR (400 MHz, CDCl3) δ 7.54 (d,
J = 8.4 Hz, 2H), 7.36 – 7.24 (m, 3H), 6.88 (d, J = 7.8 Hz, 1H), 6.81 (td, J = 7.7, 0.8 Hz, 1H), 6.45 (d, J =
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7.5 Hz, 1H), 4.75 (s, 1H), 3.29 (s, 3H); C NMR (101 MHz, CDCl3) δ 171.3, 145.2, 132.2, 131.6,
130.3, 128.8, 123.5, 122.7, 122.6, 120.5, 108.7, 64.4, 61.5, 26.6. The minor isomer cisꢀ3ag (12 mg,
16%), a pale yellow solid; mp: 166ꢀ168 oC; 1H NMR (400 MHz, CDCl3) δ 7.54 – 7.44 (m, 4H), 7.41 (td,
J = 7.8, 1.2 Hz, 1H), 7.24 – 7.20 (m, 1H), 7.13 (dd, J = 11.0, 4.1 Hz, 1H), 6.90 (d, J = 7.8 Hz, 1H), 4.61
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(s, 1H), 3.16 (s, 3H); C NMR (101 MHz, CDCl3)δ 169.7, 144.6, 130.9, 130.7, 130.4, 129.1, 123.2,
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123.0, 122.7, 121.6, 108.7, 66.8, 61.8, 26.5. HRMS−ESI ([M + H]+) Calcd for C16H13BrNO2 330.0124,
found 330.0133.
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3'-(Furan-2-yl)-1-methylspiro[indoline-3,2'-oxiran]-2-one (3ah). Table 2, entry 16; prepared
according to the typical procedure, isatin 1a (32 mg, 0.2 mmol) and aldehyde 2h (23 mg, 0.24 mmol)
were employed to give 3ah as a diastereomeric mixture with transꢀ3ah being the major (22 mg, 45%, dr
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86:14), a pale red solid, mp: 167ꢀ171 C; H NMR (400 MHz, CDCl3) for the major isomer: δ 9.37 (s,
1H), 8.15 (dd, J = 8.0, 1.4 Hz, 1H), 7.63 – 7.48 (m, 3H), 7.39 – 7.28 (m, 2H), 6.62 (dd, J = 3.5, 1.9 Hz,
1H), 3.74 (s, 3H); 1H NMR (400 MHz, CDCl3) for the minor isomer: δ 7.48 – 7.44 (m, 1H), 7.25 – 7.19
(m, 2H), 6.97 (td, J = 7.6, 0.7 Hz, 1H), 6.88 (d, J = 7.9 Hz, 1H), 6.59 (d, J = 3.3 Hz, 1H), 6.44 (dd, J =
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3.3, 1.8 Hz, 1H), 4.67 (s, 1H), 3.27 (s, 3H); C NMR (101 MHz, CDCl3) δ 160.3, 155.7, 147.1, 145.4,
143.4, 139.7, 138.4, 131.3, 130.5, 124.3, 124.1, 122.7, 121.9, 120.5, 115.8, 113.8, 112.1, 111.2, 111.1,
110.6, 108.7, 101.3, 59.5, 29.5, 26.7; HRMS−ESI ([M + H]+) Calcd for C14H12NO3 242.0812, found
242.0823.
1-Methyl-3'-(thiophen-2-yl)spiro[indoline-3,2'-oxiran]-2-one (3ai). Table 2, entry 17; prepared
according to the typical procedure, isatin 1a (32 mg, 0.2 mmol) and aldehyde 2i (27 mg, 0.24 mmol)
were employed to give 3ai (combined yields 53%, dr 75:25). The major isomer transꢀ3ai (20 mg, 39%),
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a pale yellow solid; mp: 136ꢀ138 C; H NMR (400 MHz, CDCl3) δ 7.37 – 7.29 (m, 2H), 7.17 (d, J =
3.5 Hz, 1H), 7.06 (dd, J = 5.0, 3.6 Hz, 1H), 6.87 (dd, J = 16.6, 7.8 Hz, 2H), 6.72 (d, J = 7.5 Hz, 1H),
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4.89 (s, 1H), 3.29 (s, 3H); C NMR (101 MHz, CDCl3) δ 171.2, 145.2, 135.8, 130.4, 127.0, 126.8,
125.9, 123.7, 122.5, 120.5, 108.6, 62.2, 61.7, 26.6; HRMS−ESI ([M + H]+) Calcd for C14H12NO2S
258.0583, found 258.0599.
