Chemoselective P(NMe2)3-Mediated Reductive Epoxidation between

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Article Cite This: J. Org. Chem. 2018, 83, 8272−8280

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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† †

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

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‡

S Supporting Information *

ABSTRACT: Herein, we report a chemoselective P(NMe2)3mediated 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.

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INTRODUCTION 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 for generating this class of compounds.2−6 Among them, alkene epoxidations such as Sharpless 3 and Shi 4 epoxidations have been demonstrated to be powerful tools in both industrial- and academic-scale syntheses for olefinic substrates (Scheme 1, eq a). Furthermore, the cyclization of sulfur ylides5 or αhaloenolates6 with carbonyl compounds provides alternative valuable approaches to epoxides in an oxidant-free manner (Scheme 1, eqs b and c). Despite the efficiency of the existing methods, there remains significant room for the development of additional complementary epoxidation strategies, especially with the aim of synthesizing highly functionalized epoxides from readily available and bench stable precursors under oxidant-free conditions. 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 because of the competing reactions between homo- and heterocoupling 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 © 2018 American Chemical Society

epoxide product. Keeping this in mind, we envisioned that a chemoselective reductive epoxidation of α-dicarbonyl compounds such as α-keto esters/amides and α-diketones with carbonyls, including aldehydes and ketones, under the influence of trivalent phosphorus reagents would be feasible. It is well-known that the α-dicarbonyl compounds could readily undergo the Kukhtin−Ramirez addition with trivalent phosphorus reagents to afford the reactive dipolar adducts.8 Our group and others have recently demonstrated in a series of studies that the Kukhtin−Ramirez adducts could serve as a versatile C1 synthon in reactions with both nucleophiles9 and electrophiles10,11 because of their dipolar structural properties. We therefore proposed that the Kukhtin−Ramirez adduct would be selectively generated first from an α-dicarbonyl compound and a 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)3-mediated reductive epoxidation of readily available α-dicarbonyl compounds such as isatins, α-keto esters, and α-diketones with aldehydes and ketones, leading to the 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 Received: April 19, 2018 Published: June 5, 2018 8272

DOI: 10.1021/acs.joc.8b00995 J. Org. Chem. 2018, 83, 8272−8280

Article

The Journal of Organic Chemistry Table 1. Screening of the Reaction Conditionsa

Scheme 1. Different Epoxidation Methodologies

entry

isatin 1

solvent

PR′3

yield (%)b

drc

1 2 3 4 5 6 7 8 9 10

1a 1a 1a 1a 1a 1a 1a 1a 1b 1c

CH2Cl2 CHCl3 toluene THF CH3CN CHCl3 CHCl3 CHCl3 CHCl3 CHCl3

P(NMe2)3 P(NMe2)3 P(NMe2)3 P(NMe2)3 P(NMe2)3 P(OMe)3 PBu3 PPh3 P(NMe2)3 P(NMe2)3

3aa, 60 3aa, 88 3aa, 56 3aa, 20 3aa, 36 3aa, 44 3aa, 0 3aa, 0 3ba, 51 3ca, 65

88:12 90:10 75:25 70:30 89:11 80:20 − − 62:38 52:48

a

Reaction conditions: isatin 1 (0.2 mmol), benzaldehyde 2a (0.24 mmol), PR′3 (0.22 mmol), and 4 Å molecular sieves in solvent (2.0 mL), −78 °C to rt, 12 h. bThe combined yields of two isolated diastereomers based on 1. cDetermined by a 1H NMR assay of the crude mixture and referring to the ratio of trans-3 to cis-3.

reductive epoxidation of two different carbonyl electrophiles and also complements the existing methods for generating epoxides.7,12

Both electron-donating and electron-withdrawing R1 groups were well tolerated, readily affording the corresponding spiroepoxides 3 with representative aldehyde 2a in moderate to good yields and diastereoselectivities (entries 1−9). Furthermore, substituted aldehydes with different electronic and steric properties were investigated with representative isatin 1a. Aromatic aldehydes bearing either electron-donating or electron-withdrawing aryl groups proceeded smoothly in the epoxidation (entries 10−15). Notably, sterically demanding substrates such as aldehydes 2e and 2f afforded the corresponding epoxides in higher diastereoselectivities without any loss of reactivity (entries 13 and 14, respectively). Heteroaromatic aldehydes such as furylaldehyde, thienylaldehyde, and pyridylaldehyde were readily accommodated, as well (entries 16−20). An α,β-unsaturated 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 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). 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 to extend this methodology to other common ketones such as acetophenone and 2butanone gave negative results, and no reactions occurred. Furthermore, activated ketones such as trifluoroacetophenone also failed to give the desired epoxide product. Fortunately, a majority of the two diastereomeric products listed in Table 2 and Scheme 2 could be separated using column chromatography isolations.

