One-pot regioselective synthesis of functionalized and fused furans from Morita–Baylis–Hillman and Rauhut–Currier adducts of nitroalkenes

Abstract

Highly functionalized and fused furans have been synthesized via cascade reactions of Morita–Baylis–Hillman and Rauhut–Currier adducts of nitroalkenes with active methylene compounds. The reactions involving S_N2′-intramolecular Michael addition or Michael addition-intra-molecular nucleophilic substitution take place in a regioselective manner to afford synthetically and biologically useful furans in moderate to good yields.

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Introduction

Furans belong to a unique class of five membered aromatic oxygen heterocycles which constitute the core structure of numerous natural products, drugs and other bioactive molecules.¹ The diverse biological properties exhibited by furan containing compounds are well-documented in the literature.² The wide applicability of furans as valuable synthons in multi-step reactions, including total synthesis, is well-recognized.³ Among the several methods reported for the synthesis of furans,⁴ Paal–Knorr synthesis (from 1,4-dicarbonyl compounds)⁵ and Feist–Benary synthesis (typically from α-haloketones and β-dicarbonyl compounds)⁶ are the prominent ones. Many highly efficient transition metal catalyzed cycloisomerization strategies have emerged in recent years.⁷

Despite the availability of numerous methods, development of novel and efficient diversity oriented approaches for the synthesis of functionalized and fused furans would be very valuable both from synthetic and biological perspectives. As part of the studies on the Morita–Baylis–Hillman (MBH)⁸ and Rauhut–Currier (RC)⁹ reactions of nitroalkenes and the applications of the products,^10–20 we and others have utilized the MBH acetates of nitroalkenes 1 (LG = OAc) for the synthesis of several carbocycles¹¹ and heterocycles.^12,13 The methodology involves a cascade S_N2′ reaction of a binucleophile with MBH acetate 1 followed by an intramolecular Michael addition taking advantage of the 1,2 or 1,3-bi-electrophilic character of 1 as outlined in Scheme 1a. We and Chen et al. have reported the synthesis of furans via base mediated addition of 1,3-dicarbonyl compounds and arenols to the 1,2-bielectrophilic MBH acetates 1 (Scheme 1b).¹³ Herein we report the role of α-nitroacetophenone 4 as the bi-nucleophile towards the MBH acetates 1 resulting in synthetically and biologically useful highly substituted nitrofurans 5 as single regioisomers (Scheme 1c). The vinylogous MBH (Rauhut–Currier, RC) reaction of nitroalkenes¹⁴ and its applications for the synthesis of novel carbocyclic and heterocyclic scaffolds have also been of interest to us. We and others have employed RC adducts of nitroalkenes for the synthesis of functionalized pyrazoles,¹⁵ decalins,¹⁶ cycloalkanones,¹⁷ spirocycles¹⁸ and bridged heterobicyclics such as epibatidine.¹⁹ The reactivity profile of a representative RC adduct 6, derived from the imidazole/LiCl mediated RC reaction of nitroalkene with MVK, is outlined in Scheme 2a. Recently, we have reported a highly diastereoselective Michael initiated intramolecular aldol reaction involving compound 6 and cyclohexanone 7 for the synthesis of highly substituted trans-decalins 8 (Scheme 2b).¹⁶ The compound 6 reacts as a 1,4-electrophile-nucleophile in this case. Chen et al. have reported the formation of spirocyclic compound 10 upon addition of indane-1,3-dione 9 to compound 6 in which compound 6 reacted as a 1,5-bielectrophile.¹⁸ Surprisingly, when a 1,3-cyclohexanedione such as 11 (R = Me, dimedone) is added to compound 6, a new reactivity profile emerges in which compound 6 reacts as a 1,2-bielectrophile without the participation of the ketoalkyl moiety to provide fused furans 12, the results of which are also reported here.

Scheme 1

Scheme 2

Results and discussion

Initially, acetate 1a and nitroketone 4 were selected as model substrates for our optimization studies for the synthesis of nitrofurans 5a (Table 1). In the presence of 1 equiv. of DABCO, at room temperature, in dichloromethane as solvent, we isolated furan 5a in low yield (17%, entry 1). The increase in the amount of base to 2 equiv. rendered the product 5a in improved yield (36%) and in lower reaction time (18 h, entry 2). Further improvement in the yield to 45% and decrease in reaction time to 12 h were observed when the solvent was changed to THF (entry 3). The reaction in the presence of a non-polar solvent such as toluene also resulted in low product yield (24%, entry 4). Next, we screened Et₃N in THF which afforded the product only in low yield (22%, entry 5). However, the yield improved to 40% when the solvent was changed to dichloromethane (entry 6). In the same solvent (dichloromethane), various other organic amine bases such as diisopropylamine, Hünig's base, DMAP and DBU either provided lower yields or complex reaction mixtures (entries 7–10). The reaction in the presence of inorganic bases such as K₂CO₃ and Cs₂CO₃ also resulted in complex reaction mixtures (entries 11–13). Finally, the effect of temperature in the DABCO mediated reaction was investigated by carrying out the reaction in THF at elevated temperatures (45 °C and 65 °C, entries 14–15). Although the reaction rate improved, the yield remained unaffected at 45 °C (entries 3 and 14). At 65 °C, appreciable drop in the yield to 25% with considerable decomposition was observed (entry 15). Interestingly, the weakest base among the above, DABCO (pK_a 8.7), was best suited for nitroacetophenone 4 (pK_a 5.4), affording the product 5a in highest yield suggesting that slow generation of the enolate was desirable in our reaction.

Table 1 Optimization studies^a

Entry	Base	Solvent	Time (h)	% yield^b
a The reactions were carried out with 0.3 mmol each of 1a and 4 in 4 mL solvent.b After silica gel column chromatography.c 1 equivalent of DABCO was used.d Complex mixture.e Reaction temperature 45 °C.f Reaction temperature 65 °C.
1	DABCO^c	DCM	26	17
2	DABCO	DCM	18	36
3	DABCO	THF	12	45
4	DABCO	PhCH3	22	24
5	NEt3	THF	20	22
6	NEt3	DCM	22	40
7	iPr2NH	DCM	18	16
8	iPr2EtN	DCM	25	18
9	DMAP	DCM	24	—^d
10	DBU	DCM	20	26
11	Cs2CO3	DCM	22	—^d
12	Cs2CO3	THF	24	—^d
13	K2CO3	DCM	28	—^d
14^e	DABCO	THF	9	44
15^f	DABCO	THF	6	25

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After screening different conditions, we identified DABCO as the best base and THF as the best solvent to afford the desired product 5a. Thus, the above optimized conditions, viz. 2 equiv. of DABCO, in THF, at room temperature (Table 1, entry 3), were employed to explore the scope of the reaction between different MBH acetates 1a–i and α-nitroacetophenone 4 (Table 2). Besides compound 1a which provided the product 5a in 45% yield (entry 1), MBH acetates bearing sterically and electronically diverse aryl groups 1b–i have been treated with compound 4 under our optimized conditions to afford tetrasubstituted furans 5b–i (entries 2–9). These include MBH acetate bearing parent phenyl group 1b, those bearing strongly electron donating substituents 1c,d and weakly electron donating substituent 1e, fused aromatic substituent 1f, weakly and strongly electron withdrawing substituents 1g,h and a heteroaryl substituent 1i. Although no appreciable substituent effect was discernible and the isolated yields of these nitrofurans 5 were consistently moderate (52–59%) in all the cases, the fact that such furans with well-defined substitution pattern could be easily synthesized from readily available compound 1 and compound 5a made our approach very attractive.

