N-Phenoxyamides as Multitasking Reagents: Base-Controlled

Jun 13, 2019 - This result might be an evidence for the generation of alkylidene carbene. ... N–O bond in the intramolecular reaction mode could be ...
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Cite This: J. Org. Chem. 2019, 84, 8523−8530

N‑Phenoxyamides as Multitasking Reagents: Base-Controlled Selective Construction of Benzofurans or Dihydrobenzofuro[2,3‑d]oxazoles Ming Li, Jia-Hui Wang, Wei Li, Cheng-Dong Lin, Lin-Bao Zhang,* and Li-Rong Wen* State Key Laboratory Base of Eco-Chemical Engineering, College of Chemistry and Molecular Engineering, Qingdao University of Science & Technology, Qingdao 266042, China Downloaded via GUILFORD COLG on July 17, 2019 at 09:12:52 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.

S Supporting Information *

ABSTRACT: An efficient method to selectively construct benzofuran and dihydrobenzofuro[2,3-d]oxazole derivatives has been successfully established by means of base-controlled cyclization of N-phenoxyamides with 1-[(triisopropylsilyl)ethynyl]1,2-benziodoxol-3(1H)-one (TIPS-EBX). N-phenoxyamides as multitasking reagents have triggered two different cascade reaction sequences. This is the first example of using TIPS-EBX for the transformation of C(sp) to either C(sp2) or C(sp3) under metal-free conditions.

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INTRODUCTION The benzofuran skeleton is a significant heterocyclic motif in many biologically active natural products.1 Some benzofurans have been reported to possess various pharmacological activities.2 For example, amurensin H (I)1a has antiinflammatory activity, malibatol A (II)1b shows HIV inhibitory activity, and compound III2d is an adenosine A2A receptor antagonist (Figure 1). Oxyamides (CONHOR) as a multifunctional warhead rendered proliferation of the reaction controlled by either the catalyst or additives and allow direct access to structurally diverse heterocyles.3 Lu et al. developed a mild Rh- or Rucatalyzed C−H functionalization for the synthesis of benzofuran derivatives using the ONHCOR directing group.4 Zhao et al. developed a C−H functionalization catalyzed by [Cp*RhCl2]2 and Ag2CO3 as the oxidant for the synthesis of dihydrobenzofuro[2,3-d]oxazoles using N-phenoxyamide.5 Very recently, Zhao et al. reported the synthesis of benzofurans from N-phenoxyamides and ethyl 3-bromopropiolates or N,Ndiethylacetamides in the presence of t-BuONa.6 Until now, there is no protocol for the synthesis of benzofurans or dihydrobenzofuro[2,3-d]oxazoles by the use of N-phenoxyamides and TIPS-EBX under metal-free conditions. The use of ethynylbenziodoxolones (EBXs) as an efficient alkynylating reagent has recently received increasing attention in organic synthesis. Various meaningful research of transitionmetal-catalyzed C−H alkynylation has been developed by Waser et al.,7a−e Li et al.,7f,g Loh and Feng,7h Nachtsheim et al.,7i Cheng et al.,7j and others8 (Scheme 1, eq 1). However, © 2019 American Chemical Society

the cyclization other than simple alkynylations of EBXs under a transition-metal-free condition is still much less explored.9 Our group has recently reported a K2CO3-promoted reaction to synthesize 2-(oxazol-5-yl)phenols from N-phenoxyamides and EBX reagents, which involves the cleavage of the N−O bond and insertion of alkylidene carbene (Scheme 1, eq 2).10 A bench-stable reagent of TIPS-EBX was commonly used as an exceptional reagent for the ethynylation under metal-free conditions.11 However, a careful survey of the literature revealed that the application of TIPS-EBX to form benzofurans or dihydrobenzofuro[2,3-d]oxazoles is largely unexplored. Based on our ongoing interest in hypervalent iodine reagents,9b,12 herein, we report a [3,3]-rearrangement/ insertion of alkylidene carbene/cyclization controlled by different bases for the construction of benzofurans or dihydrobenzofuro[2,3-d]oxazoles from N-phenoxyacetamides and TIPS-EBX (Scheme 1, eq 3). This strategy not only complements previous methods but also offers new opportunity for rapid assembly of structurally diverse heterocycles by avoiding the use of transition-metal reagents. Results and Discussion. In our previous work,10 TIPSEBX (2a) and TMS-EBX (2b) did not achieve the corresponding 2-(oxazol-5-yl)phenol, but an unexpected product N-(benzofuran-2-yl)acetamide (3a) was obtained in yields of 9 and 35%,(Table 1, entries 1 and 2, respectively). These results indicated that TMS-EBX has a higher reactivity Received: March 27, 2019 Published: June 13, 2019 8523

DOI: 10.1021/acs.joc.9b00858 J. Org. Chem. 2019, 84, 8523−8530

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The Journal of Organic Chemistry

Figure 1. Selected benzofurans with pharmacological activities.

ratio of 1:1.3 in the presence of TBAF (1.3 equiv) in DCE (c = 0.1 M) at −30 °C for 1 h. With the optimized conditions established, we first sought to investigate the scope and limitation of N-phenoxyacetamide substrates. As given in Table 2, a great variety of substituted N-

Scheme 1. Multiple Reactions Involving EBXs

Table 2. Scope for Substituted N-Phenoxamides 1a,b

Table 1. Optimization of Reaction Conditions for 3aa

entry

reaction conditions

yield (%)b

1 2 3 4 5 6 7

2a, K2CO3, DCE, rt, 24 h 2b, K2CO3, DCE, rt, 5 h 2b, K2CO3, DCE, 0 °C, TBAF, 1 h 2b, K2CO3, DCE, −30 °C, TBAF, 1 h 2a, K2CO3, DCE, −30 °C, TBAF, 1 h 2a, DCE, −30 °C, TBAF, 1 h 2a, THF, −78 °C, TBAF, 1 h

9 35 50 66 92 94 85

a

The reactions were performed with 1a (0.2 mmol), 2 (0.26 mmol), K2CO3 (0.4 mmol), TBAF (0.26 mmol), and solvent (2 mL); DCE: 1,2-dichloroethane; THF: tetrahydrofuran; TBAF: tetrabutylammonium fluoride. bIsolated yield.