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RESULTS AND DISCUSSION We commenced with the proposed epoxidation by treating Nmethyl isatin 1a with benzaldehyde 2a under the predetermined conditions listed in Table 1. To our delight, the expected spirooxindole-epoxide 3aa was exclusively afforded in 60% isolated yield and 88:12 diastereoselectivity with trans-3aa (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 homocoupling byproducts (Table 1, entry 1). It therefore represents a highly chemoselective reductive epoxidation between two different carbonyls and also provides a facile synthesis of multifunctionalized 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 that were surveyed, CHCl3 was the optimal reaction medium, affording product 3aa in 88% yield and 90:10 diastereoselectivity (entries 1−5). 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 6−8). Other substituents R instead of a methyl group on the nitrogen atom of isatin 1 were examined, as well. Both the yields and the diastereoselectivities decreased when either an allyl or a benzyl group was introduced to the nitrogen atom (entries 9 and 10). Employing the optimal reaction conditions listed in entry 2 of Table 1, the generality of the epoxidations was investigated (Table 2). The isatins bearing a different R1 group on the phenyl ring of the oxindole framework were first examined. 8273

DOI: 10.1021/acs.joc.8b00995 J. Org. Chem. 2018, 83, 8272−8280

Article

The Journal of Organic Chemistry

Table 3. P(NMe2)3-Mediated Reductive Epoxidation of αKeto Esters and α-Diketones 6 with Aldehydes 2a

Table 2. P(NMe2)3-Mediated Reductive Epoxidation of Isatins 1 and Aldehydes 2a

entry

R1 in 1

R2 in 2

time (h)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

H (1a) 5-MeO (1d) 5-Me (1e) 4-Br (1f) 5-Br (1g) 6-Br (1h) 4-Cl (1i) 5-Cl (1j) 5-NO2 (1k) 1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1a 1a

Ph (2a) 2a 2a 2a 2a 2a 2a 2a 2a 4-MeOC6H4 (2b) 4-MeC6H4 (2c) 4-ClC6H4 (2d) 2-ClC6H4 (2e) 2,4-Cl2C6H4 (2f) 4-BrC6H4 (2g) 2-furyl (2h) 2-thienyl (2i) 2-pyridyl (2j) 3-pyridyl (2k) 4-pyridyl (2l) (E)-cinnamyl (2m) Et (2n) phenylethynyl (2o)

24 8 12 12 8 24 12 12 21 8 8 12 7 7 12 24 24 8 7 8 12 8 7

R3, R4 in 6

entry

yield (%)b

drc

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 3ah, 45 3ai, 53 3aj, 65 3ak, 98 3al, 43 3am, 48 3an, 67 3ao, 89

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 78:22 86:14 75:25 60:40 95:5 94:6 90:10 74:26 60:40

1 2

Ph, OEt (6a) 6a

3

6a

4 5 6 7 8

6a 4-MeC6H4, OEt (6b) 4-BrC6H4, OEt (6c) Ph, Ph (6d) acenaphthoquinone (6e)

R2 in 2 Ph (2a) 4-MeC6H4 (2c) 4-BrC6H4 (2g) 3-pyridyl (2k) 2k 2k 2k 2k

time (h)

yield (%)b

drc

7 12

7aa, 71 7ac, 67

80:20 71:29

12

7ag, 72

90:10

7 7 7 8 8

7ak, 93 7bk, 92 7ck, 94 7dk, 88 7ek, 99

82:18 71:29 68:32 51:49 98:2

Reaction conditions: α-dicarbonyl compound 6 (0.2 mmol), aldehyde 2 (0.24 mmol), P(NMe2)3 (0.22 mmol), and 4 Å molecular sieves in CHCl3 (2.0 mL), −78 °C to rt. bThe combined yields of two isolated diastereomers based on 6. cDetermined by a 1H NMR assay of the crude mixture and referring to the ratio of trans-7 to cis-7. a