Table 2 Scope of MBH-acetates 1^a

Entry	1, Ar	Time (h)	5	% yield^b
a The reactions were carried out with 0.3 mmol each of 1 and 4 in 4 mL THF.b After silica gel column chromatography. No side products were observed in these reactions.
1	1a, 4-OMeC6H4	12	5a	45
2	1b, C6H5	13	5b	53
3	1c, 2,4-(OMe)2C6H3	7	5c	57
4	1d, 3,4-(OCH2O)C6H3	8	5d	57
5	1e, 4-MeC6H4	8	5e	56
6	1f, 1-naphthyl	7	5f	59
7	1g, 4-ClC6H4	8	5g	54
8	1h, 2-NO2C6H4	7	5h	58
9	1i, 2-furyl	9	5i	52

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The structure and regiochemistry of products 5a–i were confirmed by detailed spectral analysis. A peak for ester group at 1736–1740 cm⁻¹ and two peaks for the nitro group at 1504–1519 and 1350–1366 were characteristic in the IR spectra. The protons of CH₂ group attached to furyl appeared, in general, as singlets at δ 3.51–3.92 in ¹H NMR. However, these protons appeared as AB spin systems in 5f and 5h which was attributable to atropisomerism due to restricted rotation about the C–C bond connecting the furyl moiety and the aryl group at position 3. Surprisingly, such a pattern is not observed in the case of 5c. The methylene carbon attached to furyl appeared at δ 32.8–34.0 in ¹³C NMR. Finally, the regiochemistry was unambiguously established from a medium NOE interaction observed between the deshielded anisyl protons (meta to methoxy) and the methylene protons attached furyl in 5a by ¹H–¹H NOESY experiment.

The proposed mechanism for the formation of highly substituted furans 5 is outlined in Scheme 3. DABCO mediated nucleophilic addition of α-nitroketone 4 to acetate 1 followed by elimination of acetate group in an overall S_N2′ fashion generates intermediate III. A second enolization of the nitroketone moiety in III, facilitated by DABCO, followed by an intramolecular oxa-Michael addition in a 5-exo-trig fashion generates intermediate IV which further undergoes DABCO assisted elimination of HNO₂ to afford highly substituted furans 5.

Scheme 3 Plausible pathway for the formation of tetrasubstituted furans 5.

Having synthesized a variety of nitrofurans 5 in satisfactory yield from the MBH acetates of nitroalkenes 1, we turned to RC adducts 6 as the key precursors for the synthesis of fused furans 12 as mentioned before (see Scheme 2) using six-membered cyclic 1,3-dicarbonyl compounds based on our own previous experience that 5-membered and 6-membered 1,3-dicarbonyls behaved differently in such reactions (see Scheme 1b).²⁰

We have chosen compound 6a and compound 11a as the model substrates for our optimization studies (Table 3). When this reaction was performed in the presence of 1 equiv. of K₂CO₃ in CH₃CN under reflux conditions, fused furan 12a was isolated in 23% yield within 9 h (entry 1). In order to improve the yield further, we screened various bases and solvents as summarized below.

Table 3 Optimization studies^a

Entry	Base (equiv.)	Solvent	Time (h)	% yield^b
a The reactions were carried out with 0.92 mmol of 6a and 0.92 mmol (1 equiv.) of 11a in 3 mL of solvent under reflux.b After silica gel column chromatography.c +20 mol% p-anisic acid.d +10 mol% TFA.e With acid work up.f Without acid work up.
1	K2CO3 (1)	MeCN	9	23
2	DABCO (1)	MeCN	10	15
3	Et3N (1)	MeCN	9	22
4	Et3N (1)^c	MeCN	9	45
5	DBU (1)^d	MeCN	3.5	20
6	NaOAc (1)	MeCN	9	29
7	KOAc (1)	MeCN	7	33
8	KOAc (1)^c	MeCN	3.5	28
9	KOAc (2)	MeCN	8	42^e
10	KOAc (2)	MeCN	8	68^f
11	KOAc (2)	THF	8	42
12	KOAc (2)	EtOH	8	51
13	KOAc (3)	MeCN	7	35

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The yields of furan 12a remained low (15–22%) when the reaction was conducted in CH₃CN under reflux in the presence of 1 equiv. of different amine bases such as DABCO and Et₃N (entries 2–3). Attempted improvement in the yield using Brønsted acid additives in conjunction with amine bases such as p-anisic acid and TFA met with only limited success (entries 4–5). Changing the base to NaOAc and KOAc, the latter even with p-anisic acid as additive, did not improve the yield (28–33%, entries 6–8). At this juncture, a reaction was carried out in the presence of 2 equiv. of KOAc which led to the formation of furan 12a in 42% yield (entry 9). This could be further improved to 68% by employing non-acidic workup conditions (entry 10). Other solvents such as THF and EtOH were less effective for our reaction (entries 11–12). Increasing the amount of base to 3 equiv. was detrimental as the yield dropped to 35% (entry 13).

As in the previous scheme (Tables 1 and 2), the weakest base, KOAc (pK_a 4.7), appeared to give the best results in the addition of compound 11a (pK_a 5.2) to compound 6a. The complex reaction pattern in the presence of stronger bases, including DABCO, leading to lower yields of the desired product 12a is attributable to side reactions involving the enolizable ketone side chain. Finally, the optimal conditions for the reaction, 2 equiv. of KOAc in CH₃CN under reflux, were employed to study the scope of the reaction as reported in Tables 4 and 5.

