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Abstract

A synthetic method for the preparation of 3,3a,4,6,7,8,9,9a-octahydro-1H-benzo[f]isoindole-1,5(2H)-diones from 1,6-dienes and vinyl iodides is developed using PdCl₂(PPh₃)₂ as the catalyst. The presented approach exhibits a good functional group tolerance and affords moderate yields of the products. A mechanism is also proposed.

Keywords

1,6-dienes cascade reactions enones and their derivatives Pd-catalyzed polycyclic compounds

Introduction

Due to the benefits of atom economy, saving time, and less waste generation, cascade reactions that allow the generation of molecular complexity in a single operation have attracted significant attention.^1–5 Although cascade reactions have been successfully employed for the synthesis of the core skeleton of many important natural products, the design and performance of cascade reactions remains a challenging aspect of organic chemistry.^6–10 Recently, the α-arylation of enones and their derivatives has been developed.^11–14 For example, Liu reported an efficient synthesis of N-fused polycyclic indoles via a palladium-catalyzed annulation/acyl migration cascade reaction (Scheme 1a).¹¹ McGlacken reported that 1,3-diketone-derived enol ethers could undergo Heck cyclization, offering tricyclic oxoisochromene derivatives in good yields (Scheme 1b).¹² In these cases, the introduction of a halogen atom into certain molecules was necessary.^15,16 Meanwhile, reports on alkylations at the α-position of enones and their derivatives are comparatively scarce.^17,18 Starting from electron-deficient vinyl iodides and propargyl ethers, Huang provided an efficient synthesis of structurally complex polycycles with 2,3-dihydrofuran units (Scheme 1c).¹⁸ Given this background, we envisioned that Pd-catalyzed reactions of 1,6-dienes and vinyl iodides would proceed via a cascade reaction to form polycyclic compounds through alkylation of the α-position of the enone (Scheme 1d).

Scheme 1.

Previous work and our synthetic strategy: (a) Liu’s work, (b) McGlacken’s work, (c) Huang’s work, and (d) this work.

Results and discussion

Our initial study was carried out with the reaction between N-allyl-N-benzylacrylamide (1a) and 3-iodocyclohex-2-en-1-one (2a) in order to examine the reaction parameters (Table 1). When the reaction was performed in the presence of Pd(OAc)₂ in toluene at 130 °C under a nitrogen atmosphere using K₂CO₃ as the base and TBAB as an additive, 2-benzyl-3,3a,4,6,7,8,9,9a-octahydro-1H-benzo[f]isoindole-1,5(2H)-dione (3a) was obtained in 36% yield (Table 1, Entry 1). Subsequently, various palladium salts were tested, among which PdCl₂(PPh₃)₂ provided the best result (Table 1, Entries 1–3). A series of bases, including DABCO, n-Bu₃N, LiOH, and KOAc, also gave compound (3a), albeit in lower yields (Table 1, Entries 4–7). Furthermore, as revealed in Table 1, other solvents such as DMSO, DMF, and DMAc were investigated (Table 1, Entries 8–10), with DMSO found to be optimal, giving (3a) in 60% yield. Moreover, when TCAB¹⁹ was used as the additive, the product (3a) could be obtained in 61% yield (Table 1, Entry 11). Finally, the reaction temperature was investigated and after a brief screening of different temperatures, we found that the highest yield was achieved at 130 °C (Table 1, Entries 11–13).

Table 1.

