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Abstract

An efficient [3 + 2] cycloaddition reaction of cyanocyclopropanecarbonates and (E)-3-aryl-2-cyanoacrylates mediated by 1,8-diazabicyclo[5.4.0]undec-7-ene for the synthesis of highly functionalized cyclopentane derivatives in moderate to good yields (79%−87%) was developed. The structures of two typical products were confirmed by X-ray crystallography.

Keywords

1,8-diazabicyclo[5.4.0]undec-7-ene [3 + 2] cycloaddition reaction donor–acceptor cyclopropane highly functionalized cyclopentane

Introduction

Five-membered carbocycles are usefully structural units as important building blocks that are widely found in lots of natural products,^1,2 for example, sepaconitine,³ phomopsterone B,⁴ nitidasin,⁵ retigeranic acid A,⁶ (+)-podoandin,⁷ steroids: dehydroepiandrosterone, and vitamin D (Figure 1). Such compounds containing five-membered carbocycles have been identified to have significant pharmaceutical values such as potential anti-HIV agents⁸ (Figure 1), mannosidase inhibitors,⁹ cyclooxygenase-2 (COX-2) inhibitors,¹⁰ nucleoside-type antibodies,¹¹ and potent potentiators of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors.¹²

Figure 1.

Examples of five-membered carbocycle-containing natural products and bioactive molecules.

Due to the excellent biological and pharmaceutical activities of these compounds, the construction of the five-membered carbocycle systems has become a topic of great interest among synthetic chemists.^13–15 A range of methods have been reported for their synthesis including the Sm-promoted reductive dimerization cyclization of gem-diactivated alkenes,¹⁶ catalytic tandem Michael addition/radical cyclization/oxygenation reactions of γ-unsaturated esters, amides, ketones, and nitriles with gem-diactivated alkenes,¹⁷ phosphine-catalyzed [3 + 2] cycloadditions of allenoates and dual activated olefins,¹⁸ and Pd/organic amine co-catalytic cascade reaction of γ-unsaturated esters and substituted enals.¹⁹ Later, Pd/organocatalysis-promoted stereoselective [3 + 2] cycloaddition between vinylcyclopropanes and α,β-unsaturated aldehydes results in the synthesis of highly substituted cyclopentanes.^20–22

Although a variety of methodologies and protocols have been reported for the formation of densely substituted cyclopentanes, it is of importance to explore a novel and efficient synthetic method. The annulations and cycloadditions of donor–acceptor cyclopropanes (D-A cyclopropanes) with all-carbon partners have proved to be powerful synthetic tools to form carbocyclic compounds. D-A cyclopropanes have a prominent role in the synthesis of five-membered carbocycle synthesis based on the [3 + 2] cycloaddition of functionalized D-A cyclopropanes with alkenes, alkynes, allenes, enol ethers, and enamines.²³ As a new type of D-A cyclopropanes as three-carbon synthons, 2-aroyl-3-aryl-1-cyanocyclopropane-1-carboxylates with one donor (aryl) and three acceptor (aroyl, cyano, and carboxylate) substituents in the vicinal positions have been used in the construction of heterocycles and carbocycles. Because of the high polarization of two of three C–C bonds of the ring, the cyclopropanes may be transformed into two 1,3-dipoles via a ring-opening reaction for the diversity of reactions.⁴ Recently, we have reported the opening ring of 1-cyanocyclopropane-1-carboxylates promoted by various bases.^24–27 Among them is an efficient and straightforward synthetic protocol for the preparation of fully substituted cyclopentadienes via [3 + 2] cycloaddition of 1-cyanocyclopropane-1-carboxy esters with β-nitrostyrenes.²⁸

In continuation of our interests in constructing the heterocycles and carbocycles, based on our studies on the reactivity of 2-aroyl-3-aryl-1-cyanocyclopropane carbonates, we envisioned that the reaction of 2-aroyl-3-aryl-1-cyanocyclopropane carbonates with substituted 3-aryl-2-cyanoacrylates may offer an efficient approach to cyclopentane skeletons via [3 + 2] cycloadditions. Herein, we report a new approach for the synthesis of highly functionalized cyclopentane derivatives via a simple [3 + 2] cycloaddition reaction of cyanocyclopropanecarbonates and (E)-3-aryl-2-cyanoacrylates.