1-Methyl-3'-(pyridin-2-yl)spiro[indoline-3,2'-oxiran]-2-one (3aj). Table 2, entry 18; prepared
according to the typical procedure, isatin 1a (32.2 mg, 0.2 mmol) and aldehyde 2j (26 mg, 0.24 mmol)
were employed to give 3aj as two separable diastereomers (combined yields 65%, dr 60:40). The major
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isomer transꢀ3aj (20 mg, 39%), a white solid; mp: 159ꢀ161 C; H NMR (400 MHz, CDCl3) δ 8.60
(ddd, J = 4.8, 1.6, 0.9 Hz, 1H), 7.82 (td, J = 7.7, 1.7 Hz, 1H), 7.68 (d, J = 7.8 Hz, 1H), 7.36 – 7.24 (m,
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2H), 6.86 (d, J = 7.8 Hz, 1H), 6.81 – 6.73 (m, 1H), 6.60 (dd, J = 7.5, 0.7 Hz, 1H), 4.85 (s, 1H), 3.28 (s,
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3H); C NMR (101 MHz, CDCl3) δ 171.0, 153.4, 149.7, 145.4, 136.5, 130.4, 123.5, 123.3, 122.4,
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121.8, 120.5, 108.7, 65.1, 61.7, 26.6. The minor isomer cisꢀ3aj (13 mg, 26%), a white solid; mp: 176ꢀ
177 oC; 1H NMR (400 MHz, CDCl3) δ 8.45 (d, J = 4.7 Hz, 1H), 7.83 (d, J = 7.9 Hz, 1H), 7.72 (td, J =
7.8, 1.5 Hz, 1H), 7.31 (t, J = 7.8 Hz, 1H), 7.17 (d, J = 7.4 Hz, 2H), 7.04 (t, J = 7.5 Hz, 1H), 6.81 (d, J =
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7.8 Hz, 1H), 4.73 (s, 1H), 3.07 (s, 3H); C NMR (101 MHz, CDCl3) δ 169.7, 152.3, 148.7, 144.6,
135.7, 130.4, 123.5, 123.0, 122.8, 121.9, 108.7, 67.0, 61.6, 26.5. HRMS−ESI [([M + H]+) Calcd for
C15H13N2O2 253.0972, found 253.0983.
1-Methyl-3'-(pyridin-3-yl)spiro[indoline-3,2'-oxiran]-2-one (3ak). Table 2; entry 19; prepared
according to the typical procedure, isatin 1a (32.2 mg, 0.2 mmol) and aldehyde 2k (26 mg, 0.24 mmol)
were employed to give 3ak as two separable diastereomers (combined yields 98%, dr 95:5). The major
isomer transꢀ3ak (45 mg, 93%), a purple solid, mp: 120ꢀ122 oC; 1H NMR (400 MHz, CDCl3) δ 8.71 (d,
J = 1.5 Hz, 1H), 8.64 (d, J = 3.6 Hz, 1H), 7.79 (d, J = 7.9 Hz, 1H), 7.33 (ddd, J = 15.5, 7.8, 2.2 Hz, 2H),
6.90 (d, J = 7.8 Hz, 1H), 6.79 (t, J = 7.6 Hz, 1H), 6.41 (d, J = 7.5 Hz, 1H), 4.81 (s, 1H), 3.30 (s, 3H); 13C
NMR (101 MHz, CDCl3 δ 171.0, 149.9, 148.3, 145.2, 134.4, 130.5, 129.1, 123.3, 123.1, 122.5, 120.0,
108.8, 62.8, 61.5, 26.6; HRMS−ESI ([M + H]+) Calcd for C15H13N2O2 253.0972, found 253.0984.