Reaction conditions: 1 (0.3 mmol), 2a (0.39 mmol), TBAF (0.39 mmol), DCE (3 mL), −30 °C, 1 h. bIsolated yield. cThe ratio is determined by 1H NMR analysis. dYield on a gram scale (8 mmol).

than TIPS-EBX.11b Then, TMS-EBX was selected as the model substrate for the following test. Delightedly, the introduction of tetrabutylammonium fluoride (TBAF) and lowering the temperature led to an obviously increased yield of 3a (Table 1, entries 3 and 4), but moderate decomposition of the EBX was observed. However, TIPS-EBX provided a significant improved yield under the same conditions at −30 °C (Table 1, entry 5). A control experiment suggested that an additional base was not an essential factor to this transformation, which should be due to TBAF that works as both a desilication agent for 2 and a base11b (Table 1, entry 6). Further lowering the temperature to −78 °C, the yield of 3a was slightly decreased to 85% (Table 1, entry 7). Consequently, we confirmed the optimal reaction conditions by employing 1a and 2a with a

phenoxyamides 1 reacted smoothly with 2a to afford the corresponding N-(benzofuran-2-yl)amides in moderate to excellent isolated yields. Both electron-donating and electronwithdrawing groups at the para-, ortho-, and meta-positions as well as disubstituted N-phenoxyacetamides are well tolerated (3a−3o). However, the substrates 1l, 1m, and 1o gave a mixture of two regioisomeric products (3l, 3m, and 3o), which may be caused by the steric hindrance. The polyaromatic naphthalene substrate 1p was exclusively reacted at the 3position to produce 3p in a synthetically useful yield. To better define the scope of this reaction, we further explored other Nphenoxyamides, such as N-phenoxypentanamide (1q), Nphenoxypivalamide (1r), and N-phenoxycyclopropanecarboxamide (1s), and the corresponding products (3q−3s) were

a

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DOI: 10.1021/acs.joc.9b00858 J. Org. Chem. 2019, 84, 8523−8530

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The Journal of Organic Chemistry obtained in moderate to good yields. Furthermore, N-phenoxy2-(p-tolyl)acetamide (1t) showed a similar reactivity to provide the desired product 3t in 45% yield. Having successfully achieved efficient synthesis of N(benzofuran-2-yl)acetamides (3a−3p) and their analogues (3q−3t), we switched our focus on exploring a range of Nphenoxyarylamides. To our surprise, when we performed the reaction of N-phenoxybenzamide (1u) with 2a under the standard conditions, an unexpected product 2-phenyldihydrobenzofuro[2,3-d]oxazole (4a) in majority was obtained along with a minority of 3u. We speculated that the selectivity of the reaction may be improved by regulating the alkali properties of the reaction system. Based on this conjecture, we investigated the effect of different additional bases on the selectivity of the reaction. As given in Table 3, when 1,8-

Scheme 2. Control Experiments

Table 3. Scope for Substituted N-Phenoxamide 1a,b

Tetramethylpiperidine N-oxide (TEMPO) or 2,6-di-tertbutyl-4-methylphenol (BHT), as an efficient radical scavenger, was added in the reaction. The product 3a could be isolated in 93 and 88% yields, which indicates a radical pathway might not proceed in progress (Scheme 2, eq 3). The crossover experiment combining two different phenoxyamides 1c and 1q under the standard conditions was carried out (Scheme 2, eq 4). The result shows that no cross products were generated, which reveals the cleavage/migration of the N−O bond in the intramolecular reaction mode could be confirmed. In the carbene trapping test, the corresponding intermediate 5 was not obtained, which infers that alkylidene carbene is a kind of highly active reaction intermediate (Scheme 2, eq 5). A stoichiometric amount of D2O was added into the reaction system; a mixture of products 3a and 3a-D was obtained in a ratio of 1:1 (Scheme 2, eq 6), and this result shows that the alkynyl H of the intermediate B is from H2O in the reaction system. Although the mechanistic details of this reaction remain unclear at present, a conceivable mechanism was proposed based on the present findings and previous reports,10 as shown in Scheme 3. Initially, the reactive intermediate B is generated from bench-stable TIPS-EBX 2a in the presence of TBAF.11 Then, nucleophilic oxygen in the intermediate A from the deprotonation of N-phenoxyamides 1 with TBAF attacks the electrophilic iodine of B to form intermediate C, which undergoes [3,3]-rearrangement to furnish vinyliodonium ylide D. Then, the key intermediate alkylidene carbene E is yielded through the removal of 2-iodobenzoic acid from D. Next, two pathways can take place under different base-controlled conditions. In the presence of DBU, alkylidene carbene E from N-phenoxybenzamides would more easily form the

a

Reaction conditions: 1 (0.3 mmol), 2a (0.39 mmol), TBAF (0.39 mmol), base (0.6 mmol), DCE (3 mL), −30 °C, 1 h. bIsolated yield.

diazabicyclo[5.4.0]undec-7-ene (DBU) was used as the additional base, N-(benzofuran-2-yl)arylamides (3u−3z) in majority were obtained in moderate to good yields. When Na 2 CO 3 was used as the additional base, 2-aryldihydrobenzofuro[2,3-d]oxazoles (4a−4g) as major products were obtained in moderate yields. From the above experimental results, it can be seen that the reactivity of Nphenoxyacetamides is higher than that of N-phenoxybenzamides so that the reaction of the former can be completed without an additional base. However, it is not clear why different bases (DBU or Na2CO3) were added to produce different products. To get a better understanding of the reaction mechanism, a series of control experiments were performed (Scheme 2). To gain further insights into the conversion of key intermediates, a substrate N-(mesityloxy)acetamide (1A) in which two orthopositions on the benzene ring was installed by the methyl group that was used to get some valuable intermediates. Fortunately, we observed two possible intermediates (1C and 1F) by LC−MS (see the Supporting Information) (Scheme 2, eq 1). This result might be an evidence for the generation of alkylidene carbene.11,13 Moreover, N-(benzofuran-2-yl)benzamide (3u) was subjected to the reaction system under standard conditions; however, 2-phenyl-dihydrobenzofuro[2,3d]oxazole (4a) was not detected, and a similar result was got in the case of 4a, suggesting that 3u and 4a might undergo different reaction routes (Scheme 2, eq 2). 2,2,6,68525