Results and discussion

In order to explore the optimal reaction conditions, we began our investigation by studying the [3 + 2] annulation of D-A cyclopropane 1a and (E)-3-aryl-2-cyanoacrylates 2a. Initially, based on our more recent results,^{24,26,28–30} the reaction of D-A cyclopropane 1a (1.0 mmol) and (E)-3-aryl-2-cyanoacrylates 2a (1.2 mmol) was examined in dichloromethane (15 mL) using trimethylamine (1 equiv.) as a promoter for 12 h under reflux, and the desired product 3a was obtained in only 35% yield. When the trimethylamine was replaced with 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), or K₂CO₃ for the reaction under the same condition, the desired product diethyl 4-(4-chlorobenzoyl)-2-(3-chlorophenyl)-1,3-dicyano-5-(p-tolyl)cyclopentane-1,3-dicarboxylate (3a) was obtained in 75%, 87%, and 5% yields, respectively. We found that the reaction proceeded smoothly under reflux in the presence of DBU (1.0 equiv.) with a better regioselectivity. This condition was selected as optimal for further research. Subsequently, reducing the amount of DBU from 1.0 to 0.75 equiv. gave the expected product 1,3-dicyanocyclopentane-1,3-dicarboxylate 3a in a slightly low yield of 83%. Further increasing the amount of DBU from 1.0 to 1.2 equiv. afforded the product in nearly the same yield. With the aim of yield optimization, we turned our attention to the reaction temperature; the decrease of the reaction temperature to 25 °C brought in a lower yield (44%) even with a much longer reaction time. To summarize, the optimal reaction conditions were selected as 1.0 equiv. of D-A cyclopropane 1a–i, 1.2 equiv. of (E)-3-aryl-2-cyanoacrylates 2a–f, and 1.0 equiv. of DBU in dichloromethane under reflux for 12 h.

Using the optimized reaction conditions, the scope of this DBU-mediated [3 + 2] cycloaddition reaction of cyanocyclopropanecarbonates and (E)-3-aryl-2-cyanoacrylates was probed. As shown in Table 1, both electron-deficient and electron-rich aromatic groups were similarly viable affording the products in good yields (79%−87%). Substrates bearing methoxy, methyl, chloro, and bromo at the 3- or 4-position of the aryl displayed similar reactivity, but substrates bearing chloro and bromo at the 2-position of the aryl showed slightly lower activities to furnish the products (Table 1, entries 5 and 6).

Table 1.

Synthesis of 1,3-dicyanocyclopentane-1,3-dicarboxylates 3a–j.

Entry	R¹	R²	R³	Product	Yield (%)^a
1	p-CH₃	p-Cl (1a)	m-Cl (2a)	3a	87
2	m-Cl	p-CH₃O (1b)	m-Cl (2a)	3b	82
3	m-CH₃	H (1c)	m-CH₃ (2b)	3c	84
4	m-Cl	H (1d)	m-Cl (2a)	3d	82
5	o-Br	p-Cl (1e)	o-Br (2c)	3e	80
6	o-Cl	H (1f)	o-Cl (2d)	3f	81
7	p-Br	p-Cl (1g)	p-Br (2e)	3g	85
8	p-Br	p-CH₃O (1h)	p-Br (2e)	3h	83
9	p-CH₃	p-Cl (1a)	p-CH₃ (2f)	3i	82
10	p-CH₃	p-Br (1i)	m-CH₃ (2b)	3j	79

Yields were isolated.

The molecular structures of all 1,3-dicyanocyclopentane-1,3-dicarboxylates 3a–j were elucidated from their spectroscopic analyses as described herein for 3a. In the infrared (IR) spectrum of 3a, a sharp absorption band at 1744 and 1676 cm⁻¹ could be related to CO₂Et and ArCO stretching frequencies, respectively. The mass spectrum of 3a displayed the molecular ion peak at m/z = 625.1271 (M + Na), which is in good agreement with the proposed structure. The ¹H nuclear magnetic resonance (NMR) spectrum of 3a exhibited two double peaks at 5.02 ppm (1H) and 4.93 ppm (1H) and one sharp signal at 5.01 ppm (1H) for C(4)–H, C(5)–H, and C(2)–H of the cyclopentane ring, respectively. Characteristic ¹H chemical shift unequivocally indicated the exclusive chemical environment of 1,3-dicyanocyclopentane-1,3-dicarboxylate 3a protons. The coupling constants J_{[C(4)–H/C(5)–H]} = 12.9 Hz and J_{[C(5)–H/C(4)–H]} = 12.2 Hz of the cyclopentane ring, respectively, indicated that C(4)–H and C(5)–H possess trans relations. The ¹H-decoupled ¹³C NMR spectrum of 3a showed 29 distinct signals containing four repeats in agreement with the suggested structure. The important peaks were related to the ArCOCH, two CO₂Et, and two CN groups which appeared at 191.3, 166.2, 165.6, 117.6, and 114.0 ppm, respectively. Unambiguous evidence for the structures and stereochemistry of 3d and 3g was obtained from a single-crystal X-ray analysis. ORTEP diagram of 3d and 3g is shown inFigure 2. The crystallographic data of 3d and 3g are listed in Table 2.