1-Methyl-3'-(pyridin-4-yl)spiro[indoline-3,2'-oxiran]-2-one (3al). Table 2, entry 20; prepared
according to the typical procedure, isatin 1a (32 mg, 0.2 mmol) and aldehyde 2l (26 mg, 0.24 mmol)
were employed to give 3al as two separable diastereomers (combined yields 43%, dr 94:6). The major
isomer transꢀ3al (20 mg, 40%), a white solid; mp: 135ꢀ137 oC; 1H NMR (400 MHz, CDCl3) δ 8.69 (d, J
= 4.9 Hz, 2H), 7.40 (t, J = 9.7 Hz, 2H), 7.31 (dd, J = 14.4, 6.6 Hz, 1H), 6.89 (t, J = 9.0 Hz, 1H), 6.80 (t,
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J = 7.6 Hz, 1H), 6.46 (d, J = 7.5 Hz, 1H), 4.78 (s, 1H), 3.31 (s, 3H); C NMR (101 MHz, CDCl3) δ
170.9, 149.9, 145.3, 142.3, 130.7, 123.4, 122.7, 121.6, 119.9, 108.9, 63.4, 61.5, 26.7; HRMS−ESI ([M +
H]+) Calcd for C15H13N2O2 253.0972, found 253.0986 .
(E)-1-methyl-3'-styrylspiro[indoline-3,2'-oxiran]-2-one (3am). Table 2, entry 21; prepared according
to the typical procedure, isatin 1a (32 mg, 0.2 mmol) and aldehyde 2m (32 mg, 0.24 mmol) were
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employed to give 3am as two separable diastereomers (combined yields 48%, dr 90:10). The major
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isomer transꢀ3am (25 mg, 43%), a pale yellow solid; mp:166ꢀ168 C; H NMR (400 MHz, CDCl3) δ
7.45 (d, J = 7.8 Hz, 2H), 7.41 – 7.24 (m, 4H), 7.16 (d, J = 7.3 Hz, 1H), 7.10 (t, J = 7.5 Hz, 1H), 6.95 –
6.82 (m, 3H), 4.20 (d, J = 7.2 Hz, 1H), 3.26 (d, J = 0.6 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 171.1,
144.5, 138.0, 135.8, 130.1, 128.6, 128.5, 126.9, 123.3, 122.7, 121.7, 121.6, 108.7, 67.1, 62.2, 26.6;
HRMS−ESI ([M + H]+) Calcd for C18H16NO2 278.1176, found 278.1188.
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3'-Ethyl-1-methylspiro[indoline-3,2'-oxiran]-2-one (3an). Table 2, entry 22; prepared according to
the typical procedure, isatin 1a (32 mg, 0.2 mmol) and aldehyde 2n (17 mg, 0.24 mmol) were employed
to give 3an as two separable diastereomers (combined yields 67%, dr 74:26). The major isomer transꢀ
3an (20 mg, 50%), a yellow colloid; 1H NMR (400 MHz, CDCl3) δ 7.41 – 7.33 (m, 1H), 7.12 – 7.04 (m,
2H), 6.90 (d, J = 7.8 Hz, 1H), 3.65 – 3.54 (m, 1H), 3.27 (s, 3H), 2.30 – 1.96 (m, 2H), 1.09 (t, J = 7.6 Hz,
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3H); C NMR (101 MHz, CDCl3) δ 171.7, 144.3, 129.9, 124.2, 122.6, 121.5, 108.5, 68.5, 59.7, 26.6,
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19.7, 10.5. The minor isomer cisꢀ3an (7 mg, 17%), a white solid; mp: 79ꢀ81 C; H NMR (400 MHz,
CDCl3) δ 7.32 (td, J = 7.8, 1.1 Hz, 1H), 7.13 (d, J = 7.0 Hz, 1H), 7.01 (t, J = 7.3 Hz, 1H), 6.86 (d, J =
7.8 Hz, 1H), 3.61 – 3.50 (m, 1H), 3.20 (s, 3H), 1.98 – 1.67 (m, 2H), 1.01 (t, J = 7.6 Hz, 3H); 13C NMR
(101 MHz, CDCl3) δ 172.7, 145.3, 130.0, 123.8, 122.5, 121.9, 108.8, 66.6, 60.5, 26.6, 21.6, 10.4;
HRMS−ESI ([M + H]+) Calcd for C12H14NO2 204.1019, found 204.1023.