DOI: 10.1021/acs.joc.9b00858 J. Org. Chem. 2019, 84, 8523−8530

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The Journal of Organic Chemistry Scheme 3. Possible Reaction Mechanism

synthesized according to the procedure.15 All hypervalent iodine reagents 2a and 2b were synthesized according to the literature.16 General Procedure for the Synthesis of 3a−3t. The mixture of N-phenoxyamides 1 (0.3 mmol), alkynyliodonium salts 2a (0.39 mmol), and TBAF (0.39 mmol) in DCE (3 mL) was stirred at −30 °C in a tube for about 1 h until complete consumption of starting materials as monitored by TLC. After the completion of the reaction and evaporation of the solvent, the mixture was purified by silica gel column chromatography (PE/EA = 4:1) to afford the desired products 3. N-(Benzofuran-2-yl)acetamide (3a). White solid, yield 94% (49.4 mg). Mp: 125−126 °C. 1H NMR (500 MHz, DMSO-d6, δ): 11.25 (s, 1H), 7 .49 (d, J = 6.8 Hz, 1H), 7.45 (d, J = 7.6 Hz, 1H), 7.17 (p, J = 7.3 Hz, 2H), 6.63 (s, 1H), 2.11 (s, 3H). 13C{1H} NMR (125 MHz, DMSO-d6, δ): 167.6, 149.9, 149.2, 129.6, 123.5, 122.8, 120.2, 110.5, 88.9, 23.6. HRMS (ESI-TOF, [M + Na]+): calcd for C10H9NO2Na, 198.0531; found, 198.0532. N-(5-Methylbenzofuran-2-yl)acetamide (3b). White solid, yield 86% (48.8 mg). Mp: 133−134 °C. 1H NMR (500 MHz, DMSO-d6, δ): 11.18 (s, 1H), 7.31 (d, J = 8.3 Hz, 1H), 7.27 (s, 1H), 6.97 (d, J = 8.3 Hz, 1H), 6.55 (s, 1H), 2.35 (s, 3H), 2.10 (s, 3H). 13C{1H} NMR (125 MHz, DMSO-d6, δ): 167.5, 149.9, 147.6, 132.4, 129.7, 123.7, 120.2, 110.0, 88.8, 23.6, 21.4. HRMS (ESI-TOF, [M + Na]+): calcd for C11H11NO2Na, 212.0687; found, 212.0690. N-(5-Methoxybenzofuran-2-yl)acetamide (3c). White solid, yield 73% (44.9 mg). Mp: 136−138 °C. 1H NMR (400 MHz, DMSO-d6, δ): 11.19 (s, 1H), 7.33 (d, J = 8.8 Hz, 1H), 7.03 (d, J = 2.5 Hz, 1H), 6.73 (dd, J = 8.8, 2.6 Hz, 1H), 6.56 (s, 1H), 3.76 (s, 3H), 2.10 (s, 3H). 13C{1H} NMR (100 MHz, DMSO-d6, δ): 167.6, 156.3, 150.6, 144.0, 130.4, 110.9, 110.5, 103.6, 89.4, 55.9, 23.6. HRMS (ESI-TOF, [M + Na]+): calcd for C11H11NO3Na, 228.0637; found, 228.0637. N-(5-(tert-Butyl)benzofuran-2-yl)acetamide (3d). White solid, yield 78% (54.1 mg). Mp: 140−141 °C. 1H NMR (500 MHz, DMSO-d6, δ): 11.14 (s, 1H), 7.46 (s, 1H), 7.31 (d, J = 8.6 Hz, 1H), 7.22−7.14 (m, 1H), 6.55 (s, 1H), 2.07 (s, 3H), 1.29 (s, 9H). 13C{1H} NMR (125 MHz, DMSO-d6, δ): 167.5, 149.9, 147.4, 146.0, 129.3, 120.3, 116.6, 109.7, 89.2, 34.8, 32.0, 23.6. HRMS (ESI-TOF, [M + Na]+): calcd for C14H17NO2Na, 254.1157; found, 254.1156. N-(5-Phenylbenzofuran-2-yl)acetamide (3e). White solid, yield 90% (67.8 mg). Mp: 159−161 °C. 1H NMR (500 MHz, DMSO-d6, δ): 11.30 (s, 1H), 7.76 (s, 1H), 7.66 (d, J = 7.8 Hz, 2H), 7.52 (d, J = 8.4 Hz, 1H), 7.45 (q, J = 8.0 Hz, 3H), 7.34 (t, J = 7.3 Hz, 1H), 6.68 (s, 1H), 2.12 (s, 3H). 13C{1H} NMR (125 MHz, DMSO-d6, δ): 167.6, 150.5, 148.9, 141.2, 136.2, 130.3, 129.3, 127.3, 121.9, 118.4,

terminal alkyne intermediate F through a 1,2-hydride shift, and after [3,3]-rearrangement and cyclization, products 3 are obtained (path a). Similarly, the reactions of N-phenoxyacetamides with 2a in the absence of DBU also proceed via path a. On the other hand, in the presence of Na2CO3, alkylidene carbene E can undergo sequent intramolecular alkylidene carbene insertion/[3,3]-rearrangement/Michael addition/biscyclization to provide dihydrobezofuro[2,3-d] oxazoles 4 (path b).

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CONCLUSIONS In conclusion, we have developed an effective method for selective synthesis of benzofuran or dihydrobenzofuro[2,3d]oxazole derivatives from TIPS-EBX and N-phenoxyamides. Unlike previous reports, N-phenoxyamides as a multitasking reagent have triggered two different cascade reactions, which enable increasing molecular complexity of diverse heterocycles. To our knowledge, the current study implements the first example of using TIPS-EBX for the independent transformation of C(sp) to either C(sp2) or C(sp3). The protocol was featured by the metal-free reaction system, wide substrate scope, mild reaction conditions, and easy-to-handle nature. Further employing this protocol to synthesize other heterocyclic compounds and clarifying the detailed mechanism are currently ongoing in our laboratory.

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EXPERIMENTAL SECTION

General Information. All reagents and solvents were obtained from commercial suppliers and used without further purification. All reagents were weighed and handled in air at room temperature. Melting points were recorded on an RY-1 microscopic melting apparatus and uncorrected. 1H NMR spectra were recorded at 500 MHz (or 400 MHz), and 13C NMR spectra were recorded at 125 MHz (or 100 MHz) by using a Bruker Avance 500 spectrometer. Chemical shifts were reported in parts per million (δ) relative to tetramethylsilane (TMS). HRMS were performed on an Ultima Global spectrometer with an ESI source. The X-ray single crystal diffraction was performed on a Saturn 724+ instrument. General Procedure for the Synthesis of Starting Materials 1 and 2. N-Phenoxyacetamides 1a−1p were synthesized according to the procedure,4a,14 and N-phenoxyamides 1q−1z and 1z′−1z″ were 8526