Optimization of the reaction conditions.^a


Entry	Base	Solvent	Pd source	Additive	Temp	Reaction time (h)	Yield (%)^b
1	K₂CO₃	Toluene	Pd(OAc)₂	TBAB	130	12	36
2	K₂CO₃	Toluene	PdCl₂	TBAB	130	12	30
3	K₂CO₃	Toluene	PdCl₂(PPh₃)₂	TBAB	130	12	42
4	DABCO	Toluene	PdCl₂(PPh₃)₂	_____	130	12	40
5	n-Bu₃N	Toluene	PdCl₂(PPh₃)₂	_____	130	12	35
6	LiOH	Toluene	PdCl₂(PPh₃)₂	TBAB	130	12	12
7	KOAc	Toluene	PdCl₂(PPh₃)₂	TBAB	130	12	39
8	K₂CO₃	DMSO	PdCl₂(PPh₃)₂	TBAB	130	12	60
9	K₂CO₃	DMF	PdCl₂(PPh₃)₂	TBAB	130	12	56
10	K₂CO₃	DMAc	PdCl₂(PPh₃)₂	TBAB	130	12	34
11	K₂CO₃	DMSO	PdCl₂(PPh₃)₂	TCAB	130	12	61
12	K₂CO₃	DMSO	PdCl₂(PPh₃)₂	TCAB	120	12	52
13	K₂CO₃	DMSO	PdCl₂(PPh₃)₂	TCAB	140	12	50

Reaction conditions: 1a (0.30 mmol), 2a (0.36 mmol), Pd (5.0 mol%), additive (10.0 mol%), base (0.36 mmol), solvent (5.0 mL).

Yield of isolated product.

With optimized reaction conditions in hand, we next explored the scope and generality of the method. Pleasingly, N-allyl-N-benzylacrylamides substituted with an electron-donating group (Me) or an electron-withdrawing group (Cl) on the aromatic ring were tolerated, leading to the formation of target products 3b, 3c in moderate yields (Table 2, Entries 2 and 3). To further study the scope of this method, the reactions of different N-allyl-N-phenylacrylamides with 3-iodocyclohex-2-en-1-one (2a) were investigated (Table 2, Entries 4–8). Gratifyingly, all the reactions proceeded smoothly and gave the expected products in moderate yields. A substrate with an electron-withdrawing substituent on the phenyl ring gave a slightly higher yield than that with an electron-donating substituent (Table 2, Entries 7 and 8). The generality of the reaction was also examined by the employment of 3-iodo-5,5-dimethylcyclohex-2-en-1-one, and the results are given in Table 2 (Entries 9–15). All the reactions proceeded smoothly under the standard conditions, affording the desired products 3i-o in moderate yields (35%–63%). The crystal structure of 3K is shown in Figure 1 with the relevant crystal data given in Table 3.²⁰ We can see from the crystal structure that the five and six member rings are transfused.

Table 2.

Substrate scope of the reaction.^a


Entry	R	R¹	Product	Reaction time (h)	Yield (%)^b
1	Bn	H	3a	12	67
2	p-MeC₆H₄CH₂	H	3b	12	62
3	p-ClC₆H₄CH₂	H	3c	12	64
4	C₆H₅	H	3d	12	47
5	p-MeC₆H₅	H	3e	12	46
6	m-MeC₆H₅	H	3f	12	42
7	p-MeOC₆H₅	H	3g	12	32
8	p-ClC₆H₅	H	3h	12	53
9	C₆H₅	Me	3i	12	46
10	p-MeC₆H₅	Me	3j	12	48
11	p-MeOC₆H₅	Me	3k	12	35
12	p-ClC₆H₅	Me	3l	12	55
13	Bn	Me	3m	12	58
14	p-MeC₆H₄CH₂	Me	3n	12	52
15	p-ClC₆H₄CH₂	Me	3o	12	63

Reaction conditions: 1 (0.30 mmol), 2 (0.36 mmol), PdCl₂(PPh₃)₂ (5.0 mol%), TCAB (10.0 mol%), and K₂CO₃ (0.36 mmol), DMSO (5.0 mL).

Yield of isolated product.

Figure 1.

Molecular structure of 3k.

Table 3.