1-Methyl-3'-(phenylethynyl)spiro[indoline-3,2'-oxiran]-2-one (3ao) Table 2, entry 23; prepared
according to the typical procedure, isatin 1a (32 mg, 0.2 mmol) and aldehyde 2o (31 mg, 0.24 mmol)
were employed to give 3ao as a diastereomeric mixture with transꢀ3ao being the major (44 mg, 89%, dr
60:40), a yellow solid; mp 185ꢀ188 oC; H NMR (400 MHz, CDCl3) for the major isomer: δ H NMR
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(400 MHz, CDCl3) δ 7.43 – 7.28 (m, 6H), 7.16 – 7.11 (m, 2H), 6.92 (d, J = 7.9 Hz, 1H), 4.29 (s, 1H),
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3.30 (s, 3H); H NMR (400 MHz, CDCl3) for the minor isomer: H NMR (400 MHz, CDCl3) δ 7.56 –
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7.45 (m, 7H), 7.10 – 7.05 (m, 1H), 6.95 (d, J = 7.9 Hz, 1H), 4.37 (s, 1H), 3.29 (s, 3H); C NMR (101
MHz, CDCl3) δ170.4, 169.1, 145.3, 145.0, 132.3, 132.0, 130.7, 129.4, 129.1, 128.5, 128.2, 124.4, 122.8,
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122.7, 121.8, 121.7, 121.6, 121.2, 120.4, 108.8, 88.1, 87.9, 82.0, 80.9, 61.9, 61.6, 53.1, 52.2, 26.8, 26.7;
HRMS−ESI ([M + H]+) Calcd for C18H14NO2 276.1019, found 276.1016.
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1,3'-Dimethyl-3'-(phenylethynyl)spiro[indoline-3,2'-oxiran]-2-one (5aa). Scheme 2; prepared
according to the typical procedure, isatin 1a (32 mg, 0.2 mmol) and ynones 4a (32 mg, 0.24 mmol) were
employed to give 5aa as two separable diastereomers (combined yields 35%, dr 71:29). The major
isomer transꢀ5aa (15 mg, 26%), a red solid; mp:140ꢀ142 oC; 1H NMR (400 MHz, CDCl3) δ 7.55 (dt, J =
8.7, 4.0 Hz, 2H), 7.41 (t, J = 7.8 Hz, 1H), 7.35 – 7.28 (m, 3H), 7.21 (d, J = 7.3 Hz, 1H), 7.08 (t, J = 7.6
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Hz, 1H), 6.93 (d, J = 7.8 Hz, 1H), 3.29 (s, 3H), 1.95 (s, 3H); C NMR (101 MHz, CDCl3) δ 170.2,
145.6, 132.2, 130.4, 128.8, 128.2, 124.6, 122.1, 122.0, 121.1, 108.7, 86.7, 84.9, 66.4, 58.4, 26.8, 20.6.