DOI: 10.1021/acs.joc.9b00858 J. Org. Chem. 2019, 84, 8523−8530

Article

The Journal of Organic Chemistry 110.8, 89.1, 23.6. HRMS (ESI-TOF, [M + H]+): calcd for C16H14NO2, 252.1025; found, 252.1028. N-(5-Fluorobenzofuran-2-yl)acetamide (3f). White solid, yield 95% (55.0 mg). Mp: 143−144 °C. 1H NMR (500 MHz, DMSO-d6, δ): 11.33 (s, 1H), 7.46 (dd, J = 8.8, 4.2 Hz, 1H), 7.30 (dd, J = 9.1, 2.6 Hz, 1H), 6.97 (td, J = 9.3, 2.7 Hz, 1H), 6.64 (s, 1H), 2.12 (s, 3H). 13 C{1H} NMR (125 MHz, DMSO-d6, δ): 167.7, 159.3 (d,1JC−F = 235.7 Hz), 151.6, 145.5, 131.0, 111.5, 109.8, 109.6, 106.0 (d,2JC−F = 25.6 Hz), 89.2, 23.6. HRMS (ESI-TOF, [M + Na]+): calcd for C10H8NO2NaF, 216.0437; found, 216.0439. N-(5-Chlorobenzofuran-2-yl)acetamide (3g). White solid, yield 86% (53.9 mg). Mp: 149−151 °C. 1H NMR (500 MHz, DMSO-d6, δ): 11.33 (s, 1H), 7.52 (s, 1H), 7.44 (d, J = 8.4 Hz, 1H), 7.13 (d, J = 8.6 Hz, 1H), 6.60 (s, 1H), 2.09 (s, 3H). 13C{1H} NMR (125 MHz, DMSO-d6, δ): 167.8, 151.4, 147.8, 131.6, 128.0, 122.5, 119.7, 112.0, 88.6, 23.7. HRMS (ESI-TOF, [M + H]+): calcd for C10H9NO2Cl, 210.0322; found, 210.0321. N-(5-Bromobenzofuran-2-yl)acetamide (3h). White solid, yield 74% (56.2 mg). Mp: 165−166 °C. 1H NMR (500 MHz, DMSO-d6, δ): 11.34 (s, 1H), 7.66 (s, 1H), 7.40 (d, J = 8.6 Hz, 1H), 7.26 (d, J = 6.8 Hz, 1H), 6.60 (s, 1H), 2.09 (s, 3H). 13C{1H} NMR (125 MHz, DMSO-d6, δ): 167.7, 151.1, 148.1, 132.1, 125.2, 122.6, 115.9, 112.4, 88.4, 23.6. HRMS (ESI-TOF, [M + H]+): calcd for C10H9NO2Br, 253.9817; found, 253.9815. N-(5-(Trifluoromethyl)benzofuran-2-yl)acetamide (3i). White solid, yield 80% (58.3 mg). Mp: 155−156 °C. 1H NMR (500 MHz, DMSO-d6, δ): 11.46 (s, 1H), 7.92 (s, 1H), 7.67 (d, J = 8.5 Hz, 1H), 7.50 (d, J = 7.1 Hz, 1H), 6.77 (s, 1H), 2.15 (s, 3H). 13C{1H} NMR (125 MHz, DMSO-d6, δ): 167.9, 151.7, 150.9, 130.4, 125.2 (d,1JC−F = 271.9 Hz), 125.2, 124.7 (d,2JC−F = 31.4 Hz). 124.3, 119.7, 119.7, 117.7, 117.6, 111.3, 88.9, 23.7. HRMS (ESI-TOF, [M + H]+): calcd for C11H9NO2F3, 244.0585; found, 244.0588. Ethyl 2-acetamidobenzofuran-5-carboxylate (3j). White solid, yield 88% (65.2 mg). Mp: 161−162 °C. 1H NMR (500 MHz, DMSO-d6, δ): 11.36 (s, 1H), 8.11 (s, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 8.5 Hz, 1H), 6.71 (s, 1H), 4.29 (q, J = 6.9 Hz, 2H), 2.10 (s, 3H), 1.30 (t, J = 7.0 Hz, 3H). 13C{1H} NMR (125 MHz, DMSOd6, δ): 167.8, 166.3, 151.9, 151.2, 130.0, 125.7, 124.3, 121.8, 110.7, 89.1, 61.0, 23.6, 14.7. HRMS (ESI-TOF, [M + H]+): calcd for C13H14NO4, 248.0923; found, 248.0925. N-(7-Methylbenzofuran-2-yl)acetamide (3k). White solid, yield 42% (23.8 mg). Mp: 129−131 °C. 1H NMR (500 MHz, DMSO-d6, δ): 11.25 (s, 1H), 7.28 (d, J = 7.6 Hz, 1H), 7.05 (t, J = 7.5 Hz, 1H), 6.96 (d, J = 7.3 Hz, 1H), 6.58 (s, 1H), 2.40 (s, 3H), 2.07 (s, 3H). 13 C{1H} NMR (125 MHz, DMSO-d6, δ): 167.5, 149.6, 148.1, 129.1, 123.9, 123.5, 120.0, 117.8, 89.3, 23.5, 15.1. HRMS (ESI-TOF, [M + Na]+): calcd for C11H11NO2Na, 212.0687; found, 212.0692. N-(6-Methylbenzofuran-2-yl)acetamide (3l) and N-(4-methylbenzofuran-2-yl)acetamide (3l′). White solid, yield 82% (46.5 mg). Mp: 121−123 °C. 1H NMR (500 MHz, DMSO-d6, δ): 11.19 (s, 1H), 11.13 (s, 1.18H), 7.33 (d, J = 7.8 Hz, 1.16H), 7.23 (d, J = 6.7 Hz, 2.24H), 7.03 (t, J = 7.7 Hz, 1.08H), 6.97 (t, J = 7.8 Hz, 2.26H), 6.60 (s, 1.09H), 6.53 (s, 1.21H), 2.38 (s, 3.02H), 2.35 (s, 3.35H), 2.08 (s, 3.04H), 2.06 (s, 3.44H). 13C{1H} NMR (125 MHz, DMSO-d6, δ): 167.5, 167.4, 149.6, 149.4, 149.3, 148.9, 132.4, 129.6, 129.05, 126.94, 124.63, 123.81, 122.69, 119.79, 110.70, 107.92, 88.94, 87.69, 23.55, 21.52, 18.56. HRMS (ESI-TOF, [M + Na] + ): calcd for C11H11NO2Na, 212.0687; found, 212.0688. N-(6-Methoxybenzofuran-2-yl)acetamide (3m) and N-(4-methoxybenzofuran-2-yl)acetamide (3m′). White solid, yield 85% (52.2 mg). Mp: 144−145 °C. 1H NMR (500 MHz, DMSO-d6, δ): 11.18 (s, 0.26H), 11.07 (s, 0.96H), 7.33 (d, J = 8.2 Hz, 0.99H), 7.12− 7.01 (m, 1.5H), 6.79 (d, J = 8.6 Hz, 0.97H), 6.73 (d, J = 7.8 Hz, 0.26H), 6.55 (s, 0.23H), 6.50 (s, 0.9H), 3.84 (s, 0.79H), 3.75 (s, 3.00H), 2.07 (s, 0.78H), 2.06 (s, 3.09H). 13C{1H} NMR (125 MHz, DMSO-d6, δ): 167.6, 167.4, 156.8, 152.7, 150.3, 148.9, 148.6, 123.7, 122.6, 120.4, 119.0, 111.7, 104.9, 103.9, 96.3, 89.2, 86.4, 56.0, 55.9, 23.6, 23.5. HRMS (ESI-TOF, [M + Na]+): calcd for C11H11NO3Na, 228.0637; found, 228.0636.

