FeCl3-Promoted [3 + 2] Annulations of γ-Butyrolactone Fused

Article Cite This: J. Org. Chem. 2018, 83, 174−184

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FeCl3‑Promoted [3 + 2] Annulations of γ‑Butyrolactone Fused Cyclopropanes with Heterocumulenes Manli Feng, Pengfei Yang, Gaosheng Yang,* Wenlong Chen, and Zhuo Chai Key Laboratory of Functionalized Molecular Solids, Ministry of Education, Anhui Key Laboratory of Molecule-Based Materials (State Key Laboratory Cultivation Base), College of Chemistry and Materials Science, Anhui Normal University, Wuhu, Anhui 241000, China S Supporting Information *

ABSTRACT: The [3 + 2] annulations of γ-butyrolactone fused donor− acceptor (D−A) cyclopropanes with aromatic isothiocyanates and dialkyl carbodiimides promoted by FeCl3 is reported. A series of bicyclic/polycyclic γ-butyrolactone fused thioimidates and γ-butyrolactone fused amidines containing four contiguous stereogenic centers were obtained in excellent yields as single stereoisomers.

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Scheme 1. Lewis Acid Mediated [3 + 2] Annulations of γButyrolactone Fused Cyclopropanes

INTRODUCTION

Over the past decades, D−A cyclopropanes have evolved into a versatile synthon for the construction of diverse useful molecular skeletons. In particular, the [3 + x] annulation reaction of D−A cyclopropane 1,1-diesters as three-carbon dipoles with a range of dipolarophiles provides facile access to a variety of useful heterocycles.1 The incorporation of either D− A cyclopropanes or dipolarophiles with novel structures into such annulations has been one of the primary motivations for the development of such chemistry. As inspired by the fruitful studies on the chemistry of 2-monosubstituted-1,1-diester cyclopropanes,2 considerable attention has recently been directed toward the synthesis and application of 1,2,3-fully substituted D−A cyclopropanes in [3 + x] annulations, which could provide products with rich structural diversity and complexity.3 Among these, two independent elegant works by Johnson3b and Zhang,3c respectively, on the Lewis acid catalyzed [3 + 2] annulation of γ-butyrolactone fused D−A cyclopropanes with aldehydes are particular intriguing in that they enable facile access to bicyclic γ-butyrolactone fused tetrahydrofurans bearing four contiguous stereogenic centers (Scheme 1). Despite these sporadic examples, to the best of our knowledge, no systematic study on the ring-opening chemistry of γ-butyrolactone fused D−A cyclopropanes has heretofore been reported.4 On the other hand, while heterocumulenes are easily available and highly reactive synthetic building blocks, only some limited examples have showed they could serve as dipolarophiles in annulations with D−A cyclopropanes for the construction of various heterocyclic structures of significant biological relevance.5−8 Stoltz and co-workers have realized [3 + 2] annulations of isocyanates, isothiocyanates, and carbodiimides with 2-substituted-1,1-diester cyclopropanes under the promotion of stoichiometric amounts of SnCl2 or FeCl3.5a Das and co-workers have very recently disclosed FeCl3-promoted [3 + 2] annulations of spirocyclopropyl© 2017 American Chemical Society

pyrazolones with phenyl isothiocyanate to provide spiropyrazolone fused 2-iminothiophene derivatives.6 Our group has been interested in exploring the potential of 2,3-disubstituted 1,1-diester cyclopropanes for the syntheses of useful compounds. It is been revealed that, compared to the cis isomers of this type of D−A cyclopropanes, the trans isomers are much less reactive toward the [3 + 2] annulation with isothiocyanates.7 We then found that a simple reduction followed by acid-catalyzed lactonization of these less reactive trans D−A cyclopropanes 69 could produce new γ-butyrolactone fused D−A cyclopropanes 1 in excellent yields as a single diastereomer. As compared to the parent cyclopropanes, Received: October 9, 2017 Published: December 8, 2017 174

DOI: 10.1021/acs.joc.7b02561 J. Org. Chem. 2018, 83, 174−184

Article

The Journal of Organic Chemistry

With the optimum reaction conditions in hand, we then probed the substrate scope with regard to isothiocyanate 2 (Table 2). First, a series of aromatic isothiocyanates were

it is presumed that the fused cyclopropanes 1 might be more reactive toward ring openings, owing to the more compact bicyclic structures and significantly modified electronic properties brought in by the reduction of the aroyl group. Herein, we report the first [3 + 2] annulation of γ-butyrolactone fused D− A cyclopropanes 1 with isothiocynates and carbodiimides promoted by FeCl3.

Table 2. Scope of Isothiocyanates in the [3 + 2] Annulation with Fused Cyclopropanesa

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RESULTS AND DISCUSSION Our study commenced with the optimization of reaction conditions for the model reaction between γ-butyrolactone fused D−A cyclopropane 1a and phenyl isothiocyanate 2a (Table 1). First, several Lewis acids were tested in promoting Table 1. Optimization of Reaction Conditionsa

entry

Lewis acid

solvent

t (h)

yield (%)b

1 2 3 4 5 6 7 8 9 10 11 12c 13d 14e

AlCl3 TiCl4 BF3·Et2O ZnCl2 FeCl3 FeCl3 FeCl3 FeCl3 FeCl3 FeCl3 FeCl3 FeCl3 FeCl3 FeCl3

CH3NO2 CH3NO2 CH3NO2 CH3NO2 CH3NO2 DCM 1,2-DCE THF CHCl3 CCl4 toluene 1,2-DCE 1,2-DCE 1,2-DCE

0.3 0.3 12.0 24.0 1.0 1.0 0.8 48.0 1.0 1.0 1.0 2.5 1.0 1.5

93 60 40 51 94 85 99 NR 94 82 98 50 98 97

a

entry

2 (R)

t (h)

3 (yield %)b

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

2a (Ph) 2b (4-MeC6H4) 2c (2-MeC6H4) 2d (4-MeOC6H4) 2e (3-MeOC6H4) 2f (2-MeOC6H4) 2g (4-ClC6H4) 2h (2-ClC6H4) 2i (4-FC6H4) 2j (4-F3CC6H4) 2k (4-O2NC6H4) 2l (3-O2NC6H4) 2m (2-O2NC6H4) 2n (benzyl) 2o (4-FC6H4CH2) 2p (allyl) 2q (PhCH2CH2) 2r (n-butyl) 2s (cyclohexyl)

1.5 1.0 1.0 1.0 0.8 1.0 1.2 1.2 1.2 1.2 1.3 1.5 0.8 1.0 1.2 0.5 0.8 0.8 0.8

3aa (97) 3ab (98) 3ac (98) 3ad (95) 3ae (96) 3af (97) 3ag (98) 3ah (98) 3ai (99) 3aj (96) 3ak (97) 3al (96) 3am (93) 3an (97) 3ao (99) 3ap (99) 3aq (98) 3ar (98) 3as (95)

Run with 0.3 mmol of 1a, 0.36 mmol of 2. bIsolated yield.

examined in the reaction, and neither the electronic nature nor the positions of the substituents on the benzene ring showed any appreciable influence on the reaction (entries 1−13). Benzylic, allylic, and simple alkyl isothiocyanates were also equally well tolerated in the reaction to furnish the corresponding γ-butyrolactone fused thioimidates in excellent yields within a short reaction time. Notably, the result (95% yield, entry 19) obtained with the cyclohexyl isothiocyanate 2s is much better than the one (64% yield) obtained with the cis2,3-disubstituted cyclopropane in our previous study.7 In all of these cases, the products bearing four contiguous stereogenic centers were isolated in diastereomerically pure form. Subsequently, the reaction scope with regard to γbutyrolactone fused cyclopropanes 1 was probed (Table 3). When a series of cyclopropanes with differently substituted phenyl group were subjected to the reaction, the corresponding thioimidate products were obtained in excellent yields irrespective of the electronic nature and positions of the substituents (R1) on the benzene ring (entries 1−12). It is worth noting that relating nonfused cis-2,3-disubstituted cyclopropanes bearing an electron-donating substituent were not well tolerated in the reaction, with only a moderate yield (R1 = 4-Me) or a complex system being obtained (R1 = 4MeO).5 These results highlight the advantageous reactivities of such new γ-butyrolactone fused cyclopropanes 1 in this annulation. Similarly, variations in the substitutions on the Ar2 group (R2) of the cyclopropanes 1 also produced little influence on the annulation, and excellent yields of the desired products were invariably obtained (entries 13−20). Notably, the tetracyclic cyclopropane 1q bearing four contiguous

a

Unless otherwise noted, the reaction was conducted with 0.3 mmol of 1a, 3.0 mmol (10.0 equiv) of 2a. bIsolated yield. c1.0 equiv of FeCl3 was used. d5.0 equiv of 2a was used. e1.2 equiv of 2a was used.

the [3 + 2] annulation, and AlCl3 and FeCl3 were found to be almost equally efficient promoters for this reaction to provide the desired product γ-butyrolactone fused thioimidate 3aa in excellent yield as a single diastereomer within 0.3 or 1.0 h (entries 1 and 5). In contrast, the parent trans-2,3-disubstituted cyclopropane gave only 49% of the desired annulation product with 5.0 equiv of an isothiocyanate after 12 h under similar conditions.7 Given the environmentally benign nature and lower cost of FeCl3, it was selected for further optimization of other reaction parameters including solvent and amounts of the reactants and FeCl3. Except for the weakly polar CCl4, other noncoordinative chlorinated solvents and aromatic toluene are suitable for the reaction, with 1,2-dichloroethane (1,2-DCE) being the optimum one (entry 7). The reaction did not occur in a coordinative solvent such as THF, leaving the cyclopropane unconsumed (entry 8). Halving the amount of the Lewis acid promoter led to a correspondingly halved yield (entry 12), which might be ascribed to the highly coordinative nature of the thioimidate product. The amount of 2a could be reduced to 1.2 equiv, and an excellent yield of 97% could still be obtained within 1.5 h (entry 14). Thus, the reaction was best performed with 1.2 equiv of an isothiocyanate in 1,2-DCE at 30 °C in the presence of 2.0 equiv of FeCl3. 175

DOI: 10.1021/acs.joc.7b02561 J. Org. Chem. 2018, 83, 174−184

Article

The Journal of Organic Chemistry Table 3. Scope of γ-Butyrolactone Fused Cyclopropanes in the Annulation with Isothiocyanatesa

Figure 1. X-ray structures of compounds 3ja and 5ab.

Scheme 2. Substrate Scope of [3 + 2] Annulation with Carbodiimidesa,b

a

a

Run with 0.3 mmol of 1, 0.36 mmol of 2. bIsolated yield.

Run with 0.3 mmol of 1, 1.5 mmol of 4. bIsolated yield.

observed on the Ar2 group, which is relatively distal to the reacting sites (donor sites) of the cyclopropanes 1 (5ob and 5pb). Interestingly, the configuration of the imine moiety (E) in the product 5 is different from the one (Z) in the product 3. The structure of compound 5ab was also confirmed by X-ray crystallographic analysis (Figure 1).10 To illustrate the synthetic utility of the reaction, treating the product 3sa with sodium chloride following a literature method11 selectively removed the pendant ethyl ester group to give a new bicyclic compound 6aa in 90% yield (Scheme 3). Based on the experimental results and previous related studies,1 a tentative mechanism for the [3 + 2] annulations between the γ-butyrolactone fused cyclopropanes and heterocumulenes is proposed in Scheme 4. First, FeCl3 may

stereocenters including a quaternary carbon also participated in the reaction well to provide the desired product 3qa in 93% yield as a single diastereomer (entry 19). The reaction efficiency was also inert to a change in the ester group (R) of the cyclopropanes 1 from an ethyl to a methyl group (entry 21). The structure of the product 3ja was confirmed by X-ray crystallographic analysis (Figure 1).10 The above-mentioned success with isothiocyanates 2 prompted us to examine the suitability of carbodiimides, another common heterocumulenes, for the [3 + 2] annulation with γ-butyrolactone fused cyclopropanes 1 (Scheme 2). Under nearly the same reaction conditions, cyclopropanes 1 with substituents of different electronic nature and positions were well tolerated in the reaction to provide a series of γbutyrolactone fused amidines 5 in excellent yields as single diastereomers, though a large excess (5.0 equiv) of the carbodiimides 4 were required. When an electron-donating substituent is present on the Ar1 group of the cyclopropanes 1, the reaction proceeded relatively more sluggishly but could still provide excellent yields and diastereoselectivities (5fb and 5jb). Surprisingly, a very similar substituent electronic effect was also

Scheme 3. Selective Deesterification of 3sa

176

DOI: 10.1021/acs.joc.7b02561 J. Org. Chem. 2018, 83, 174−184

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The Journal of Organic Chemistry