Table 4 Synthesis of furans 12 from RC adduct 6 and dimedone 11a^a

Entry	6, Ar	Time (h)	12	% yield^b
a The reactions were carried out with 0.92 mmol of 6, 0.92 mmol of 11a 1.80 mmol of KOAc in acetonitrile, reflux.b After silica-gel column chromatography. No side products were observed in these reactions.
1	6a, C6H5	9	12a	68
2	6b, 4-MeC6H4	11	12b	31
3	6c, 3-OMeC6H4	15	12c	37
4	6d, 4-OMeC6H4	6	12d	52
5	6e, 3,4-(OMe)2C6H3	4	12e	37
6	6f, 3,4-(OCH2O)C6H3	5	12f	34
7	6g, 4-ClC6H4	7	12g	55
8	6h, 4-BrC6H4	2	12h	35
9	6i, 2-thienyl	15	12i	29
10	6j, 1-naphthyl	17	12j	39

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Table 5 Synthesis of furans 13 from RC adducts 6 and 1,3-cyclohexanedione 11b^a

Entry	6, Ar	Time (h)	13	% yield^b
a The reaction were carried out with 0.92 mmol of 6, 0.92 mmol of 11b and 1.80 mmol of KOAc in acetonitrile, reflux.b After silica-gel column chromatography; no side products were observed in these reactions.
1	6a, C6H5	12	13a	33
2	6b, 4-MeC6H4	8	13b	46
3	6c, 3-OMeC6H4	22	13c	38
4	6d, 4-OMeC6H4	4	13d	46
5	6e, 3,4-(OMe)2C6H3	4	13e	30
6	6h, 4-BrC6H4	5	13f	42
7	6i, 2-thienyl	7	13g	15
8	6j, 1-naphthyl	20	13h	44

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The reaction of dimedone 11a with different RC adducts 6a–j was undertaken to obtain fused furans 12a–j (Table 4). Besides the RC adduct bearing parent phenyl group 6a which afforded the product 12a in 68% yield (entry 1), the RC adducts with aryl groups possessing a strongly electron donating substituent and a weakly electron withdrawing substituent at the para position, 6d and 6g, respectively, delivered the corresponding products 13d and 13g in decent yields (52% and 55%, entries 4 and 7). The yields of fused furans from other RC adducts possessing various electron donating and withdrawing substituents on the aromatic ring viz. 6b,c, 6e,f and 6h, remained low (31–37%, entries 2–3, 5–6 and 8). While low yield of the product 12i was encountered in the case of heteroaryl compound 6i (entry 9), the product yield was moderate (39%) in the case of a fused arylated compound 6j (entry 10).

After the successful demonstration of the reactivity of different types of RC adducts 6 with dimedone 11a, we focused our attention for the reaction of 1,3-cyclohexanedione 11b with different types of RC adducts 6 and the results are summarized in Table 5.

In this reaction, when Ar was Ph, the product was formed in poor yield (33%, entry 1) and electron donating groups on the phenyl ring of RC adducts provided poor to moderate yield of the products (30–46%, entry 2–5). RC adducts bearing bromo and naphthyl substituents also provided moderate yields (42–44%, entries 6 and 8) and in the case of heteroaryl substituent, a substantial decrease in the yield to 15% was observed (entry 7).

It may be noted that the reaction of 6i with 11a and 11b afforded the corresponding products 12i and 13g in lowest yields (29% and 15%, respectively, Table 4, entry 9 and Table 5 entry 7). This may be due to side reactions such as intermolecular Diels–Alder reaction between the thiophene moiety as the diene and the nitroalkene moiety as the dienophile under our experimental conditions.

As in the case of 5, the structure and regiochemistry of products 12 and 13 were established by analysis of their spectral data. While the saturated carbonyl appears in IR at 1713–1717 cm⁻¹, the unsaturated carbonyl appears at 1672–1679 cm⁻¹. The two isolated methylene protons in 12 appear, in general, as singlets at δ 2.34–2.36 and 2.71–2.74. The corresponding protons in 12j appear as AB spin system presumably due to atropisomerism about the C–C bond connecting the furyl and the aryl group at position 3. The regiochemistry was amply evident from a medium NOE interaction between the phenyl protons and the deshielded methylene protons of the oxobutyl side chain in 12a.

Scheme 4 outlines the plausible mechanism for the one-pot synthesis of furan by the present protocol. KOAc mediated Michael addition of 1,3-dicarbonyl compound 11 to compound 6 affords intermediate V. In the next step, an intramolecular oxa-Mannich type reaction takes place in a 5-exo-trig manner affording the intermediate VI, which on elimination affords the desired product 12 or 13.²¹

Scheme 4 Plausible mechanism of furan formation.

Conclusions

Novel methods for the synthesis of highly substituted furans from the Morita–Baylis–Hillman and Rauhut–Currier adducts of nitroalkenes have been developed. These include a cascade S_N2′-intramolecular oxa-Michael addition and a cascade Michael-intramolecular oxa-Mannich reaction. Although the yields in these reactions are moderate, our approach is distinguished by the convenient access to highly functionalized and fused furans from readily available MBH and RC adducts of nitroalkenes.

Experimental section

General experimental details

The melting points recorded are uncorrected. NMR spectra (¹H, ¹H decoupled ¹³C and ¹H–¹H NOESY) were recorded with TMS as the internal standard. The coupling constants (J values) are given in Hz. High resolution mass spectra were recorded under ESI Q-TOF conditions. MBH acetates 1,²² nitroacetophenone 4 ²³ and RC adducts 6 (ref. 14) were prepared by literature methods.

General procedure for the preparation of tetrasubstituted furans 5 from MBH acetates 1 and α-nitroacetophenone 4

To a stirred solution of compound 1 (0.1 mmol) and compound 4 (33 mg, 0.2 mmol, 2 equiv.) in THF (3 mL) at room temperature was added DABCO (22 mg, 0.2 mmol, 2 equiv.) and the stirring was continued till the completion of the reaction (monitored by TLC, see Table 2). The reaction mixture was concentrated in vacuo and the crude residue was purified by silica gel column chromatography by eluting with 4–10% ethyl acetate/petroleum ether (gradient elution).

Ethyl-2-(3-(4-methoxyphenyl)-4-nitro-5-phenylfuran-2-yl)acetate (5a)

Yellow oily liquid; yield 17 mg, 45%; IR (KBr, cm⁻¹) 1739 (s), 1514 (vs.), 1360 (m); ¹H NMR (400 MHz, CDCl₃) δ 7.81–7.84 (m, 2H), 7.46–7.50 (m, 3H), 7.28 (d, J = 8.8 Hz, 2H), 6.97 (d, J = 8.8 Hz, 2H), 4.20 (q, J = 7.1 Hz, 2H), 3.84 (s, 3H), 3.65 (s, 2H), 1.27 (t, J = 7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 14.3, 32.8, 55.4, 61.8, 114.2, 121.2, 121.3, 127.6, 128.3, 128.6, 130.6, 130.9, 131.4, 144.8, 151.4, 159.8, 168.6; MS (ES⁺, Ar) m/z (rel intensity) 404 (MNa⁺, 30), 399 ([M + H₂O]⁺,49), 382 (MH⁺, 100); HRMS (ES⁺, Ar) calcd for C₂₁H₂₀NO₆ (MH⁺) 382.1291, found 382.1301. Confirmed by ¹H–¹H NOESY experiment.