Figure 2.

Molecular structure of 1,3-dicyanocyclopentane-1,3-dicarboxylates 3d and 3g; non-hydrogen atoms are shown at the 30% probability level.

Table 2.

Crystal data and structure refinement for 3d and 3g.

Identification code	3d	3g
Empirical formula	C₃₂H₂₆Cl₂N₂O₅	C₃₂H₂₅Br₂ClN₂O₅
Formula weight	589.45	712.79
Temperature	298 K	296 K
Wavelength	0.71073 Å	0.71073 Å
Crystal system, space group	Triclinic, P-1	Triclinic, P-1
Unit cell dimensions	a = 7.7854(13) Å	a = 7.184(7) Å
	alpha = 82.01(4) degrees	alpha = 82.238(6) degrees
	b = 10.0986(19) Å	b = 13.753(12) Å
	beta = 84.538(5) degrees	beta = 81.42(2) degrees
	c = 19.162(3) Å	c = 15.920(14) Å
	gamma = 82.582(6) degrees	gamma = 77.957(18) degrees
Volume	1475.6(4) Å³	1512(2) Å³
Z, Calculated density	2, 1.327 Mg/m³	2, 1.566 Mg/m³
Absorption coefficient	0.263 mm⁻¹	2.813 mm⁻¹
F(000)	612	716
Crystal size	0.35 × 0.33 × 0.3 mm³	0.35 × 0.33 × 0.3 mm³
Theta range for data collection	1.08–27.45 degrees	1.30–25.00 degrees
Limiting indices	−10 ⩽ h ⩽ 10 −13 ⩽ k ⩽ 13 −24 ⩽ l ⩽ 24	−8 ⩽ h ⩽ 8 −16 ⩽ k ⩽ 16 −18 ⩽ l ⩽ 18
Reflections collected/unique	22,777/6752 (R(int) = 0.1144)	33,488/5319 (R(int) = 0.0407)
Completeness to theta = 25.00	98.5%	100.0%
Refinement method	Full-matrix least squares on F²	Full-matrix least squares on F²
Data/restraints/parameters	6654/0/372	5318/0/381
Goodness-of-fit on F²	1.063	1.084
Final R indices (I > 2sigma(I))	R¹ = 0.1280 wR² = 0.3547	R¹ = 0.0330 wR² = 0.0797
R indices (all data)	R¹ = 0.2663 wR² = 0.4300	R¹ = 0.0495 wR² = 0.0960
Largest diff. peak and hole	2.709 and −0.973e Å⁻³	0.313 and −0.456e Å⁻³

Based on the above experimental results, a possible mechanism is proposed in Scheme 1. First, in the presence of DBU, the deprotonation of D-A cyclopropane 1a–i affords a cyclopropan-1-ide [A], which undergoes opening ring to produce prop-2-en-1-ide [B].²⁸ Next, [3 + 2] annulation via crossing nucleophilic addition of intermediate prop-2-en-1-ide [B] and (E)-3-aryl-2-cyanoacrylates 2a–f gives 1,3-dicyano-4-(hydroxymethylene)-2,5-diphenylcyclopentane-1,3-dicarboxylate [C].²⁴ Finally, the enol-keto tautomerism of [C] mediated by base DBU yields the products 3a–j.

Scheme 1.

The proposed mechanism.