EtOAc mixtures) to afford the γ-butyrolactone fused cyclopropanes 1 (yields over two steps are given below for each cyclopropane). Ethyl r-1,2-Oxo-cis-4,cis-6-Diphenyl-3-oxabicyclo[3.1.0]hexane-1carboxylate (1a). The lactonization step was run at 50 °C for 4.0 h. Purified by column chromatography (petroleum ether/ethyl acetate = 6/1) to afford a white solid in 92% yield (1.48 g). 1H NMR (CDCl3, 500 MHz): δ 7.51−7.39 (m, 5H), 7.35−7.27 (m, 5H), 5.51 (s, 1H), 4.05−3.92 (m, 2H), 3.34 (d, J = 5.4 Hz, 1H), 3.07 (d, J = 5.5 Hz, 1H), 0.91 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 169.7, 163.4, 138.4, 131.8, 129.4, 129.2, 128.7, 128.5, 128.3, 126.0, 79.8, 61.8, 38.5, 37.7, 33.7, 13.7. HRMS (APCI-TOF, m/z) calcd for C20H19O4 [M + H]+: 323.1278, found: 323.1279. Ethyl r-1,2-Oxo-cis-4-phenyl-cis-6-(p-tolyl)-3-oxabicyclo[3.1.0]hexane-1-carboxylate (1b). The lactonization step was run at 50 °C for 3.0 h. Purified by column chromatography (petroleum ether/ ethyl acetate = 6/1) to afford a white solid in 89% yield (1.50 g). 1H NMR (CDCl3, 500 MHz): δ 7.52−7.36 (m, 5H), 7.19−7.07 (m, 4H), 5.44 (s, 1H), 4.05−3.92 (m, 2H), 3.31 (d, J = 5.5 Hz, 1H), 3.04 (d, J = 5.5 Hz, 1H), 2.32 (s, 3H), 0.95 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 169.7, 163.4, 138.4, 138.1, 129.3, 129.2, 128.7, 128.6, 126.0, 79.8, 61.8, 38.5, 37.7, 33.8, 21.2, 13.8. HRMS (APCI-TOF, m/ z) calcd for C21H21O4 [M + H]+: 337.1434, found: 337.1433. Ethyl r-1,cis-6-(4-Anisyl)-2-oxo-cis-4-phenyl-3-oxabicyclo[3.1.0]hexane-1-carboxylate (1c). The lactonization step was run at rt for 12.0 h. Purified by column chromatography (petroleum ether/ethyl acetate = 4/1) to afford a white solid in 88% yield (1.55 g). 1H NMR (CDCl3, 500 MHz): δ 7.51−7.36 (m, 5H), 7.19 (d, J = 8.6 Hz, 2H), 6.84 (d, J = 8.8 Hz, 2H), 5.43 (s, 1H), 4.06−3.95(m, 2H), 3.79 (s, 3H), 3.29 (d, J = 5.5 Hz, 1H), 3.03 (d, J = 5.5 Hz, 1H), 0.97 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 169.7, 163.5, 159.6, 138.5, 130.0, 129.3, 129.2, 126.0, 123.6, 113.9, 79.8, 61.8, 55.3, 38.6, 37.6, 33.9, 13.8. HRMS (APCI-TOF, m/z) calcd for C21H21O5 [M + H]+: 353.1384, found: 353.1386. Ethyl r-1,cis-6-(3-Anisyl)-2-oxo-cis-4-phenyl-3-oxabicyclo[3.1.0]hexane-1-carboxylate (1d). The lactonization step was run at rt for 18.0 h. Purified by column chromatography (petroleum ether/ethyl acetate = 5/1) to afford a white solid in 94% yield (1.66 g). 1H NMR (CDCl3, 500 MHz): δ 7.49−7.38 (m, 5H), 7.22 (t, J = 7.9 Hz, 1H), 6.88−6.78 (m, 3H), 5.44 (s, 1H), 4.07−3.96 (m, 2H), 3.78 (s, 3H), 3.31 (d, J = 5.4 Hz, 1H), 3.03 (d, J = 5.4 Hz, 1H), 0.94 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 169.7, 163.3, 159.6, 138.3, 133.3, 129.5, 129.4, 129.2, 126.0, 120.9, 114.3, 114.0, 79.8, 61.8, 55.3, 38.4, 37.6, 33.8, 13.8. HRMS (APCI-TOF, m/z) calcd for C21H21O5 [M + H]+: 353.1384, found: 353.1383. Ethyl r-1,cis-6-(2-Anisyl)-2-oxo-cis-4-phenyl-3-oxabicyclo[3.1.0]hexane-1-carboxylate (1e). The lactonization step was run at rt for 14.0 h. Purified by column chromatography (petroleum ether/ethyl acetate = 5/1) to afford a white solid in 91% yield (1.60 g). 1H NMR (CDCl3, 500 MHz): δ 7.50−7.37 (m, 5H), 7.29 (t, J = 7.9 Hz, 1H), 7.12 (d, J = 7.5 Hz, 1H), 6.95−6.83 (m, 2H), 5.44 (s, 1H), 3.95 (q, J = 7.1 Hz, 2H), 3.85 (s, 3H), 3.31 (d, J = 5.9 Hz, 1H), 3.15 (d, J = 5.9 Hz, 1H), 0.89 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 170.0, 163.9, 158.7, 138.7, 129.6, 129.2, 129.1, 128.9, 125.9, 120.5, 120.0, 110.2, 79.6, 61.4, 55.6, 37.0, 34.4, 34.1, 13.7. HRMS (APCI-TOF, m/ z) calcd for C21H21O5 [M + H]+: 353.1384, found: 353.1385. Ethyl r-1,cis-6-(4-Bromophenyl)-2-oxo-cis-4-phenyl-3-oxabicyclo[3.1.0]hexane-1-carboxylate (1f). The lactonization step was run at 50 °C for 4.0 h. Purified by column chromatography (petroleum ether/ethyl acetate = 7/1) to afford a white solid in 95% yield (1.91 g). 1 H NMR (CDCl3, 500 MHz): δ 7.53−7.35 (m, 7H), 7.15 (d, J = 8.3 Hz, 2H), 5.45 (s, 1H), 4.02 (q, J = 7.1 Hz, 2H), 3.30 (d, J = 5.4 Hz, 1H), 3.01 (d, J = 5.4 Hz, 1H), 0.99 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 169.4, 163.2, 138.1, 131.6, 130.8, 130.4, 129.5, 129.2, 125.9, 122.4, 79.7, 62.0, 38.3, 36.9, 33.8, 13.8. HRMS (APCITOF, m/z) calcd for C20H18O4Br [M + H]+: 401.0383, found: 401.0382. Ethyl r-1,cis-6-(4-Chlorophenyl)-2-oxo-cis-4-phenyl-3-oxabicyclo[3.1.0]hexane-1-carboxylate (1g). The lactonization step was run at 50 °C for 4.0 h. Purified by column chromatography (petroleum ether/ethyl acetate = 5/1) to afford a white solid in 94% yield (1.68 g).

Scheme 4. Possible Mechanism for the [3 + 2] Annulations

coordinate to the diester group to activate the cyclopropanes 1, which would then undergo ring opening by nucleophilic attacks of the heterocumulenes 2 or 4 in an SN2 manner.5 A bond rotation would be necessary for the resulting zwitterionic intermediates II and II′ followed by cyclization to furnish the desired products. The difference in the configurations of the imine moiety in the two products embodies the distinct stereoelectronic properties of these two types of heterocumulenes as well as the stereospecificity of the annulation processes.

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CONCLUSION In summary, we have developed a FeCl3-promoted [3 + 2] annulation reaction of γ-butyrolactone fused D−A cyclopropanes with aryl isothiocyanates and dialkyl carbodiimides. This method features readily available starting materials, a cheap and environmentally benign metal promoter, a broad scope, excellent stereoselectivity, and mild reaction conditions. A range of bicyclic/polycyclic thioimidates and γ-butyrolactone fused amidines containing four contiguous stereogenic centers were obtained in excellent yields and stereomerically pure forms.

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EXPERIMENTAL SECTION

General Information. All the [3 + 2] annulation reactions were carried out with flame-dried Schlenk-type glassware using a Schlenk line. All the other reagents were purchased from commercial suppliers and purified by standard techniques. Flash column chromatography was performed using silica gel (200−400 mesh). For thin-layer chromatography (TLC), silica gel plates (HSGF 254) were used and compounds were visualized by irradiation with UV light. 1H NMR (500 MHz) and 13C NMR (125 MHz) spectra were recorded in CDCl3. All chemical shifts (δ) are given in ppm relative to TMS (δ = 0 ppm) as the internal standard. Data are reported as follows: chemical shift, multiplicity, coupling constants, and integration. Melting points were uncorrected. IR spectra were reported in frequency of absorption (cm−1). High resolution mass spectral (HRMS) data were obtained with an ionization mode of APCI and a TOF analyzer. General Procedure for the Syntheses of γ-Butyrolactone Fused Cyclopropanes 1. To a solution of cyclopropane 69 (5.0 mmol) in MeOH (5.0 mL) was added NaBH4 (190 mg, 5.0 mmol) at rt. The reaction was stirred at rt and monitored by TLC (reaction time: 10−15 min). Next, saturated NH4Cl solution (5 mL) was added. The reaction mixture was extracted with dichloromethane (3 × 10 mL), and the combined organic layers were dried over Na2SO4. Evaporation of the solvent under vacuum provided the crude product which could be used in the next step without further purification. The above obtained crude product was dissolved in toluene (10 mL), followed by the addition of p-toluenesulfonic acid (1.5 mmol, 0.3 equiv). The reaction mixture was stirred at 50 °C or room temperature until the disappearance of the starting material as monitored by TLC. Then the reaction mixture was treated with sat. aq. Na2CO3 followed by extraction with AcOEt (3 × 10 mL). The combined organic extracts were dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash chromatography (hexane/ 177

DOI: 10.1021/acs.joc.7b02561 J. Org. Chem. 2018, 83, 174−184

Article

The Journal of Organic Chemistry H NMR (CDCl3, 500 MHz): δ 7.53−7.37 (m, 5H), 7.31 (d, J = 8.6 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 5.45 (s, 1H), 4.03 (q, J = 7.0 Hz, 2H), 3.30 (d, J = 5.4 Hz, 1H), 3.02 (d, J = 5.5 Hz, 1H), 1.00 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 169.3, 163.2, 138.2, 134.3, 130.4, 130.1, 129.5, 129.2, 128.7, 126.0, 79.8, 62.0, 38.5, 36.9, 33.9, 13.8. HRMS (APCI-TOF, m/z) calcd for C20H18O4Cl [M + H]+: 357.0888, found: 357.0891. Ethyl r-1,cis-6-(3-Chlorophenyl)-2-oxo-cis-4-phenyl-3-oxabicyclo [3.1.0]hexane-1-carboxylate (1h). The lactonization step was run at 50 °C for 3.5 h. Purified by column chromatography (petroleum ether/ethyl acetate = 5/1) to afford a white solid in 90% yield (1.61 g). 1 H NMR (CDCl3, 500 MHz): δ 7.53−7.37 (m, 5H), 7.33−7.23 (m, 3H), 7.17 (dd, J = 7.1, 1.7 Hz, 1H), 5.45 (s, 1H), 4.11−3.97 (m, 2H), 3.30 (d, J = 5.4 Hz, 1H), 3.02 (d, J = 5.4 Hz, 1H), 0.98 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 169.3, 163.1, 138.1, 134.4, 133.9, 129.8, 129.5, 129.2, 128.8, 128.5, 127.1, 125.9, 79.7, 62.0, 38.3, 36.7, 33.8, 13.8. HRMS (APCI-TOF, m/z) calcd for C20H18O4Cl [M + H]+: 357.0888, found: 357.0889. Ethyl r-1,cis-6-(2-Chlorophenyl)-2-oxo-cis-4-phenyl-3-oxabicyclo[3.1.0]hexane-1-carboxylate (1i). The lactonization step was run at 50 °C for 4.0 h. Purified by column chromatography (petroleum ether/ethyl acetate = 6/1) to afford a white solid in 88% yield (1.57 g). 1 H NMR (CDCl3, 500 MHz): δ 7.55−7.35 (m, 6H), 7.33−7.20 (m, 3H), 5.48 (s, 1H), 4.10−3.94 (m, 2H), 3.34 (d, J = 5.8 Hz, 1H), 3.15 (d, J = 5.8 Hz, 1H), 0.95 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 169.3, 163.6, 138.3, 136.2, 130.4, 129.7, 129.6, 129.5, 129.4, 129.2, 126.6, 125.8, 79.4, 61.8, 37.0, 36.5, 35.1, 13.7. HRMS (APCITOF, m/z) calcd for C20H18O4Cl [M + H]+: 357.0888, found: 357.0886. Ethyl r-1,cis-6-(4-Nitrophenyl)-2-oxo-cis-4-phenyl-3-oxabicyclo[3.1.0]hexane-1-carboxylate (1j). The lactonization step was run at 50 °C for 4.0 h. Purified by column chromatography (petroleum ether/ethyl acetate = 3/1) to afford a yellow solid in 84% yield (1.54 g). 1H NMR (CDCl3, 500 MHz): δ 8.21 (d, J = 8.8 Hz, 2H), 7.56− 7.37 (m, 7H), 5.50 (s, 1H), 4.05 (q, J = 7.1 Hz, 2H), 3.37 (d, J = 5.4 Hz, 1H), 3.10 (d, J = 5.4 Hz, 1H), 1.03 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 168.9, 163.1, 147.8, 139.4, 137.8, 129.71, 129.68, 129.3, 126.0, 123.7, 79.8, 62.4, 38.7, 36.3, 34.4, 13.9. HRMS (APCI-TOF, m/z) calcd for C20H18NO6 [M + H]+: 368.1129, found: 368.1131. Ethyl r-1,2-Oxo-cis-6-phenyl-cis-4-(p-tolyl)-3-oxabicyclo[3.1.0]hexane-1-carboxylate (1k). The lactonization step was run at 50 °C for 3.0 h. Purified by column chromatography (petroleum ether/ ethyl acetate = 6/1) to afford a white solid in 87% yield (1.46 g). 1H NMR (CDCl3, 500 MHz): δ 7.37−7.28 (m, 5H), 7.28−7.19 (m, 4H), 5.41 (s, 1H), 4.07−3.89 (m, 2H), 3.32 (d, J = 5.4 Hz, 1H), 3.04 (d, J = 5.4 Hz, 1H), 2.38 (s, 3H), 0.90 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 169.7, 163.4, 139.3, 135.4, 131.8, 129.8, 128.7, 128.4, 128.2, 126.0, 79.8, 61.7, 38.5, 37.6, 33.7, 21.2, 13.7. HRMS (APCITOF, m/z) calcd for C21H21O4 [M + H]+: 337.1434, found: 337.1432. Ethyl r-1,cis-4-(4-Anisyl)-2-oxo-cis-6-phenyl-3-oxabicyclo[3.1.0]hexane-1-carboxylate (1l). The lactonization step was run at rt for 8.0 h. Purified by column chromatography (petroleum ether/ethyl acetate = 5/1) to afford a white solid in 69% yield (1.22 g). 1H NMR (CDCl3, 500 MHz): δ 7.39−7.24 (m, 7H), 6.96 (d, J = 8.7 Hz, 2H), 5.40 (s, 1H), 4.07−3.93 (m, 2H), 3.84 (s, 3H), 3.32 (d, J = 5.4 Hz, 1H), 3.03 (d, J = 5.4 Hz, 1H), 0.92 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 169.7, 163.5, 160.5, 132.0, 130.4, 128.7, 128.5, 128.2, 127.7, 114.6, 79.9, 61.8, 55.4, 38.8, 37.6, 33.6, 13.8. HRMS (APCI-TOF, m/z) calcd for C21H21O5 [M + H]+: 353.1384, found: 353.1385. Ethyl r-1,cis-4-(3-Anisyl)-2-oxo-cis-6-phenyl-3-oxabicyclo[3.1.0]hexane-1-carboxylate (1m). The lactonization step was run at rt for 10.0 h. Purified by column chromatography (petroleum ether/ethyl acetate = 6/1) to afford a white solid in 75% yield (1.32 g). 1H NMR (CDCl3, 500 MHz): δ 7.41−7.23 (m, 6H), 7.00 (d, J = 7.7 Hz, 1H), 6.98−6.91 (m, 2H), 5.42 (s, 1H), 4.06−3.90 (m, 2H), 3.84 (s, 3H), 3.34 (d, J = 5.4 Hz, 1H), 3.05 (d, J = 5.4 Hz, 1H), 0.90 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 169.7, 163.3, 160.1, 139.8, 131.8, 130.3, 128.7, 128.5, 128.2, 118.0, 114.8, 111.4, 79.6, 61.8, 55.4, 1