Ethyl-2-(4-nitro-3,5-diphenylfuran-2-yl)acetate (5b)

Yellow oily liquid; yield 19 mg, 53%; IR (KBr, cm⁻¹) 1740 (vs.), 1513 (m), 1358 (m); ¹H NMR (400 MHz, CDCl₃) δ 7.81–7.84 (m, 2H), 7.46–7.50 (m, 3H), 7.41–7.45 (m, 3H), 7.34–7.37 (m, 3H), 4.20 (q, J = 7.1 Hz, 2H), 3.66 (s, 2H), 1.27 (t, J = 7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 14.3, 32.9, 61.8, 121.8, 127.6, 128.4, 128.7, 128.7, 128.8, 129.3, 129.7, 130.7, 134.6, 144.9, 151.6, 168.5; MS (ES⁺) m/z (rel intensity) 413 ([M + Na + K]⁺, 100), 390 (MK⁺, 35), 374 (MNa⁺, 91), 343 (15); HRMS (ESI) calcd for C₂₀H₁₇NNaO₅ (MNa⁺) 374.0999, found 374.1002.

Ethyl-2-(3-(2,4-dimethoxyphenyl)-4-nitro-5-phenylfuran-2-yl)acetate (5c)

Yellow oily liquid; yield 23 mg, 57%; IR (KBr, cm⁻¹) 1738 (vs.), 1511 (s), 1366 (m); ¹H NMR (400 MHz, CDCl₃) δ 7.83–7.80 (m, 2H), 7.48–7.45 (m, 3H), 7.24 (d, J = 8.3 Hz, 1H), 6.57 (dd, J = 8.3, 2.3 Hz, 1H), 6.52 (d, J = 2.3 Hz, 1H), 4.20 (q, J = 7.1 Hz, 2H), 3.85 (s, 3H), 3.72 (s, 3H), 3.65 (s, 2H), 1.29 (t, J = 7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 14.3, 33.0, 55.5, 55.6, 61.8, 99.1, 104.8, 111.0, 118.1, 127.8, 128.4, 128.6, 130.4, 131.1, 144.5, 150.9, 158.3, 161.6, 168.8; MS (ES⁺) m/z (rel intensity) 450 (MK⁺, 69), 434 (MNa⁺, 78), 413 ([M + 2]⁺, 100), 391 (10); HRMS (ES⁺) calcd for C₂₂H₂₁NNaO₇ (MNa⁺) 434.1210, found 434.1211.

Ethyl-2-(3-(benzo[d][1,3]dioxol-5-yl)-4-nitro-5-phenylfuran-2-yl)acetate (5d)

Light yellow oily liquid; yield 67 mg, 57%; IR (KBr, cm⁻¹) 1738 (vs.), 1504 (vs.), 1359 (s); ¹H NMR (400 MHz, CDCl₃) δ 7.81–7.79 (m, 2H), 7.48–7.46 (m, 3H), 7.25 (s, 1H), 6.88–6.82 (m, 3H), 6.02 (s, 1H), 4.23–4.18 (q, J = 7.2 Hz, 2H), 3.65 (s, 2H), 1.28 (t, J = 7.2 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 14.3, 32.8, 61.9, 101.5, 108.6, 110.2, 121.4, 122.6, 123.4, 127.6, 128.4, 128.7, 130.7, 145.0, 148.0, 148.1, 151.4, 168.5; MS (ES⁺) m/z (rel intensity) 434 (MK⁺, 60), 418 (MNa⁺, 100), 393 ([M − 2]⁺, 51), 355 (11), 331 (10), 307 (9); HRMS (ES⁺) calcd for C₂₁H₁₇NNaO₇ (MNa⁺) 418.0897, found 418.0898.

Ethyl-2-(4-nitro-5-phenyl-3-p-tolylfuran-2-yl)acetate (5e)

Light yellow oily liquid; yield 61 mg, 56%; IR (KBr, cm⁻¹) 1738 (vs.), 1513, 1358 (m); ¹H NMR (400 MHz, CDCl₃) δ 7.83–7.80 (m, 2H), 7.44–7.41 (m, 3H), 7.29–7.21 (m, 4H), 4.20 (q, J = 7.2 Hz, 2H), 3.65 (s, 2H), 2.41 (s, 3H), 1.28 (t, J = 7.2 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 14.3, 21.5, 32.9, 61.8, 121.7, 126.2, 127.7, 128.4, 128.7, 129.3, 129.5, 130.4, 130.6, 138.6, 144.8, 151.5, 168.6; MS (ES⁺) m/z (rel intensity) 404 (MK⁺, 23), 388 (MNa⁺, 100), 366 (MH⁺, 25), 301 (20); HRMS (ES⁺) calcd for C₂₁H₁₉NNaO₅ (MNa⁺) 388.1155, found 388.1155.

Ethyl-2-(3-(naphthalen-1-yl)-4-nitro-5-phenylfuran-2-yl)acetate (5f)

Light yellow oily liquid; yield 71 mg (59%); IR (KBr, cm⁻¹) 1739 (vs.), 1510 (vs.), 1354 (m); ¹H NMR (400 MHz, CDCl₃) δ 7.96–7.92 (m, 4H), 7.75 (d, J = 8.0 Hz, 1H), 7.57–7.46 (m, 7H), 4.14–4.08 (q, J = 7.2 Hz, 2H), 3.59, 3.53 (AB, J = 17.0 Hz, 2H), 1.19 (t, J = 7.2 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 14.2, 32.8, 61.7, 119.9, 125.1, 125.5, 126.4, 126.9, 127.7, 128.4, 128.7 (× 2), 128.7, 129.5, 130.8, 132.5, 133.7, 135.4, 145.9, 152.2, 168.3; MS (ES⁺) m/z (rel intensity) 440 (MK⁺, 77), 424 (MNa⁺, 100), 397 (20), 357 (23), 301 (35), 243 (69), 213 (100); HRMS (ES⁺) calcd for C₂₄H₁₉NNaO₅ (MNa⁺) 424.1155, found 424.1154.

Ethyl-2-(3-(4-chlorophenyl)-4-nitro-5-phenylfuran-2-yl)acetate (5g)

Light yellow oily liquid; yield 62 mg, 54%; IR (KBr, cm⁻¹) 1739 (m), 1514 (m), 1358 (w), 739 (vs.); ¹H NMR (400 MHz, CDCl₃) δ 7.83–7.80 (m, 2H), 7.50–7.47 (m, 3H), 7.42, 7.31 (AB, J = 8.5 Hz, 4H), 4.20 (q, J = 7.1 Hz, 2H), 3.63 (s, 2H), 1.28 (t, J = 7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 14.3, 32.8, 62.0, 120.8, 127.5, 127.8, 128.6, 128.7, 129.0, 130.9, 131.1, 134.9, 145.1, 152.1, 168.4; MS (ES⁺) m/z (rel intensity) 426 ([M + 2]K⁺, 10), 424 (MK⁺, 30), 413 (100), 410 ([M + 2]Na⁺, 5), 408 (MNa⁺, 15), 386 (MH⁺, 80); HRMS (ES⁺) calcd for C₂₀H₁₇ClNO₅ (MH⁺) 386.0790, found 386.0784.