The structures of epoxides 3, 5, and 7 were identified by 1H and 13C NMR and HRMS-ESI/MALDI measurements. Representative compounds were further confirmed by NOESY (7ag and 7ck) and X-ray crystallographic analyses (for the crystal structure of 3af, see the Supporting Information). A proposed mechanism to account for the formation of epoxides is exemplified in Scheme 3 based on the experimental

a

Reaction conditions: isatin 1 (0.2 mmol), aldehyde 2 (0.24 mmol), P(NMe2)3 (0.22 mmol), and 4 Å molecular sieves in CHCl3 (2.0 mL), −78 °C to rt. bThe combined yields of two isolated diastereomers based on 1. cDetermined by a 1H NMR assay of the crude mixture and referring to the ratio of trans-3 to cis-3.

Scheme 3. A Proposed Mechanism for the Formation of Epoxide

Scheme 2. P(NMe2)3-Mediated Reductive Epoxidation of Isatin 1a with Ynones 4

The scope of this epoxidation was further extended to other α-dicarbonyl compounds such as α-keto esters and αdiketones. Under the standard reaction conditions (Table 3), aryl-substituted α-keto esters 6a−c bearing either electrondonating or electron-withdrawing aryl groups and α-diketones such as benzil 6d and acenaphthoquinone 6e were all capable of affording their corresponding epoxides 7 with representative aldehydes 2 in good to excellent yields with moderate to excellent diastereoselectivities (entries 1−8).

results and the closely related reports from our group and others.10,11 Presumably, the epoxidation is initiated with the in situ generation of Kukhtin−Ramirez adduct I or II from an αdicarbonyl compound such as isatin 1a and hexamethylphosphorous triamide. Through its dipolar structure II, the Kukhtin−Ramirez adduct then triggers a nucleophilic addition in a manner similar to aldol reaction to an aldehyde such as 2a 8274

DOI: 10.1021/acs.joc.8b00995 J. Org. Chem. 2018, 83, 8272−8280

Article

The Journal of Organic Chemistry

1H), 4.83 (s, 1H), 3.29 (s, 3H); 13C 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 cis-3aa (4 mg, 9%): white solid; 1H NMR (400 MHz, CDCl3) δ 7.63−7.57 (m, 2H), 7.43−7.34 (m, 4H), 7.25−7.21 (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. Allyl-3′-phenylspiro[indoline-3,2′-oxiran]-2-one (3ba). Table 1, entry 9; prepared according to the typical procedure. N-Allylic 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 of 51%, dr 62:38). The major isomer trans-3ba (18 mg, 33%): yellow colloid; 1H 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, 2H); 13C 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 cis-3ba (10 mg, 18%): pale yellow solid; mp 156−158 °C; 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 (m, 2H), 4.69 (s, 1H), 4.27 (d, J = 5.4 Hz, 2H); 13C 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. N-Benzylic 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 of 65%, dr 52:48). The major isomer trans-3ca (22 mg, 34%): white solid; mp 140−142 °C; 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 (m, 2H), 6.47 (d, J = 7.4 Hz, 1H), 5.06−4.93 (m, 2H), 4.90 (s, 1H); 13C 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 cis-3ca (20 mg, 31%): pale yellow solid; mp 151−153 °C; 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 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); 13C 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. 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 of 78%, dr 74:26). The major isomer trans-3da (34 mg, 60%): white solid; mp 155−157 °C; 1H NMR (400 MHz, CDCl3) δ 7.63− 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); 13C 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 cis-3da (10 mg, 18%): white solid; mp 167−169 °C; 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), 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); 13C 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 (35 mg, 0.2 mmol) and aldehyde 2a (25 mg, 0.24 mmol) were employed to give 3ea as two separable diastereomers (combined yields of 58%, dr 73:27). The major isomer trans-3ea (24 mg, 46%): white solid; mp 172−173 °C; 1H NMR (400 MHz, CDCl3) δ 7.51−

