Formal [4 + 1] cycloaddition of o-quinone methides: facile synthesis of dihydrobenzofurans

Abstract

An efficient and straightforward method for the rapid synthesis of 2-substituted dihydrobenzofurans has been developed via reaction of sulfur ylides with o-quinone methides (o-QMs), which were generated under mild conditions. The products could be obtained in excellent yields with various kinds of sulfur ylides.

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Introduction

ortho-Quinone methides (o-QMs) have been of great interest to the chemical and biological community due to their distinctive properties as Michael acceptors.^1,2 Until now, various methodologies for the generation of o-QMs in situ have been developed, including tautomerization, oxidation, acid or base catalysis, thermolysis, photolysis and olefination of o-quinones.^3,4 Moreover, the Rokita group reported that O-silylated phenols exposed to fluoride could also produce o-QMs under mild reaction conditions.⁵ In contrast to Rokita's method for generating o-QMs, other methods have several disadvantages, such as harsh reaction conditions (e.g. photolysis, high reaction temperature), long reaction time, or using transition metals as oxidants.

o-QMs undergo rapid rearomatization through either Michael addition with nucleophiles, or [4 + 2] cycloaddition with dienophiles, or oxa-6π-electrocyclisation to give benzopyrans.^3,6 Recently, the Scheidt and Ye groups reported NHC-catalyzed enantioselective formal [4 + 3] cycloaddition of α,β-unsaturated aldehydes with reactive o-QMs to give 2-benzoxopinones, providing a new reaction mode for o-QMs.⁷ On the other hand, the Zhou and Osyanin groups disclosed that o-QMs, which were generated from inaccessible substrates or in the presence of an oxidant, underwent formal [4 + 1] cycloaddition with sulfur ylides or pyridinium methylides to afford trans-2,3-dihydrobenzofurans.⁸ Herein, we report an efficient and straightforward method for the rapid synthesis of 2-substituted dihydrobenzofurans, which widely exist in natural products,⁹ via reaction of sulfur ylides with o-QMs.

Results and discussion

Our initial investigation was focused on the model reaction of O-silylated phenol 1a with sulfur ylide 2a. The reaction proceeded smoothly to provide the desired product 3a in 81% yield at 0 °C when TBAF was employed as the fluoride source (entry 1, Table 1). When the equivalent of sulfur ylide 2a was raised to 1.5 equiv., the product yield increased to 89% (entry 3, Table 1). Considering the crucial role of the fluoride source in triggering the generation of o-QMs intermediates, other fluorides such as CsF were examined. We found that CsF displayed the same reactivity with that of TBAF (entry 4, Table 1). Subsequently, the equivalent of fluoride and different temperature were examined, and it was found that the best result could be obtained at room temperature with 2.5 equiv. of TBAF (entry 8, Table 1). Finally, the influence of solvents was examined. In all solvents tested, including CH₂Cl₂, CHCl₃, THF, Et₂O, toluene, DMF, MeCN, and MeOH, the desired product was obtained in satisfactory yields (entries 8–15, Table 1), indicating a good solvent tolerance of this reaction. In terms of the product yields and operation convenience, CH₂Cl₂ was chosen as the best solvent.

Table 1 Optimization for the reaction of O-silylated phenol 1a with sulfur ylide 2a^a

Entry	F^− source	X	Y	Solvent	Temp. (°C)	Yield^b (%)
a 1a (0.5 mmol), 2a, solvent (5 mL), room temperature, 12 h. [TBAF (1 M in THF solution)].b Isolated yields.
1	TBAF	1.0	2.5	DCM	0	81
2	TBAF	1.2	2.5	DCM	0	85
3	TBAF	1.5	2.5	DCM	0	89
4	CsF	1.5	2.5	DCM	0	85
5	TBAF	1.5	1.5	DCM	0	88
6	TBAF	1.5	1.0	DCM	0	82
7	TBAF	1.5	2.5	DCM	−30	36
8	TBAF	1.5	2.5	DCM	rt	89
9	TBAF	1.5	2.5	CHCl3	rt	86
10	TBAF	1.5	2.5	THF	rt	88
11	TBAF	1.5	2.5	Et2O	rt	86
12	TBAF	1.5	2.5	Toluene	rt	74
13	TBAF	1.5	2.5	DMF	rt	70
14	TBAF	1.5	2.5	MeCN	rt	77
15	TBAF	1.5	2.5	MeOH	rt	71