38.4, 37.6, 33.7, 13.7. HRMS (APCI-TOF, m/z) calcd for C21H21O5 [M + H]+: 353.1384, found: 353.1379. Ethyl r-1,cis-4-(2-Anisyl)-2-oxo-cis-6-phenyl-3-oxabicyclo[3.1.0]hexane-1-carboxylate (1n). The lactonization step was run at rt for 8.0 h. Purified by column chromatography (petroleum ether/ethyl acetate = 5/1) to afford a white solid in 80% yield (1.41 g). 1H NMR (CDCl3, 500 MHz): δ 7.44−7.35 (m, 1H), 7.35−7.24 (m, 6H), 7.00 (t, J = 7.5 Hz, 1H), 6.96 (d, J = 8.3 Hz, 1H), 5.56 (s, 1H), 4.04−3.91 (m, 2H), 3.86 (s, 3H), 3.32 (d, J = 5.6 Hz, 1H), 3.08 (d, J = 5.6 Hz, 1H), 0.90 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 170.4, 163.8, 157.2, 132.3, 130.5, 128.9, 128.4, 128.1, 127.9, 126.1, 120.8, 111.0, 78.0, 61.4, 55.4, 38.8, 38.7, 33.5, 13.8. HRMS (APCI-TOF, m/ z) calcd for C21H21O5 [M + H]+: 353.1384, found: 353.1381. Ethyl r-1,cis-4-(4-Bromophenyl)-2-oxo-cis-6-phenyl-3-oxabicyclo[3.1.0]hexane-1-carboxylate (1o). The lactonization step was run at 50 °C for 4.0 h. Purified by column chromatography (petroleum ether/ethyl acetate = 7/1) to afford a white solid in 91% yield (1.83 g). 1 H NMR (500 MHz, CDCl3): δ 7.63−7.51 (m, 2H), 7.38−7.20 (m, 7H), 5.42 (s, 1H), 4.06−3.90 (m, 2H), 3.29 (d, J = 5.4 Hz, 1H), 3.06 (d, J = 5.4 Hz, 1H), 0.90 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 169.4, 163.2, 137.4, 132.4, 131.6, 128.6, 128.5, 128.4, 127.6, 123.5, 79.0, 61.9, 38.4, 37.6, 33.5, 13.7. HRMS (APCI-TOF, m/z) calcd for C20H18O4Br [M + H]+: 401.0383, found: 401.0379. Ethyl r-1,cis-4-(4-Nitrophenyl)-2-oxo-cis-6-phenyl-3-oxabicyclo[3.1.0]hexane-1-carboxylate (1p). The lactonization step was run at 50 °C for 5.0 h. Purified by column chromatography (petroleum ether/ethyl acetate = 4/1) to afford a white solid in 80% yield (1.47 g). 1 H NMR (CDCl3, 500 MHz): δ 8.33 (d, J = 8.7 Hz, 2H), 7.62 (d, J = 13.4 Hz, 2H), 7.37−7.31 (m, 3H), 7.30−7.24 (m, 2H), 5.56 (s, 1H), 4.03−3.92 (m, 2H), 3.31 (d, J = 5.4 Hz, 1H), 3.12 (d, J = 5.4 Hz, 1H), 0.91 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 168.9, 163.0, 148.3, 145.2, 131.3, 128.64, 128.62, 128.56, 126.8, 124.5, 78.2, 62.1, 38.2, 37.7, 33.5, 13.7. HRMS (APCI-TOF, m/z) calcd for C20H18NO6 [M + H]+: 368.1129, found: 368.1123. Ethyl 2-Oxo-1-phenyl-1a,2,3a,8-tetrahydro-1H-cyclopropa[c]indeno[1,2-b]furan-1a-carboxylate (1q). The lactonization step was run at 50 °C for 5.0 h. Purified by column chromatography (petroleum ether/ethyl acetate = 7/1) to afford a white solid in 86% yield (1.44 g). 1 H NMR (CDCl3, 500 MHz): δ 7.51 (d, J = 7.3 Hz, 1H), 7.45−7.28 (m, 8H), 5.75 (s, 1H), 4.09−3.89 (m, 3H), 3.75 (d, J = 16.7 Hz, 1H), 3.33 (s, 1H), 0.99 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 170.4, 163.8, 140.9, 138.2, 132.4, 129.8, 129.1, 128.5, 128.1, 127.8, 125.4, 125.2, 86.0, 61.5, 46.2, 39.0, 38.0, 30.0, 13.8. HRMS (APCITOF, m/z) calcd for C21H19O4 [M + H]+: 335.1278, found: 335.1275. Ethyl r-1,cis-6-(4-Chlorophenyl)-2-oxo-cis-4-(p-tolyl)-3oxabicyclo[3.1.0]hexane-1-carboxylate (1r). The lactonization step was run at 50 °C for 3.5 h. Purified by column chromatography (petroleum ether/ethyl acetate = 6/1) to afford a white solid in 87% yield (1.61 g). 1H NMR (CDCl3, 500 MHz): δ 7.35−7.26 (m, 4H), 7.23 (d, J = 7.9 Hz, 2H), 7.9 (d, J = 8.4 Hz, 2H), 5.41 (s, 1H), 4.00 (q, J = 7.1 Hz, 2H), 3.27 (d, J = 5.4 Hz, 1H), 2.99 (d, J = 5.4 Hz, 1H), 2.37 (s, 3H), 0.97 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 169.4, 163.2, 139.3, 135.1, 134.1, 130.4, 130.0, 129.7, 128.5, 125.9, 79.6, 61.8, 38.3, 36.7, 33.8, 21.2, 13.7. HRMS (APCI-TOF, m/z) calcd for C21H20O4Cl [M + H]+: 371.1045, found: 371.1043. Methyl r-1,2-Oxo-cis-4,cis-6-diphenyl-3-oxabicyclo[3.1.0]hexane1-carboxylate (1s). The lactonization step was run at 50 °C for 4.0 h. Purified by column chromatography (petroleum ether/ethyl acetate = 6/1) to afford a white solid in 94% yield (1.45 g). 1H NMR (500 MHz, CDCl3): δ 7.52−7.38 (m, 5H), 7.37−7.22 (m, 5H), 5.47 (s, 1H), 3.54 (s, 3H), 3.35 (d, J = 5.5 Hz, 1H), 3.09 (d, J = 5.5 Hz, 1H). 13 C NMR (CDCl3, 125 MHz): δ 169.6, 163.9, 138.2, 131.6, 129.4, 129.2, 128.6, 128.5, 128.3, 125.9, 79.8, 52.8, 38.5, 38.0, 34.0. HRMS (APCI-TOF, m/z) calcd for C19H17O4 [M + H]+: 309.1121, found: 309.1118. General Procedure for the [3 + 2] Annulation Reactions of γButyrolactone Fused Cyclopropanes (1) with Heterocumulenes. To a solution of γ-butyrolactone fused cyclopropanes (1) (0.3 mmol) isothiocyanates (2) (0.36 mmol) or carbodiimides (4) (1.5 mmol) in 3.0 mL of 1,2-dichloroethane was added FeCl3 (0.6 mmol). 178

DOI: 10.1021/acs.joc.7b02561 J. Org. Chem. 2018, 83, 174−184

Article

The Journal of Organic Chemistry The reaction mixture was stirred at 30 °C and monitored by TLC. Upon completion, the reaction mixture was cooled down to room temperature followed by the addition of 2.0 mL of saturated aqueous sodium bicarbonate solution. Then the mixture was extracted with dichloromethane (5.0 mL × 3), and the combined organic layers were dried with anhydrous Na2SO4, filtered, and concentrated in vacuo. The crude products were purified by flash chromatography to give the pure product 3 (from 2) or 5 (from 4). Ethyl 3-Oxo-1,6-diphenyl-4-(phenylimino)hexahydrothieno[3,4c]furan-3a-carboxylate (3aa). Purified by column chromatography (petroleum ether/ethyl acetate = 7/1) to afford a white solid in 97% yield (133 mg). Mp: 158−159 °C. IR (KBr, cm−1): ν 1792, 1749, 1639, 1591, 1489, 1454. 1H NMR (CDCl3, 500 MHz): δ 7.42 (t, J = 7.9 Hz, 2H), 7.25−7.13 (m, 7H), 7.13−7.02 (m, 4H), 6.65 (d, J = 7.4 Hz, 2H), 5.43 (d, J = 5.9 Hz, 1H), 5.27 (d, J = 8.5 Hz, 1H), 4.46 (q, J = 7.1 Hz, 2H), 4.08 (dd, J = 8.5, 6.0 Hz, 1H), 1.43 (t, J = 7.1 Hz, 3H). 13 C NMR (CDCl3, 125 MHz): δ 167.1, 165.7, 161.8, 151.0, 136.9, 133.2, 129.2, 128.9, 128.73, 128.65, 128.3, 127.8, 126.7, 125.6, 119.9, 79.7, 71.9, 63.5, 59.4, 52.8, 14.1. HRMS (APCI-TOF, m/z) calcd for C27H24NO4S [M + H]+: 458.1421, found: 458.1427. Ethyl 3-Oxo-1,6-diphenyl-4-(p-tolylimino)hexahydrothieno[3,4c]furan-3a-carboxylate (3ab). Purified by column chromatography (petroleum ether/ethyl acetate = 7/1) to afford a white solid in 98% yield (138 mg). Mp: 155−156 °C. IR (KBr, cm−1): ν 1790, 1740, 1632, 1599, 1504, 1476, 1450. 1H NMR (CDCl3, 500 MHz): δ 7.25− 7.11 (m, 8H), 7.11−6.99 (m, 4H), 6.66 (d, J = 7.6 Hz, 2H), 5.42 (d, J = 5.9 Hz, 1H), 5.26 (d, J = 8.5 Hz, 1H), 4.45 (q, J = 7.1 Hz, 2H), 4.07 (dd, J = 8.5, 6.0 Hz, 1H), 2.37 (s, 3H), 1.42 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 167.1, 165.7, 161.0, 148.4, 136.9, 135.4, 133.3, 129.7, 128.8, 128.7, 128.6, 128.3, 127.8, 126.7, 120.0, 79.7, 71.9, 63.4, 59.3, 52.8, 21.2, 14.0. HRMS (APCI-TOF, m/z) calcd for C28H26NO4S [M + H]+: 472.1577, found: 472.1573. Ethyl 3-Oxo-1,6-diphenyl-4-(o-tolylimino)hexahydrothieno[3,4c]furan-3a-carboxylate (3ac). Purified by column chromatography (petroleum ether/ethyl acetate = 7/1) to afford a white solid in 98% yield (138 mg). Mp: 147−148 °C. IR (KBr, cm−1): ν 1778, 1740, 1634, 1597, 1582, 1495, 1450. 1H NMR (CDCl3, 500 MHz): δ 7.26− 7.02 (m, 11H), 6.90 (d, J = 7.7 Hz, 1H), 6.66 (d, J = 7.4 Hz, 2H), 5.42 (d, J = 5.8 Hz, 1H), 5.28 (d, J = 8.4 Hz, 1H), 4.54−4.41 (m, 2H), 4.10 (dd, J = 8.3, 5.9 Hz, 1H), 2.25 (s, 3H), 1.44 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 167.0, 165.8, 162.0, 150.3, 137.0, 133.2, 130.7, 128.8, 128.7, 128.6, 128.4, 128.3, 127.7, 126.61, 126.56, 125.4, 117.8, 79.8, 71.5, 63.5, 59.9, 52.6, 17.5, 14.1. HRMS (APCI-TOF, m/ z) calcd for C28H26NO4S [M + H]+: 472.1577, found: 472.1579. Ethyl 4-((4-Anisyl)imino)-3-oxo-1,6-diphenylhexahydrothieno[3,4-c]furan-3a-carboxylate (3ad). Purified by column chromatography (petroleum ether/ethyl acetate = 6/1) to afford a white solid in 95% yield 139 mg). Mp: 140−141 °C. IR (KBr, cm−1): ν 1788, 1732, 1628, 1601, 1578, 1503, 1450. 1H NMR (CDCl3, 500 MHz): δ 7.24− 7.10 (m, 8H), 7.06 (t, J = 7.6 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 6.65 (d, J = 7.6 Hz, 2H), 5.43 (d, J = 5.9 Hz, 1H), 5.25 (d, J = 8.5 Hz, 1H), 4.44 (q, J = 7.1 Hz, 2H), 4.06 (dd, J = 8.4, 6.0 Hz, 1H), 3.83 (s, 3H), 1.41 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 167.2, 165.9, 159.7, 157.6, 143.8, 136.9, 133.3, 128.8, 128.7, 128.6, 128.3, 127.8, 126.6, 121.8, 114.2, 79.6, 72.0, 63.4, 59.1, 55.5, 52.9, 14.1. HRMS (APCI-TOF, m/z) calcd for C28H26NO5S [M + H]+: 488.1526, found: 488.1525. Ethyl 4-((3-Anisyl)imino)-3-oxo-1,6-diphenylhexahydrothieno[3,4-c]furan-3a-carboxylate (3ae). Purified by column chromatography (petroleum ether/ethyl acetate = 6/1) to afford a white solid in 96% yield (140 mg). Mp: 150−151 °C. IR (KBr, cm−1): ν 1790, 1738, 1634, 1593, 1483, 1456. 1H NMR (CDCl3, 500 MHz): δ 7.31 (t, J = 8.0 Hz, 1H), 7.27−7.11 (m, 6H), 7.06 (t, J = 7.6 Hz, 2H), 6.76 (dd, J = 8.2, 2.2 Hz, 1H), 6.70 (d, J = 8.5 Hz, 1H), 6.68−6.62 (m, 3H), 5.43 (d, J = 5.9 Hz, 1H), 5.27 (d, J = 8.6 Hz, 1H), 4.45 (q, J = 7.1 Hz, 2H), 4.08 (dd, J = 8.4, 6.0 Hz, 1H), 3.83 (s, 3H), 1,42 (t, J = 7.1 Hz, 3H). 13 C NMR (CDCl3, 125 MHz): δ 167.1, 165.6, 162.1, 160.3, 152.1, 136.8, 133.1, 129.9, 128.8, 128.7, 128.6, 128.3, 127.7, 126.6, 111.9, 111.5, 105.7, 79.7, 71.9, 63.5, 59.3, 55.5, 52.8, 14.1. HRMS (APCI-