via two different modes, affording intermediates IIIa and IIIb. Because of the possible π−π stacking interaction between the phenyl groups and less steric hindrance between the small hydrogen and the bulky phosphonium moiety, intermediate IIIa is predominantly generated, which then undergoes an intramolecular substitution similar to an SN2 substitution to finish the ring closure, affording the major product trans-3aa and the phosphoric triamide byproduct.10e,11b,c On the other hand, ring closure of intermediate IIIb through a similar process provides the minor product cis-3aa. The chemoselectivity of this epoxidation was attributed by the exclusive Kukhtin−Ramirez addition of hexamethylphosphorous triamide to an α-dicarbonyl compound such as 1a among the two carbonyl electrophiles 1a and 2a.

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CONCLUSION In summary, 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 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 Kukhtin− Ramirez addition of α-dicarbonyl 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 substrate scope, mild and oxidant-free conditions, and readily available and bench stable starting material and complements the existing 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.

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EXPERIMENTAL SECTION

Unless otherwise noted, all reactions were performed in a nitrogen atmosphere under anhydrous conditions. All solvents were purified according to standard procedures. 1H and 13C NMR spectra were recorded in CDCl3 with tetramethylsilane (TMS) as the internal standard. HRMS spectra were acquired in ESI mode with the mass analyzer of TOF used. Column chromatography was performed on silica gel (200−300 mesh) using a petroleum ether/ethyl acetate mixture as the eluant. Isatins 113 and aryl-substituted α-keto esters 614 were prepared according to the reported procedures. General Procedure for the Chemoselective Epoxidation of α-Dicarbonyl Compound 1 or 6 with Aldehyde 2 or Ynone 4. Under a N2 atmosphere at −78 °C, P(NMe2)3 (40 μL, 0.22 mmol) in chloroform (0.5 mL) was added dropwise to a mixture of αdicarbonyl compound 1 or 5 (0.2 mmol), aldehyde 2 or ynone 4 (0.24 mmol), and 4 Å molecular sieves (150 mg) in chloroform (1.5 mL) by means of a syringe. The resulting reaction mixture was then slowly warmed to room temperature and stirred at rt for a time indicated in Table 2 or 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 a petroleum ether/ethyl acetate mixture (20:1− 3:1) to give 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. NMethyl 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 of 88%, dr 90:10). The major isomer trans-3aa (40 mg, 79%): white solid; mp 158−159 °C; 1H 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, J = 7.5, 0.6 Hz, 8275

DOI: 10.1021/acs.joc.8b00995 J. Org. Chem. 2018, 83, 8272−8280

Article

The Journal of Organic Chemistry

107.1, 66.3, 62.4, 26.9. The minor isomer cis-3ia (11 mg, 19%): pale yellow solid; mp 173−175 °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), 6.79 (dd, J = 7.8, 0.6 Hz, 1H), 5.43 (s, 1H), 3.13 (s, 3H); 13C 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 of 63%, dr 69:31). The major isomer trans-3ja (25 mg, 44%): white solid; mp 188−189 °C; 1H 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 cis-3ja (11 mg, 19%): white solid; mp 180−182 °C; 1H 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 Hz, 1H), 6.82 (d, J = 8.3 Hz, 1H), 4.65 (s, 1H), 3.14 (d, J = 0.7 Hz, 3H); 13 C 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. 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 of 64%, dr 80:20). The major isomer trans-3ka (28 mg, 47%): white solid; mp 180−181 °C; 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 Hz, 1H), 4.79 (s, 1H), 3.23 (s, 3H); 13C 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 cis-3ka (10 mg, 17%): white solid; mp 189−190 °C; 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), 3.23 (s, 3H); 13C 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 of 84%, dr 62:38). The major isomer trans-3ab (29 mg, 52%): white solid; mp 148−150 °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 cis-3ab (18 mg, 32%): white solid; mp 164−166 °C; 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), 6.99−6.85 (m, 3H), 4.61 (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, 123.6, 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. 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 of 85%, dr 51:49). The major isomer trans-3ac (22 mg, 43%): white solid; mp 159−160 °C; 1H 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, 21.29. The minor isomer cis-3ac (21 mg, 42%): white solid; mp 167−168 °C; 1H NMR