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With the optimized reaction conditions in hand, we explored the reaction scope with using a variety of O-silylated phenols 1 and sulfur ylides 2 (Table 2). Sulfur ylide derivatives bearing electron-donating and withdrawing groups on the phenyl group were well-tolerated (3a–j), affording the corresponding products in 83–92% yields. In general, other aromatic substitutes (2-nathyl, 2-furyl, 2-thiazolyl, 2-pyridyl) derived sulfur ylides had little influence on the yields (77–89% yields, entries 12–15, Table 2). Interestingly, ester and amide derived sulfur ylides could be obtained in situ, affording the desired products in 42% and 85% yield, respectively (entries 16 and 17, Table 2). Furthermore, the 4-Br substituted O-silylated phenols 1b reacted well with 2a to afford 2-substituted dihydrobenzofuran (3q) in 90% yield (entry 18, Table 2).

Table 2 Substrate scope for the reaction of O-silylated phenols 1 and sulfur ylides 2^a

Entry	R^1	X	R^2	Yield^b (%)
a 1 (0.5 mmol), 2 (0.75 mmol), TBAF (2.5 equiv., 1 M in THF solution), CH2Cl2 (5 mL), room temperature, 12 h.b Isolated yields.c Sulfonium salts was used instead of sulfur ylides, using Cs2CO3 (1.5 equiv.) as a base.
1	H	Br	Ph	89 (3a)
2	H	Cl	Ph	92 (3a)
3	H	Br	4-MeC6H4	81 (3b)
4	H	Br	4-MeOC6H4	80 (3c)
5	H	Br	3-MeOC6H4	91 (3d)
6	H	Br	4-FC6H4	86 (3e)
7	H	Br	2-FC6H4	85 (3f)
8	H	Br	4-ClC6H4	92 (3g)
9	H	Br	3-ClC6H4	90 (3h)
10	H	Br	4-BrC6H4	83 (3i)
11	H	Br	3-BrC6H4	84 (3j)
12	H	Br	2-Naphthyl	84 (3k)
13	H	Br	2-Furyl	81 (3l)
14	H	Br	2-Thiazolyl	95 (3m)
15	H	Br	2-Pyridyl	77 (3n)
16^c	H	Br	OEt	42 (3o)
17^c	H	Br	NEt2	85 (3p)
18	4-Br	Br	Ph	90 (3q)

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We further turned our attention to the reaction with chiral sulfonium salts derived from camphor. As shown in Scheme 1, moderate enantioselectivity (63% ee) was observed in reaction of 1a with chiral sulfonium salt 4a (R′ = H),¹⁰ affording optically active amide 3p′ in only 25% yield. When using the chiral sulfonium salt 4b (R′ = Me),¹¹ the yield of the desired product could be increased to 69%, but with the similar enantioselectivity (60% ee).

Scheme 1 Reaction of 1a with chiral sulfonium salt 4.

2-Substituted dihydrobenzofurans could be further converted into the corresponding aromatic benzofurans with using DDQ as the oxidizing agent. Thus, 2-benzoyl dihydrobenzofuran 3a was transformed smoothly to benzofuran 5a in 81% yield according to the known literature method.¹² When using 2-furoyl dihydrobenzofuran 3l and 2-picolinyl dihydrobenzofuran 3n under the same conditions, the desired products 5l and 5n were obtained in moderate yields (53–56% yields), Notably, 2-thiazole formyl dihydrobenzofuran 3m was employed in the reaction, affording the product 5m with 81% yield. When the 2-substituted dihydrobenzofuran 3o and 3p was employed, the corresponding benzofuran 5o and 5p could be obtained in 75% and 69% yield, respectively (Scheme 2).

Scheme 2 Synthesis of benzofuran 5.

A plausible mechanism for this formal [4 + 1] cycloaddition reaction is depicted in Scheme 3. We proposed that the highly reactive o-QMs A generated through desilylation/elimination reaction. Then sulfur ylides as nucleophiles attacked at the external carbon of o-QMs, affording the phenoxide B. Finally, the intermediate B lost one molecular dimethyl sulfide through nucleophilic attack, providing the 2-substituted dihydrobenzofuran.

Scheme 3 Proposed mechanism.