Conclusion

In summary, we have demonstrated that highly functionalized cyclopentane derivatives can be successfully prepared with complete relative stereoselectivity via a simple [3 + 2] cycloaddition reaction of cyanocyclopropanecarbonates and (E)-3-aryl-2-cyanoacrylates. This reaction involves a highly efficient domino sequence consisting of ring opening of donor–acceptor cyclopropanes and regioselective cycloaddition as key unit steps. The reaction appears to be general for a variety of cyanocyclopropanecarbonates and (E)-3-aryl-2-cyanoacrylates and tolerates the presence of aromatic moieties with electron-withdrawing and electron-donating substituents.

Experimental

General

All melting points (m.p.) were determined in a Yanaco melting point apparatus and are uncorrected. IR spectra were recorded on a Nicolet FT-IR 5DX spectrometer. The ¹H NMR (400 MHz) and ¹³C NMR (100 MHz) spectra were recorded on a Bruker AV-400 spectrometer with tetramethylsilane (TMS) as an internal reference in CDCl₃ solution. The J values are given in hertz. Only discrete or characteristic signals for the ¹H NMR are reported. High-resolution electrospray ionization (ESI) mass spectra were obtained on a maXis UHR-TOF (ESI) mass spectrometer. X-ray crystallographic analysis was performed with a SMART APEX-II diffractometer using monochromatic Mo KR radiation (λ) 0.71073 Å and integrated with the SAINT-Plus program. All calculations were performed with programs from the SHELXTL crystallographic software package. Flash chromatography was performed on silica gel (230–400 mesh) eluted with the ethyl acetate–hexane mixture. All reactions were monitored by thin-layer chromatography (TLC). (E)-Acrylates 2a–f and other reagents and solvents were purchased from commercial suppliers and purified by standard techniques; ethyl 1-cyanocyclopropanecarbonates 1a–i were synthesized following a procedure described in the literature.^30,31

General procedure for the synthesis of 1,3-dicyanocyclopentane-1,3-dicarboxylate derivatives

To a mixture of ethyl (1RS,2RS,3SR)-2-aroyl-3-aryl-1-cyanocyclopropanecarbonates 1a–i (1 mmol) and ethyl (E)-3-aryl-2-cyanoacrylates 2a–f (1.2 mmol) in dichloromethane (15 mL) was added DBU (152 mg, 1.0 mmol). The mixture was stirred under reflux for 12 h. After completion of the reaction (monitored by TLC), the cooled reaction mixture was added with water (15 mL) and extracted with dichloromethane (10 mL × 2). The organic phase was washed with water (10 mL) and brine (10 mL), and dried over anhydrate sodium sulfate. After the removal of dichloromethane, the crude product was purified by flash chromatography (EtOAc/hexanes, 1/30, silica gel) to give the desirable products 3a–j.

Diethyl (1RS,2SR,3RS,4RS,5SR)-4-(4-chlorobenzoyl)-2-(3-chlorophenyl)-1,3-dicyano-5-(p-tolyl)cyclopentane-1,3-dicarboxylate (3a): White solid, yield: 87%; m.p. 151.8–152.3 °C (EA/PE); IR (KBr, cm⁻¹): ν 2986, 1744, 1676, 1477, 1251, 1026; ¹H NMR (400 MHz, CDCl₃) δ (ppm): 7.85 (d, J = 8.0 Hz, 2H), 7.82–7.75 (m, 1H), 7.52 (s, 1H), 7.44 (d, J = 8.0 Hz, 2H), 7.41–7.33 (m, 2H), 7.20 (d, J = 7.5 Hz, 2H), 7.09 (d, J = 7.5 Hz, 2H), 5.02 (d, J = 12.9 Hz, 1H), 5.01 (s, 1H), 4.93 (d, J = 12.2 Hz, 1H), 4.03–3.78 (m, 2H), 3.77–3.53 (m, 2H), 2.26 (s, 3H), 0.80 (t, J = 7.1 Hz, 3H), 0.74 (t, J = 7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ (ppm): 191.3, 166.2, 165.6, 141.2, 139.2, 134.7, 134.3, 133.0, 130.4, 130.3, 130.1, 129.9, 129.8, 129.5, 129.3, 127.9, 127.5, 117.6, 114.0, 64.2, 63.9, 57.4, 56.9, 56.7, 56.1, 54.5, 21.0, 13.6, 13.1; HR-MS (ESI) calcd for C₃₃H₂₈Cl₂N₂NaO₅ [(M + Na)⁺]: 625.1273; found: 625.1271.