TOF, m/z) calcd for C28H26NO5S [M + H]+: 488.1526, found: 488.1520. Ethyl 4-((2-Anisyl)imino)-3-oxo-1,6-diphenylhexahydrothieno[3,4-c]furan-3a-carboxylate (3af). Purified by column chromatography (petroleum ether/ethyl acetate = 6/1) to afford a white solid in 97% yield (141 mg). Mp: 147−148 °C. IR (KBr, cm−1): ν 1784, 1740, 1638, 1591, 1497, 1462, 1450. 1H NMR (CDCl3, 500 MHz): δ 7.25− 7.11 (m, 7H), 7.06 (t, J = 7.6 Hz, 2H), 7.03−6.94 (m, 3H), 6.66 (d, J = 7.5 Hz, 2H), 5.43 (d, J = 5.9 Hz, 1H), 5.29 (d, J = 8.4 Hz, 1H), 4.46 (q, J = 7.1 Hz, 2H), 4.09 (dd, J = 8.4, 6.0 Hz, 1H), 3.84 (s, 3H), 1.43 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 166.9, 165.5, 162.9, 149.5, 140.6, 137.0, 133.4, 128.8, 128.6, 128.5, 128.3, 127.8, 126.6, 126.3, 120.9, 119.9, 112.6, 79.6, 71.5, 63.5, 59.7, 56.0, 52.6, 14.1. HRMS (APCI-TOF, m/z) calcd for C28H26NO5S [M + H]+: 488.1526, found: 488.1527. Ethyl 4-((4-Chlorophenyl)imino)-3-oxo-1,6-diphenylhexahydrothieno[3,4-c]furan-3a-carboxylate (3ag). Purified by column chromatography (petroleum ether/ethyl acetate = 7/1) to afford a white solid in 98% yield (144 mg). Mp: 135−136 °C. IR (KBr, cm−1): ν 1788, 1734, 1638, 1589, 1495, 1483, 1450. 1H NMR (CDCl3, 500 MHz): δ 7.38 (d, J = 8.6 Hz, 2H), 7.25−7.12 (m, 6H), 7.12−7.00 (m, 4H), 6.65 (d, J = 7.4 Hz, 2H), 5.44 (d, J = 6.0 Hz, 1H), 5.26 (d, J = 8.5 Hz, 1H), 4.45 (q, J = 7.1 Hz, 2H), 4.08 (dd, J = 8.5, 6.0 Hz, 1H), 1.42 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 166.9, 165.6, 162.8, 149.4, 136.8, 133.0, 131.0, 129.3, 128.9, 128.8, 128.7, 128.4, 127.7, 126.6, 121.4, 79.7, 71.9, 63.6, 59.5, 53.1, 14.0. HRMS (APCITOF, m/z) calcd for C27H23ClNO4S [M + H]+: 492.1031, found: 492.1038. Ethyl 4-((2-Chlorophenyl)imino)-3-oxo-1,6-diphenylhexahydrothieno[3,4-c]furan-3a-carboxylate (3ah). Purified by column chromatography (petroleum ether/ethyl acetate = 7/1) to afford a white solid in 98% yield (144 mg). Mp: 141−142 °C. IR (KBr, cm−1): ν 1780, 1742, 1630, 1585, 1495, 1482, 1458. 1H NMR (CDCl3, 500 MHz): δ 7.46 (d, J = 7.1 Hz, 1H), 7.30 (t, J = 7.7 Hz, 1H), 7.25−7.10 (m, 7H), 7.06 (t, J = 7.6 Hz, 2H), 7.00 (dd, J = 7.8, 1.1 Hz, 1H), 6.67 (d, J = 7.5 Hz, 2H), 5.47 (d, J = 5.9 Hz, 1H), 5.31 (d, J = 8.5 Hz, 1H), 4.53−4.42 (m, 2H), 4.14 (dd, J = 8.5, 6.0 Hz, 1H), 1.44 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 166.6, 165.4, 165.2, 148.5, 136.7, 133.0, 130.2, 128.9, 128.8, 128.7, 128.4, 127.7, 127.6, 126.7, 126.1, 124.3, 120.1, 79.7, 71.5, 63.6, 59.9, 52.8, 14.1. HRMS (APCITOF, m/z) calcd for C27H23ClNO4S [M + H]+: 492.1031, found: 492.1038. Ethyl 4-((4-Fluorophenyl)imino)-3-oxo-1,6-diphenylhexahydrothieno[3,4-c]furan-3a-carboxylate (3ai). Purified by column chromatography (petroleum ether/ethyl acetate = 7/1) to afford a white solid in 99% yield (141 mg). Mp: 147−148 °C. IR (KBr, cm−1): ν 1786, 1736, 1639, 1499. 1H NMR (CDCl3, 500 MHz): δ 7.25−7.01 (m, 12H), 6.65 (d, J = 7.7 Hz, 2H), 5.44 (d, J = 5.9 Hz, 1H), 5.26 (d, J = 8.5 Hz, 1H), 4.45 (q, J = 7.1 Hz, 2H), 4.08 (dd, J = 8.4, 6.0 Hz, 1H), 1.42 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 167.0, 165.6, 162.1, 160.5 (d, 1JFC = 244.4 Hz), 146.9, 136.8, 133.1, 128.9, 128.8, 128.7, 128.4, 127.8, 126.7, 121.7 (d, 3JFC = 8.2 Hz), 116.0 (d, 2JFC = 22.7 Hz), 79.7, 72.1, 63.6, 59.3, 53.0, 14.1. HRMS (APCI-TOF, m/z) calcd for C27H23FNO4S [M + H]+: 476.1326, found: 476.1328. Ethyl 3-Oxo-1,6-diphenyl-4-((4-(trifluoromethyl)phenyl)imino)hexahydrothieno[3,4-c]furan-3a-car-boxylate (3aj). Purified by column chromatography (petroleum ether/ethyl acetate = 6/1) to afford a white solid in 96% yield (151 mg). Mp: 103−104 °C. IR (KBr, cm−1): ν 1788, 1736, 1639, 1607, 1495, 1452. 1H NMR (CDCl3, 500 MHz): δ 7.67 (d, J = 8.4 Hz, 2H), 7.25−7.12 (m, 8H), 7.07 (t, J = 7.6 Hz, 2H), 6.66 (d, J = 7.5 Hz, 2H), 5.46 (d, J = 6.0 Hz, 1H), 5.28 (d, J = 8.5 Hz, 1H), 4.46 (q, J = 7.1 Hz, 2H), 4.11 (dd, J = 8.4, 6.0 Hz, 1H), 1.43 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 166.8, 165.4, 164.1, 153.9, 136.7, 132.7, 128.90, 128.86, 128.7, 128.4, 127.7, 127.4 (q, 2JFC = 32.6 Hz), 126.6, 126.5 (q, 3JFC = 3.5 Hz), 124.2 (q, 1JFC = 271.8 Hz), 119.9, 79.8, 72.1, 63.6, 59.5, 53.1, 14.1. HRMS (APCITOF, m/z) calcd for C28H23F3NO4S [M + H]+: 526.1294, found: 526.1293. Ethyl 4-((4-Nitrophenyl)imino)-3-oxo-1,6-diphenylhexahydrothieno[3,4-c]furan-3a-carboxylate (3ak). Purified by column chro179

DOI: 10.1021/acs.joc.7b02561 J. Org. Chem. 2018, 83, 174−184

Article

The Journal of Organic Chemistry

7.4 Hz, 2H), 6.13−5.97 (m, 1H), 5.42 (d, J = 5.9 Hz, 1H), 5.31 (dd, J = 17.2, 1.6 Hz, 1H), 5.25−5.15 (m, 2H), 4.40 (q, J = 7.1 Hz, 2H), 4.27−4.13 (m, 2H), 4.02 (dd, J = 8.4, 5.9 Hz, 1H), 1.38 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 167.2, 165.8, 160.4, 137.0, 133.5, 133.2, 128.9, 128.7, 128.6, 128.3, 127.8, 126.6, 116.5, 79.5, 71.4, 63.3, 61.2, 59.7, 52.6, 14.1. HRMS (APCI-TOF, m/z) calcd for C24H24NO4S [M + H]+: 422.1421, found: 422.1428. Ethyl 3-Oxo-4-(phenethylimino)-1,6-diphenylhexahydrothieno[3,4-c]furan-3a-carboxylate (3aq). Purified by column chromatography (petroleum ether/ethyl acetate = 6/1) to afford a white solid in 98% yield (142 mg). Mp: 120−121 °C. IR (KBr, cm−1): ν 1782, 1730, 1639, 1493, 1452. 1H NMR (CDCl3, 500 MHz): δ 7.32−7.16 (m, 5H), 7.15−7.02 (m, 4H), 7.02−6.92 (m, 4H), 6.52 (d, J = 7.5 Hz, 2H), 5.20 (d, J = 5.9 Hz, 1H), 4.74 (d, J = 8.8 Hz, 1H), 4.39−4.25 (m, 2H), 3.98−3.84 (m, 2H), 3.60−3.52 (m, 1H), 3.12−2.96 (m, 2H), 1.30 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 167.1, 165.6, 160.1, 139.7, 136.7, 133.5, 129.5, 128.7, 128.6, 128.5, 128.4, 128.2, 127.7, 126.7, 126.2, 79.2, 71.4, 63.3, 61.0, 59.4, 51.9, 36.0, 14.1. HRMS (APCI-TOF, m/z) calcd for C29H28NO4S [M + H]+: 486.1734, found: 486.1734. Ethyl 4-(Butylimino)-3-oxo-1,6-diphenylhexahydrothieno[3,4-c]furan-3a-carboxylate (3ar). Purified by column chromatography (petroleum ether/ethyl acetate = 7/1) to afford a white solid in 98% yield (128 mg). Mp: 105−106 °C. IR (KBr, cm−1): ν 1788, 1736, 1639, 1597, 1495, 1458, 1449. 1H NMR (CDCl3, 500 MHz): δ 7.32− 7.15 (m, 5H), 7.12 (t, J = 7.4 Hz, 1H), 7.03 (t, J = 7.6 Hz, 2H), 6.62 (d, J = 7.4 Hz, 2H), 5.38 (d, J = 5.8 Hz, 1H), 5.19 (d, J = 8.4 Hz, 1H), 4.37 (q, J = 7.1 Hz, 2H), 3.99 (dd, J = 8.4, 5.9 Hz, 1H), 3.63−3.52 (m, 1H), 3.52−3.41 (m, 1H), 1.84−1.70 (m, 2H), 1.51−1.38 (m, 2H), 1.36 (t, J = 7.1 Hz, 3H), 0.96 (t, J = 7.4 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 167.3, 165.9, 158.4, 137.0, 133.5, 128.8, 128.6, 128.5, 128.2, 127.7, 126.6, 79.4, 71.1, 63.1, 59.6, 59.2, 52.2, 31.6, 20.5, 14.0, 13.8. HRMS (APCI-TOF, m/z) calcd for C25H28NO4S [M + H]+: 438.1734, found: 438.1733. Ethyl 4-(Cyclohexylimino)-3-oxo-1,6-diphenylhexahydrothieno[3,4-c]furan-3a-carboxylate (3as). Purified by column chromatography (petroleum ether/ethyl acetate = 7/1) to afford a white solid in 95% yield (132 mg). Mp: 146−147 °C. IR (KBr, cm−1): ν 1786, 1749, 1734, 1638, 1497, 1456. 1H NMR (CDCl3, 500 MHz): δ 7.31−7.09 (m, 6H), 7.04 (t, J = 7.6 Hz, 2H), 6.63 (d, J = 7.5 Hz, 2H), 5.37 (d, J = 5.9 Hz, 1H), 5.20 (d, J = 8.5 Hz, 1H), 4.38 (q, J = 7.1 Hz, 2H), 3.97 (dd, J = 8.5, 5.9 Hz, 1H), 3.24−3.12 (m, 1H), 1.93−1.78 (m, 4H), 1.71−1.55 (m, 3H), 1.48−1.23 (m, 6H). 13C NMR (CDCl3, 125 MHz): δ 167.4, 166.1, 155.9, 137.2, 133.7, 128.8, 128.6, 128.5, 128.2, 127.8, 126.7, 79.4, 71.1, 68.9, 63.2, 59.6, 52.2, 32.5, 31.8, 25.6, 24.7, 24.5, 14.0. HRMS (APCI-TOF, m/z) calcd for C27H30NO4S [M + H]+: 464.1890, found: 464.1897. Ethyl 3-Oxo-1-phenyl-4-(phenylimino)-6-(p-tolyl)hexahydrothieno[3,4-c]furan-3a-carboxylate (3ba). Purified by column chromatography (petroleum ether/ethyl acetate = 6/1) to afford a white solid in 96% yield (135 mg). Mp: 153−154 °C. IR (KBr, cm−1): ν 1782, 1746, 1630, 1591, 1514, 1487, 1454. 1H NMR (CDCl3, 500 MHz): δ 7.41 (t, J = 7.9 Hz, 2H), 7.21 (t, J = 7.5 Hz, 1H), 7.16 (t, J = 7.4 Hz, 1H), 7.13−7.02 (m, 6H), 6.95 (d, J = 8.0 Hz, 2H), 6.67 (d, J = 7.5 Hz, 2H), 5.39 (d, J = 6.0 Hz, 1H), 5.26 (d, J = 8.5 Hz, 1H), 4.45 (q, J = 7.1 Hz, 2H), 4.05 (dd, J = 8.4, 6.0 Hz, 1H), 2.27 (s, 3H), 1.42 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 167.1, 165.7, 162.0, 151.1, 138.7, 137.0, 130.1, 129.4, 129.1, 128.6, 128.2, 127.6, 126.7, 125.5, 119.9, 79.7, 71.9, 63.4, 59.6, 52.6, 20.9, 14.1. HRMS (APCI-TOF, m/z) calcd for C28H26NO4S [M + H]+: 472.1577, found: 472.1573. Ethyl 6-(4-Anisyl)-3-oxo-1-phenyl-4-(phenylimino)hexahydrothieno[3,4-c]furan-3a-carboxylate (3ca). Purified by column chromatography (petroleum ether/ethyl acetate = 5/1) to afford a white solid in 92% yield (134 mg). Mp: 160−161 °C. IR (KBr, cm−1): ν 1788, 1742, 1628, 1591, 1512, 1487, 1454. 1H NMR (CDCl3, 500 MHz): δ 7.41 (d, J = 7.9 Hz, 2H), 7.24−7.14 (m, 2H), 7.14−7.04 (m, 6H), 6.71 (d, J = 7.4 Hz, 2H), 6.67 (d, J = 8.7 Hz, 2H), 5.38 (d, J = 6.0 Hz, 1H), 5.26 (d, J = 8.5 Hz, 1H), 4.45 (q, J = 7.1 Hz, 2H), 4.04 (dd, J = 8.4, 6.0 Hz, 1H), 3.74 (s, 3H), 1.42 (t, J = 7.1 Hz, 3H). 13C NMR