Crystal data and structure refinement for 3K.²¹

Identification code	3K
Empirical formula	C₂₁H₂₅NO₃
Formula weight	339.42
Temperature (K)	200.00(10)
Crystal system	Monoclinic
Space group	P2₁/n
a (Å)	15.8287(10)
b (Å)	5.8305(4)
c (Å)	20.2846(13)
α (°)	90
β (°)	112.131(7)
γ (°)	90
Volume (Å³)	1734.1(2)
Z	4
ρ_calc (g cm⁻³)	1.300
μ (mm⁻¹)	0.086
F(000)	728.0
Crystal size/mm³	0.14 × 0.13 × 0.12
Radiation	Mo Kα (λ = 0.71073)
2Θ range for data collection (°)	4.118 to 50
Index ranges	−16 ⩽ h ⩽ 18, –6 ⩽ k ⩽ 5, –24 ⩽ l ⩽ 23
Reflections collected	7416
Independent reflections	3041 (R_int = 0.0242, R_sigma = 0.0334)
Data/restraints/parameters	3041/0/249
Goodness-of-fit on F²	1.059
Final R indexes [I >= 2σ (I)]	R₁ = 0.0516, wR₂ = 0.1217
Final R indexes [all data]	R₁ = 0.0634, wR₂ = 0.1303
Largest diff. peak/hole / e Å⁻³	0.44/–0.40

A plausible reaction mechanism has been proposed (Scheme 2). Initial oxidative addition and carbo-palladation gives Intermediate I, which undergoes an intramolecular tandem reaction to provide Intermediate III. Considering a standard Heck mechanism, the Intermediate III does not allow for syn-β-hydride elimination from C-1-H. Alternatively, C-2-H in the appropriate configuration can be eliminated to give Intermediate IV. Subsequent isomerization would lead to the observed product.

Scheme 2.

A plausible reaction mechanism.

Conclusion

In summary, we have developed an efficient method for the synthesis of polycyclic oxindole moieties in the presence of a PdCl₂(PPh₃)₂ catalytic system under mild conditions. The ready accessibility of the starting materials, the wide range of compatibility of the substrates, and the generality of this make the reported process advantageous.

Experimental

All starting materials and reagents are commercially available and were used without further purification. The organic solvents used in this study were dried over appropriate drying agents and distilled prior to use. Melting points were determined with an X-4 apparatus and are uncorrected. IR spectra were recorded with a Shimadzu FTIR-8300 spectrophotometer. High-resolution mass spectra (HRMS) were obtained on a waters G2-Xs with an ESI source (Waters, Manchester, UK). The ¹H NMR spectra were determined in CDCl₃ using TMS as an internal reference with a Bruker 500 FT NMR spectrometer operating at 500 MHz. The ¹³C NMR spectra were determined in CDCl₃ using TMS as an internal reference with a Bruker 500 FT NMR spectrometer operating at 125 MHz.

Polycyclic Oxindoles 3 general procedure

The 1,6-diene 1 (0.30 mmol), vinyl iodide 2 (0.36 mmol), PdCl₂(PPh₃)₂ (5 mol%, 0.015 mmol, 10.5 mg), TCAB (10 mol%, 0.03 mmol, 8.33 mg), and K₂CO₃ (0.36 mmol, 49.68 mg) were stirred in DMSO (5.0 mL) at 130 °C in a 20 mL tube under a N₂ atmosphere. When the reaction was complete (monitoring by TLC), the mixture was cooled to room temperature. The reaction was quenched with HCl (5%, 10 mL) and extracted with Et₂O (3 × 10 mL). The combined organic layers were dried over anhydrous MgSO₄ and then evaporated in vacuum. The residue was purified by column chromatography on silica gel (hexanes/ethyl acetate) to afford the corresponding polycyclic oxindoles 3.

2-Benzyl-3,3a,4,6,7,8,9,9a-octahydro-1H-benzo[f]isoindole-1,5(2H)-dione (3a): Yield: 59.3 mg (67%); white solid; m.p. 218 °C–224 °C (PE/EtOAc); IR (film) 2984, 2938, 2902, 1700, 1672, 1510, 1087, 732 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 7.35–7.26 (m, 3H), 7.23–7.22 (m, 2H), 4.51 (d, J = 15 Hz, 1H), 4.44 (d, J = 15 Hz, 1H), 3.34–3.31 (m, 1H), 3.03 (t, J = 9.5 Hz, 1H), 2.71–2.69 (m, 1H), 2.64–2.59 (m, 1H), 2.47–2.35 (m, 6H), 2.19–2.13 (m, 1H), 2.02–1.91 (m, 4H); ¹³C NMR (125 MHz, CDCl₃): δ 201.0, 174.6, 136.6, 132.1, 128.8, 128.1, 127.7, 50.9, 64.6, 43.8, 37.8, 37.4, 32.2, 31.6, 26.5, 22.3; HRMS (ESI): m/z [M+H]⁺ calcd for C₁₉H₂₂NO₂: 296.1651; found: 296.1647.