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), 3.27 (s, 3H), 2.06 (s, 3H); 13C 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 cis-3ea (7 mg, 12%): white solid; mp 179−181 °C; 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), 2.38 (s, 3H); 13C 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. 4-Bromo-1-methyl-3′-phenylspiro[indoline-3,2′-oxiran]-2-one (3fa). Table 2, entry 4; prepared 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 of 61%, dr 75:25). The major isomer trans-3fa (30 mg, 46%): white solid; mp 165−167 °C; 1H NMR (400 MHz, CDCl3) δ 7.39− 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), 3.32 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 171.9, 146.9, 130.9, 128.7, 128.3, 128.2, 127.8, 119.7, 119.6, 107.6, 66.4, 62.4, 26.9. The minor isomer cis-3fa (10 mg, 15%): white solid; mp 175−177 °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), 6.93−6.78 (m, 1H), 5.49 (s, 1H), 3.12 (s, 3H); 13C 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 of 67%, dr 80:20). The major isomer trans-3ga (36 mg, 55%): white solid; mp 177−179 °C; 1H 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), 3.28 (s, 3H); 13C 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 cis-3ga (8 mg, 12%): white solid; mp 168−170 °C; 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 of 53%, dr 71:29). The major isomer trans-3ha (26 mg, 39%): pale yellow solid; mp 163−165 °C; 1H NMR (400 MHz, CDCl3) δ 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 cis-3ha (9 mg, 14%): pale yellow solid; mp 168− 170 °C; 1H NMR (400 MHz, CDCl3) δ 7.50−7.32 (m, 5H), 7.02 (d, 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); 13C 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 (39 mg, 0.2 mmol) and aldehyde 2a (25 mg, 0.24 mmol) were employed to give 3ia as two separable diastereomers (combined yields of 56%, dr 66:34). The major isomer trans-3ia (21 mg, 37%): white solid; mp 165−167 °C; 1H 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, 8276

DOI: 10.1021/acs.joc.8b00995 J. Org. Chem. 2018, 83, 8272−8280

Article

The Journal of Organic Chemistry (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), 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); 13C 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 of 60%, dr 64:36). The major isomer trans-3ad (21 mg, 38%): white solid; mp 162−164 °C; 1H NMR (400 MHz, CDCl3) δ 7.40 (d, 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, J = 7.3 Hz, 1H), 4.77 (s, 1H), 3.29 (s, 3H); 13C 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 cis-3ad (12 mg, 22%): white solid; mp 175−177 °C; 1H 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), 3.16 (s, 3H); 13C 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. 3′-(2-Chlorophenyl)-1-methylspiro[indoline-3,2′-oxiran]-2-one (3ae). Table 2, entry 13; prepared 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 of 82%, dr 90:10). The major isomer trans-3ae (42 mg, 74%): pale red solid; mp 166−168 °C; 1H NMR (400 MHz, CDCl3) δ 7.72 (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. 3′-(2,4-Dichlorophenyl)-1-methylspiro[indoline-3,2′-oxiran]-2one (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 of 78%, dr 96:4). The major isomer trans-3af (47 mg, 76%): white solid; mp 171−173 °C; 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); 13C NMR (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 of 67%, dr 78:22). The major isomer trans-3ag (32 mg, 51%): white solid; mp 158−160 °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 = 7.5 Hz, 1H), 4.75 (s, 1H), 3.29 (s, 3H); 13C 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 cis-3ag (12 mg, 16%): pale yellow solid; mp 166−168 °C; 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 (s, 1H), 3.16 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 169.7, 144.6, 130.9, 130.7, 130.4, 129.1, 123.2, 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. 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 trans-3ah being the major isomer (22 mg, 45%, dr 86:14): pale red solid; mp 167−171 °C; 1H NMR (400 MHz, CDCl3) 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); 13C 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. The minor isomer: 1H NMR (400 MHz, CDCl3) 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 = 3.3, 1.8 Hz, 1H), 4.67 (s, 1H), 3.27 (s, 3H). 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 of 53%, dr 75:25). The major isomer trans-3ai (20 mg, 39%): pale yellow solid; mp 136−138 °C; 1H 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), 4.89 (s, 1H), 3.29 (s, 3H); 13C 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 of 65%, dr 60:40). The major isomer trans-3aj (20 mg, 39%): white solid; mp 159−161 °C; 1H 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, 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, 3H); 13C NMR (101 MHz, CDCl3) δ 171.0, 153.4, 149.7, 145.4, 136.5, 130.4, 123.5, 123.3, 122.4, 121.8, 120.5, 108.7, 65.1, 61.7, 26.6. The minor isomer cis-3aj (13 mg, 26%): white solid; mp 176−177 °C; 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 = 7.8 Hz, 1H), 4.73 (s, 1H), 3.07 (s, 3H); 13C 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 of 98%, dr 95:5). The major isomer trans-3ak (45 mg, 93%): purple solid; mp 120−122 °C; 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); 13 C 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 of 43%, dr 94:6). The major isomer trans-3al (20 mg, 40%): white solid; mp 135−137 °C; 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, J = 7.6 Hz, 1H), 6.46 (d, J = 7.5 Hz, 1H), 4.78 (s, 1H), 3.31 (s, 3H); 13C 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 employed to give 3am as two separable diastereomers (combined yields of 48%, dr 90:10). The major isomer trans-3am (25 mg, 43%): pale yellow solid; mp 166−168 °C; 1H NMR (400 MHz, CDCl3) δ 8277