N-(4,6-Difluorobenzofuran-2-yl)acetamide (3n). White solid, yield 73% (46.2 mg). Mp: 153−154 °C. 1H NMR (500 MHz, DMSO-d6, δ): 11.40 (s, 1H), 7.39 (d, J = 8.6 Hz, 1H), 7.11 (td, J = 10.2, 1.8 Hz, 1H), 6.61 (s, 1H), 2.11 (s, 3H). 13C{1H} NMR (125 MHz, DMSO-d6, δ): 167.7, 159.8 (d,3JC−F = 11.6 Hz), 157.9 (d,3JC−F = 12.1 Hz), 154.9 (d,3JC−F = 15.2 Hz), 152.9 (d,3JC−F = 14.8 Hz), 150.5, 150.3, 114.6 (d,2JC−F = 22.3 Hz), 99.4, 99.2, 99.0, 96.1, 95.9, 84.2, 23.5. HRMS (ESI-TOF, [M + Na]+): calcd for C10H7NO2NaF2, 234.0343; found, 234.0338. N-(5,6-Dimethylbenzofuran-2-yl)acetamide (3o) and N-(4,5dimethylbenzofuran-2-yl)acetamide (3o′). White solid, yield 80% (48.7 mg). Mp: 155−157 °C. 1H NMR (500 MHz, DMSO-d6, δ): 11.16 (s, 0.76H), 11.13 (s, 1.01H), 7.23 (s, 2.09H), 7.15 (d, J = 8.2 Hz, 0.77H), 6.95 (d, J = 8.2 Hz, 0.75H), 6.62 (s, 0.76H), 6.51 (s, 1H), 2.30 (s, 2.29H), 2.27 (s, 2.95H), 2.27 (s, 2.53H), 2.25 (s, 3.13H), 2.11 (s, 2.25H), 2.09 (s, 3.01H). 13C{1H} NMR (125 MHz, DMSO-d6, δ): 167.4, 167.4, 149.4, 149.1, 148.1, 147.5, 131.4, 131.2, 130.3, 129.5, 127.4, 127.2, 124.5, 120.5, 110.9, 107.4, 88.7, 87.9, 23.5, 20.2, 19.9, 19.4, 15.7. HRMS (ESI-TOF, [M + Na]+): calcd for C12H13NO2Na, 226.0844; found, 226.0846. N-(Naphtho[2,3-b]furan-2-yl)acetamide (3p). White solid, yield 88% (59.4 mg). Mp: 177−178 °C. 1H NMR (500 MHz, DMSO-d6, δ): 11.31 (s, 1H), 8.19 (d, J = 8.1 Hz, 1H), 7.96 (d, J = 8.1 Hz, 1H), 7.67 (s, 2H), 7.54 (t, J = 6.9 Hz, 1H), 7.46 (t, J = 7.5 Hz, 1H), 7.19 (s, 1H), 2.12 (s, 3H). 13C{1H} NMR (125 MHz, DMSO-d6, δ): 167.5, 149.5, 145.9, 130.5, 129.0, 127.0, 126.4, 124.9, 124.6, 124.1, 123.3, 111.9, 89.0, 23.6. HRMS (ESI-TOF, [M + Na]+): calcd for C14H11NO2Na, 248.0687; found, 248.0683. N-(Benzofuran-2-yl)pentanamide (3q). White solid, yield 81% (52.7 mg). Mp: 112−113 °C. 1H NMR (500 MHz, DMSO-d6, δ): 11.18 (s, 1H), 7.49 (d, J = 7.0 Hz, 1H), 7.44 (d, J = 7.6 Hz, 1H), 7.17 (p, J = 7.1 Hz, 2H), 6.63 (s, 1H), 2.38 (t, J = 7.4 Hz, 2H), 1.58 (p, J = 7.4 Hz, 2H), 1.32 (dd, J = 14.8, 7.3 Hz, 2H), 0.90 (t, J = 7.4 Hz, 3H). 13 C{1H} NMR (125 MHz, DMSO-d6, δ): 170.6, 149.9, 149.2, 129.6, 123.5, 122.8, 120.2, 110.4, 89.0, 35.7, 27.3, 22.1, 14.1. HRMS(ESITOF, [M + H]+): calcd for C13H16NO2, 218.1187; found, 218.1174. N-(Benzofuran-2-yl)pivalamide (3r). White solid, yield 56% (36.5 mg). Mp: 139−141 °C. 1H NMR (500 MHz, DMSO-d6, δ): 10.70 (s, 1H), 7.51 (d, J = 5.8 Hz, 1H), 7.45 (d, J = 6.9 Hz, 1H), 7.22−7.14 (m, 2H), 6.65 (s, 1H), 1.24 (s, 9H). 13C{1H} NMR (125 MHz, DMSO-d6, δ): 176.0, 150.3, 149.4, 141.2, 133.6, 130.8, 129.5, 128.7, 123.5, 122.8, 120.3, 110.3, 89.9, 65.6, 27.3, 27.2. HRMS (ESI-TOF, [M + Na]+): calcd for C13H15NO2Na, 240.1000; found, 240.1003. N-(Benzofuran-2-yl)cyclopropanecarboxamide (3s). White solid, yield 36% (21.7 mg). Mp: 142−143 °C. 1H NMR (500 MHz, DMSO-d6, δ): 11.50 (s, 1H), 7.44 (d, J = 17.6 Hz, 2H), 7.13 (s, 2H), 6.57 (s, 1H), 1.85 (s, 1H), 0.84 (s, 4H). 13C{1H} NMR (125 MHz, DMSO-d6, δ): 171.0, 149.9, 149.2, 129.6, 123.5, 122.7, 120.2, 110.4, 88.9, 14.4, 8.3. HRMS (ESI-TOF, [M + H]+): calcd for C12H12NO2, 202.0868; found, 202.0868. N-(Benzofuran-2-yl)-2-(p-tolyl)acetamide (3t). White solid, yield 45% (35.8 mg). Mp: 162−163 °C. 1H NMR (500 MHz, DMSO-d6, δ): 11.45 (s, 1H), 7.44 (dd, J = 16.7, 6.9 Hz, 2H), 7.19 (d, J = 7.6 Hz, 2H), 7.16−7.08 (m, 4H), 6.58 (s, 1H), 3.63 (s, 2H), 2.25 (s, 3H). 13 C{1H} NMR (125 MHz, DMSO-d6, δ): 168.6, 149.7, 149.3, 136.2, 132.6, 129.5, 129.3, 123.6, 122.9, 120.3, 110.5, 89.3, 42.4, 21.0. HRMS (ESI-TOF, [M + Na]+): calcd for C17H15NO2Na, 288.1000; found, 288.1003. General Procedure for the Synthesis of 3u−3z. The mixture of N-phenoxyamides 1 (0.3 mmol), alkynyliodonium salts 2a (0.39 mmol), TBAF (0.39 mmol), and DBU (0.6 mmol) in DCE (3 mL) was stirred at −30 °C in a tube for about 1 h until complete consumption of starting materials as monitored by TLC. After the completion of the reaction and evaporation of the solvent, the mixture was purified by silica gel column chromatography (PE/EA = 8:1) to afford the desired products 3. N-(Benzofuran-2-yl)benzamide (3u). White solid, yield 75% (53.3 mg). Mp: 180−181 °C. 1H NMR (500 MHz, DMSO-d6, δ): 11.65 (s, 1H), 8.03 (d, J = 7.3 Hz, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.53 (q, J = 7.1 Hz, 3H), 7.48 (d, J = 8.6 Hz, 1H), 7.20 (td, J = 6.8, 6.0, 4.0 Hz, 2H), 8527