2-(4-Methylbenzyl)-3,3a,4,6,7,8,9,9a-octahydro-1H-benzo[f]isoindole-1,5(2H)-dione (3b): Yield: 57.5 mg (62%); white solid; m.p. 178 °C–180 °C (PE/EtOAc); IR (film) 2935, 2897, 2836, 1668, 1623, 1496, 1169, 726 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 7.14–7.10 (m, 4H), 4.46 (d, J = 15 Hz, 1H), 4.40 (d, J = 15 Hz, 1H), 3.33–3.31 (m, 1H), 3.01 (t, J = 10 Hz, 1H), 2.71–2.68 (m, 1H), 2.63–2.58 (m, 1H), 2.47–2.33 (m, 8H), 2.17–2.11 (m, 1H), 2.02–1.88 (m, 4H); ¹³C NMR (125 MHz, CDCl₃): δ 198.8, 174.5, 156.5, 173.3, 133.6, 132.1, 129.4, 128.1, 50.8, 46.3, 43.8, 37.8, 37.4, 32.2, 31.6, 26.5, 22.3, 21.1; HRMS (ESI): m/z [M+H]⁺ calcd for C₂₀H₂₄NO₂: 310.1807; found: 310.1809.

2-(4-Chlorobenzyl)-3,3a,4,6,7,8,9,9a-octahydro-1H-benzo[f]isoindole-1,5(2H)-dione (3c): Yield: 63.2 mg (62%); white solid; m.p. 182 °C–186 °C (PE/EtOAc); IR (film) 2943, 2928, 2895, 1702, 1656, 1490, 1135, 772 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 7.30 (d, J = 8.5 Hz, 2H), 7.17 (d, J = 8.5 Hz, 2H), 4.48 (d, J = 15 Hz, 1H), 4.40 (d, J = 15 Hz, 1H), 3.34–3.32 (m, 1H), 3.03 (t, J = 10 Hz, 1H), 2.73–2.70 (m, 1H), 2.64–2.59 (m, 1H), 2.48–2.36 (m, 5H), 2.18–2.12 (m, 1H), 2.04–1.89 (m, 4H); ¹³C NMR (125 MHz, CDCl₃): δ 198.6, 174.6, 156.3, 135.2, 133.5, 132.0, 129.4, 128.9, 50.9, 45.9, 43.7, 37.8, 37.4, 32.1, 31.6, 26.5, 22.3; HRMS (ESI): m/z [M+H]⁺ calcd for C₁₉H₂₁ClNO₂: 330.1261; found: 330.1257.

2-Phenyl-3,3a,4,6,7,8,9,9a-octahydro-1H-benzo[f]isoindole-1,5(2H)-dione (3d): Yield: 39.6 mg (47%); white solid; m.p. 221 °C–227 °C (PE/EtOAc); IR (film) 2924, 2887, 1686, 1658, 1613, 1500, 1368, 755 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 7.63–7.61 (m, 2H), 7.39–7.36 (m, 2H), 7.16–7.13 (m, 1H), 3.94–3.91 (m, 1H), 3.64 (t, J = 9.5 Hz, 1H), 2.88–2.85 (m, 1H), 2.68–2.63 (m, 1H), 2.51–2.32 (m, 6H), 2.11–1.96 (m, 4H); ¹³C NMR (125 MHz, CDCl3): δ 198.7, 173.8, 156.3, 139.6, 131.9, 128.9, 124.4, 119.6, 53.0, 45.1, 37.8, 36.5, 32.1, 31.6, 26.6, 22.3; HRMS (ESI): m/z [M+H]⁺ calcd for C₁₈H₂₀NO₂: 282.1494; found: 282.1496.