DOI: 10.1021/acs.joc.8b00995 J. Org. Chem. 2018, 83, 8272−8280

Article

The Journal of Organic Chemistry

CDCl3) δ 8.13 (dd, J = 8.2, 1.1 Hz, 1H), 7.58 (ddd, J = 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, 1H), 4.34−4.23 (m, 2H), 1.29 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 169.3, 137.9, 131.5, 130.0, 129.1, 128.7, 128.5, 128.1, 127.6, 126.7, 65.1, 63.6, 62.1, 21.1, 14.0; HRMS-ESI ([M + H]+) calcd for C17H17O3 269.1172, found 269.1174. The minor isomer: 1H NMR (400 MHz, CDCl3) δ 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 (t, J = 7.1 Hz, 3H). Ethyl 2-Phenyl-3-(p-tolyl)oxirane-2-carboxylate (7ac). Table 3, entry 2; prepared according to the typical procedure. α-Keto ester 6a (36 mg, 0.2 mmol) and aldehyde 2c (29 mg, 0.24 mmol) were employed to give 7ac as a diastereomeric mixture with trans-7ac being the major isomer (38 mg, 67%, dr 71:29): yellow liquid; 1H NMR (400 MHz, CDCl3) 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); 13C 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; HRMSESI ([M + H]+) calcd for C18H19O3 283.1329, found 283.1335. The minor isomer: 1H NMR (400 MHz, CDCl3) 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), 2.33 (s, 3H), 1.14 (td, J = 7.1, 2.1 Hz, 3H). Ethyl 3-(4-Bromophenyl)-2-phenyloxirane-2-carboxylate (7ag). Table 3, entry 3; prepared according to the typical procedure. α-Keto 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 of 72%, dr 90:10). The major isomer trans-7ag (45 mg, 65%): colorless liquid; 1H NMR (400 MHz, CDCl3) δ 7.30−7.19 (m, 7H), 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); 13C 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. αKeto ester 6a (36 mg, 0.2 mmol) and aldehyde 2k (26 mg, 0.24 mmol) were employed to give 7ak as a diastereomeric mixture with trans-7ak being the major isomer (50 mg, 93%, dr 82:18): yellow liquid; 1H NMR (400 MHz, CDCl3) 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, 1H), 4.60 (s, 1H), 4.35−4.21 (m, 2H), 1.33−1.25 (m, 3H); 13C 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. The minor isomer: 1H NMR (400 MHz, CDCl3) 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 = 7.1 Hz, 3H). Ethyl 3-(Pyridin-3-yl)-2-(p-tolyl)oxirane-2-carboxylate (7bk). Table 3, entry 5; prepared according to the typical procedure. αKeto 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 trans-7bk being the major isomer (52 mg, 92%, dr 71:29): yellow liquid; 1H NMR (400 MHz, CDCl3) 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); 13C 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. The minor isomer: 1H NMR (400 MHz, CDCl3) 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 = 7.1 Hz, 3H). Ethyl 2-(4-Bromophenyl)-3-(pyridin-3-yl)oxirane-2-carboxylate (7ck). Table 3, entry 6; prepared according to the typical procedure.