Experimental section

General procedure for the reaction of O-silylated phenols and sulfur ylides

To a solution of sulfur ylides 2 (0.75 mmol, 1.5 equiv.) in dry CH₂Cl₂ (4 mL), a solution of O-silylated phenol 1 (0.5 mmol, 1.0 equiv.) in dry CH₂Cl₂ (1 mL) was added at room temperature under N₂. Then TBAF (1.0 M in THF, 1.25 mL, 2.5 equiv.) was added dropwise. After the addition, the mixture was stirred at room temperature for 4 h. The reaction was concentrated under reduced pressure and purified by flash chromatography on silica gel (petroleum ether : ethyl acetate = 20 : 1).

3a¹³. White solid, 89% yield, m.p. 93–95 °C. ¹H NMR (300 MHz, CDCl₃) δ 8.07 (d, J = 7.2 Hz, 2H), 7.64 (t, J = 7.4 Hz, 1H), 7.53 (t, J = 7.5 Hz, 2H), 7.21 (d, J = 7.8 Hz, 1H), 7.15 (d, J = 7.8 Hz, 1H), 6.91 (dd, J = 7.4, 4.3 Hz, 2H), 6.02–5.86 (m, 1H), 3.91–3.23 (m, 2H).

3b. Colorless oil, 81% yield. ¹H NMR (300 MHz, CDCl₃) δ 7.95 (d, J = 8.2 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 7.18 (d, J = 7.4 Hz, 1H), 7.13 (d, J = 7.8 Hz, 1H), 6.94–6.82 (m, 2H), 5.90 (m, 1H), 3.60–3.52 (m, 2H), 2.44 (s, 3H). ¹³C NMR (75 MHz, CDCl₃) δ 194.6, 158.6, 144.2, 131.5, 129.0, 128.8, 127.8, 124.8, 124.4, 120.6, 109.3, 82.1, 32.3, 21.3. HRMS (ESI): exact mass calcd for C₁₆H₁₄O₂Na [M + Na]⁺ 261.0891, found: 261.0883.

3c¹⁴. White solid, 80% yield, m.p. 108.5–110 °C. ¹H NMR (300 MHz, CDCl₃) δ 8.04 (d, J = 8.8 Hz, 2H), 7.19 (d, J = 7.4 Hz, 1H), 7.13 (d, J = 7.8 Hz, 1H), 6.98 (d, J = 8.9 Hz, 2H), 6.88 (dd, J = 7.5, 5.6 Hz, 2H), 5.89 (dd, J = 10.2, 7.6 Hz, 1H), 3.89 (s, 3H), 3.61 (dd, J = 15.8, 7.7 Hz, 1H), 3.52 (dd, J = 15.8, 10.4 Hz, 1H).

3d. White solid, 91% yield, m.p. 94–95.8 °C. ¹H NMR (300 MHz, CDCl₃) δ 7.67–7.54 (m, 2H), 7.43 (t, J = 7.9 Hz, 1H), 7.20 (d, J = 7.3 Hz, 1H), 7.15 (d, J = 7.9 Hz, 1H), 6.97–6.84 (m, 2H), 5.95 (t, J = 8.9 Hz, 1H), 3.87 (s, 3H), 3.59 (d, J = 8.9 Hz, 2H). ¹³C NMR (75 MHz, CDCl₃) δ 195.3, 159.9, 159.0, 135.7, 129.7, 128.3, 125.1, 124.8, 121.6, 121.1, 120.2, 113.3, 109.8, 82.6, 55.4, 32.8. HRMS (ESI): exact mass calcd for C₁₆H₁₄O₃Na [M + Na]⁺ 277.0841, found: 277.0851.

3e. White solid, 86% yield, m.p. 118.0–120.2 °C. ¹H NMR (300 MHz, CDCl₃) δ 8.12 (dd, J = 8.6, 5.5 Hz, 2H), 7.21 (dd, J = 6.0, 2.7 Hz, 3H), 7.15 (d, J = 8.1 Hz, 1H), 6.98–6.84 (m, 2H), 5.89 (dd, J = 10.3, 7.3 Hz, 1H), 3.66 (dd, J = 15.8, 7.2 Hz, 1H), 3.55 (dd, J = 15.8, 10.4 Hz, 1H). ¹³C NMR (75 MHz, CDCl₃) δ 194.0, 167.7, 164.3, 158.8, 132.0, 131.9, 128.3, 125.1, 124.9, 121.3, 116.0, 115.7, 82.7, 32.2. HRMS (ESI): exact mass calcd for C₁₅H₁₁O₂FNa [M + Na]⁺ 265.0641, found: 265.0634.