Ethyl-2-(4-nitro-3-(2-nitrophenyl)-5-phenylfuran-2-yl)acetate (5h)

Light yellow oily liquid; yield 69 mg, 58%, mixture of atropisomers; IR (KBr, cm⁻¹) 1736 (vs.), 1527 (vs.), 1512 (vs.), 1350 (vs.); ¹H NMR (400 MHz, CDCl₃) δ 8.26–8.22 (m, 1H), 8.14–8.10 (m, 0.5H, due to atropisomerism), 7.90–7.86 (m, 2H), 7.74–7.69 (m, 1H), 7.66–7.60 (m, 1.5H, due to atropisomerism), 7.53–7.46 (m, 4 + 1H), 4.15 (q, J = 7.1 Hz, 2H), 3.62, 3.51 (AB, J = 16.9 Hz, 2H), 1.24 (t, J = 7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 14.2, 33.0, 62.1, 118.8, 125.4, 127.4, 128.6, 129.2, 130.2, 130.4, 131.1, 132.9, 133.7, 134.4, 144.8, 148.8, 153.2, 168.0; MS (ES⁺) m/z (rel intensity) 435 (MK⁺, 16), 419 (MNa⁺, 100), 397 (14), 303 (23); HRMS (ES⁺) calcd for C₂₀H₁₆N₂NaO₇ (MNa⁺) 419.0850, found 419.0848.

Ethyl-2-(4′-nitro-5′-phenyl-2,3′-bifuran-2′-yl)acetate (5i)

Yellow oily liquid; yield 18 mg (52%); IR (KBr, cm⁻¹) 1739 (vs.), 1519 (s); ¹H NMR (400 MHz, CDCl₃) δ 7.78–7.74 (m, 2H), 7.50 (dd, J = 1.8, 0.6 Hz, 1H), 7.49–7.45 (m, 3H), 6.67 (dd, J = 3.4, 0.6 Hz, 1H), 6.50 (m, J = 3.4, 1.8 Hz, 1H), 4.20 (q, J = 7.1 Hz, 2H), 3.92 (s, 2H), 1.28 (t, J = 7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 14.3, 34.0, 42.5, 61.9, 110.9, 111.5, 127.2, 128.3, 128.8, 130.8, 142.8, 143.2, 145.5, 151.8, 168.4; MS (ES⁺) m/z (rel intensity) 380 (MK⁺, 34), 364 (MNa⁺, 58), 360 (39), 349 (100); HRMS (ES⁺) calcd for C₁₈H₁₅NNaO₆ (MNa⁺) 364.0792, found 364.0792.

Representative procedure for the synthesis of substituted furans 12 and 13

To a stirred solution of 1,3-diketone 11 (0.92 mmol) in MeCN (3 mL) was added potassium acetate (0.180 g, 1.84 mmol, 2 equiv.) followed by Rauhut–Currier adduct 6 (0.92 mmol, 1 equiv.). The resulting reaction mixture was refluxed till the completion of the reaction. After the completion of the reaction (monitored by TLC, see Tables 4 and 5), the reaction mixture was concentrated in vacuo and the crude residue was purified by silica gel column chromatography (pet ether : ethyl acetate 5–10%, gradient elution).

6,6-Dimethyl-2-(3-oxobutyl)-3-phenyl-6,7-dihydrobenzofuran-4(5H)-one (12a)

White solid; yield 194 mg, 68%; mp 88–89 °C; IR (KBr, cm⁻¹) 1717 (s), 1678 (vs.); ¹H NMR (CDCl₃, 400 MHz) δ 7.39–7.28 (m, 5H), 2.93 (t, J = 7.0 Hz, 2H), 2.78 (t, J = 7.0 Hz, 2H), 2.74 (s, 2H), 2.36 (s, 2H), 2.13 (s, 3H), 1.15 (s, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ 20.5, 28.7, 30.0, 35.1, 37.8, 41.8, 53.1, 118.7, 119.6, 127.4, 128.1, 129.9, 131.4, 151.2, 165.2, 193.6, 207.1; MS (ES⁺) m/z (rel intensity) 333 (MNa⁺, 75), 311 (MH⁺, 100), 254 (6), 253 (29); HRMS (ES⁺) calcd for C₂₀H₂₃O₃ (MH⁺) 311.1647, found 311.1651.

3-(4-Methylphenyl)-6,6-dimethyl-2-(3-oxobutyl)-6,7-dihydro-benzenefuran-4(5H)-one (12b)

Brown solid; yield 92 mg, 31%; mp 128–130 °C; IR (KBr, cm⁻¹) 1717 (s), 1677 (vs.); ¹H NMR (CDCl₃, 400 MHz) δ 7.25, 7.18 (AB, J = 7.9 Hz, 4H), 2.93 (t, J = 7.1 Hz, 2H), 2.77 (t, J = 7.1 Hz, 2H), 2.73 (s, 2H), 2.36 (s, 3H), 2.35 (s, 2H), 2.13 (s, 3H), 1.15 (s, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ 20.5, 21.4, 28.8, 30.0, 35.1, 37.8, 41.8, 53.2, 118.8, 119.5, 128.3, 128.9, 129.8, 137.1, 151.0, 165.1, 193.6, 207.1; MS (ES⁺) m/z (rel intensity) 347 (MNa⁺, 38), 325 (MH⁺, 100), 268 (10), 267 (48); HRMS (ES⁺) calcd for C₂₁H₂₅O₃ (MH⁺), 325.1804, found 325.1797.

3-(3-Methoxyphenyl)-6,6-dimethyl-2-(3-oxobutyl)-6,7-dihydro-benzofuran-4(5H)-one (12c)

Yellow brown amorphous solid; yield 116 mg, 37%; IR (KBr, cm⁻¹) 1714 (s), 1678 (vs.); ¹H NMR (CDCl₃, 500 MHz) δ 7.28 (t, J = 7.9 Hz, 1H), 6.94 (d, J = 2.2 Hz, 1H), 6.93 (d, J = 7.9 Hz, 1H), 6.85 (dd, J = 7.9, 2.4 Hz, 1H), 3.82 (s, 3H), 2.94 (t, J = 7.5 Hz, 2H), 2.77 (t, J = 7.5 Hz, 2H), 2.73 (s, 2H), 2.36 (s, 2H), 2.13 (s, 3H), 1.15 (s, 6H); ¹³C NMR (CDCl₃, 125 MHz) δ 20.6, 28.8, 30.0, 35.1, 37.8, 41.8, 53.2, 55.4, 113.3, 115.7, 119.5, 122.4, 129.1, 132.7, 151.3, 159.3, 165.2, 193.5, 207.1; MS (ES⁺) m/z (rel intensity) 379 (MK⁺, 100), 363 (MNa⁺, 30), 341 (MH⁺, 5); HRMS (ES⁺) calcd for C₂₁H₂₄O₄K (MK⁺), 379.1306, found 379.1306.