2-(p-Tolyl)-3,3a,4,6,7,8,9,9a-octahydro-1H-benzo[f]isoindole-1,5(2H)-dione (3e): Yield: 40.7 mg (46%); white solid; m.p. 193 °C–196 °C (PE/EtOAc); IR (film) 2941, 2910, 2864, 1702, 1660, 1508, 1198, 825 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 7.50 (d, J = 8.5 Hz, 2H), 7.19 (d, J = 8.5 Hz, 2H), 3.92–3.89 (m, 1H), 3.63 (t, J = 9.5 Hz, 1H), 2.88–2.86 (m, 1H), 2.68–2.64 (m, 1H), 2.50–2.31 (m, 9H), 2.12–1.98 (m, 4H); ¹³C NMR (125 MHz, CDCl₃): δ 198.7, 173.6, 156.4, 137.1, 133.9, 131.9, 129.4, 119.6, 53.0, 44.9, 37.8, 36.5, 32.1, 31.6, 26.5, 22.3, 20.9; HRMS (ESI): m/z [M+H]⁺ calcd for C₁₉H₂₂NO₂: 296.1651; found: 296.1655.

2-(m-Tolyl)-3,3a,4,6,7,8,9,9a-octahydro-1H-benzo[f]isoindole-1,5(2H)-dione (3f): Yield: 37.2 mg (42%); white solid; m.p. 200 °C–206 °C (PE/EtOAc); IR (film) 2952, 2906, 2852, 1687, 1654, 1322, 1206, 738 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 7.45–7.39 (m, 2H), 7.25–7.24 (m, 1H), 6.97–6.95 (m, 1H), 3.92–3.89 (m, 1H), 3.65–3.61 (m, 1H), 2.87–2.84 (m, 1H), 2.66–2.62 (m, 1H), 2.51–2.32 (m, 9H), 2.10–1.96 (m, 4H); ¹³C NMR (125 MHz, CDCl₃): δ 198.8, 173.7, 156.4, 139.5, 138.8, 131.9, 128.7, 125.2, 120.4, 116.7, 53.1, 45.0, 37.8, 36.5, 32.1, 31.6, 26.6, 22.3, 21.7; HRMS (ESI): m/z [M+H]⁺ calcd for C₁₉H₂₂NO₂: 296.1651; found: 296.1655.

2-(4-Methoxyphenyl)-3,3a,4,6,7,8,9,9a-octahydro-1H-benzo[f]isoindole-1,5(2H)-dione (3g): Yield: 29.9 mg (32%); white solid; m.p. 205 °C–213 °C (PE/EtOAc); IR (film) 2961, 2928, 2904, 1688, 1680, 1659, 1619, 835 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 7.52 (d, J = 9.0 Hz, 2H), 6.92 (d, J = 9.5 Hz, 2H), 3.90–3.87 (m, 1H), 3.82 (s, 3H), 3.65–3.61 (m, 1H), 2.88–2.86 (m, 1H), 2.69–2.64 (m, 1H), 2.53–2.33 (m, 6H), 2.12–1.98 (m, 4H); ¹³C NMR (125 MHz, CDCl₃): δ 198.8, 173.5, 156.5, 156.4, 132.8, 131.9, 121.4, 114.1, 55.5, 53.4, 44.8, 37.8, 36.7, 32.2, 31.6, 26.6, 22.3; HRMS (ESI): m/z [M+H]⁺ calcd for C₁₉H₂₂NO₃: 312.1600; found: 296.1596.

2-(4-Chlorophenyl)-3,3a,4,6,7,8,9,9a-octahydro-1H-benzo[f]isoindole-1,5(2H)-dione (3h) : Yield: 50.1 mg (53%); white solid; m.p. 215 °C–220 °C (PE/EtOAc); IR (film) 2934, 2900, 2894, 1700, 1658, 1564, 1154, 732 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 7.60 (d, J = 8.5 Hz, 2H), 7.34 (d, J = 8.5 Hz, 2H), 3.93–3.90 (m, 1H), 3.65–3.61 (m, 1H), 2.90–2.87 (m, 1H), 2.68–2.64 (m, 1H), 2.53–2.33 (m, 6H), 2.13–1.97 (m, 4H); ¹³C NMR (125 MHz, CDCl₃): δ 198.7, 173.8, 156.1, 138.1, 131.8, 129.4, 128.9, 120.6, 52.9, 45.0, 37.8, 36.4, 32.0, 31.6, 21.6, 22.3; HRMS (ESI): m/z [M+H]⁺ calcd for C₁₈H₁₉ClNO₂: 316.1104; found: 316.1109.