The minor isomer cisꢀ5aa (5 mg, 9%), a red colloid; 1H NMR (400 MHz, CDCl3) δ 7.58 (d, J = 7.5 Hz,
1H), 7.48 – 7.30 (m, 6H), 7.10 (t, J = 7.6 Hz, 1H), 6.92 (d, J = 7.8 Hz, 1H), 3.29 (s, 3H), 2.09 (s, 3H);
13C NMR (101 MHz, CDCl3) δ 170.8, 144.8, 131.9, 130.3, 129.1, 128.4, 124.9, 122.3, 122.1, 121.6,
108.4, 86.5, 86.0, 64.8, 60.0, 26.7, 17.9. HRMS−ESI ([M + H]+) Calcd for C19H16NO2 290.1176, found
290.1182.
1,3'-Dimethyl-3'-(p-tolylethynyl)spiro[indoline-3,2'-oxiran]-2-one (5ab). Scheme 2; prepared
according to the typical procedure, isatin 1a (32 mg, 0.2 mmol) and ynones 4b (41 mg, 0.24 mmol) were
employed to give 5ab (combined yields 31%, dr 84:16). The major isomer transꢀ5ab (16 mg, 26%), a
red solid; mp: 141ꢀ143 oC; 1H NMR (400 MHz, CDCl3) δ 7.41 – 7.30 (m, 3H), 7.13 (d, J = 6.6 Hz, 1H),
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7.07 – 6.97 (m, 3H), 6.86 (d, J = 7.8 Hz, 1H), 3.22 (s, 3H), 2.27 (s, 3H), 1.87 (s, 3H); C NMR (101
MHz, CDCl3) δ 170.3, 145.6, 139.0, 132.2, 130.3, 129.0, 124.6, 122.1, 118.9, 108.7, 86.9, 84.2, 66.4,
58.5, 26.8, 21.5, 20.7; HRMS−ESI ([M + H]+) Calcd for C20H18NO2 304.1332, found 304.1342.
Ethyl 2,3-diphenyloxirane-2-carboxylate (7aa). Table 3, entry 1; prepared according to the typical
procedure,αꢀketo ester 6a (36 mg, 0.2 mmol) and aldehyde 2a (25 mg, 0.24 mmol) were employed to
give7aa as a diastereomeric mixture with transꢀ7aa being the major (38 mg, 71%, dr 80:20), a yellow
liquid; 1H NMR (400 MHz, CDCl3) for the major isomer: δ 8.13 (dd, J = 8.2, 1.1 Hz, 1H), 7.58 (ddd, J =
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5.7, 4.6, 1.7 Hz, 1H), 7.49 – 7.39 (m, 2H), 7.20 (dd, J = 4.1, 2.4 Hz, 3H), 7.15 – 7.09 (m, 3H), 4.56 (s,
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1H), 4.34 – 4.23 (m, 2H), 1.29 (t, J = 7.1 Hz, 3H); H NMR (400 MHz, CDCl3) for the minor isomer: δ
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7.48 (s, 1H), 7.32 – 7.27 (m, 4H), 7.02 (dt, J = 6.0, 2.4 Hz, 5H), 6.14 (s, 1H), 4.24 – 4.11 (m, 2H), 1.23
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8
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(t, J = 7.1 Hz, 3H); C NMR (101 MHz, CDCl3) δ 169.3, 137.9, 131.5, 130.0, 129.1, 128.7, 128.5,
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128.1, 127.6, 126.7, 65.1, 63.6, 62.1, 21.1, 14.0; HRMS−ESI ([M + H]+) Calcd for C17H17O3269.1172,
found 269.1174.