3-(4-Methoxyphenyl)-6,6-dimethyl-2-(3-oxobutyl)-6,7-dihydrobenzofuran-4(5H)-one (12d)

Yellow solid; yield 163 mg, 52%; mp 109–110 °C; IR (KBr, cm⁻¹) 1716 (s), 1675 (vs.); ¹H NMR (CDCl₃, 400 MHz) δ 7.29 (d, J = 9.5 Hz, 2H), 6.91 (d, J = 9.5 Hz, 2H), 3.82 (s, 3H), 2.92 (t, J = 7.1 Hz, 2H), 2.77 (t, J = 7.1 Hz, 2H), 2.72 (s, 2H), 2.35 (s, 2H), 2.13 (s, 3H), 1.15 (s, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ 20.5, 28.7, 30.0, 35.0, 37.8, 41.8, 53.1, 55.4, 113.6, 118.7, 119.2, 123.6, 131.0, 150.8, 159.0, 165.1, 193.7, 207.2; MS (ES⁺) m/z (rel intensity) 363 (MNa⁺, 60), 341 (MH⁺, 100), 284 (19), 283 (85), 190 (4); HRMS (ES⁺) calcd for C₂₁H₂₅O₄ (MH⁺), 341.1753, found 341.1750.

3-(3,4-Dimethoxyphenyl)-6,6-dimethyl-2-(3-oxobutyl)-6,7-dihydrobenzofuran-4(5H)-one (12e)

Yellow solid; yield 126 mg, 37%; 112–113 °C; IR (KBr, cm⁻¹) 1716 (s), 1676 (s); ¹H NMR (CDCl₃, 400 MHz) δ 7.00 (s, 1H), 6.89, 6.86 (AB, J = 8.2 Hz, 2H), 3.89 (s, 3H), 3.88 (s, 3H), 2.94 (t, J = 7.8 Hz, 2H), 2.79 (t, J = 7.8 Hz, 2H), 2.72 (s, 2H), 2.35 (s, 2H), 2.13 (s, 3H), 1.14 (s, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ 20.5, 28.6, 29.9, 34.9, 37.7, 41.5, 53.1, 55.9, 56.0, 110.7, 113.6, 118.5, 119.2, 122.0, 123.8, 148.3, 150.7, 165.1, 193.6, 207.0; MS (ES⁺) m/z (rel intensity) 393 (MNa⁺, 10), 371 (MH⁺, 100), 314 (7), 313 (29); HRMS (ES⁺) calcd for C₂₂H₂₇O₅ (MH⁺), 371.1858, found 371.1873.

3-(Benzo[d][1,3]dioxol-5-yl)-6,6-dimethyl-2-(3-oxobutyl)-6,7-dihydrobenzofuran-4(5H)-one (12f)

Yellow solid; yield 111 mg, 34%; mp 109–111 °C; IR (KBr, cm⁻¹) 1716 (s), 1677 (vs.); ¹H (CDCl₃, 400 MHz) δ 6.84 (s, 1H), 6.81–6.77 (m, unresolved AB, 2H), 5.95 (s, 2H), 2.90 (t, J = 7.4 Hz, 2H), 2.76 (t, J = 7.4 Hz, 2H), 2.71 (s, 2H), 2.34 (s, 2H), 2.13 (s, 3H), 1.14 (s, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ 20.5, 28.7, 30.0, 35.0, 37.8, 41.7, 53.1, 101.1, 108.1, 110.6, 118.7, 119.3, 123.3, 125.0, 147.0, 147.4, 151.0, 165.1, 193.6, 207.1; MS (ES⁺) m/z (rel intensity) 393 (MK⁺, 100), 377 (MNa⁺, 25); HRMS (ES⁺) calcd for C₂₁H₂₂O₅K (MK⁺) 393.1099, found 393.1098.

3-(4-Chlorophenyl)-6,6-dimethyl-2-(3-oxobutyl)-6,7-dihydro-benzofuran-4(5H)-one (12g)

White solid; yield 174 mg, 55%; mp 86–88 °C; IR (KBr, cm⁻¹) 1713 (s), 1672 (vs.), 737 (s); ¹H NMR (CDCl₃, 400 MHz) δ 7.34, 7.31 (AB, J = 8.6 Hz, 4H), 2.90 (t, J = 7.4 Hz, 2H), 2.78 (t, J = 7.4 Hz, 2H), 2.73 (s, 2H), 2.35 (s, 2H), 2.14 (s, 3H), 1.15 (s, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ 20.4, 28.7, 30.0, 35.1, 37.8, 41.5, 53.1, 118.5, 118.6, 128.3, 129.9, 131.3, 133.4, 151.4, 165.4, 193.7, 206.9; MS (ES⁺) m/z (rel intensity) 347 ([M + 2]H⁺, 35), 345 (MH⁺, 100), 289 (27), 287 (81), 242 (4), 192 (7); HRMS (ES⁺) calcd for C₂₀H₂₂ClO₃ (MH⁺) 345.1257, found 345.1259.

3-(4-Bromophenyl)-6,6-dimethyl-2-(3-oxobutyl)-6,7-dihydro-benzofuran-4(5H)-one (12h)

Brown solid; yield 125 mg, 35%; mp 109–110 °C; IR (KBr, cm⁻¹) 1716 (s), 1677 (vs.), 758 (m); ¹H NMR (CDCl₃, 500 MHz) δ 7.51 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 8.4 Hz, 2H), 2.92 (t, J = 7.4 Hz, 2H), 2.79 (t, J = 7.4 Hz, 2H), 2.75 (s, 2H), 2.37 (s, 2H), 2.16 (s, 3H), 1.17 (s, 6H); ¹³C NMR (CDCl₃, 125 MHz) δ 20.4, 28.7, 30.0, 35.1, 37.8, 41.5, 53.1, 118.5, 118.6, 121.6, 130.4, 131.3, 131.6, 151.4, 165.4, 193.7, 206.9; MS (ES⁺) m/z (rel intensity) 429 (MK + 2]⁺, 90), 427 (MK⁺, 91), 413 ([MNa + 2]⁺, 98), 411 (MNa⁺, 100), 129 (12); HRMS (ES⁺) calcd for C₂₀H₂₁O₃BrNa (MNa⁺) 411.0566, found 411.0570.

6,6-Dimethyl-2-(3-oxobutyl)-3-(thiophen-2-yl)-6,7-dihydrobenzofuran-4(5H)-one (12i)

Black solid; yield 84 mg, 29%; mp 128–130 °C; IR (KBr, cm⁻¹) 717 (s), 1677 (s); ¹H NMR (CDCl₃, 400 MHz) δ 7.36 (dd, J = 3.5 Hz, J = 1.1 Hz, 1H), 7.30 (dd, J = 5.2 Hz, J = 1.1 Hz, 1H), 7.05 (dd, J = 5.2 Hz, J = 3.5 Hz, 1H), 3.07 (t, J = 7.2 Hz, 2H), 2.81 (t, J = 7.2 Hz, 2H), 2.72 (s, 2H), 2.38 (s, 2H), 2.16 (s, 3H), 1.15 (s, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ 21.2, 28.7, 30.0, 34.9, 37.8, 41.7, 53.2, 113.1, 118.6, 125.4, 127.2, 128.6, 131.9, 151.9, 165.3, 193.4, 207.0; MS (ES⁺) m/z (rel intensity) 317 (MH⁺, 84), 259 (100); HRMS (ES⁺) calcd for C₁₈H₂₁O₃S (MH⁺) 317.1211, found 317.1218.