7,7-Dimethyl-2-phenyl-3,3a,4,6,7,8,9,9a-octahydro-1H-benzo[f]isoindole-1,5(2H)-dione (3i): Yield: 42.8 mg (46%); white solid; m.p. 242 °C–246 °C (PE/EtOAc); IR (film) 2962, 2920, 2885, 1687, 1662, 1619, 1169, 757 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 7.64–7.62 (m, 2H), 7.41–7.37 (m, 2H), 7.18–7.15 (m, 1H), 3.96–3.93 (m, 1H), 3.68–3.64 (m, 1H), 2.92–2.90 (m, 1H), 2.64–2.61 (m, 1H), 2.43–2.27 (m, 6H), 2.12–2.09 (m, 2H), 1.10 (s, 3H), 1.03 (s, 3H); ¹³C NMR (125 MHz, CDCl₃): δ 198.8, 173.7, 153.8, 139.6, 130.7, 128.9, 124.4, 119.6, 53.0, 51.4, 45.7, 45.1, 36.6, 33.1, 32.3, 29.4, 27.1, 26.3; HRMS (ESI): m/z [M+H]⁺ calcd for C₂₀H₂₄NO₂: 310.1807; found: 310.1811.

7,7-Dimethyl-2-(p-tolyl)-3,3a,4,6,7,8,9,9a-octahydro-1H-benzo[f]isoindole-1,5(2H)-dione (3j): Yield: 46.5 mg (48%); white solid; m.p. 195 °C–200 °C (PE/EtOAc); IR (film) 2952, 2922, 1678, 1653, 1615, 1426, 1367, 799 cm⁻¹; ¹H NMR (500 MHz, CDCl3): δ 7.48 (d, J = 11 Hz, 2H), 7.17 (d, J = 10.5 Hz, 2H), 3.90–3.87 (m, 1H), 3.64–3.59 (m, 1H), 2.89–2.87 (m, 1H), 2.63–2.58 (m, 1H), 2.41–2.25 (m, 9H), 2.10–2.06 (m, 2H), 1.07 (s, 3H), 1.00 (s, 3H); ¹³C NMR (125 MHz, CDCl₃): δ 198.8, 173.5, 153.8, 130.8, 129.4, 119.7, 53.1, 51.4, 45.7, 45.1, 36.7, 33.2, 32.3, 29.4, 27.1, 26.3, 20.9; HRMS (ESI): m/z [M+H]⁺ calcd for C₂₁H₂₆NO₂: 324.1964; found: 324.1961.

2-(4-Methoxyphenyl)-7,7-dimethyl-3,3a,4,6,7,8,9,9a-octahydro-1H-benzo[f]isoin-isdole-1,5(2H)-dione (3k):

Yield: 35.6 mg (35%); white solid; m.p. 192 °C–198 °C (PE/EtOAc); IR (film) 2962, 2936, 1700, 1668, 1635, 1426, 1389, 810 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 7.51 (d, J = 9.0 Hz, 2H), 6.92 (d, J = 9.0 Hz, 2H), 3.90–3.87 (m, 1H), 3.82 (s, 3H), 3.64 (t, J = 9.5 Hz, 1H), 2.91–2.88 (m, 1H), 2.64–2.60 (m, 1H), 2.42–2.23 (m, 6H), 2.12–2.09 (m, 2H), 1.09 (s, 3H), 1.03 (s, 3H); ¹³C NMR (125 MHz, CDCl₃): δ 198.8, 173.4, 156.4, 153.9, 132.8, 130.7, 121.3, 114.0, 55.5, 53.3, 51.4, 45.7, 44.9, 36.7, 33.1, 32.3, 29.4, 27.0, 26.2; HRMS (ESI): m/z [M+H]⁺ calcd for C₂₁H₂₆NO₃: 340.1913; found: 340.1912.