DOI: 10.1021/acs.joc.9b00858 J. Org. Chem. 2019, 84, 8523−8530

Article

The Journal of Organic Chemistry 6.87 (s, 1H). 13C{1H} NMR (125 MHz, DMSO-d6, δ): 164.5, 150.1, 149.6, 133.5, 132.6, 129.5, 128.9, 128.3, 123.6, 123.1, 120.5, 110.5, 90.7. HRMS (ESI-TOF, [M + Na]+): calcd for C15H11NO2Na, 260.0687; found, 260.0691. N-(Benzofuran-2-yl)-4-methylbenzamide (3v). White solid, yield 74% (55.7 mg). Mp: 193−194 °C. 1H NMR (500 MHz, DMSO-d6, δ): 11.58 (s, 1H), 7.97 (d, J = 6.4 Hz, 2H), 7.56 (d, J = 6.6 Hz, 1H), 7.50 (d, J = 8.6 Hz, 1H), 7.36 (d, J = 8.0 Hz, 2H), 7.27−7.17 (m, 2H), 6.87 (s, 1H), 2.39 (s, 3H). 13C{1H} NMR (125 MHz, DMSOd6, δ): 164.4, 150.2, 149.6, 142.8, 130.7, 129.5, 129.1, 128.4, 127.9, 123.6, 123.1, 120.5, 110.5, 90.6, 21.5. HRMS (ESI-TOF, [M + Na]+): calcd for C16H13NO2Na, 274.0844; found, 274.0847. N-(Benzofuran-2-yl)-4-fluorobenzamide (3w). White solid, yield 63% (48.2 mg). Mp: 188−189 °C. 1H NMR (500 MHz, DMSO-d6, δ): 11.70 (s, 1H), 8.16−8.11 (m, 2H), 7.60−7.55 (m, 1H), 7.53−7.48 (m, 1H), 7.43−7.37 (m, 2H), 7.26−7.19 (m, 2H), 6.88 (s, 1H). 13 C{1H} NMR (125 MHz, DMSO-d6, δ): 164.9 (d,1JC−F = 250.2 Hz), 163.4, 150.0, 149.7, 131.2, 131.1, 130.0, 129.4, 123.4 (d,2JC−F = 58.0 Hz), 120.6, 118.4 (d,1JC−F = 249.2 Hz), 116.0, 115.9, 110.5, 90.8. HRMS (ESI-TOF, [M + Na]+): calcd for C15H10NO2FNa, 278.0593; found, 278.0595. N-(Benzofuran-2-yl)-4-chlorobenzamide (3x). White solid, yield 72% (58.5 mg). Mp: 195−196 °C. 1H NMR (500 MHz, DMSO-d6, δ): 11.74 (s, 1H), 8.04 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 8.5 Hz, 2H), 7.57−7.51 (m, 1H), 7.51−7.45 (m, 1H), 7.23−7.15 (m, 2H), 6.86 (s, 1H). 13C{1H} NMR (125 MHz, DMSO-d6, δ): 163.5, 149.9, 149.7, 137.5, 132.3, 130.3, 129.8, 129.4, 129.1, 123.7, 123.2, 120.6, 110.5, 90.9. HRMS (ESI-TOF, [M + Na]+): calcd for C15H10NO2NaCl, 294.0298; found, 294.0297. N-(Benzofuran-2-yl)-4-bromobenzamide (3y). White solid, yield 65% (41.7 mg). Mp: 202−203 °C. 1H NMR (500 MHz, DMSO-d6, δ): 11.74 (s, 1H), 7.96 (d, J = 8.5 Hz, 2H), 7.73 (d, J = 8.5 Hz, 2H), 7.56−7.52 (m, 1H), 7.47 (d, J = 9.3 Hz, 1H), 7.23−7.15 (m, 2H), 6.86 (s, 1H). 13C{1H} NMR (125 MHz, DMSO-d6, δ): 163.6, 149.9, 132.6, 132.0, 130.4, 129.4, 126.5, 123.6, 123.2, 120.6, 110.5, 90.9. HRMS (ESI-TOF, [M + Na]+): calcd for C15H10NO2NaBr, 337.9793; found, 337.9790. N-(Benzofuran-2-yl)-4-(trifluoromethyl)benzamide (3z). White solid, yield 42% (38.4 mg). Mp: 192−194 °C. 1H NMR (500 MHz, DMSO-d6, δ): 11.92 (s, 1H), 8.21 (d, J = 8.1 Hz, 2H), 7.91 (d, J = 8.2 Hz, 2H), 7.59−7.53 (m, 1H), 7.51−7.46 (m, 1H), 7.24−7.18 (m, 2H), 6.89 (s, 1H). 13C{1H} NMR (125 MHz, DMSO-d6, δ): 163.4, 149.7, 137.3, 132.3 (d,2JC−F = 31.8 Hz), 129.3, 128.7, 125.9, 125.6, 123.7, 123.4, 123.2, 120.7, 118.5 (d,1JC−F = 256.1 Hz), 110.6, 91.1. HRMS (ESI-TOF, [M + H]+): calcd for C16H11NO2F3, 306.0742; found, 306.0742. General Procedure for the Synthesis of 4. The mixture of Nphenoxyamides 1 (0.3 mmol), alkynyliodonium salts 2a (0.39 mmol), TBAF (0.39 mmol), and Na2CO3 (0.6 mmol) in DCE (3 mL) was stirred at −30 °C in a tube for about 1 h until complete consumption of starting materials as monitored by TLC. After the completion of the reaction and evaporation of the solvent, the mixture was purified by silica gel column chromatography (PE/EA = 8:1) to afford the desired products 4. 2-Phenyl-3a,8b-dihydrobenzofuro[2,3-d]oxazole (4a). White solid, yield 40% (28.4 mg). Mp: 148−150 °C. 1H NMR (500 MHz, DMSO-d6, δ): 7.91 (d, J = 7.2 Hz, 2H), 7.59 (d, J = 6.6 Hz, 1H), 7.56 (d, J = 7.4 Hz, 1H), 7.48 (t, J = 7.7 Hz, 2H), 7.32 (t, J = 7.8 Hz, 1H), 6.97 (t, J = 7.4 Hz, 1H), 6.93 (d, J = 8.1 Hz, 1H), 6.76 (d, J = 6.7 Hz, 1H), 6.34 (d, J = 6.7 Hz, 1H). 13C{1H} NMR (125 MHz, DMSO-d6, δ): 166.8, 158.8, 133.1, 132.2, 129.3, 128.9, 127.6, 126.6, 123.9, 121.7, 111.0, 104.3, 83.0. HRMS (ESI-TOF, [M + H]+): calcd for C15H12NO2, 238.0868; found, 238.0874. 2-(p-Tolyl)-3a,8b-dihydrobenzofuro[2,3-d]oxazole (4b). White solid, yield 45% (33.9 mg). Mp: 157−159 °C. 1H NMR (500 MHz, DMSO-d6, δ): 7.83 (d, J = 8.1 Hz, 2H), 7.58 (d, J = 7.4 Hz, 1H), 7.35 (d, J = 8.2 Hz, 1H), 7.31 (d, J = 8.1 Hz, 2H), 6.99 (t, J = 7.5 Hz, 1H), 6.95 (d, J = 8.1 Hz, 1H), 6.77 (d, J = 6.7 Hz, 1H), 6.34 (d, J = 6.7 Hz, 1H), 2.36 (s, 3H). 13C{1H} NMR (125 MHz, DMSO-d6, δ): 166.8, 158.8, 143.3, 132.2, 129.8, 128.9, 127.6, 123.8, 121.7, 111.0,