Diethyl (1RS,2SR,3RS,4SR,5RS)-2,4-bis(3-chlorophenyl)-1,3-dicyano-5-(4-methoxy benzoyl)cyclopentane-1,3-dicarboxylate (3b): White solid, yield: 82%; m.p. 191.6–192.5 °C (EA/PE); IR (KBr, cm⁻¹): ν 2971, 1765, 1686, 1476, 1253, 1026; ¹H NMR (400 MHz, CDCl₃) δ (ppm): 7.91 (d, J = 8.9 Hz, 2H), 7.83–7.77 (m, 1H), 7.52 (s, 1H), 7.38 (d, J = 5.0 Hz, 2H), 7.33 (s, 1H), 7.24 (d, J = 8.2 Hz, 3H), 6.94 (d, J = 8.8 Hz, 2H), 5.06 (d, J = 12.3 Hz, 1H), 5.03 (s, 1H), 4.88 (d, J = 12.3 Hz, 1H), 4.01–3.91 (m, 1H), 3.86 (s, 3H), 3.84–3.73 (m, 2H), 3.72–3.62 (m, 1H), 0.85–0.75 (m, 6H); ¹³C NMR (100 MHz, CDCl₃) δ (ppm): 189.9, 166.1, 165.5, 164.8, 135.3, 134.8, 134.7, 132.9, 131.1, 130.5, 130.4, 130.1, 130.0, 129.2, 128.7, 128.0, 127.8, 126.6, 117.4, 114.2, 114.0, 64.1, 64.1, 57.4, 56.8, 56.5, 56.0, 55.7, 54.0, 13.3, 13.2; HR-MS (ESI) calcd for C₃₃H₂₈Cl₂N₂NaO₆ [(M + Na)⁺]: 641.1222; found: 641.1225.

Diethyl (1RS,2SR,3RS,4RS,5SR)-4-benzoyl-1,3-dicyano-2,5-di-m-tolyl cyclopentane-1,3-dicarboxylate (3c): White solid, yield: 84%; m.p. 273.5–274.3 °C (EA/PE); IR (KBr, cm⁻¹): ν 2960, 1743, 1697, 1472, 1249, 1021; ¹H NMR (400 MHz, CDCl₃) δ (ppm): 7.91 (d, J = 7.8 Hz, 2H), 7.58 (dd, J = 7.9, 7.6 Hz, 2H), 7.49–7.42 (m, 3H), 7.28 (d, J = 7.7 Hz, 1H), 7.19 (d, J = 7.5 Hz, 2H), 7.14 (d, J = 7.4 Hz, 1H), 7.10 (d, J = 7.6 Hz, 1H), 7.06 (d, J = 7.3 Hz, 1H), 5.07 (s, 1H), 5.05 (d, J = 12.3 Hz, 1H), 5.00 (d, J = 12.3 Hz, 1H), 3.91–3.72 (m, 2H), 3.70–3.53 (m, 2H), 2.35 (s, 3H), 2.28 (s, 3H), 0.77–0.68 (m, 6H); ¹³C NMR (100 MHz, CDCl₃) δ (ppm): 192.5, 166.4, 165.7, 138.6, 138.5, 136.2, 134.3, 133.3, 131.0, 130.6, 130.4, 129.8, 129.7, 128.9, 128.8, 128.6, 128.5, 126.9, 125.0, 118.0, 114.3, 63.8, 63.6, 57.9, 57.0, 56.9, 56.3, 54.8, 21.4, 21.3, 13.2, 13.1; HR-MS (ESI) calcd for C₃₄H₃₂N₂NaO₅ [(M + Na)⁺]: 571.2209; found: 571.2206.