2-(4-Chlorophenyl)-7,7-dimethyl-3,3a,4,6,7,8,9,9a-octahydro-1H-benzo[f]isoindole-1,5(2H)-dione (3l): Yield: 56.6 mg (55%); white solid; m.p. 232 °C–237 °C (PE/EtOAc); IR (film) 2957, 2928, 2871, 1705, 1661, 1490, 1367, 844 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 7.58 (d, J = 9.0 Hz, 2H), 7.35 (d, J = 9.0 Hz, 2H), 3.93–3.90 (m, 1H), 3.64 (t, J = 9.5 Hz, 1H), 2.93–2.90 (m, 1H), 2.63–2.61 (m, 1H), 2.42–2.23 (m, 6H), 2.13–2.06 (m, 2H), 1.10 (s, 3H), 1.00 (s, 3H); ¹³C NMR (125 MHz, CDCl₃): δ 198.8, 173.8, 153.7, 138.1, 130.7, 129.4, 128.9, 120.6, 52.9, 51.4, 45.7, 45.1, 36.5, 33.2, 32.2, 29.4, 27.0, 26.2; HRMS (ESI): m/z [M+H]⁺ calcd for C₂₀H₂₃ClNO₂: 344.1417; found: 344.1419.

2-Benzyl-7,7-dimethyl-3,3a,4,6,7,8,9,9a-octahydro-1H-benzo[f]isoindole-1,5(2H)-dione (3m): Yield: 56.2 mg (58%); white solid; m.p. 195 °C–198 °C (PE/EtOAc); IR (film) 2956, 2910, 2878, 1689, 1643, 1527, 1169, 698 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 7.35–7.22 (m, 5H), 4.53 (d, J = 15 Hz, 1H), 4.43 (d, J = 15 Hz, 1H), 3.35–3.32 (m, 1H), 3.04 (t, J = 10 Hz, 1H), 2.75–2.72 (m, 1H), 2.60–2.56 (m, 1H), 2.34–2.16 (m, 6H), 1.96–1.92 (m, 2H), 1.06 (s, 3H), 0.98 (s, 3H); ¹³C NMR (125 MHz, CDCl3): δ 198.8, 174.5, 154.0, 136.6, 130.9, 128.7, 128.4, 127.6, 51.4, 50.8, 46.5, 45.7, 43.9, 37.5, 33.1, 32.3, 29.5, 27.0, 26.2; HRMS (ESI): m/z [M+H]⁺ calcd for C₂₁H₂₆NO₂: 324.1964; found: 324.1967.

7,7-Dimethyl-2-(4-methylbenzyl)-3,3a,4,6,7,8,9,9a-octahydro-1H-benzo[f]isoindole-1,5(2H)-dione (3n): Yield: 50.7 mg (52%); white solid; m.p. 178 °C–180 °C (PE/EtOAc); IR (film) 2969, 2934, 2875, 168,7 1654, 1507, 1224, 773 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 7.14–7.10 (m, 4H), 4.46 (d, J = 15 Hz, 1H), 4.39 (d, J = 15 Hz, 1H), 3.32–3.29 (m, 1H), 3.01 (t, J = 10 Hz, 1H), 2.73–2.70 (m, 1H), 2.59–2.54 (m, 1H), 2.35–2.14 (m, 9H), 1.94–1.89 (m, 2H), 1.05 (s, 3H), 0.97 (s, 3H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ 198.8, 174.4, 154.0, 137.3, 133.6, 130.9, 129.4, 128.1, 51.4, 50.7, 46.2, 45.7, 43.9, 37.5, 33.1, 32.4, 29.5, 27.0, 26.2, 21.1; HRMS (ESI): m/z [M+H]⁺ calcd for C₂₁H₂₅ClNO₂: 338.2120; found: 338.2116.