6,6-Dimethyl-3-(naphthalen-1-yl)-2-(3-oxobutyl)-6,7-dihydro-benzofuran-4(5H)-one (12j)

Brown solid; yield 129 mg, 39%; mp 116–118 °C; IR (KBr, cm⁻¹) 1717 (s), 1679 (vs.); ¹H NMR (CDCl₃, 400 MHz) δ 7.86 (t, J = 7.2 Hz, 2H), 7.59 (d, J = 8.5 Hz, 1H), 7.52–7.35 (m, 4H), 2.85, 2.80 (AB, J = 16.0 Hz, 2H), 2.78–2.71 (m, 2H), 2.70–2.62 (m, 2H), 2.45, 2.33 (AB, J = 16.0 Hz, 2H), 2.00 (s, 3H), 1.21 (s, 3H), 1.18 (s, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ 20.6, 28.8, 28.8, 29.8, 35.2, 37.8, 41.6, 52.7, 117.1, 120.4, 125.3, 125.7, 125.8, 126.0, 127.9, 128.3, 128.4, 129.5, 132.7, 133.6, 152.2, 164.9, 192.9, 206.9; MS (ES⁺) m/z (rel intensity) 399 (MK⁺, 399), 383 (MNa⁺, 100), 361 (20), HRMS (ES⁺) calcd for C₂₄H₂₄O₃Na (MNa⁺) 383.1618, found 383.1617.

2-(3-Oxobutyl)-3-phenyl-6,7-dihydrobenzofuran-4(5H)-one (13a)

Dark brown solid; yield 86 mg, 33%; mp 63–65 °C; IR (KBr, cm⁻¹) 1716 (s), 1676 (vs.); ¹H NMR (CDCl₃, 500 MHz) δ 7.38–7.28 (m, 5H), 2.92 (t, J = 7.5 Hz, 2H), 2.86 (t, J = 6.4 Hz, 2H), 2.76 (t, J = 7.5 Hz, 2H), 2.46 (t, J = 6.4 Hz, 2H), 2.16 (quint, J = 6.4 Hz, 2H), 2.12 (s, 3H); ¹³C NMR (CDCl₃, 125 MHz) δ 20.4, 22.6, 23.8, 29.9, 38.7, 41.7, 119.7, 119.9, 127.4, 128.1, 129.9, 131.5, 150.9, 166.1, 194.1, 207.0; HRMS (ES⁺) calcd for C₁₈H₁₈O₃Na (MNa⁺) 305.1148 found 305.1150.

2-(3-Oxobutyl)-3-p-tolyl-6-7-dihydrobenzenefuran-4(5H)-one (13b)

Brown solid; yield 125 mg, 46%; mp 91–92 °C; IR (KBr, cm⁻¹) 1716 (s), 1677 (s); ¹H NMR (CDCl₃, 400 MHz) δ 7.25, 7.18 (AB, J = 8.0 Hz, 4H), 2.91 (t, J = 7.3 Hz, 2H), 2.86 (t, J = 6.2 Hz, 2H), 2.76 (t, J = 7.3 Hz, 2H), 2.46 (t, J = 6.2 Hz, 2H), 2.36 (s, 3H), 2.16 (quint, J = 6.2 Hz, 2H), 2.12 (s, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ 20.4, 21.4, 22.6, 23.8, 30.0, 38.8, 41.8, 119.6, 120.0, 128.4, 128.9, 129.7, 137.1, 150.7, 166.0, 194.1, 207.1; MS (ES⁺) m/z (rel intensity) 297 (MH⁺, 90), 239 (100), 204 (5), 200 (7); HRMS (ES⁺) calcd for C₁₉H₂₁O₃ (MH⁺) 297.1491, found 297.1493.

3-(3-Methoxyphenyl)-2-(3-oxobutyl)-6,7-dihydrobenzofuran-4(5H)-one (13c)

Brown solid; yield 109 mg, 38%; mp 117–119 °C; IR (KBr, cm⁻¹) 1716 (s), 1676 (vs.); ¹H NMR (CDCl₃, 500 MHz) δ 7.27 (t, J = 7.9 Hz, 1H), 6.94 (dd, J = 2.4, 1.5 Hz, 1H), 6.91 (dd, J = 7.9, 1.5 Hz, 1H), 6.85 (dd, J = 7.9, 2.4 Hz, 1H), 3.81 (s, 3H), 2.93 (t, J = 7.5 Hz, 2H), 2.86 (t, J = 6.4 Hz, 2H), 2.76 (t, J = 7.5 Hz, 2H), 2.46 (t, J = 6.4 Hz, 2H), 2.16 (quint, J = 6.4 Hz, 2H), 2.12 (s, 3H); ¹³C NMR (CDCl₃, 125 MHz) δ 20.5, 22.6, 23.9, 30.0, 38.8, 41.7, 55.4, 113.3, 115.6, 119.6, 119.9, 122.3, 129.0, 132.8, 151.0, 159.3, 166.1, 194.0, 207.0; MS (ES⁺) m/z (rel intensity) 351 (MK⁺, 98), 335 (MNa⁺, 100); HRMS (ES⁺) calcd for C₁₉H₂₀O₄Na (MNa⁺) 335.1254, found 335.1253.

3-(4-Methoxyphenyl)-2-(3-oxobutyl)-6,7-dihydrobenzofuran-4(5H)-one (13d)

Yellow solid; yield 132 mg, 46%; mp 136–137 °C; IR (KBr, cm⁻¹) 1716 (m), 1673 (s); ¹H NMR (CDCl₃, 400 MHz) δ 7.29 (d, J = 8.6 Hz, 2H), 6.90 (d, J = 8.6 Hz, 2H), 3.81 (s, 3H), 2.90 (t, J = 7.8 Hz, 2H), 2.86 (t, J = 6.3 Hz, 2H), 2.76 (t, J = 7.8 Hz, 2H), 2.46 (t, J = 6.3 Hz, 2H), 2.17 (quint, J = 6.3 Hz, 2H), 2.12 (s, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ 20.4, 22.6, 23.9, 30.0, 38.8, 41.8, 55.4, 113.6, 119.3, 120.0, 123.7, 131.0, 150.5, 158.9, 166.0, 194.3, 207.1; MS (ES⁺) m/z (rel intensity) 335 (MNa⁺, 50), 313 (MH⁺, 100), 256 (18), 255 (96); HRMS (ES⁺) calcd for C₁₉H₂₁O₄ (MH⁺) 313.1440, found 313.1437.