Diethyl (1RS,2SR,3RS,4RS,5SR)-4-benzoyl-2,5-bis(3-chlorophenyl)-1,3-dicyanocyclopentane-1,3-dicarboxylate (3d): White solid, yield: 82%; m.p. 183.2–184.6 °C (EA/PE); IR (KBr, cm⁻¹): ν 2982, 1746, 1689, 1479, 1251, 1027; ¹H NMR (400 MHz, CDCl₃) δ (ppm): 7.90 (d, J = 7.8 Hz, 2H), 7.79 (s, 1H), 7.62 (d, J = 7.2 Hz, 1H), 7.50 (d, J = 7.2 Hz, 3H), 7.42–7.32 (m, 3H), 7.29–7.22 (m, 3H), 5.06 (d, J = 11.8 Hz, 1H), 5.04 (s, 1H), 4.93 (d, J = 12.2 Hz, 1H), 3.96–3.79 (m, 2H), 3.75–3.60 (m, 2H), 0.81 (t, J = 7.1 Hz, 3H), 0.73 (t, J = 7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ (ppm): 192.0, 166.0, 165.3, 135.9, 135.3, 134.9, 134.7, 134.6, 132.8, 130.4, 130.4, 130.2, 130.0, 129.3, 129.0, 128.7, 128.5, 127.8, 126.6, 117.4, 113.9, 64.2, 64.1, 57.3, 56.7, 56.3, 55.9, 54.8, 13.2, 13.1; HR-MS (ESI) calcd for C₃₂H₂₆Cl₂N₂NaO₅ [(M + Na)⁺]: 611.1116; found: 611.1119.

Diethyl (1RS,2SR,3RS,4RS,5RS)-2,4-bis(2-bromophenyl)-5-(4-chloro benzoyl)-1,3-dicyanocyclopentane-1,3-dicarboxylate (3e): White solid, yield: 80%; m.p. 205.8–206.7 °C (EA/PE); IR (KBr, cm⁻¹): ν 2942, 1745, 1682, 1475, 1252, 1025; ¹H NMR (400 MHz, CDCl₃) δ (ppm): 8.50 (d, J = 7.7 Hz, 1H), 7.88 (d, J = 7.5 Hz, 2H), 7.62 (d, J = 7.6 Hz, 2H), 7.58–7.47 (m, 1H), 7.40 (d, J = 7.6 Hz, 2H), 7.34–7.28 (m, 1H), 7.25 (d, J = 7.9 Hz, 2H), 7.17–7.08 (m, 1H), 5.79 (s, 1H), 5.60 (d, J = 11.8 Hz, 1H), 5.21 (d, J = 11.8 Hz, 1H), 4.07–3.88 (m, 2H), 3.82–3.69 (m, 2H), 0.89 (t, J = 6.7 Hz, 3H), 0.84 (t, J = 6.6 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ (ppm): ¹³C NMR (100 MHz, CDCl₃) δ 192.1, 165.7, 165.3, 141.0, 134.2, 133.9, 133.5, 133.4, 131.8, 131.2, 130.6, 130.3, 130.2, 129.1, 128.5, 128.3, 128.2, 127.5, 126.4, 116.8, 114.1, 64.4, 64.0, 57.1, 55.5, 55.4, 55.3, 54.2, 13.4, 13.3; HR-MS (ESI) calcd for C₃₂H₂₅Br₂ClN₂NaO₅ [(M + Na)⁺]: 734.9696; found: 734.9694.

Diethyl (1RS,2SR,3RS,4RS,5RS)-4-benzoyl-2,5-bis(2-chlorophenyl)-1,3-dicyanocyclopentane-1,3-dicarboxylate (3f): White solid, yield: 81%; m.p. 184.2–185.3 °C (EA/PE); IR (KBr, cm⁻¹): ν 2984, 1746, 1698, 1478, 1252, 1028; ¹H NMR (400 MHz, CDCl₃) δ (ppm): 8.60 (d, J = 7.1 Hz, 1H), 7.99 (d, J = 7.4 Hz, 2H), 7.82 (d, J = 7.3 Hz, 1H), 7.59 (d, J = 7.3 Hz, 1H), 7.53–7.45 (m, 3H), 7.42 (d, J = 7.7 Hz, 2H), 7.34 (d, J = 7.5 Hz, 2H), 7.25 (s, 1H), 5.59 (s, 1H), 5.37 (d, J = 11.5 Hz, 1H), 5.05 (d, J = 11.6 Hz, 1H), 4.22–4.04 (m, 2H), 3.82 (q, J = 7.1 Hz, 2H), 1.07 (t, J = 7.1 Hz, 3H), 0.85 (t, J = 7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ (ppm): 192.3, 164.7, 164.1, 135.8, 135.7, 135.4, 134.2, 130.9, 130.7, 130.6, 130.1, 130.1, 130.0, 129.1, 128.9, 128.6, 128.2, 127.6, 127.3, 117.8, 115.8, 64.2, 64.1, 59.1, 58.6, 54.1, 52.0, 49.6, 13.5, 13.1; HR-MS (ESI) calcd for C₃₂H₂₆Cl₂N₂NaO₅ [(M + Na)⁺]: 611.1116; found: 611.1113.