2-(4-Chlorobenzyl)-7,7-dimethyl-3,3a,4,6,7,8,9,9a-octahydro-1H-benzo[f]isoindole-1,5(2H)-dione (3o): Yield: 67.5 mg (63%); white solid; m.p. 184 °C–188 °C (PE/EtOAc); IR (film) 2952, 2926, 2910, 1682, 1652, 1490, 1091, 667 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 7.30 (d, J = 8.0 Hz, 2H), 7.17 (d, J = 8.5 Hz, 2H), 4.49 (d, J = 15 Hz, 1H), 4.39 (d, J = 15 Hz, 1H), 3.34–3.31 (m, 1H), 3.04 (t, J = 10.5 Hz, 1H), 2.76–2.73 (m, 1H), 2.60–2.55 (m, 1H), 2.36–2.14 (m, 6H), 1.96–1.91 (m, 2H), 1.06 (s, 3H), 0.98 (s, 3H); ¹³C NMR (125 MHz, CDCl₃): δ 198.7, 174.5, 153.8, 135.2, 133.4, 130.8, 129.4, 128.9, 51.3, 50.8, 45.8, 45.7, 43.7, 37.5, 33.1, 32.2, 29.4, 26.9, 26.1; HRMS (ESI): m/z [M+H]⁺ calcd for C₂₁H₂₅ClNO₂: 358.1514; found: 358.1512.

Supplemental Material

sj-cif-1-chl-10.1177_17475198211058653 – Supplemental material for A palladium-catalyzed cascade approach for the synthesis of 3,3a,4,6,7,8,9,9a-octahydro-1H-benzo[f]isoindole-1,5(2H)-diones

Supplemental material, sj-cif-1-chl-10.1177_17475198211058653 for A palladium-catalyzed cascade approach for the synthesis of 3,3a,4,6,7,8,9,9a-octahydro-1H-benzo[f]isoindole-1,5(2H)-diones by Dong Cheng, Xiangzhen Meng, Dan Wang, Xuan Zhao, Yusheng Wang and Zhiyu Ji in Journal of Chemical Research

Supplemental Material

sj-docx-1-chl-10.1177_17475198211058653 – Supplemental material for A palladium-catalyzed cascade approach for the synthesis of 3,3a,4,6,7,8,9,9a-octahydro-1H-benzo[f]isoindole-1,5(2H)-diones

Supplemental material, sj-docx-1-chl-10.1177_17475198211058653 for A palladium-catalyzed cascade approach for the synthesis of 3,3a,4,6,7,8,9,9a-octahydro-1H-benzo[f]isoindole-1,5(2H)-diones by Dong Cheng, Xiangzhen Meng, Dan Wang, Xuan Zhao, Yusheng Wang and Zhiyu Ji 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: We acknowledge the Key Natural Science Foundation of Anhui Higher Education Institution (KJ2017A446), the Excellent Young Talents Support Program of Anhui Higher Education Institutions (gxyq2018075), and the Innovation and Entrepreneurship Project of College Students in Anhui Province (S202010380031).

ORCID iD

Dong Cheng

Supplemental material

Supplemental material for this article is available online.

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CCDC 2113876 (3k) contain the supplementary crystallographic data for this paper. These data can be obtained free charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/datarequest/cif

Supplementary Material

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A palladium-catalyzed cascade approach for the synthesis of 3,3a,4,6,7,8,9,9a-octahydro-1 H -benzo[ f ]isoindole-1,5(2 H )-diones

Abstract

Keywords

Introduction

Results and discussion

Conclusion

Experimental

Polycyclic Oxindoles 3 general procedure

Supplemental Material

sj-cif-1-chl-10.1177_17475198211058653 – Supplemental material for A palladium-catalyzed cascade approach for the synthesis of 3,3a,4,6,7,8,9,9a-octahydro-1H-benzo[f]isoindole-1,5(2H)-diones

Supplemental Material

sj-docx-1-chl-10.1177_17475198211058653 – Supplemental material for A palladium-catalyzed cascade approach for the synthesis of 3,3a,4,6,7,8,9,9a-octahydro-1H-benzo[f]isoindole-1,5(2H)-diones

Footnotes

Declaration of conflicting interests

Funding

ORCID iD

Supplemental material

References

Supplementary Material