3f. Yellow oil, 85% yield. ¹H NMR (300 MHz, CDCl₃) δ 7.94 (t, J = 7.4 Hz, 1H), 7.60 (m, 1H), 7.29 (t, J = 7.5 Hz, 1H), 7.25–7.12 (m, 3H), 6.92 (d, J = 7.7 Hz, 1H), 6.88 (d, J = 7.4 Hz, 1H), 5.99–5.82 (m, 1H), 3.69 (dd, J = 15.8, 10.9 Hz, 1H), 3.43 (dd, J = 15.9, 5.7 Hz, 1H). ¹³C NMR (75 MHz, CDCl₃) δ 194.7, 163.3, 160.0, 159.3, 135.3, 135.2, 131.3, 131.3, 128.3, 124.8, 124.8, 124.7, 121.0, 116.7, 116.3, 109.6, 85.0, 84.9, 32.5, 32.5. HRMS (ESI): exact mass calcd for C₁₅H₁₁O₂FNa [M + Na]⁺ 265.0641, found: 265.0634.

3g. White solid, 92% yield, m.p. 113.8–115.6 °C. ¹H NMR (300 MHz, CDCl₃) δ 8.01 (d, J = 8.6 Hz, 2H), 7.48 (d, J = 8.6 Hz, 2H), 7.24–7.06 (m, 2H), 6.91 (d, J = 7.4 Hz, 1H), 6.86 (d, J = 7.7 Hz, 1H), 5.86 (dd, J = 10.3, 7.3 Hz, 1H), 3.64 (dd, J = 15.8, 7.2 Hz, 1H), 3.53 (dd, J = 15.8, 10.4 Hz, 1H). ¹³C NMR (75 MHz, CDCl₃) δ 194.0, 158.3, 139.7, 132.4, 130.2, 128.6, 127.9, 124.6, 124.5, 120.8, 109.3, 82.3, 31.8. HRMS (ESI): exact mass calcd for C₁₅H₁₁O₂ClNa [M + Na]⁺ 281.0345, found: 281.0338.

3h. Yellow oil, 90% yield. ¹H NMR (300 MHz, CDCl₃) δ 8.05 (s, 1H), 7.95 (d, J = 7.7 Hz, 1H), 7.60 (dd, J = 4.9, 4.0 Hz, 1H), 7.47 (t, J = 7.9 Hz, 1H), 7.22 (d, J = 7.4 Hz, 1H), 7.16 (d, J = 7.5 Hz, 1H), 6.96–6.87 (m, 2H), 5.88 (dd, J = 10.2, 7.3 Hz, 1H), 3.65 (dd, J = 16.2, 7.7 Hz, 1H), 3.61–3.50 (m, 1H). ¹³C NMR (75 MHz, CDCl₃) δ 193.9, 158.3, 135.6, 134.6, 133.1, 129.6, 128.7, 127.9, 126.8, 124.5, 124.4, 120.8, 109.3, 82.1, 31.8. HRMS (ESI): exact mass calcd for C₁₅H₁₁O₂ClNa [M + Na]⁺ 281.0345, found: 281.0351.

3i. Yellow solid, 90% yield, m.p. 119.5–120.0 °C. ¹H NMR (300 MHz, CDCl₃) δ 7.94 (d, J = 7.8 Hz, 2H), 7.67 (d, J = 7.8 Hz, 2H), 7.26–7.11 (m, 2H), 6.93 (d, J = 7.5 Hz, 1H), 6.88 (d, J = 7.7 Hz, 1H), 5.87 (dd, J = 9.9, 7.7 Hz, 1H), 3.65 (dd, J = 15.8, 7.2 Hz, 1H), 3.54 (dd, J = 15.8, 10.4 Hz, 1H). ¹³C NMR (75 MHz, CDCl₃) δ 194.7, 158.8, 133.3, 132.0, 130.7, 128.9, 128.4, 125.0, 124.9, 121.3, 109.8, 82.7, 32.2. HRMS (ESI): exact mass calcd for C₁₅H₁₁O₂BrNa [M + Na]⁺ 324.9840, found: 324.9851.