Diethyl (1RS,2SR,3RS,4SR,5RS)-2,4-bis(4-bromophenyl)-5-(4-chloro benzoyl)-1,3-dicyanocyclopentane-1,3-dicarboxylate (3g): White solid, yield: 85%; m.p. 199.6–200.4 °C (EA/PE); IR (KBr, cm⁻¹): ν 2933, 1739, 1680, 1482, 1249, 1001; ¹H NMR (400 MHz, CDCl₃) δ (ppm): 7.84 (d, J = 8.4 Hz, 2H), 7.59 (d, J = 8.6 Hz, 2H), 7.54 (d, J = 8.6 Hz, 2H), 7.44 (d, J = 8.1, 7.1 Hz, 4H), 7.20 (d, J = 8.4 Hz, 2H), 5.01 (d, J = 12.0 Hz, 1H), 4.97 (s, 1H), 4.88 (d, J = 12.3 Hz, 1H), 3.99–3.79 (m, 2H), 3.79–3.60(m, 2H), 0.83–0.76 (m, 6H); ¹³C NMR (100 MHz, CDCl₃) δ (ppm): 191.0, 166.1, 165.4, 141.4, 134.0, 132.3, 132.1, 132.0, 131.6, 130.1, 129.9, 129.7, 129.4, 124.5, 123.4, 117.4, 113.9, 64.3, 64.1, 57.6, 56.8, 56.4, 55.9, 54.5, 13.3, 13.2; HR-MS (ESI) calcd for C₃₂H₂₅Br₂ClN₂NaO₅ [(M + Na)⁺]: 734.9696; found: 734.9697.

Diethyl (1RS,2SR,3RS,4SR,5RS)-2,4-bis(4-bromophenyl)-1,3-dicyano-5-(4-methoxybenzoyl)cyclopentane-1,3-dicarboxylate (3h): White solid, yield: 83%; m.p. 184.2–185.6 °C (EA/PE); IR (KBr, cm⁻¹): ν 2976, 1749, 1656, 1479, 1243, 1010; ¹H NMR (400 MHz, CDCl₃) δ (ppm): 7.89 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 8.1 Hz, 2H), 7.53 (d, J = 8.1 Hz, 2H), 7.41 (d, J = 7.9 Hz, 2H), 7.21 (d, J = 7.8 Hz, 2H), 6.93 (d, J = 8.4 Hz, 2H), 5.05 (d, J = 12.3 Hz, 1H), 5.03 (s, 1H), 4.88 (d, J = 12.3 Hz, 1H), 3.97–3.89 (m, 1H), 3.86 (s, 3H), 3.83–3.72 (m, 2H), 3.71–3.58 (m, 1H), 0.86–0.71 (m, 6H); ¹³C NMR (100 MHz, CDCl₃) δ (ppm): 189.9, 166.2, 165.5, 164.8, 132.2, 132.0, 131.7, 131.0, 130.1, 129.9, 128.8, 124.4, 123.2, 117.6, 114.3, 114.2, 114.1, 64.1, 64.0, 57.4, 56.9, 56.5, 55.9, 55.7, 54.0, 13.3, 13.2; HR-MS (ESI) calcd for C₃₃H₂₈Br₂N₂NaO₆ [(M + Na)⁺]: 731.0191; found: 731.0193.

Diethyl (1RS,2SR,3RS,4RS,5SR)-4-(4-chlorobenzoyl)-1,3-dicyano-2,5-di-p-tolylcyclopentane-1,3-dicarboxylate (3i): White solid, yield: 82%; m.p. 269.5–270.3 °C (EA/PE); IR (KBr, cm⁻¹): ν 2963, 1746, 1685, 1478, 1248, 1023; ¹H NMR (400 MHz, CDCl₃) δ (ppm): 7.86 (d, J = 8.3 Hz, 2H), 7.59 (d, J = 7.9 Hz, 2H), 7.43 (d, J = 8.3 Hz, 2H), 7.20 (d, J = 7.2 Hz, 1H), 7.10 (d, J = 7.2 Hz, 2H), 7.07 (d, J = 7.7 Hz, 2H), 5.03 (d, J = 11.8 Hz, 1H), 5.00 (s, 1H), 4.96 (d, J = 12.3 Hz, 1H), 3.98–3.80 (m, 2H), 3.79–3.54 (m, 2H), 2.33 (s, 3H), 2.25 (s, 3H), 0.79 (t, J = 7.2 Hz, 3H), 0.74 (t, J = 7.2 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ (ppm): 191.6, 166.4, 165.8, 141.0, 139.7, 139.0, 134.4, 130.2, 130.0, 129.8(2C), 129.6, 129.4(2C), 129.2(2C), 128.3, 128.0(2C), 117.9, 114.3, 63.9, 63.6, 58.0, 57.0, 56.8, 56.4, 54.6, 21.2, 21.0, 13.3, 13.1; HR-MS (ESI) calcd for C₃₄H₃₁ClN₂NaO₅ [(M + Na)⁺]: 605.1819; found: 605.1816.