matography (petroleum ether/ethyl acetate = 6/1) to afford a white solid in 97% yield (146 mg). Mp: 190−191 °C. IR (KBr, cm−1): ν 1788, 1744, 1647, 1589, 1514. 1H NMR (CDCl3, 500 MHz): δ 8.30 (d, J = 8.8 Hz, 2H), 7.28−7.14 (m, 8H), 7.08 (t, J = 7.6 Hz, 2H), 6.66 (d, J = 7.6 Hz, 2H), 5.48 (d, J = 6.0 Hz, 1H), 5.29 (d, J = 8.5 Hz, 1H), 4.47 (q, J = 7.1 Hz, 2H), 4.12 (dd, J = 8.4, 6.1 Hz, 1H), 1.44 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 166.6, 165.3, 165.1, 156.5, 145.2, 136.6, 132.5, 129.0, 128.9, 128.4, 127.7, 126.6, 125.3, 120.2, 79.9, 72.2, 63.8, 59.6, 53.5, 14.1. HRMS (APCI-TOF, m/z) calcd for C27H23N2O6S [M + H]+: 503.1271, found: 503.1278. Ethyl 4-((3-Nitrophenyl)imino)-3-oxo-1,6-diphenylhexahydrothieno[3,4-c]furan-3a-carboxylate (3al). Purified by column chromatography (petroleum ether/ethyl acetate = 6/1) to afford a white solid in 96% yield (144 mg). Mp: 163−164 °C. IR (KBr, cm−1): ν 1788, 1736, 1639, 1526. 1H NMR (CDCl3, 500 MHz): δ 8.08 (d, J = 8.2 Hz, 1H), 7.96 (t, J = 2.0 Hz, 1H), 7.59 (t, J = 8.1 Hz, 1H), 7.41 (d, J = 7.8 Hz, 1H), 7.28−7.13 (m, 6H), 7.08 (t, J = 7.6 Hz, 2H), 6.67 (d, J = 7.5 Hz, 2H), 5.48 (d, J = 6.0 Hz, 1H), 5.29 (d, J = 8.5 Hz, 1H), 4.48 (q, J = 7.1 Hz, 2H), 4.12 (dd, J = 8.5, 6.0 Hz, 1H), 1.45 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 166.8, 165.4, 165.3, 151.9, 148.9, 136.6, 132.6, 130.2, 129.0, 128.8, 128.4, 127.7, 126.7, 126.4, 120.3, 114.8, 79.8, 72.3, 63.8, 59.5, 53.5, 14.1. HRMS (APCI-TOF, m/ z) calcd for C27H23N2O6S [M + H]+: 503.1271, found: 503.1275. Ethyl 4-((2-Nitrophenyl)imino)-3-oxo-1,6-diphenylhexahydrothieno[3,4-c]furan-3a-carboxylate (3am). Purified by column chromatography (petroleum ether/ethyl acetate = 6/1) to afford a white solid in 93% yield (140 mg). Mp: 160−161 °C. IR (KBr, cm−1): ν 1784, 1748, 1651, 1601, 1568, 1519, 1472, 1454. 1H NMR (CDCl3, 500 MHz): δ 8.16 (d, J = 8.3 Hz, 1H), 7.66 (t, J = 8.1 Hz, 1H), 7.33 (t, J = 7.8 Hz, 1H), 7.25−7.12 (m, 6H), 7.12−7.02 (m, 3H), 6.69 (d, J = 7.5 Hz, 2H), 5.53 (d, J = 5.9 Hz, 1H), 5.39 (d, J = 8.7 Hz, 1H), 4.58− 4.45 (m, 2H), 4.20 (dd, J = 8.6, 6.0 Hz, 1H), 1.47 (t, J = 7.1 Hz, 3H). 13 C NMR (CDCl3, 125 MHz): δ 166.3, 165.8, 164.9, 145.7, 138.9, 136.5, 134.7, 132.8, 128.93, 128.91, 128.7, 128.3, 127.7, 126.8, 125.6, 125.4, 121.5, 79.7, 71.9, 63.9, 59.9, 53.4, 14.1. HRMS (APCI-TOF, m/ z) calcd for C27H23N2O6S [M + H]+: 503.1271, found: 503.1279. Ethyl 4-(Benzylimino)-3-oxo-1,6-diphenylhexahydrothieno[3,4c]furan-3a-carboxylate (3an). Purified by column chromatography (petroleum ether/ethyl acetate = 6/1) to afford a white solid in 97% yield (137 mg). Mp: 137−138 °C. IR (KBr, cm−1): ν 1786, 1736, 1632, 1601, 1584, 1495, 1450. 1H NMR (CDCl3, 500 MHz): δ 7.32 (d, J = 7.6 Hz, 2H), 7.26 (t, J = 7.6 Hz, 2H), 7.22−7.02 (m, 7H), 6.97 (t, J = 7.6 Hz, 2H), 6.57 (d, J = 7.4 Hz, 2H), 5.35 (d, J = 5.9 Hz, 1H), 5.14 (d, J = 8.5 Hz, 1H), 4.73 (d, J = 15.2 Hz, 1H), 4.64 (d, J = 15.2 Hz, 1H), 4.30 (q, J = 7.1 Hz, 2H), 3.96 (dd, J = 8.2, 6.0 Hz, 1H), 1.26 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 167.1, 165.8, 160.8, 138.0, 137.0, 133.3, 128.8, 128.7, 128.5, 128.3, 128.2, 127.7, 127.6, 126.9, 126.6, 79.5, 71.5, 63.3, 62.1, 59.6, 52.7, 14.0. HRMS (APCI-TOF, m/z) calcd for C28H26NO4S [M + H]+: 472.1577, found: 472.1581. Ethyl 4-((4-Fluorobenzyl)imino)-3-oxo-1,6-diphenylhexahydrothieno[3,4-c]furan-3a-carboxylate (3ao). Purified by column chromatography (petroleum ether/ethyl acetate = 6/1) to afford a white solid in 97% yield (142 mg). Mp: 153−154 °C. IR (KBr, cm−1): ν 1782, 1730, 1618, 1599, 1508, 1460, 1449. 1H NMR (CDCl3, 500 MHz): δ 7.44−7.33 (m, 2H), 7.31−7.17 (m, 5H), 7.14 (t, J = 7.3 Hz, 1H), 7.11−6.99 (m, 4H), 6.64 (d, J = 7.5 Hz, 2H), 5.44 (d, J = 4.7 Hz, 1H), 5.22 (d, J = 8.0 Hz, 1H), 4.76 (d, J = 14.8 Hz, 1H), 4.67 (d, J = 14.9 Hz, 1H), 4.38 (q, J = 7.0 Hz, 2H), 4.09−3.99 (m, 1H), 1.35 (t, J = 7.0 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 167.1, 165.9, 162.0 (d, 1 JFC = 244.6 Hz), 161.2, 137.0, 133.8, 133.3, 129.3 (d, 3JFC = 8.0 Hz), 128.9, 128.8, 128.6, 128.3, 127.8, 126.7, 115.2 (d, 2JFC = 21.3 Hz), 79.6, 71.6, 63.4, 61.4, 59.8, 52.9, 14.1. HRMS (APCI-TOF, m/z) calcd for C28H25FNO4S [M + H]+: 490.1483, found: 490.1480. Ethyl 4-(Allylimino)-3-oxo-1,6-diphenylhexahydrothieno[3,4-c]furan-3a-carboxylate (3ap). Purified by column chromatography (petroleum ether/ethyl acetate = 8/1) to afford a white solid in 99% yield (125 mg). Mp: 114−115 °C. IR (KBr, cm−1): ν 1786, 1753, 1634, 1599, 1493, 1450. 1H NMR (CDCl3, 500 MHz): δ 7.31−7.17 (m, 5H), 7.14 (t, J = 7.4 Hz, 1H), 7.05 (t, J = 7.6 Hz, 2H), 6.64 (d, J = 180

DOI: 10.1021/acs.joc.7b02561 J. Org. Chem. 2018, 83, 174−184

Article

The Journal of Organic Chemistry (CDCl3, 125 MHz): δ 167.1, 165.7, 161.9, 160.0, 151.1, 137.0, 129.1, 128.9, 128.7, 128.3, 126.7, 125.6, 125.1, 119.9, 114.2, 79.6, 72.0, 63.5, 59.6, 55.4, 52.3, 14.1. HRMS (APCI-TOF, m/z) calcd for C28H26NO5S [M + H]+: 488.1526, found: 488.1524. Ethyl 6-(4-Anisyl)-4-((4-anisyl)imino)-3-oxo-1-phenylhexahydrothieno[3,4-c]furan-3a-carboxylate (3 cd). Purified by column chromatography (petroleum ether/ethyl acetate = 5/1) to afford a white solid in 95% yield (147 mg). Mp: 151−152 °C. IR (KBr, cm−1): ν 1786, 1734, 1630, 1600, 1503, 1458, 1450. 1H NMR (CDCl3, 500 MHz): δ 7.21−7.04 (m, 7H), 6.94 (d, J = 8.8 Hz, 2H), 6.71 (d, J = 7.5 Hz, 2H), 6.67 (d, J = 8.6 Hz, 2H), 5.38 (d, J = 6.0 Hz, 1H), 5.24 (d, J = 8.5 Hz, 1H), 4.43 (q, J = 7.1 Hz, 2H), 4.01 (dd, J = 8.4, 6.0 Hz, 1H), 3.82 (s, 3H), 3.74 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 167.3, 165.9, 159.94, 159.87, 157.6, 143.8, 137.0, 128.9, 128.6, 128.3, 126.7, 125.2, 121.9, 114.2, 114.1, 79.7, 72.1, 63.4, 59.4, 55.4, 52.4, 14.1. HRMS (APCI-TOF, m/z) calcd for C29H28NO6S [M + H]+: 518.1632, found: 518.1637. Ethyl 6-(3-Anisyl)-3-oxo-1-phenyl-4-(phenylimino)hexahydrothieno[3,4-c]furan-3a-carboxylate (3da). Purified by column chromatography (petroleum ether/ethyl acetate = 5/1) to afford a white solid in 96% yield (140 mg). Mp: 165−166 °C. IR (KBr, cm−1): ν 1782, 1745, 1628, 1594, 1582, 1490. 1H NMR (CDCl3, 500 MHz): δ 7.41 (t, J = 7.8 Hz, 2H), 7.24−7.15 (m, 2H), 7.15−7.04 (m, 5H), 6.81 (d, J = 7.6 Hz, 1H), 6.78−6.67 (m, 3H), 6.62 (s, 1H), 5.38 (d, J = 5.9 Hz, 1H), 5.26 (d, J = 8.5 Hz, 1H), 4.46 (q, J = 7.1 Hz, 2H), 4.08 (dd, J = 8.5, 6.0 Hz, 1H), 3.59 (s, 3H), 1.43 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 167.0, 165.8, 161.7, 160.0, 151.0, 137.0, 134.7, 129.9, 129.2, 128.7, 128.3, 126.8, 125.6, 119.9, 114.5, 113.4, 79.7, 71.8, 63.5, 59.4, 55.3, 52.7, 14.2. HRMS (APCI-TOF, m/z) calcd for C28H26NO5S [M + H]+: 488.1526, found: 488.1527. Ethyl 6-(2-Anisyl)-3-oxo-1-phenyl-4-(phenylimino)hexahydrothieno[3,4-c]furan-3a-carboxylate (3ea). Purified by column chromatography (petroleum ether/ethyl acetate = 5/1) to afford a white solid in 93% yield (136 mg). Mp: 183−184 °C. IR (KBr, cm−1): ν 1784, 1742, 1641, 1591, 1487, 1458. 1H NMR (CDCl3, 500 MHz): δ 7.52−7.38 (m, 3H), 7.25−7.13 (m, 3H), 7.13−7.03 (m, 4H), 6.92 (t, J = 7.5 Hz, 1H), 6.64 (d, J = 7.5 Hz, 2H), 6.36 (d, J = 8.2 Hz, 1H), 5.57 (d, J = 5.8 Hz, 1H), 5.07 (d, J = 8.8 Hz, 1H), 4.53−4.43 (m, 2H), 4.40 (dd, J = 8.7, 5.9 Hz, 1H), 3.28 (s, 3H), 1.43 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 167.6, 166.1, 161.7, 156.9, 151.2, 136.9, 129.9, 129.1, 128.5, 128.1, 127.8, 127.0, 125.5, 122.0, 120.3, 119.9, 110.2, 80.2, 71.9, 63.3, 56.4, 54.8, 48.6, 14.1. HRMS (APCI-TOF, m/ z) calcd for C28H26NO5S [M + H]+: 488.1526, found: 488.1519. Ethyl 6-(4-Bromophenyl)-3-oxo-1-phenyl-4-(phenylimino)hexahydrothieno[3,4-c]furan-3a-carboxyl-ate (3fa). Purified by column chromatography (petroleum ether/ethyl acetate = 6/1) to afford a white solid in 95% yield (152 mg). Mp: 165−166 °C. IR (KBr, cm−1): ν 1782, 1726, 1647, 1591, 1485, 1458. 1H NMR (CDCl3, 500 MHz): δ 7.42 (t, J = 7.8 Hz, 2H), 7.30−7.17 (m, 4H), 7.17−7.07 (m, 4H), 7.04 (d, J = 8.4 Hz, 2H), 6.71 (d, J = 7.5 Hz, 2H), 5.36 (d, J = 5.9 Hz, 1H), 5.17 (d, J = 8.7 Hz, 1H), 4.46 (q, J = 7.1 Hz, 2H), 4.09 (dd, J = 8.7, 6.0 Hz, 1H), 1.43 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 166.7, 165.5, 161.1, 150.9, 136.4, 132.4, 131.8, 129.3, 129.2, 129.0, 128.5, 126.8, 125.7, 122.7, 119.8, 79.7, 71.8, 63.6, 59.3, 51.9, 14.1. HRMS (APCI-TOF, m/z) calcd for C27H23BrNO4S [M + H]+: 536.0526, found: 536.0529. Ethyl 6-(4-Chlorophenyl)-3-oxo-1-phenyl-4-(phenylimino)hexahydrothieno[3,4-c]furan-3a-carboxylate (3ga). Purified by column chromatography (petroleum ether/ethyl acetate = 6/1) to afford a white solid in 98% yield (144 mg). Mp: 175−176 °C. IR (KBr, cm−1): ν 1790, 1736, 1636, 1591, 1489, 1474. 1H NMR (CDCl3, 500 MHz): δ 7.42 (t, J = 7.8 Hz, 2H), 7.25−7.17 (m, 2H), 7.17−7.06 (m, 8H), 6.72 (d, J = 7.5 Hz, 2H), 5.38 (d, J = 5.9 Hz, 1H), 5.18 (d, J = 8.7 Hz, 1H), 4.46 (q, J = 7.1 Hz, 2H), 4.09 (dd, J = 8.6, 6.0 Hz, 1H), 1.43 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 166.7, 165.5, 161.2, 151.0, 136.4, 134.6, 131.9, 129.2, 129.0, 128.95, 128.85, 128.4, 126.6, 125.7, 119.8, 79.7, 72.0, 63.7, 59.3, 51.9, 14.1. HRMS (APCI-TOF, m/z) calcd for C27H23ClNO4S [M + H]+: 492.1031, found: 492.1035. Ethyl 6-(3-Chlorophenyl)-3-oxo-1-phenyl-4-(phenylimino)hexahydrothieno[3,4-c]furan-3a-carboxyl-ate (3ha). Purified by column