104.4, 82.8, 21.5. HRMS (ESI-TOF, [M + H]+): calcd for C16H14NO2, 252.1025; found, 252.1031. 2-(4-Methoxyphenyl)-3a,8b-dihydrobenzofuro[2,3-d]oxazole (4c). White solid, yield 42% (33.6 mg). Mp: 161−162 °C. 1H NMR (500 MHz, DMSO-d6, δ): 7.88 (d, J = 8.8 Hz, 2H), 7.58 (d, J = 7.4 Hz, 1H), 7.34 (t, J = 7.7 Hz, 1H), 7.04 (d, J = 8.9 Hz, 2H), 6.99 (t, J = 7.4 Hz, 1H), 6.95 (d, J = 8.1 Hz, 1H), 6.75 (d, J = 6.7 Hz, 1H), 6.32 (d, J = 6.7 Hz, 1H), 3.81 (s, 3H). 13C{1H} NMR (125 MHz, DMSOd6, δ): 166.6, 163.0, 158.9, 132.1, 130.9, 127.6, 124.1, 121.6, 118.7, 114.6, 111.0, 104.5, 82.8, 55.9. HRMS (ESI-TOF, [M + H]+): calcd for C16H14NO3, 268.0974; found, 268.0975. 2-(4-(Trifluoromethyl)phenyl)-3a,8b-dihydrobenzofuro[2,3-d]oxazole (4d). White solid, yield 32% (29.3 mg). Mp: 173−175 °C. 1 H NMR (500 MHz, CDCl3, δ): 8.17 (d, J = 7.9 Hz, 2H), 7.70 (d, J = 7.9 Hz, 2H), 7.54 (d, J = 7.5 Hz, 1H), 7.35 (t, J = 7.8 Hz, 1H), 7.02 (t, J = 7.5 Hz, 1H), 6.98 (d, J = 8.4 Hz, 1H), 6.79 (d, J = 7.8 Hz, 1H), 6.22 (d, J = 6.6 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3, δ): 166.6, 158.9, 133.9 (q,2JC−F = 32.3 Hz), 132.0, 129.9, 129.4, 127.7, 126.7, 125.9, 125.3, 123.5 (d,1JC−F = 272.4 Hz), 123.4, 123.2, 122.7 , 121.5,120.6 111.3, 103.9, 83.4. HRMS (ESI-TOF, [M + H]+): calcd for C16H11NO2F3, 306.0742; found, 306.0744. 2-(4-Bromophenyl)-3a,8b-dihydrobenzofuro[2,3-d]oxazole (4e). White solid, yield 38% (35.9 mg). Mp: 182−183 °C. 1H NMR (500 MHz, DMSO-d6, δ): 7.83 (d, J = 8.5 Hz, 2H), 7.69 (d, J = 8.5 Hz, 2H), 7.55 (d, J = 7.5 Hz, 1H), 7.32 (t, J = 7.7 Hz, 1H), 6.97 (t, J = 7.4 Hz, 1H), 6.93 (d, J = 8.1 Hz, 1H), 6.75 (d, J = 6.7 Hz, 1H), 6.35 (d, J = 6.7 Hz, 1H). 13C{1H} NMR (125 MHz, DMSO-d6, δ): 166.1, 158.8, 132.4, 132.3, 130.9, 127.6, 127.0, 125.7, 123.8, 121.8, 111.1, 104.3, 83.3. HRMS (ESI-TOF, [M + H]+): calcd for C15H11NO2Br, 315.9973; found, 315.9975. 2-(4-Chlorophenyl)-3a,8b-dihydrobenzofuro[2,3-d]oxazole (4f). White solid, yield 35% (28.5 mg). Mp: 175−176 °C. 1H NMR (500 MHz, DMSO-d6, δ): 7.94 (d, J = 8.6 Hz, 2H), 7.59 (d, J = 8.7 Hz, 3H), 7.35 (t, J = 8.4 Hz, 1H), 7.00 (t, J = 7.4 Hz, 1H), 6.96 (d, J = 8.1 Hz, 1H), 6.79 (d, J = 6.7 Hz, 1H), 6.39 (d, J = 6.7 Hz, 1H). 13 C{1H} NMR (125 MHz, CDCl3, δ): 138.7, 131.9, 130.4, 128.7, 126.7, 125.0, 121.4, 111.3, 104.0, 83.2. HRMS (ESI-TOF, [M + H]+): calcd for C15H11NO2Cl, 272.0478; found, 272.0485. 2-(Thiophen-2-yl)-3a,8b-dihydrobenzofuro[2,3-d]oxazole (4g). White solid, yield 50% (36.4 mg). Mp: 162−164 °C. 1H NMR (500 MHz, CDCl3, δ): 7.75 (d, J = 3.7 Hz, 1H), 7.54 (dd, J = 12.3, 6.2 Hz, 2H), 7.34 (t, J = 7.9 Hz, 1H), 7.11 (t, J = 4.4 Hz, 1H), 7.01 (t, J = 7.4 Hz, 1H), 6.97 (d, J = 8.2 Hz, 1H), 6.74 (d, J = 6.7 Hz, 1H), 6.17 (d, J = 6.6 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3, δ): 163.6, 159.0, 132.3, 131.9, 131.7, 129.0, 127.8, 126.7, 122.8, 121.4, 111.3, 104.1, 83.4. HRMS (ESI-TOF, [M + H]+): calcd for C13H10NO2S, 244.0432; found, 244.0438. Gram-Scale Preparation of 3a. To a mixture of N-phenoxyacetamide (1a) (1.21 g, 8 mmol, 1.0 equiv) and TIPS-EBX (2a) (4.45 g, 10.4 mmol, 1.3 equiv) in DCE (60 mL) at −30 °C, TBAF (2.71 g, 10.4 mmol, 1.3 equiv) was added in one portion. The mixture was stirred at −30 °C for 3 h. After completion of the reaction, evaporation of the solvent, the mixture was purified by silica gel column chromatography (PE/EA = 3:1) to afford the desired product 3a (1.15 g, 82%).