Diethyl (1RS,2SR,3RS,4RS,5SR)-4-(4-bromobenzoyl)-1,3-dicyano-2-(m-tolyl)-5-(p-tolyl)cyclopentane-1,3-dicarboxylate (3j): White solid, yield: 79%; m.p. 265.4–266.6 °C (EA/PE); IR (KBr, cm⁻¹): ν 2956, 1773, 1682, 1476, 1248, 1021; ¹H NMR (400 MHz, CDCl₃) δ (ppm): 7.78 (d, J = 8.3 Hz, 2H), 7.60 (d, J = 8.3 Hz, 2H), 7.55 (d, J = 7.6 Hz, 1H), 7.42 (s, 1H), 7.29 (d, J = 7.7 Hz, 1H), 7.21 (d, J = 7.5 Hz, 3H), 7.08 (d, J = 7.7 Hz, 2H), 5.03 (d, J = 12.4 Hz, 1H), 5.00 (s, 1H), 4.95 (d, J = 12.3 Hz, 1H), 4.00–3.80 (m, 2H), 3.79–3.54 (m, 2H), 2.35 (s, 3H), 2.26 (s, 3H), 0.84–0.69 (m, 6H); ¹³C NMR (100 MHz, CDCl₃) δ (ppm): 191.8, 166.4, 165.8, 139.0, 138.6, 134.8, 132.2, 131.0, 130.6, 130.4, 130.1, 130.0, 129.8, 129.4, 128.8, 128.4, 126.8, 117.8, 114.2, 63.9, 63.7, 58.2, 57.0, 56.9, 56.4, 54.5, 21.4, 21.0, 13.3, 13.1; HR-MS (ESI) calcd for C₃₄H₃₁BrN₂NaO₅ [(M + Na)⁺]: 649.1314; found: 649.1312.

Supplemental Material

ESI – Supplemental material for Novel synthesis of highly functionalized cyclopentane derivatives via [3 + 2] cycloaddition reactions of donor–acceptor cyclopropanes and (E)-3-aryl-2-cyanoacrylates

Supplemental material, ESI for Novel synthesis of highly functionalized cyclopentane derivatives via [3 + 2] cycloaddition reactions of donor–acceptor cyclopropanes and (E)-3-aryl-2-cyanoacrylates by Chenlu Dai, Mingshuang Li, Mengjun Chen, Naili Luo and Cunde Wang in Journal of Chemical Research

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: Financial support of this research by the National Natural Science Foundation of China (NNSFC 21173181) is gratefully acknowledged by authors. A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

Supplemental material

Full details of the X-ray structure and crystal refinement of compounds 3d and 3g are available online.

Crystallographic data for 3d and 3g have been deposited with the Cambridge Crystallographic Data Center with the deposition number CCDC 1821304 and 1848037. The data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax +44 1223 336033, e-mail: deposit@ccdc.cam.ac.uk).

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Novel synthesis of highly functionalized cyclopentane derivatives via [3 + 2] cycloaddition reactions of donor–acceptor cyclopropanes and ( E )-3-aryl-2-cyanoacrylates

Abstract

Keywords

Introduction

Results and discussion

Conclusion

Experimental

General

General procedure for the synthesis of 1,3-dicyanocyclopentane-1,3-dicarboxylate derivatives

Supplemental Material

ESI – Supplemental material for Novel synthesis of highly functionalized cyclopentane derivatives via [3 + 2] cycloaddition reactions of donor–acceptor cyclopropanes and (E)-3-aryl-2-cyanoacrylates

Footnotes

Declaration of conflicting interests

Funding

Supplemental material

References

Supplementary Material