chromatography (petroleum ether/ethyl acetate = 6/1) to afford a white solid in 97% yield (143 mg). Mp: 170−171 °C. IR (KBr, cm−1): ν 1786, 1738, 1632, 1589, 1481. 1H NMR (CDCl3, 500 MHz): δ 7.42 (t, J = 7.8 Hz, 2H)., 7.25−7.02 (m, 10H), 6.74 (d, J = 7.5 Hz, 2H), 5.37 (d, J = 5.8 Hz, 1H), 5.22 (d, J = 8.8 Hz, 1H), 4.47 (q, J = 7.1 Hz, 2H), 4.11 (dd, J = 8.7, 5.9 Hz, 1H), 1.44 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 166.7, 165.4, 161.1, 150.9, 136.3, 135.4, 135.0, 130.0, 129.2, 129.1, 128.8, 128.5, 128.0, 127.0, 125.9, 125.8, 119.9, 79.7, 71.8, 63.5, 58.9, 52.0, 14.2. HRMS (APCI-TOF, m/z) calcd for C27H23ClNO4S [M + H]+: 492.1031, found: 492.1027. Ethyl 6-(2-Chlorophenyl)-3-oxo-1-phenyl-4-(phenylimino)hexahydrothieno[3,4-c]furan-3a-carboxyl-ate (3ia). Purified by column chromatography (petroleum ether/ethyl acetate = 6/1) to afford a white solid in 98% yield (144 mg). Mp: 159−160 °C. IR (KBr, cm−1): ν 1790, 1742, 1626, 1589, 1485, 1460. 1H NMR (CDCl3, 500 MHz): δ 7.65 (d, J = 7.6 Hz, 1H), 7.42 (t, J = 7.8 Hz, 2H), 7.31−7.05 (m, 8H), 6.99 (d, J = 7.9 Hz, 1H), 6.72 (d, J = 7.5 Hz, 2H), 5.71 (d, J = 5.9 Hz, 1H), 5.15 (d, J = 8.8 Hz, 1H), 4.52−4.42 (m, 3H), 1.43 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 166.8, 165.4, 160.9, 150.9, 135.7, 134.0, 131.2, 130.0, 129.95, 129.2, 128.91, 128.86, 128.3, 127.0, 126.9, 125.7, 119.9, 79.7, 71.7, 63.5, 55.5, 50.2, 14.2. HRMS (APCITOF, m/z) calcd for C27H23ClNO4S [M + H]+: 492.1031, found: 492.1028. Ethyl 6-(4-Nitrophenyl)-3-oxo-1-phenyl-4-(phenylimino)hexahydrothieno[3,4-c]furan-3a-carboxylate (3ja). Purified by column chromatography (petroleum ether/ethyl acetate = 5/1) to afford a white solid in 98% yield (147 mg). Mp: 150−151 °C. IR (KBr, cm−1): ν 1774, 1746, 1639, 1593, 1520, 1487, 1460. 1H NMR (CDCl3, 500 MHz): δ 7.94 (d, J = 8.7 Hz, 2H), 7.44 (t, J = 7.9 Hz, 2H), 7.35 (d, J = 8.7 Hz, 2H), 7.26−7.02 (m, 6H), 6.74 (d, J = 7.4 Hz, 2H), 5.49 (d, J = 5.9 Hz, 1H), 5.15 (d, J = 9.0 Hz, 1H), 4.56−4.43 (m, 2H), 4.22 (dd, J = 9.0, 5.9 Hz, 1H), 1.45 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 166.2, 165.2, 160.1, 150.7, 147.9, 140.8, 135.7, 129.4, 129.3, 128.9, 128.6, 127.1, 126.1, 123.7, 119.8, 79.5, 71.7, 63.9, 58.8, 51.8, 14.2. HRMS (APCI-TOF, m/z) calcd for C27H23N2O6S [M + H]+: 503.1271, found: 503.1274. Ethyl 4-((4-Anisyl)imino)-6-(4-nitrophenyl)-3-oxo-1-phenylhexahydrothieno[3,4-c]furan-3a-carboxyl-ate (3jd). Purified by column chromatography (petroleum ether/ethyl acetate = 5/1) to afford a white solid in 94% yield (150 mg). Mp: 182−183 °C. IR (KBr, cm−1): ν 1782, 1728, 1634, 1607, 1524, 1504, 1460. 1H NMR (CDCl3, 500 MHz): δ 7.92 (d, J = 8.6 Hz, 2H), 7.35 (d, J = 8.6 Hz, 2H), 7.22−7.10 (m, 3H), 7.05 (t, J = 7.7 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 6.73 (d, J = 7.6 Hz, 2H), 5.50 (d, J = 5.9 Hz, 1H), 5.12 (d, J = 9.0 Hz, 1H), 4.53− 4.40 (m, 2H), 4.20 (dd, J = 9.0, 5.9 Hz, 1H), 3.83 (s, 3H), 1.41 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 166.3, 165.3, 158.0, 157.9, 147.7, 143.3, 140.9, 135.6, 129.3, 128.9, 128.5, 127.0, 123.6, 121.9, 114.3, 79.3, 71.8, 63.8, 58.4, 55.5, 51.7, 14.1. HRMS (APCITOF, m/z) calcd for C28H25N2O7S [M + H]+: 533.1377, found: 533.1377. Ethyl 3-Oxo-6-phenyl-4-(phenylimino)-1-(p-tolyl)hexahydrothieno[3,4-c]furan-3a-carboxylate (3ka). Purified by column chromatography (petroleum ether/ethyl acetate = 7/1) to afford a white solid in 95% yield (134 mg). Mp: 179−180 °C. IR (KBr, cm−1): ν 1786, 1742, 1636, 1593, 1516, 1487, 1452. 1H NMR (CDCl3, 500 MHz): δ 7.41 (t, J = 7.8 Hz, 2H), 7.25−7.14 (m, 6H), 7.10 (d, J = 7.5 Hz, 2H), 6.87 (d, J = 7.9 Hz, 2H), 6.54 (d, J = 8.0 Hz, 2H), 5.42 (d, J = 5.9 Hz, 1H), 5.26 (d, J = 8.4 Hz, 1H), 4.46 (q, J = 7.1 Hz, 2H), 4.06 (dd, J = 8.4, 6.0 Hz, 1H), 2.23 (s, 3H), 1.43 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 167.1, 165.7, 161.9, 151.0, 138.5, 134.0, 133.2, 129.1, 128.9, 128.8, 128.7, 127.8, 126.5, 125.5, 119.8, 79.7, 72.0, 63.4, 59.3, 52.9, 21.1, 14.1. HRMS (APCI-TOF, m/z) calcd for C28H26NO4S [M + H]+: 472.1577, found: 472.1572. Ethyl 1-(4-Anisyl)-3-oxo-6-phenyl-4-(phenylimino)hexahydrothieno[3,4-c]furan-3a-carboxylate (3la). Purified by column chromatography (petroleum ether/ethyl acetate = 5/1) to afford a white solid in 95% yield (139 mg). Mp: 171−172 °C. IR (KBr, cm−1): ν 1786, 1734, 1636, 1591, 1514, 1489, 1450. 1H NMR (CDCl3, 500 MHz): δ 7.41 (t, J = 7.9 Hz, 2H), 7.25−7.13 (m, 6H), 7.10 (d, J = 8.4 Hz, 2H), 6.66−6.54 (m, 4H), 5.42 (d, J = 5.9 Hz, 1H), 5.24 (d, J = 8.6 181

DOI: 10.1021/acs.joc.7b02561 J. Org. Chem. 2018, 83, 174−184

Article

The Journal of Organic Chemistry Hz, 1H), 4.46 (q, J = 7.1 Hz, 2H), 4.06 (dd, J = 8.6, 6.0 Hz, 1H), 3.71 (s, 3H), 1.43 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 167.0, 165.7, 161.9, 159.7, 151.1, 133.2, 129.1, 128.9, 128.8, 128.7, 128.1, 127.7, 125.6, 119.9, 113.7, 79.6, 72.1, 63.5, 59.3, 55.2, 52.8, 14.1. HRMS (APCI-TOF, m/z) calcd for C28H26NO5S [M + H]+: 488.1526, found: 488.1524. Ethyl 1-(3-Anisyl)-3-oxo-6-phenyl-4-(phenylimino)hexahydrothieno[3,4-c]furan-3a-carboxylate (3ma). Purified by column chromatography (petroleum ether/ethyl acetate = 5/1) to afford a white solid in 97% yield (141 mg). Mp: 159−160 °C. IR (KBr, cm−1): ν 1786, 1734, 1636, 1591, 1514, 1489, 1450. 1H NMR (CDCl3, 500 MHz): δ 7.41 (t, J = 7.8 Hz, 2H), 7.26−7.15 (m, 6H), 7.09 (d, J = 7.4 Hz, 2H), 6.99 (t, J = 8.0 Hz, 1H), 6.69 (dd, J = 8.2, 2.4 Hz, 1H), 6.26 (d, J = 7.6 Hz, 1H), 6.19 (s,1H), 5.43 (d, J = 5.9 Hz, 1H), 5.24 (d, J = 8.3 Hz, 1H), 4.46 (q, J = 7.1 Hz, 2H), 4.08 (dd, J = 8.3, 6.0 Hz, 1H), 3.65 (s, 3H), 1.43 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 167.1, 165.7, 161.7, 159.4, 151.1, 138.5, 133.3, 129.5, 129.2, 128.83, 128.78, 127.9, 125.6, 119.9, 118.9, 114.7, 112.1, 79.6, 71.9, 63.5, 59.4, 55.2, 52.9, 14.2. HRMS (APCI-TOF, m/z) calcd for C28H26NO5S [M + H]+: 488.1526, found: 488.1531. Ethyl 1-(2-Anisyl)-3-oxo-6-phenyl-4-(phenylimino)hexahydrothieno[3,4-c]furan-3a-carboxylate (3na). Purified by column chromatography (petroleum ether/ethyl acetate = 5/1) to afford a white solid in 97% yield (141 mg). Mp: 167−168 °C. IR (KBr, cm−1): ν 1778, 1719, 1628, 1590, 1494, 1465. 1H NMR (CDCl3, 500 MHz): δ 7.40 (t, J = 7.8 Hz, 2H), 7.25−7.13 (m, 7H), 7.07 (d, J = 8.3 Hz, 2H), 7.76 (d, J = 8.3 Hz, 1H), 6.56 (t, J = 7.5 Hz, 1H), 6.25 (d, J = 7.5 Hz, 1H), 5.42 (d, J = 6.3 Hz, 1H), 5.26 (d, J = 7.1 Hz, 1H), 4.52−4.37 (m, 2H), 4.33 (dd, J = 6.7, 6.7 Hz, 1H), 3.77 (s, 3H), 1.41 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 167.8, 165.9, 163.3, 157.1, 151.3, 133.7, 130.3, 129.0, 128.7, 128.6, 128.4, 127.8, 125.4, 124.8, 120.0, 119.9, 111.0, 78.4, 71.4, 63.0, 56.2, 55.3, 53.8, 14.2. HRMS (APCI-TOF, m/z) calcd for C28H26NO5S [M + H]+: 488.1526, found: 488.1528. Ethyl 1-(4-Bromophenyl)-3-oxo-6-phenyl-4-(phenylimino)hexahydrothieno[3,4-c]furan-3a-carboxyl-ate (3oa). Purified by column chromatography (petroleum ether/ethyl acetate = 6/1) to afford a white solid in 94% yield (150 mg). Mp: 208−209 °C. IR (KBr, cm−1): ν 1790, 1740, 1634, 1591, 1487, 1450. 1H NMR (CDCl3, 500 MHz): δ 7.41 (t, J = 7.9 Hz, 2H), 7.29−7.15 (m, 8H), 7.14−7.06 (m, 2H), 6.50 (d, J = 8.5 Hz, 2H), 5.43 (d, J = 5.9 Hz, 1H), 5.23 (d, J = 8.5 Hz, 1H), 4.46 (q, J = 7.1 Hz, 2H), 4.00 (dd, J = 8.5, 6.0 Hz, 1H), 1.43 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 166.8, 165.5, 161.4, 150.9, 136.1, 133.2, 131.5, 129.2, 129.0, 128.9, 128.2, 127.8, 125.7, 122.8, 119.9, 78.8, 71.8, 63.6, 59.5, 52.7, 14.1. HRMS (APCI-TOF, m/z) calcd for C27H23BrNO4S [M + H]+: 536.0526, found: 536.0519. Ethyl 1-(4-Nitrophenyl)-3-oxo-6-phenyl-4-(phenylimino)hexahydrothieno[3,4-c]furan-3a-carboxylate (3pa). Purified by column chromatography (petroleum ether/ethyl acetate = 5/1) to afford a white solid in 96% yield (144 mg). Mp: 147−148 °C. IR (KBr, cm−1): ν 1791, 1740, 1640, 1623, 1594. 1536, 1490, 1452. 1H NMR (CDCl3, 500 MHz): δ 7.92 (d, J = 8.7 Hz, 2H), 7.42 (t, J = 7.8 Hz, 2H), 7.34− 7.18 (m, 6H), 7.09 (d, J = 7.4 Hz, 2H), 6.77 (d, J = 8.7 Hz, 2H), 5.45 (d, J = 5.8 Hz,1H), 5.36 (d, J = 8.5 Hz, 1H), 4.47 (q, J = 7.1 Hz, 2H), 4.00 (dd, J = 8.5, 5.9 Hz, 1H), 1.43 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 166.5, 165.3, 160.8, 150.7, 147.8, 144.0, 133.2, 129.2, 127.8, 127.6, 125.8, 123.5, 119.9, 78.0, 71.6, 63.8, 59.7, 52.6, 14.1. HRMS (APCI-TOF, m/z) calcd for C27H23N2O6S [M + H]+: 503.1271, found: 503.1276. Ethyl 4-Oxo-1-phenyl-3-(phenylimino)-1,3,3a,4,5a,10-hexahydroindeno[1,2-b]thieno[3,4-c]furan-3a-carboxylate (3qa). Purified by column chromatography (petroleum ether/ethyl acetate = 7/1) to afford a white solid in 93% yield (131 mg). Mp: 184−195 °C. IR (KBr, cm−1): ν 1791, 1728, 1623, 1590, 1485, 1456. 1H NMR (CDCl3, 500 MHz): δ 7.39 (t, J = 7.8 Hz, 2H), 7.31−7.24 (m, 2H), 7.18 (t, J = 7.4 Hz, 1H), 7.16−7.05 (m, 4H), 7.05−6.95 (m, 5H), 5.92 (s, 1H), 5.29 (s, 1H), 4.56−4.38 (m, 2H), 3.68 (d, J = 17.1 Hz, 1H), 3.25 (d, J = 17.2 Hz, 1H), 1.43 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 167.0, 165,7, 163.1, 150.6, 142.3, 136.2, 131.8, 130.2, 129.1, 128.9, 128.4, 127.8, 127.3, 126.0, 125.6, 124.1, 120.0, 85.3, 73.2, 65.3,