3j. Yellow oil, 84% yield. ¹H NMR (300 MHz, CDCl₃) δ 8.20 (s, 1H), 7.99 (d, J = 7.5 Hz, 1H), 7.76 (dd, J = 8.0, 0.9 Hz, 1H), 7.40 (t, J = 7.9 Hz, 1H), 7.22 (d, J = 7.5 Hz, 1H), 7.16 (d, J = 7.9 Hz, 1H), 6.96–6.86 (m, 2H), 5.88 (dd, J = 10.2, 7.3 Hz, 1H), 3.64 (dd, J = 16.6, 8.0 Hz, 1H), 3.55 (dd, J = 16.0, 10.6 Hz, 1H). ¹³C NMR (75 MHz, CDCl₃) δ 193.8, 158.3, 136.0, 135.8, 131.6, 129.8, 127.9, 127.2, 124.5, 124.5, 122.6, 120.9, 109.3, 82.1, 31.8. HRMS (ESI): exact mass calcd for C₁₅H₁₁O₂BrNa [M + Na]⁺ 324.9840, found: 324.9848.

3k. White solid, 84% yield. m.p. 141.5–143.7 °C. ¹H NMR (300 MHz, CDCl₃) δ 8.62 (s, 1H), 8.10 (dd, J = 8.6, 1.5 Hz, 1H), 8.05–7.89 (m, 3H), 7.63 (m, 2H), 7.23 (d, J = 7.5 Hz, 1H), 7.17 (d, J = 7.7 Hz, 1H), 6.92 (dd, J = 7.2, 5.7 Hz, 2H), 6.11 (dd, J = 10.0, 7.7 Hz, 1H), 3.71 (dd, J = 14.3, 6.1 Hz, 1H), 3.63 (dd, J = 14.3, 8.8 Hz, 1H). ¹³C NMR (75 MHz, CDCl₃) δ 195.4, 159.0, 135.8, 132.5, 131.8, 131.1, 129.7, 128.8, 128.6, 128.3, 127.8, 126.9, 125.2, 124.9, 124.4, 121.2, 109.8, 82.6, 32.6. HRMS (ESI): exact mass calcd for C₁₉H₁₄O₂Na [M + Na]⁺ 297.0891, found: 297.0896.

3l. Yellow oil, 81% yield. ¹H NMR (300 MHz, CDCl₃) δ 7.68 (s, 1H), 7.47 (d, J = 3.5 Hz, 1H), 7.21 (d, J = 6.6 Hz, 1H), 7.16 (d, J = 7.8 Hz, 1H), 6.99–6.85 (m, 2H), 6.60 (dd, J = 3.5, 1.6 Hz, 1H), 5.69 (dd, J = 10.3, 7.5 Hz, 1H), 3.63 (dd, J = 15.9, 10.4 Hz, 1H), 3.53 (dd, J = 16.0, 7.5 Hz, 1H). ¹³C NMR (75 MHz, CDCl₃) δ 184.9, 158.5, 149.9, 146.9, 127.9, 124.6, 124.4, 120.8, 119.8, 112.0, 109.2, 82.4, 32.6. HRMS (ESI): exact mass calcd for C₁₃H₁₀O₃Na [M + Na]⁺ 237.0528, found: 237.0519.

3m. Yellow oil, 95% yield. ¹H NMR (300 MHz, CDCl₃) δ 8.01 (d, J = 3.8 Hz, 1H), 7.73 (d, J = 4.9 Hz, 1H), 7.25–7.15 (m, 3H), 6.92 (t, J = 7.2 Hz, 2H), 5.68 (t, J = 8.5 Hz, 1H), 3.61 (d, J = 8.8 Hz, 2H). ¹³C NMR (75 MHz, CDCl₃) δ 189.7, 158.4, 140.0, 134.5, 133.7, 127.9, 127.8, 124.6, 124.5, 120.9, 109.3, 83.5, 32.9. HRMS (ESI): exact mass calcd. for C₁₃H₁₀O₂SNa [M + Na]⁺ 253.0299, found: 253.0305.

3n. White solid, 77% yield. m.p. 118.5–120.5 °C. ¹H NMR (300 MHz, CDCl₃) δ 8.74 (d, J = 4.1 Hz, 1H), 8.15 (d, J = 7.8 Hz, 1H), 7.90 (dt, J = 7.7, 1.6 Hz, 1H), 7.54 (dd, J = 7.0, 5.4 Hz, 1H), 7.17 (t, J = 7.4 Hz, 2H), 6.97 (d, J = 8.1 Hz, 1H), 6.88 (t, J = 7.4 Hz, 1H), 6.49 (dd, J = 10.9, 7.6 Hz, 1H), 3.85 (dd, J = 16.0, 10.9 Hz, 1H), 3.31 (dd, J = 16.1, 7.6 Hz, 1H). ¹³C NMR (75 MHz, CDCl₃) δ 196.3, 159.7, 151.6, 149.1, 137.1, 128.2, 127.6, 125.2, 124.7, 123.0, 120.8, 109.8, 82.3, 34.0. HRMS (ESI): exact mass calcd for C₁₄H₁₁NO₂Na [M + Na]⁺ 248.0687, found: 248.0680.