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Ethyl 2-phenyl-3-(p-tolyl)oxirane-2-carboxylate (7ac).Table 3, entry 2; prepared according to the
typical procedure, αꢀketo ester 6a (36 mg, 0.2 mmol) and aldehyde 2c (29 mg, 0.24 mmol) were
employed to give7ac as a diastereomeric mixture with transꢀ7ac being the major (38 mg, 67%, dr
71:29), a yellow liquid; 1H NMR (400 MHz, CDCl3) for the major isomer: δ 7.26 – 7.19 (m, 2H), 7.16 –
7.09 (m, 3H), 6.83 (q, J = 8.3 Hz, 4H), 4.43 (s, 1H), 4.23 – 4.10 (m, 2H), 2.13 (s, 3H), 1.20 (t, J = 7.1
Hz, 3H); 1H NMR (400 MHz, CDCl3) for the minor isomer: δ 8.10 – 8.04 (m, 1H), 7.94 (d, J = 8.2 Hz,
1H), 7.51 (dd, J = 4.9, 2.7 Hz, 2H), 7.43 – 7.31 (m, 4H), 6.07 (s, 1H), 6.05 (s, 1H), 4.14 – 4.06 (m, 2H),
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2.33 (s, 3H), 1.14 (td, J = 7.1, 2.1 Hz, 3H); C NMR (101 MHz, CDCl3)δ 169.3, 165.9, 133.4, 133.1,
131.4, 130.0, 129.2, 128.8, 128.7, 128.4, 128.2, 128.1, 127.8, 127.6, 126.8, 75.0, 65.1, 63.5, 62.2, 61.7,
14.1; HRMS−ESI ([M + H]+) Calcd for C18H19O3 283.1329, found 283.1335.
Ethyl 3-(4-bromophenyl)-2-phenyloxirane-2-carboxylate (7ag). Table 3, entry 3; prepared according
to the typical procedure, αꢀketo ester 6a (36 mg, 0.2 mmol) and aldehyde 2g (44 mg, 0.24 mmol) were
employed to give 7ag as two separable diastereomers (combined yields 72%, dr 90:10). The major
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isomer transꢀ7ag (45 mg, 65%), a colorless liquid; H NMR (400 MHz, CDCl3) δ 7.30 – 7.19 (m, 7H),
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6.89 (d, J = 8.4 Hz, 2H), 4.51 (s, 1H), 4.30 – 4.21 (m, 2H), 1.28 (t, J = 7.1 Hz, 3H); C NMR (101
MHz, CDCl3) δ 168.9, 132.2, 131.0, 128.6, 128.4, 128.4, 127.8, 122.4, 65.1, 62.9, 62.3, 14.0;
HRMS−ESI ([M + H]+) Calcd for C17H16BrO3 347.0277, found 347.0272.
Ethyl 2-phenyl-3-(pyridin-3-yl)oxirane-2-carboxylate (7ak). Table 3, entry 4; prepared according to
the typical procedure, αꢀketo ester 6a (36 mg, 0.2 mmol) and aldehyde 2k (26 mg, 0.24 mmol) were
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employed to give 7ak as a diastereomeric mixture with transꢀ7ak being the major (50 mg, 93%, dr
82:18), a yellow liquid; 1H NMR (400 MHz, CDCl3) for the major isomer: δ 8.46 – 8.35 (m, 2H), 7.68 –
7.60 (m, 1H), 7.46 – 7.38 (m, 1H), 7.33 – 7.28 (m, 2H), 7.23 – 7.15 (m, 2H), 7.01 (dd, J = 7.9, 4.8 Hz,
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1H), 4.60 (s, 1H), 4.35 – 4.21 (m, 2H), 1.33 – 1.25 (m, 3H); H NMR (400 MHz, CDCl3) for the minor
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isomer: δ 8.70 (d, J = 1.8 Hz, 1H), 8.59 (dd, J = 4.8, 1.4 Hz, 1H), 7.73 (dt, J = 8.0, 1.8 Hz, 1H), 7.45 –
7.42 (m, 1H), 7.19 (dt, J = 7.9, 1.8 Hz, 4H), 6.99 (s, 1H), 4.18 (s, 1H), 4.09 – 3.98 (m, 2H), 1.01 (t, J =
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7.1 Hz, 3H); C NMR (101 MHz, CDCl3) δ 168.6, 166.1, 149.7, 149.4, 148.4, 148.1, 134.1, 134.0,
133.6, 130.6, 129.7, 129.1, 129.0, 128.6, 128.5, 127.9, 126.2, 123.1, 122.6, 66.8, 65.1, 63.4, 62.4, 61.7,
61.3, 14.0, 13.8; HRMS−ESI ([M + H]+) Calcd for C16H16NO3 270.1125, found 270.1136.