63.0, 58.7, 37.7, 14.3. HRMS (APCI-TOF, m/z) calcd for C28H24NO4S [M + H]+: 470.1421, found: 470.1428. Ethyl 6-(4-Chlorophenyl)-3-oxo-4-(phenylimino)-1-(p-tolyl)hexahydrothieno[3,4-c]furan-3a-carboxyl-ate (3ra). Purified by column chromatography (petroleum ether/ethyl acetate = 7/1) to afford a white solid in 96% yield (145 mg). Mp: 130−131 °C. IR (KBr, cm−1): ν 1790, 1736, 1636, 1591, 1489, 1449. 1H NMR (CDCl3, 500 MHz): δ 7.41 (t, J = 7.9 Hz, 2H), 7.21 (t, J = 7.4 Hz, 1H), 7.16−7.04 (m, 6H), 6.93 (d, J = 7.9 Hz, 2H), 6.60 (d, J = 8.1 Hz, 2H), 5.37 (d, J = 6.0 Hz, 1H), 5.17 (d, J = 8.7 Hz, 1H), 4.46 (q, J = 7.1 Hz, 2H), 4.06 (dd, J = 8.7, 6.0 Hz, 1H), 2.27 (s, 3H), 1.43 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 167.8, 165.6, 161.3, 150.9, 139.0, 134.6, 133.4, 131.9, 129.2, 129.1, 129.0, 128.8, 126.7, 125.7, 119.8, 79.6, 71.9, 63.6, 59.2, 52.0, 21.2, 14.1. HRMS (APCI-TOF, m/z) calcd for C28H25ClNO4S [M + H]+: 506.1187, found: 506.1185. Methyl 3-Oxo-1,6-diphenyl-4-(phenylimino)hexahydrothieno[3,4-c]furan-3a-carboxylate (3sa). Purified by column chromatography (petroleum ether/ethyl acetate = 7/1) to afford a white solid in 97% yield (129 mg). Mp: 201−202 °C. IR (KBr, cm−1): ν 1792, 1749, 1639, 1591, 1489, 1452. 1H NMR (CDCl3, 500 MHz): δ 7.42 (t, J = 7.7 Hz, 2H), 7.25−7.10 (m, 9H), 7.06 (t, J = 7.6 Hz, 2H), 6.65 (d, J = 7.6 Hz, 2H), 5.45 (d, J = 5.9 Hz, 1H), 5.28 (d, J = 8.6 Hz, 1H), 4.11 (dd, J = 8.4, 6.0 Hz, 1H), 4.01 (s, 3H). 13C NMR (CDCl3, 125 MHz): δ 167.0, 166.2, 161.6, 150.8, 136.7, 133.1, 129.1, 128.8, 128.72, 128.67, 128.3, 127.7, 126.7, 125.7, 120.0, 79.7, 71.9, 59.2, 54.3, 52.9. HRMS (APCI-TOF, m/z) calcd for C26H22NO4S [M + H]+: 444.1264, found: 444.1268. Ethyl 5-Cyclohexyl-4-(cyclohexylimino)-3-oxo-1,6-diphenylhexahydro-1H-furo[3,4-c]pyrrole-3a-car-boxylate (5aa). Purified by column chromatography (petroleum ether/ethyl acetate/triethylamine = 96/16/1) to afford a white solid in 99% yield (157 mg). Mp: 160− 161 °C. IR (KBr, cm−1): ν 1791, 1745, 1653. 1H NMR (CDCl3, 500 MHz): δ 7.62−7.20 (m, 4H), 7.19−6.92 (m, 4H), 6.67 (d, J = 6.7 Hz, 2H), 5.02 (d, J = 5.4 Hz, 1H), 4.92 (d, J = 7.8 Hz, 1H), 4.22 (dq, J = 10.7, 7.1 Hz, 1H), 4.13 (dq, J = 10.7, 7.1 Hz, 1H), 3.70−3.58 (m, 1H), 3.44 (dd, J = 7.7, 5.4 Hz, 1H), 3.37−3.26 (m, 1H), 2.31−2.18 (m, 1H), 1.94−1.85 (m, 1H), 1.84−1.69 (m, 5H), 1.69−1.50 (m, 4H), 1.48−0.99 (m, 12H). 13C NMR (CDCl3, 125 MHz): δ 168.8, 168.2, 148.3, 138.8, 138.5, 128.9, 128.5, 128.4, 128.2, 125.5, 78.7, 62.9, 62.6, 61.9, 59.2, 57.0, 56.6, 34.6, 34.1, 29.7, 27.0, 26.4, 26.2, 26.1, 25.8, 24.5, 24.3, 13.8. HRMS (APCI-TOF, m/z) calcd for C33H41N2O4 [M + H]+: 529.3061, found: 529.3060. Ethyl 5-Isopropyl-4-(isopropylimino)-3-oxo-1,6-diphenylhexahydro-1H-furo[3,4-c]pyrrole-3a-car-boxylate (5ab). Purified by column chromatography (petroleum ether/ethyl acetate/triethylamine = 96/16/1) to afford a white solid in 98% yield (131 mg). Mp: 138− 139 °C. IR (KBr, cm−1): ν 1794, 1726, 1668, 1454. 1H NMR (CDCl3, 500 MHz): δ 7.67−7.22 (m, 4H), 7.22−6.89 (m, 4H), 6.64 (d, J = 7.0 Hz, 2H), 5.07 (d, J = 5.6 Hz, 1H), 4.89 (d, J = 7.6 Hz, 1H), 4.24 (dq, J = 10.8, 7.1 Hz, 1H), 4.16 (dq, J = 10.8, 7.1 Hz, 1H), 4.02−3.93 (m, 1H), 3.71−3.62 (m, 1H), 3.43 (dd, J = 7.5, 5.7 Hz, 1H), 1.46 (d, J = 6.8 Hz, 3H), 1.25 (t, J = 7.1 Hz, 3H), 1.19 (d, J = 5.8 Hz, 3H), 1.14 (d, J = 6.7 Hz, 3H), 1.08 (d, J = 6.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 168.8, 167.9, 148.1, 138.7, 138.0, 128.9, 128.5, 128.4, 128.2, 125.4, 78.7, 63.2, 62.6, 61.9, 56.5, 51.7, 48.3, 24.6, 24.1, 19.9, 16.8, 13.7. HRMS (APCI-TOF, m/z) calcd for C27H33N2O4 [M + H]+: 449.2435, found: 449.2436. Ethyl 5-Isopropyl-4-(isopropylimino)-3-oxo-1-phenyl-6-(p-tolyl)hexahydro-1H-furo[3,4-c]pyrrole-3a-carboxylate (5bb). Purified by column chromatography (petroleum ether/ethyl acetate/triethylamine = 60/10/1) to afford a white solid in 96% yield (133 mg). Mp: 127− 128 °C. IR (KBr, cm−1): ν 1782, 1724, 1649, 1512, 1496, 1448. 1H NMR (CDCl3, 500 MHz): δ 7.49−6.75 (m, 7H), 6.69 (d, J = 7.1 Hz, 2H), 5.06 (d, J = 5.3 Hz, 1H), 4.86 (d, J = 7.7 Hz, 1H), 4.28−4.18 (m, 1H), 4.18−4.07 (m, 1H), 4.00−3.88 (m, 1H), 3.76−3.62 (m, 1H), 3.40 (dd, J = 7.3, 5.8 Hz, 1H), 2.37 (s, 3H), 1.43 (d, J = 6.9 Hz, 3H), 1.23 (t, J = 7.1 Hz, 3H), 1.19 (d, J = 5.8 Hz, 3H), 1.11 (d, J = 6.7 Hz, 3H), 1.06 (d, J = 6.0 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 169.0, 168.0, 148.1, 138.9, 138.4, 135.0, 129.6, 128.3, 128.2, 125.4, 78.7, 62.8, 62.6, 61.9, 56.6, 51.7, 48.1, 24.7, 24.0, 21.1, 19.9, 17.0, 13.7. HRMS 182

DOI: 10.1021/acs.joc.7b02561 J. Org. Chem. 2018, 83, 174−184

Article

The Journal of Organic Chemistry

= 6.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 168.8, 168.0, 148.1, 138.1, 137.9, 135.9, 129.0, 128.9, 128.5, 125.4, 78.8, 63.1, 62.7, 62.1, 56.6, 51.7, 48.4, 24.6, 24.1, 21.1, 19.9, 16.7, 13.8. HRMS (APCI-TOF, m/z) calcd for C28H35N2O4 [M + H]+: 463.2591, found: 463.2597. Ethyl 5-Isopropyl-4-(isopropylimino)-1-(4-anisyl)-3-oxo-6-phenylhexahydro-1H-furo[3,4-c]pyrrole-3a-carboxylate (5 lb). Purified by column chromatography (petroleum ether/ethyl acetate/triethylamine = 48/8/1) to afford a white solid in 98% yield (140 mg). Mp: 156− 157 °C. IR (KBr, cm−1): ν 1776, 1730, 1656, 1618, 1589, 1514, 1466, 1454. 1H NMR (CDCl3, 500 MHz): δ 7.69−6.81 (m, 5H), 6.64 (d, J = 8.6 Hz, 2H), 6.53 (d, J = 8.6 Hz, 2H), 5.05 (d, J = 6.1 Hz, 1H), 4.85 (d, J = 7.4 Hz, 1H), 4.33−4.25 (m, 1H), 4.25−4.16 (m, 1H), 4.05− 3.93 (m, 1H), 3.72 (s, 3H), 3.66−3.54 (m, 1H), 3.38 (dd, J = 6.7, 6.7 Hz, 1H), 1.48 (d, J = 6.8 Hz, 3H), 1.29 (t, J = 7.1 Hz, 3H), 1.17 (d, J = 5.7 Hz, 3H), 1.15 (d, J = 6.6 Hz, 3H), 1.07 (d, J = 6.0 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 168.7, 168.0, 159.3, 148.2, 137.7, 130.6, 128.9, 128.6, 127.2, 113.7, 78.8, 63.1, 62.6, 62.2, 56.6, 55.2, 51.7, 48.5, 24.6, 24.2, 20.0, 16.5, 13.9. HRMS (APCI-TOF, m/z) calcd for C28H35N2O5 [M + H]+: 479.2540, found: 479.2538. Ethyl 5-Isopropyl-4-(isopropylimino)-1-(3-anisyl)-3-oxo-6-phenylhexahydro-1H-furo[3,4-c]pyrrole-3a-carboxylate (5mb). Purified by column chromatography (petroleum ether/ethyl acetate/triethylamine = 32/5/1) to afford a white solid in 94% yield (134 mg). Mp: 117− 118 °C. IR (KBr, cm−1): ν 1790, 1726, 1662, 1612, 1585, 1489, 1456. 1 H NMR (CDCl3, 500 MHz): δ 7.65−6.95 (m, 6H), 6.70 (dd, J = 8.2, 2.2 Hz, 1H), 6.26 (d, J = 7.7 Hz, 1H), 6.18 (d, J = 1.8 Hz, 1H), 5.03 (d, J = 5.4 Hz, 1H), 4.88 (d, J = 7.7 Hz, 1H), 4.31−4.11 (m, 2H), 4.01−3.89 (m, 1H), 3.72−3.60 (m, 4H), 3.42 (dd, J = 7.7, 5.4 Hz, 1H), 1.44 (d, J = 6.8 Hz, 3H), 1.25 (t, J = 7.1 Hz, 3H), 1.18 (d, J = 5.8 Hz, 3H), 1.12 (d, J = 6.7 Hz, 3H), 1.06 (d, J = 6.1 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 168.8, 168.0, 159.5, 148.1, 140.5, 138.1, 129.6, 129.0, 128.6, 117.5, 114.0, 110.8, 78.6, 63.1, 62.7, 61.8, 56.5, 55.2, 51.7, 48.3, 24.7, 24.1, 19.9, 16.9, 13.8. HRMS (APCI-TOF, m/z) calcd for C28H35N2O5 [M + H]+: 479.2540, found: 479.2542. Ethyl 5-Isopropyl-4-(isopropylimino)-1-(2-anisyl)-3-oxo-6-phenylhexahydro-1H-furo[3,4-c]pyrrole-3a-carboxylate (5nb). Purified by column chromatography (petroleum ether/ethyl acetate/triethylamine = 32/5/1) to afford a white solid in 95% yield (136 mg). Mp: 146− 147 °C. IR (KBr, cm−1): ν 1787, 1738, 1665, 1605, 1589, 1493, 1464, 1456. 1H NMR (CDCl3, 500 MHz): δ 7.53−7.08 (m, 6H), 6.85−6.67 (m, 3H), 4.96 (d, J = 8.7 Hz, 1H), 4.92 (d, J = 3.2 Hz, 1H), 4.15 (dq, J = 10.8, 7.1 Hz, 1H), 4.02 (dq, J = 10.8, 7.1 Hz, 1H), 3.99−3.88 (m, 2H), 3.83 (s, 3H), 3.54 (dd, J = 8.7, 3.2 Hz, 1H), 1.33 (d, J = 6.8 Hz, 3H), 1.24 (d, J = 5.8 Hz, 3H), 1.18 (t, J = 7.1 Hz, 3H), 1.03 (d, J = 6.1 Hz, 3H), 1.00 (d, J = 6.8 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 169.8, 168.5, 155.8, 148.8, 139.4, 129.4, 128.6, 128.3, 126.7, 126.3, 120.0, 110.3, 76.9, 63.3, 62.4, 61.3, 55.3, 54.4, 51.5, 47.3, 25.1, 23.9, 19.7, 18.5, 13.6. HRMS (APCI-TOF, m/z) calcd for C28H35N2O5 [M + H]+: 479.2540, found: 479.2541. Ethyl 1-(4-Bromophenyl)-5-isopropyl-4-(isopropylimino)-3-oxo6-phenylhexahydro-1H-furo[3,4-c]pyrrole-3a-carboxylate (5ob). Purified by column chromatography (petroleum ether/ethyl acetate/ triethylamine = 60/10/1) to afford a white solid in 97% yield (153 mg). Mp: 139−140 °C. IR (KBr, cm−1): ν 1786, 1744, 1655, 1489, 1452. 1H NMR (CDCl3, 500 MHz): δ 7.65−6.86 (m, 7H), 6.43 (d, J = 8.5 Hz, 2H), 5.05 (d, J = 6.0 Hz, 1H), 4.85 (d, J = 7.4 Hz, 1H), 4.35− 4.14 (m, 2H), 4.01−3.89 (m, 1H), 3.67−3.52 (m, 1H), 3.31 (dd, J = 7.2, 6.2 Hz, 1H), 1.47 (d, J = 6.9 Hz, 3H), 1.28 (t, J = 7.2 Hz, 3H), 1.16 (d, J = 5.8 Hz, 3H), 1.15 (d, J = 6.7 Hz, 3H), 1.07 (d, J = 6.0 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 168.5, 167.7, 147.7, 137.9, 137.7, 131.5, 129.1, 128.7, 127.2, 122.4, 78.1, 63.0, 62.8, 61.9, 56.7, 51.8, 48.5, 24.6, 24.2, 20.0, 16.5, 13.9. HRMS (APCI-TOF, m/z) calcd for C27H32BrN2O4 [M + H]+: 527.1540, found: 527.1545. Ethyl 5-Isopropyl-4-(isopropylimino)-1-(4-nitrophenyl)-3-oxo-6phenylhexahydro-1H-furo[3,4-c]pyrrole-3a-carboxylate (5pb). Purified by column chromatography (petroleum ether/ethyl acetate/ triethylamine = 32/5/1) to afford a white solid in 96% yield (142 mg). Mp: 144−145 °C. IR (KBr, cm−1): ν 1790, 1734, 1665, 1603, 1522, 1456. 1H NMR (CDCl3, 500 MHz): δ 7.99 (d, J = 8.6 Hz, 2H), 7.74− 7.28 (m, 4H), 7.21−6.94 (brs, 1H), 6.70 (d, J = 8.6 Hz, 2H), 5.20 (d, J