3q¹⁵. White solid, 90% yield, m.p. 138.5–140 °C. ¹H NMR (300 MHz, CDCl₃) δ 8.07–8.00 (m, 2H), 7.63 (t, J = 7.4 Hz, 1H), 7.51 (t, J = 7.5 Hz, 2H), 7.32–7.20 (m, 2H), 6.76 (t, J = 9.8 Hz, 1H), 5.96 (dd, J = 10.1, 7.4 Hz, 1H), 3.61 (dd, J = 16.1, 7.4 Hz, 1H), 3.57–3.47 (m, 1H). ¹³C NMR (75 MHz, CDCl₃) δ 194.8, 158.2, 134.2, 133.8, 131.1, 129.1, 128.8, 127.8, 127.7, 113.0, 111.2, 82.9, 32.2.

General procedure for synthesis of 3o, 3p

A mixture of O-silylated phenol 1 (0.5 mmol, 1.0 equiv.), sulfonium salt 2 (0.75 mmol, 1.5 equiv.) and Cs₂CO₃ (0.75 mmol, 1.5 equiv.) in dry CH₂Cl₂ (5 mL) was stirred at room temperature under N₂. Then TBAF (1.0 M in THF, 1.25 mL, 2.5 equiv.) was added dropwise. After the addition, the mixture was stirred at room temperature for 24 h. The reaction was concentrated under reduced pressure and purified by flash chromatography on silica gel (petroleum ether : ethyl acetate = 10 : 1–5 : 1).

3o¹⁶. Yellow oil, 42% yield. ¹H NMR (300 MHz, CDCl₃) δ 7.17 (dd, J = 10.8, 7.8 Hz, 2H), 6.90 (t, J = 7.3 Hz, 2H), 5.20 (dd, J = 10.4, 7.1 Hz, 1H), 4.29 (q, J = 7.1 Hz, 2H), 3.58 (dd, J = 15.8, 10.6 Hz, 1H), 3.39 (dd, J = 15.8, 7.0 Hz, 1H), 1.33 (t, J = 7.1 Hz, 3H).

3p¹⁷. Colorless oil, 85% yield. ¹H NMR (500 MHz, CDCl₃) δ 7.19 (d, J = 7.3 Hz, 1H), 7.11 (t, J = 7.7 Hz, 1H), 6.86 (t, J = 7.4 Hz, 1H), 6.80 (d, J = 8.0 Hz, 1H), 5.36 (dd, J = 9.8, 7.7 Hz, 1H), 3.73 (dd, J = 15.6, 7.6 Hz, 1H), 3.57–3.39 (m, 4H), 3.32 (dd, J = 15.5, 9.9 Hz, 1H), 1.27 (t, J = 7.1 Hz, 3H), 1.16 (t, J = 7.1 Hz, 3H).

Conclusions

In summary, we have developed a straightforward and efficient approach to 2-substitiuted dihydrobenzofurans through reaction of sulfur ylides with o-quinone methides that could be generated under mild conditions. In addition, chiral sulfonium salts could also be employed in this reaction, affording the desired product with moderate enantioselectivity. The products 2-substitiuted dihydrobenzofurans could be conveniently converted to 2-substituted benzofurans with using DDQ as the oxidant. Applications of this [4 + 1] cycloaddition reaction to other substrates and to the construction of biologically relevant compounds are ongoing in our laboratory.

Acknowledgements

Financial support from National Natural Science Foundation of China (grants 81373303 and 81473080) and State Key Laboratory of Durg Research (SIMM1403KF-13) is gratefully acknowledged.

Notes and references

1. For reiews, see: (a) H. Amouri and J. Le Bras, Acc. Chem. Res., 2002, 35, 501; (b) S. B. Ferreira, F. d. C. da Silva, A. C. Pinto, D. T. G. Gonzaga and V. F. Ferreira, J. Heterocycle. Chem., 2009, 46, 1080; (c) Quinone Methides ed. S. E. Rokita, Wiley, New York, 2009.
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Footnote

† Electronic supplementary information (ESI) available: The procedure for synthesis of O-silylated phenol 1 and the copies of spectra. See DOI: 10.1039/c4ra17003b

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