Ethyl 3-(pyridin-3-yl)-2-(p-tolyl)oxirane-2-carboxylate (7bk). Table 3, entry 5; prepared according to
the typical procedure, αꢀketo ester 6b (38 mg, 0.2 mmol) and aldehyde 2k (26 mg, 0.24 mmol) were
employed to give 7bk as a diastereomeric mixture with transꢀ7bk being the major (52 mg, 92%, dr
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71:29), a yellow liquid; H NMR (400 MHz, CDCl3) for the major isomer: δ 8.45 – 8.34 (m, 2H), 7.52
(d, J = 8.2 Hz, 1H), 7.18 (dd, J = 8.5, 5.0 Hz, 2H), 7.07 – 6.98 (m, 3H), 4.57 (s, 1H), 4.35 – 4.20 (m,
2H), 2.25 (s, 3H), 1.29 (t, J = 7.1 Hz, 3H); 1H NMR (400 MHz, CDCl3) for the minor isomer: δ 8.69 (d,
J = 1.6 Hz, 1H), 8.58 (dd, J = 4.7, 1.3 Hz, 1H), 7.72 (dt, J = 7.9, 1.8 Hz, 1H), 7.29 (q, J = 4.8 Hz, 1H),
7.24 – 7.22 (m, 2H), 7.01 (d, J = 4.3 Hz, 2H), 4.17 (s, 1H), 4.08 – 3.95 (m, 2H), 2.37 (s, 3H), 1.00 (t, J =
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7.1 Hz, 3H); C NMR (101 MHz, CDCl3) δ 168.7, 166.1, 149.6, 149.3, 148.4, 148.0, 138.9, 138.2,
134.1, 133.5, 131.0, 129.7, 129.2, 129.1, 128.5, 128.4, 127.6, 127.4, 126.0, 122.9, 122.5, 66.7, 65.0,
63.3, 62.2, 61.5, 61.2, 21.1, 13.9, 13.7; HRMS−ESI ([M + H]+) Calcd for C17H18NO3 284.1281, found
284.1292.
Ethyl 2-(4-bromophenyl)-3-(pyridin-3-yl)oxirane-2-carboxylate (7ck). Table 3, entry 6; prepared
according to the typical procedure, αꢀketo ester 6c (51 mg, 0.2 mmol) and aldehyde 2k (26 mg, 0.24
mmol) were employed to give 7ck as a diastereomeric mixture with transꢀ7bk being the major (63 mg,
94%, dr 68:32), a yellow liquid; 1H NMR (400 MHz, CDCl3) for the major isomer: δ 8.42 (s, 2H), 7.54
(s, 2H), 7.39 – 7.34 (m, 2H), 7.21 – 7.16 (m, 2H), 4.62 (s, 1H), 4.28 (qd, J = 7.1, 1.6 Hz, 2H), 1.29 (t, J
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= 7.1 Hz, 3H); 1H NMR (400 MHz, CDCl3) for the minor isomer: δ 8.69 (d, J = 1.7 Hz, 1H), 8.60 (dd, J
= 4.8, 1.4 Hz, 1H), 7.72 (dt, J = 7.9, 1.8 Hz, 1H), 7.34 – 7.30 (m, 1H), 7.22 (t, J = 1.8 Hz, 1H), 7.22 (t, J
= 1.8 Hz, 1H), 7.06 (dd, J = 7.9, 4.9 Hz, 2H), 4.14 (s, 1H), 4.09 – 3.95 (m, 2H), 1.01 (t, J = 7.1 Hz, 3H);
13C NMR (101 MHz, CDCl3) δ 168.1, 165.6, 149.8, 149.6, 148.3, 148.0, 133.9, 133.6, 133.1, 131.7,
131.1, 130.2, 129.7, 129.2, 128.6, 127.9, 123.1, 123.0, 122.8, 122.7, 66.1, 64.5, 63.5, 62.5, 61.8, 61.4,
13.9, 13.7; HRMSꢀ ESI ([M + H]+) Calcd for C16H15BrNO3 348.0230, found 348.0232.