(APCI-TOF, m/z) calcd for C28H35N2O4 [M + H]+: 463.2591, found: 463.2595. Ethyl 5-Isopropyl-4-(isopropylimino)-6-(4-anisyl)-3-oxo-1-phenylhexahydro-1H-furo[3,4-c]pyrrole-3a-carboxylate (5cb). Purified by column chromatography (petroleum ether/ethyl acetate/triethylamine = 32/5/1) to afford a white solid in 99% yield (142 mg). Mp: 156− 157 °C. IR (KBr, cm−1): ν 1788, 1744, 1657, 1452. 1H NMR (CDCl3, 500 MHz): δ 7.49−7.14 (m, 4H), 7.14−6.63 (m, 5H), 5.07 (d, J = 5.1 Hz, 1H), 4.86 (d, J = 7.8 Hz, 1H), 4.22 (dq, J = 14.3, 7.1 Hz, 1H), 4.13 (dq, J = 14.3, 7.1 Hz, 1H), 4.00−3.90 (m, 1H), 3.83 (s. 3H), 3.75− 3.65 (m, 1H), 3.41 (dd, J = 7.5, 5.4 Hz, 1H), 1.42 (d, J = 6.8 Hz, 3H), 1.22 (t, J = 7.2 Hz, 3H), 1.19 (d, J = 5.7 Hz, 3H), 1.11 (d, J = 6.7 Hz, 3H), 1.06 (d, J = 6.0 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 169.0, 168.0, 159.8, 148.1, 138.8, 129.9, 128.4, 128.2, 125.3, 114.3, 78.7, 62.6, 62.4, 61.7, 56.6, 55.4, 51.7, 48.0, 24.7, 24.1, 19.8, 17.1, 13.7. HRMS (APCI-TOF, m/z) calcd for C28H35N2O5 [M + H]+: 479.2540, found: 479.2547. Ethyl 5-Isopropyl-4-(isopropylimino)-6-(3-anisyl)-3-oxo-1-phenylhexahydro-1H-furo[3,4-c]pyrrole-3a-carboxylate (5db). Purified by column chromatography (petroleum ether/ethyl acetate/triethylamine = 32/5/1) to afford a white solid in 95% yield (136 mg). Mp: 120− 121 °C. IR (KBr, cm−1): ν 1780, 1736, 1653, 1607, 1584, 1487, 1452. 1 H NMR (CDCl3, 500 MHz): δ 7.51−7.12 (m, 4H), 7.11−6.43 (m, 5H), 5.08 (d, J = 5.3 Hz, 1H), 4.96−4.76 (brs, 1H), 4.31−4.08 (m, 2H), 4.00−3.91 (m, 1H), 3.90−3.55 (m, 4H), 3.42 (dd, J = 7.0, 6.0 Hz, 1H), 1.45 (d, J = 6.8 Hz, 3H), 1.23 (t, J = 7.1 Hz, 3H), 1.18 (d, J = 5.7 Hz, 3H), 1.13 (d, J = 6.7 Hz, 3H), 1.06 (d, J = 6.0 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 168.9, 168.1, 160.3, 148.1, 139.8, 138.6, 130.0, 128.4, 128.3, 125.4, 78.7, 63.0, 62.7, 61.9, 56.5, 55.3, 51.8, 48.3, 24.7, 24.1, 20.0, 17.0, 13.8. HRMS (APCI-TOF, m/z) calcd for C28H35N2O5 [M + H]+: 479.2540, found: 479.2538. Ethyl 6-(4-Bromophenyl)-5-isopropyl-4-(isopropylimino)-3-oxo1-phenylhexahydro-1H-furo[3,4-c]pyrrole-3a-carboxylate (5fb). Purified by column chromatography (petroleum ether/ethyl acetate/ triethylamine = 60/10/1) to afford a white solid in 95% yield (150 mg). Mp: 135−136 °C. IR (KBr, cm−1): ν 1798, 1740, 1655, 1487, 1456. 1H NMR (CDCl3, 500 MHz): δ 7.78−7.23 (m, 3H), 7.23−6.77 (m, 4H), 6.71 (d, J = 7.4 Hz, 2H), 4.99 (d, J = 5.5 Hz, 1H), 4.84 (d, J = 7.7 Hz, 1H), 4.29−4.08 (m, 2H), 4.01−3.88 (m, 1H), 3.71−3.58 (m, 1H), 3.44 (dd, J = 7.2, 6.0 Hz, 1H), 1.42 (d, J = 6.8 Hz, 3H), 1.23 (t, J = 7.1 Hz, 3H), 1.17 (d, J = 5.8 Hz, 3H), 1.11 (d, J = 6.7 Hz, 3H), 1.05 (d, J = 6.0 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 168.6, 167.8, 147.9, 138.2, 137.3, 132.1, 128.5, 125.5, 122.3, 78.7, 62.8, 62.4, 61.8, 56.3, 51.7, 48.3, 24.7, 24.0, 19.9, 17.1, 13.7. HRMS (APCI-TOF, m/z) calcd for C27H32BrN2O4 [M + H]+: 527.1540, found: 527.1545. Ethyl 5-Isopropyl-4-(isopropylimino)-6-(4-nitrophenyl)-3-oxo-1phenylhexahydro-1H-furo[3,4-c]pyrrole-3a-carboxylate (5jb). Purified by column chromatography (petroleum ether/ethyl acetate/ triethylamine = 48/8/1) to afford a white solid in 98% yield (145 mg). Mp: 149−150 °C. IR (KBr, cm−1): ν 1784, 1740, 1661, 1599, 1518, 1458. 1H NMR (CDCl3, 500 MHz): δ 8.52−7.49 (m, 3H), 7.42−7.09 (m, 4H), 6.73 (d, J = 7.6 Hz, 2H), 5.00 (d, J = 7.7 Hz, 1H), 4.94 (d, J = 5.6 Hz, 1H), 4.31−4.21 (m, 1H), 4.21−4.16 (m, 1H), 4.04−3.92 (m, 1H), 3.73−3.62 (m, 1H), 3.58 (dd, J = 7.6, 5.8 Hz, 1H), 1.45 (d, J = 6.8 Hz, 3H), 1.25 (t, J = 7.1 Hz, 3H), 1.19 (d, J = 5.8 Hz, 3H), 1.12 (d, J = 6.7 Hz, 3H), 1.08 (d, J = 6.0 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 168.2, 167.5, 147.9, 147.7, 146.0, 137.5, 128.8, 128.6, 125.6, 124.1, 78.6, 63.0, 62.3, 61.9, 56.1, 51.8, 48.7, 24.6, 24.0, 20.0, 17.3, 13.8. HRMS (APCI-TOF, m/z) calcd for C27H32N3O6 [M + H]+: 494.2286, found: 494.2287. Ethyl 5-Isopropyl-4-(isopropylimino)-3-oxo-6-phenyl-1-(p-tolyl)hexahydro-1H-furo[3,4-c]pyrrole-3a-carboxylate (5kb). Purified by column chromatography (petroleum ether/ethyl acetate/triethylamine = 60/10/1) to afford a white solid in 95% yield (131 mg). Mp: 124− 125 °C. IR (KBr, cm−1): ν 1786, 1744, 1657, 1450. 1H NMR (CDCl3, 500 MHz): δ 7.64−6.96 (m, 5H), 6.93 (d, J = 8.0 Hz, 2H), 6.50 (d, J = 8.1 Hz, 2H), 5.05 (d, J = 5.8 Hz, 1H), 4.86 (d, J = 7.6 Hz, 1H), 4.32− 4.12 (m, 2H), 4.02−3.90 (m, 1H), 3.69−3.57 (m, 1H), 3.38 (dd, J = 7.5, 5.8 Hz, 1H), 2.24 (s, 3H), 1.46 (d, J = 6.9 Hz, 3H), 1.26 (t, J = 7.1 Hz, 3H), 1.17 (d, J = 5.8 Hz, 3H), 1.14 (d, J = 6.7 Hz, 3H), 1.07 (d, J 183

DOI: 10.1021/acs.joc.7b02561 J. Org. Chem. 2018, 83, 174−184

Article

The Journal of Organic Chemistry

Barløse, C. L.; Jessen, K. S.; Iversen, M. V.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2017, 56, 11831−11835. (c) Borisov, D. D.; Novikov, R. A.; Tomilov, Y. V. Tetrahedron Lett. 2017, 58, 3712−3716. For selected examples on higher order [3 + x] annulations (x > 2): (d) Wang, Z.-H.; Zhang, H.-H.; Wang, D.-M.; Xu, P.-F.; Luo, Y.-C. Chem. Commun. 2017, 53, 8521−8524. (e) Zhang, C.; Tian, J.; Ren, J.; Wang, Z. Chem. - Eur. J. 2017, 23, 1231−1236. (f) Ivanova, O. A.; Budynina, E. M.; Grishin, Y. K.; Trushkov, I. V.; Verteletskii, P. V. Angew. Chem., Int. Ed. 2008, 47, 1107−1110. (3) For examples of [3 + x] annulations of 1,2,3-fully substituted D− A cyclopropanes with aldehydes and ketones: (a) Sanders, S. D.; RuizOlalla, A.; Johnson, J. S. Chem. Commun. 2009, 5135−5137. (b) Smith, A. G.; Slade, M. C.; Johnson, J. S. Org. Lett. 2011, 13, 1996−1999. (c) Xu, X.; Lu, H.; Ruppel, J. V.; Cui, X.; Lopez de Mesa, S.; Wojtas, L.; Zhang, X. P. J. Am. Chem. Soc. 2011, 133, 15292−15295. (d) Yang, G.; Sun, Y.; Shen, Y.; Chai, Z.; Zhou, S.; Chu, J.; Chai, J. J. Org. Chem. 2013, 78, 5393−5400. (e) Ma, X.; Tang, Q.; Ke, J.; Yang, X.; Zhang, J.; Shao, H. Org. Lett. 2013, 15, 5170−5173. (f) Yang, G.; Wang, T.; Chai, J.; Chai, Z. Eur. J. Org. Chem. 2015, 2015, 1040−1046. (g) Xing, S.; Li, Y.; Li, Z.; Liu, C.; Ren, J.; Wang, Z. Angew. Chem., Int. Ed. 2011, 50, 12605−12609. For examples of annulations with other dipolarophiles: (h) Liu, J.; Zhou, L.; Ye, W.; Wang, C. Chem. Commun. 2014, 50, 9068−9071. (i) Sathishkannan, G.; Srinivasan, K. Org. Lett. 2011, 13, 6002−6005. (j) Alajarin, M.; Egea, A.; Orenes, R.-A.; Vidal, A. Org. Biomol. Chem. 2016, 14, 10275−10284. (4) For a single example of Pd-catalyzed [3 + 2] annulation of a γbutyrolactone fused D−A cyclopropane with methyl acrylate: Shimizu, I.; Ohashi, Y.; Tsuji, J. Tetrahedron Lett. 1985, 26, 3825−3828. (5) (a) Goldberg, A. F. G.; O’Connor, N. R.; Craig, R. A., II; Stoltz, B. M. Org. Lett. 2012, 14, 5314−5317. (b) Wang, H.; Yang, W.; Liu, H. Org. Biomol. Chem. 2012, 10, 5032−5035. (6) Mukherjee, P.; Das, A. J. Org. Chem. 2017, 82, 2794−2802. (7) Sun, Y.; Yang, G.; Chai, Z.; Mu, X.; Chai, J. Org. Biomol. Chem. 2013, 11, 7859−7868. (8) For an isolated single example of [3 + 2] annulation of diethyl 1,1-dicarboxylate cyclopropane with 4-nitrophenylisothiocyanate: Tsunoi, S.; Maruoka, Y.; Suzuki, I.; Shibata, I. Org. Lett. 2015, 17, 4010−4013. (9) Cyclopropanes 6 were prepared by a literature method: Yang, G.; Hua, Y.; Shen, Y. Chin. J. Chem. 2009, 27, 1811−1819. (10) CCDC 1578340 (1m), CCDC 1578341 (3ja), and CCDC 1578342 (5ab) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Center via www.ccdc.cam.ac.uk/ data_request/cif. (11) Adepu, R.; Rambabu, D.; Prasad, B.; Meda, C. L. T.; Kandale, A.; Krishna, G. R.; Reddy, C. M.; Chennuru, L. N.; Parsa, K. V. L; Pal, M. Org. Biomol. Chem. 2012, 10 (10), 5554−5569.

= 6.1 Hz, 1H), 4.88 (d, J = 7.3 Hz, 1H), 4.36−4.16 (m, 2H), 4.02− 3.91 (m, 1H), 3.65−3.53 (m, 1H), 3.31 (dd, J = 6.7, 6.7 Hz, 1H), 1.49 (d, J = 6.8 Hz, 3H), 1.29 (t, J = 7.1 Hz, 3H), 1.17 (d, J = 6.3 Hz, 6H), 1.09 (d, J = 6.0 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ 168.2, 167.6, 147.7, 147.3, 145.9, 137.6, 129.3, 129.0, 126.5, 123.7, 77.4, 63.0, 61.7, 56.8, 51.8, 48.7, 24.5, 24.2, 20.0, 16.4, 13.9. HRMS (APCI-TOF, m/z) calcd for C27H32N3O6 [M + H]+: 494.2286, found: 494.2291. Procedure for the Deesterification of 3sa to 6aa.11 Under an Ar atmosphere, a mixture of 3sa (132.9 mg, 0.3 mmol) and NaCl (140.4 mg, 2.4 mmol) in a cosolvent of DMSO (2.5 mL) and H2O (0.25 mL) was refluxed at 150 °C. The reaction was monitored by TLC until completion (8 h). After cooling down to rt, H2O (10 mL) was added. The reaction mixture was extracted with ethyl acetate (3 × 10 mL), and the combined organic layers were washed with saturated aqueous NaCl solution (30 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by flash chromatography (petroleum/dichloromethane v/v = 3/2) to afford the γ-butyrolactone fused product 6aa as a colorless viscous liquid (116 mg, 90% yield). 1H NMR (CDCl3, 500 MHz): δ 7.46−7.36 (m, 2H), 7.26−7.13 (m, 7H), 7.13−7.03 (m, 4H), 6.69−6.59 (m, 2H), 5.44−5.30 (m, 2H), 4.33 (d, J = 8.3 Hz, 1H), 3.86−3.77 (m, 1H). 13C NMR (CDCl3, 125 MHz): δ 170.7, 163.6, 151.4, 137.8, 134.0, 129.1, 128.9, 128.6, 128.4, 128.3, 127.9, 126.3, 125.4, 120.0, 81.1, 58.0, 54.1, 53.8. HRMS (APCI-TOF, m/z) calcd for C24H20NO2S [M + H]+: 386.1209, found: 386.1201.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b02561. X-ray crystallographic data for 1m, 3ja, and 5ab; copies of 1H, 13C NMR spectra for all new compounds (PDF) X-ray crystallographic data for 1m, 3ja, and 5ab (CIF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Gaosheng Yang: 0000-0002-7891-3972 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS Financial support of this project from the NNSFC (Nos. 21672005, 21472001, 21172002) is gratefully appreciated. REFERENCES

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DOI: 10.1021/acs.joc.7b02561 J. Org. Chem. 2018, 83, 174−184