3-(3,4-Dimethoxyphenyl)-2-(3-oxobutyl)-6,7-dihydrobenzofuran-4(5H)-one (13e)

Yellow solid; yield 94 mg, 30%; mp 113–114 °C; IR (KBr, cm⁻¹) 1716 (s), 1674 (vs.); ¹H NMR (CDCl₃, 400 MHz) δ 7.00 (s, 1H), 6.90–6.88 (unresolved AB, 2H), 3.90 (s, 6H), 2.95 (t, J = 7.0 Hz, 2H), 2.88 (t, J = 6.1 Hz, 2H), 2.78 (t, J = 7.0 Hz, 2H), 2.48 (t, J = 6.1 Hz, 2H), 2.18 (quint, J = 7.0 Hz, 2H), 2.14 (s, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ 20.5, 22.6, 23.9, 30.0, 38.8, 41.7, 56.0, 56.1, 110.8, 113.7, 119.5, 119.9, 122.0, 124.0, 148.4, 150.6, 166.1, 194.3, 207.1; MS (ES⁺) m/z (rel intensity) 365 (MNa⁺, 60), 343 (MH⁺, 88), 286 (21), 285 (100); HRMS (ES⁺) calcd for C₂₀H₂₃O₅ (MH⁺) 343.1545, found 343.1545.

3-(4-Bromophenyl)-2-(3-oxobutyl)-6,7-dihydrobenzofuran-4(5H)-one (13f)

Brown solid; yield 139 mg, 42%; mp 90–92 °C; IR (KBr, cm⁻¹) 1717 (s), 1676 (vs.), 762 (m); ¹H NMR (CDCl₃, 500 MHz) δ 7.49 (d, J = 8.4 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 2.90 (t, J = 7.4 Hz, 2H), 2.87 (t, J = 6.4 Hz, 2H), 2.76 (t, J = 7.4 Hz, 2H), 2.47 (t, J = 6.4 Hz, 2H), 2.17 (quint, J = 6.4 Hz, 2H), 2.13 (s, 3H); ¹³C NMR (CDCl₃, 125 MHz) δ 20.2, 22.4, 23.7, 29.9, 38.5, 41.4, 118.6, 119.6, 121.5, 130.3, 131.1, 131.4, 150.9, 166.1, 194.0, 206.7; MS (ES⁺) m/z (rel intensity) 385 ([M + 2]Na⁺, 100), 383 (MNa⁺, 98); HRMS (ES⁺) calcd for C₁₈H₁₇O₃BrNa (MNa⁺) 383.0253 found 383.0253.

2-(3-Oxobutyl)-3-(thiophen-2-yl)-6,7-dihydrobenzofuran-4(5H)-one (13g)

Black solid; yield 40 mg, 15%; mp 104–105 °C; IR (KBr, cm⁻¹) 1715 (s), 1676 (s); ¹H NMR (CDCl₃, 400 MHz) δ 7.31–7.29 (m, 2H), 7.05 (dd, J = 5.1, 3.6 Hz, 1H), 3.04 (t, J = 6.9 Hz, 2H), 2.85 (t, J = 6.1 Hz, 2H), 2.79 (t, J = 6.9 Hz, 2H), 2.48 (t, J = 6.1 Hz, 2H), 2.21–2.14 (m, 2H), 2.15 (s, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ 21.0, 22.4, 23.8, 30.0, 38.8, 41.7, 113.1, 119.8, 125.5, 127.2, 128.5, 131.9, 151.7, 166.1, 194.0, 207.0; MS (ES⁺) m/z (rel intensity) 289 (MH⁺, 70), 233 (5), 232 (15), 231 (100), 220; HRMS (ES⁺) calcd for C₁₆H₁₇O₃S (MH⁺) 289.0898, found 289.0887.

3-(Naphthalen-1-yl)-2-(3-oxobutyl)-6,7-dihydrobenzofuran-4(5H)-one (13h)

Dark brown solid; yield 134 mg, 44%; mp 91–93 °C; IR (KBr, cm⁻¹) 1715 (m), 1678 (vs.); ¹H NMR (CDCl₃, 500 MHz) δ 7.85 (t, J = 8.2 Hz, 2H), 7.59 (d, J = 8.2 Hz, 1H), 7.49–7.33 (m, 4H), 2.95 (AB, J = 6.4 Hz, 2H), 2.78–2.70 (m, 2H), 2.68–2.58 (m, 2H), 2.50–2.38 (m, 2H), 2.24–2.18 (m, 2H), 2.00 (s, 3H); ¹³C NMR (CDCl₃, 125 MHz) δ 20.6, 22.7, 23.9, 29.8, 38.5, 41.6, 117.3, 121.7, 125.4, 125.8, 125.8, 126.1, 127.9, 128.4, 128.5, 129.6, 132.7, 133.7, 151.9, 165.8, 193.7, 207.0; MS (ES⁺) m/z (rel intensity) 371 (MK⁺, 12), 355 (MNa⁺, 100), 305 (4); HRMS (ES⁺) calcd for C₂₂H₂₀O₃Na (MNa⁺) 355.1305, found 355.1303.

Acknowledgements

INNN thanks DST India for financial assistance. VM and TK thank CSIR India for a research fellowship.

References

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15. (a) R. Muruganantham and I. N. N. Namboothiri, J. Org. Chem., 2010, 75, 2197; (b) R. Kumar and I. N. N. Namboothiri, Org. Lett., 2011, 13, 4016; (c) D. Verma, R. Kumar and I. N. N. Namboothiri, J. Org. Chem., 2013, 78, 3482.
16. P. Shanbhag, V. Mane, C. Hazra and I. N. N. Namboothiri, J. Indian Chem. Soc., 2013, 90, 1713.
17. (a) Ref. 14b; (b) C. R. Reddy, M. D. Reddy and K. Haribabu, Eur. J. Org. Chem., 2012, 6414.
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20. The reaction of compound 1 with cyclopentane-1,3-dione provides fused pyran, see ref. 13a and b.
21. See for similar mechanism in the formation of pyrrole and furan from nitroalkenes: L. Li, M.-N. Zhao, Z.-H. Ren, J. Li and Z.-H. Guan, Synthesis, 2012, 532.
22. (a) I. Deb, M. Dadwal, S. M. Mobin and I. N. N. Namboothiri, Org. Lett., 2006, 8, 1201; (b) I. Deb, P. Shanbhag, S. M. Mobin and I. N. N. Namboothiri, Eur. J. Org. Chem., 2009, 4091; (c) R. J. Reddy and K. Chen, Org. Lett., 2011, 13, 1458.
23. J. J. Lee, J. Kim, Y. M. Jun, B. M. Lee and B. H. Kim, Tetrahedron, 2009, 65, 8821.

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Footnote

† Electronic supplementary information (ESI) available: Copies NMR spectra. See DOI: 10.1039/c5ra11471c

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