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Phenyl(2-phenyl-3-(pyridin-3-yl)oxiran-2-yl)methanone (7dk). Table 3, entry 7; prepared according to
the typical procedure, benzil 6d (42 mg, 0.2 mmol) and aldehyde 2k (26 mg, 0.24 mmol) were employed
to give 7dk as a diastereomeric mixture with transꢀ7dk being the major (53 mg, 88%, dr 51:49), a
yellow liquid; 1H NMR (400 MHz, CDCl3) for the major isomer: δ 8.42 (d, J = 2.1 Hz, 1H), 8.32 (dd, J
1
= 4.8, 1.5 Hz, 1H), 7.91 – 7.86 (m, 2H), 7.36 – 7.25 (m, 8H), 7.16 – 7.09 (m, 2H), 4.18 (s, 1H); H
NMR (400 MHz, CDCl3) for the minor isomer: δ 8.45 (d, J = 2.0 Hz, 1H), 8.39 (dd, J = 4.8, 1.6 Hz,
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1H), 8.05 (dd, J = 5.2, 3.4 Hz, 2H), 7.55 – 7.37 (m, 8H), 7.08 – 6.96 (m, 2H), 4.47 (s, 1H); C NMR
(101 MHz, CDCl3) δ 194.4, 193.0, 149.5, 149.2, 148.3, 148.0, 135.1, 134.8, 134.1, 134.0, 133.9, 133.7,
133.4, 131.2, 130.3, 129.8, 129.5, 129.2, 128.9, 128.7, 128.6, 128.5, 128.4, 128.3, 127.2, 125.4, 123.0,
122.6, 71.1, 70.3, 64.8, 60.9; HRMS−ESI ([M + H]+) Calcd for C20H16NO2 302.1176, found 302.1185.
3'-(Pyridin-3-yl)-2H-spiro[acenaphthylene-1,2'-oxiran]-2-one (7ek). Table 3, entry 8; prepared
according to the typical procedure, acenaphthyleneꢀ1,2ꢀdione 6e (36 mg, 0.2 mmol) and aldehyde 2k (26
mg, 0.24 mmol) were employed to give 7ek as two separable diastereomers (combined yields 99%, dr
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98:2). The major isomer transꢀ7ek (53 mg, 97%), a pale yellow solid; mp: 174ꢀ176 C; H NMR (400
MHz, CDCl3) δ 8.76 (d, J = 2.0 Hz, 1H), 8.66 (dd, J = 4.8, 1.5 Hz, 1H), 8.15 (d, J = 8.2 Hz, 1H), 8.08
(d, J = 6.8 Hz, 1H),7.94 – 7.74 (m, 3H), 7.45 – 7.35 (m, 2H), 6.72 (d, J = 7.0 Hz, 1H), 4.93 (s, 1H); 13C
NMR (101 MHz, CDCl3) δ 197.3, 149.9, 148.3, 143.0, 134.5, 132.4, 130.6, 130.4, 129.9, 129.8, 128.2,
128.1, 126.4, 123.2, 122.2, 120.5, 66.1, 63.1; HRMS−ESI ([M + H]+) Calcd for C18H12NO2 274.0863,
found 274.0877.
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Supporting Information Available: Copies of NMR (1H, C) spectra of new compounds 3, 5, and 7;
Xꢀray crystallographic data (CIF files) for compound 3af. This material is available free of charge via
the Internet at http://pubs.acs.org.
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Acknowledgment: Financial support from National Natural Science Foundation of China (Grant No.
21502135) is gratefully acknowledged.
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