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. 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 of 67%, dr 74:26). The major isomer trans-3an (20 mg, 50%): yellow colloid; 1 H 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, 3H); 13C 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, 19.7, 10.5. The minor isomer cis-3an (7 mg, 17%): white solid; mp 79−81 °C; 1H 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 trans-3ao being the major isomer (44 mg, 89%, dr 60:40): yellow solid; mp 185−188 °C; 1H NMR (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), 3.30 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 170.4, 169.1, 145.3, 145.0, 132.3, 132.0, 130.7, 129.4, 129.1, 128.5, 128.2, 124.4, 122.8, 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. The minor isomer: 1H NMR (400 MHz, CDCl3) δ 7.56−7.45 (m, 7H), 7.10−7.05 (m, 1H), 6.95 (d, J = 7.9 Hz, 1H), 4.37 (s, 1H), 3.29 (s, 3H). 1,3′-Dimethyl-3′-(phenylethynyl)spiro[indoline-3,2′-oxiran]-2one (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 of 35%, dr 71:29). The major isomer trans-5aa (15 mg, 26%): red solid; mp 140−142 °C; 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 Hz, 1H), 6.93 (d, J = 7.8 Hz, 1H), 3.29 (s, 3H), 1.95 (s, 3H); 13C 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 cis-5aa (5 mg, 9%): 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]-2one (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 of 31%, dr 84:16). The major isomer trans-5ab (16 mg, 26%): red solid; mp 141−143 °C; 1H NMR (400 MHz, CDCl3) δ 7.41−7.30 (m, 3H), 7.13 (d, J = 6.6 Hz, 1H), 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); 13C 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. α-Keto ester 6a (36 mg, 0.2 mmol) and aldehyde 2a (25 mg, 0.24 mmol) were employed to give 7aa as a diastereomeric mixture with trans-7aa being the major isomer (38 mg, 71%, dr 80:20): yellow liquid; 1H NMR (400 MHz, 8278

DOI: 10.1021/acs.joc.8b00995 J. Org. Chem. 2018, 83, 8272−8280

The Journal of Organic Chemistry

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α-Keto 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 trans-7bk being the major isomer (63 mg, 94%, dr 68:32): yellow liquid; 1H NMR (400 MHz, CDCl3) 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 = 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; HRMS-ESI ([M + H]+) calcd for C16H15BrNO3 348.0230, found 348.0232. The minor isomer: 1H NMR (400 MHz, CDCl3) 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). 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 trans-7dk being the major isomer (53 mg, 88%, dr 51:49): yellow liquid; 1H NMR (400 MHz, CDCl3) δ 8.42 (d, J = 2.1 Hz, 1H), 8.32 (dd, J = 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); 13C 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; HRMSESI ([M + H]+) calcd for C20H16NO2 302.1176, found 302.1185. The minor isomer: 1H NMR (400 MHz, CDCl3) δ 8.45 (d, J = 2.0 Hz, 1H), 8.39 (dd, J = 4.8, 1.6 Hz, 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). 3′-(Pyridin-3-yl)-2H-spiro[acenaphthylene-1,2′-oxiran]-2-one (7ek). Table 3, entry 8; prepared according to the typical procedure. Acenaphthylene-1,2-dione 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 of 99%, dr 98:2). The major isomer trans-7ek (53 mg, 97%): pale yellow solid; mp 174−176 °C; 1H 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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REFERENCES

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S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.8b00995. Copies of 1H and 13C NMR spectra of new compounds 3, 5, and 7 (PDF) X-ray crystallographic data for compound 3af (CIF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Rong Zhou: 0000-0002-0322-9199 Wen-Chao Gao: 0000-0002-1382-6210 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS Financial support from the National Natural Science Foundation of China (Grant 21502135) is gratefully acknowledged. 8279

DOI: 10.1021/acs.joc.8b00995 J. Org. Chem. 2018, 83, 8272−8280

Article

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DOI: 10.1021/acs.joc.8b00995 J. Org. Chem. 2018, 83, 8272−8280