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EXPERIMENTAL MECHANISTIC INVESTIGATION

Intermediate Trapping Test and LC−MS. The mixture of 1A (0.3 mmol, 1.0 equiv), 2a (0.36 mmol, 1.3 equiv), and TBAF (0.36 mmol, 1.3 equiv) in THF (3 mL) was stirred at −78 °C in a test tube for about 30 min. The solution of the mixture was directly analyzed by LC−MS. The result showed that intermediates 1C ([M + Na]+: 488.0335) and 1F ([M + Na]+: 240.1000) were found. Conversion Experiment. A mixture of 3u (0.2 mmol, 1.0 equiv), 2a (0.26 mmol, 1.3 equiv), TBAF (0.26 mmol, 1.3 equiv), and Na2CO3 (0.4 mmol, 2.0 equiv) in DCE (2 mL) was stirred at −30 °C in a tube for about 1 h. After the reaction was finished and monitored by TLC, 4a was not detected. A mixture of 4a (0.2 mmol, 1.0 equiv), 2a (0.26 mmol, 1.3 equiv), TBAF (0.26 mmol, 1.3 equiv), and DBU 8528

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(0.4 mmol, 2 equiv) in DCE (2 mL) was stirred at −30 °C in a tube for about 1 h. After the reaction was finished and monitored by TLC, 3u was not detected. Radical Trapping Experiment. The mixture of N-phenoxyacetamides (1a) (0.3 mmol, 1.0 equiv), alkynyliodonium salts (2a) (0.39 mmol, 1.3 equiv), TBAF (0.39 mmol, 1.3 equiv), and an radical scavenger (TEMPO or BHT) (1.2 mmol, 4.0 equiv) in DCE (3 mL) was stirred at −30 °C in a tube for about 1 h until complete consumption of starting materials as monitored by TLC. After the completion of the reaction and evaporation of the solvent, the mixture was purified by silica gel column chromatography (PE/EA = 4:1) to afford the desired products 3. Crossover Experiment. The mixture of N-(4-chlorophenoxy)acetamide (1c) (0.3 mmol, 1.0 equiv), N-phenoxypentanamide (1q) (0.3 mmol, 1.0 equiv), alkynyliodonium salts (2a) (0.78 mmol, 2.6 equiv), and TBAF (0.78 mmol, 2.6 equiv) in DCE (6 mL) was stirred at −30 °C in a tube for about 1 h until complete consumption of starting materials as monitored by TLC. After the completion of the reaction and evaporation of the solvent, the mixture was purified by silica gel column chromatography (PE/EA = 4:1) to afford the desired products 3c (81.3%) and 3q (80.6%). Carbene Trapping Test. The mixture of N-phenoxyacetamides (1a) (0.3 mmol, 1.0 equiv), alkynyliodonium salts (2a) (0.39 mmol, 1.3 equiv), 2,3-dimethyl-2-butene (4) (3.0 mmol, 10.0 equiv), and TBAF (0.39 mmol, 1.3 equiv) in THF (3 mL) was stirred at −78 °C in a tube for about 1 h. After the reaction was finished and monitored by TLC, 5 was not detected. After evaporation of the solvent, the mixture was purified by silica gel column chromatography (PE/EA = 4:1) to afford the products 3 (84%). D2O Addition Experiment. The mixture of N-phenoxyacetamide (1a) (0.3 mmol, 1.0 equiv), alkynyliodonium salts (2a) (0.39 mmol, 1.3 equiv), D2O (0.3 mmol, 1.0 equiv), and TBAF (0.39 mmol, 1.3 equiv) in THF (3 mL) was stirred at −30 °C in a tube for about 1 h until complete consumption of starting materials as monitored by TLC. After the completion of the reaction and evaporation of the solvent, the mixture was purified by silica gel column chromatography (PE/EA = 4:1) to afford the desired products 3 (89%).

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REFERENCES

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.9b00858. Experimental mechanistic studies and 1H and 13C NMR spectra of all new compounds (PDF) X-ray data for 4a (CIF) X-ray data for 3a (CIF)

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Article

AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected] (L.-B.Z.). *E-mail: [email protected] (L.-R.W.). ORCID

Ming Li: 0000-0003-4906-936X Lin-Bao Zhang: 0000-0002-8334-4188 Li-Rong Wen: 0000-0001-7976-0878 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was financially supported by the National Natural Science Foundation of China (21572110, 21801152, and 21372137). 8529

DOI: 10.1021/acs.joc.9b00858 J. Org. Chem. 2019, 84, 8523−8530

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The Journal of Organic Chemistry

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DOI: 10.1021/acs.joc.9b00858 J. Org. Chem. 2019, 84, 8523−8530