Cationic Palladium(II)-Catalyzed Reductive Cyclization of Alkynyl

Dec 20, 2017 - A cationic palladium(II)-catalyzed reductive cyclization of cyclohexadienone-containing 1,6-enynes by using ethanol as a hydrogen donor...
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Note Cite This: J. Org. Chem. 2018, 83, 1033−1040

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Cationic Palladium(II)-Catalyzed Reductive Cyclization of Alkynyl Cyclohexadienones Weiming Wu,† Tianyu Chen,†,‡ Junjie Chen,‡ and Xiuling Han*,‡ †

School of Metallurgy and Chemical Engineering, Jiangxi University of Science and Technology, Ganzhou 341000, China State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China

‡

S Supporting Information *

ABSTRACT: A cationic palladium(II)-catalyzed reductive cyclization of cyclohexadienone-containing 1,6-enynes by using ethanol as a hydrogen donor and solvent was successfully developed. This procedure offers convenient access to cyclohexenone-annulated heterocycles under mild reaction conditions. The reaction was initiated by hydropalladation of the alkyne and was quenched by addition of the intramolecular conjugate alkene. This possible mechanism was preliminarily demonstrated by deuterium-labeling experiments.

T

containing 1,6-enynes catalyzed by a cationic palladium complex using ethanol as the hydrogen donor and solvent. Initially, alkynyl cyclohexadienone 1a was selected as the model substrate to screen the reaction conditions (Table 1). In our previous work on reductive cyclization reactions, it was found that cationic palladium complexes can provide good results. Therefore, we focused on employing cationic palladium complexes in the evaluation of the reaction of 1a in ethanol. We were pleased to see that the cyclization can be realized to smoothly give the product 2a at 40 °C when catalyst-bearing diphosphine ligands, such as 1,3-bis(diphenylphosphino)propane (dppp), 1,4-bis(diphenylphosphino)butane (dppb), and 1,2-bis(diphenylphosphino)ethane (dppe), were used (entries 1−4).16 Among these, [(dppp)Pd(H2O)2](BF4)2 gave the best yield (76%). In contrast, [(bpy)Pd(H2O)2](BF4)2 had no catalytic activity for the procedure (bpy = bipyridine) (entry 5). When the reaction was conducted in dioxane (no ethanol), no reaction occurred, which showed that ethanol is important for the cyclization (entry 6). Lowering the temperature to room temperature increased the yield of 2a to 85% (entry 7). Addition of a cosolvent such as dioxane, DCE, THF, or toluene did not improve the cyclization and only resulted in lower yields (entries 8−11). Further investigation showed that no reaction occurred without the catalyst (entry 12). From the series of detailed screenings mentioned above, the combination of 1.0 equiv of 1a and 5 mol % [(dppp)Pd(H2O)2](BF4)2 in ethanol at room temperature overnight was determined as the optimum reaction condition for our new procedure. To investigate the generality and the scope of this reductive cyclization, various cyclohexadienone-containing 1,6-enynes were subjected to the optimum conditions

ransition-metal-catalyzed cyclization reactions of enynes have emerged as useful methods for efficient synthesis of functionalized cyclic and heterocyclic compounds.1 In the past two decades, the cyclization of cyclohexadienonecontaining 1,6-enynes with different nucleophiles catalyzed by transition metals provided a versatile way to access cyclohexenone-annulated systems in a highly selective, atomand step-economical manner.2 The nucleophiles include acetic acid,3 arylboronic acids,4 bis(pinacolato)diboron5, and N-pivaloxloxy(or methoxy)-benzamides.6 In 2013, Ding et al.7 employed a palladium(0)-catalyzed reductive cyclization (developed by Trost8) of cyclohexadienone-containing 1,6enynes for the total synthesis of indoxamycins, where Et3SiH and HOAc served as the hydrogen donors. Our group has been involved in the development of palladium(II)-catalyzed redox-neutral reactions.9 Very recently, we reported on intramolecular reductive cyclization reactions of alkyne-tethered ketones or aldehydes by using ethanol as the hydrogen source and solvent.10 These reactions are initiated by hydropalladation of alkynes and are quenched by addition of the carbonyl groups. On the basis of this previous work, we envisioned that a reductive cyclization of 1,6-enynes catalyzed by a palladium(II) complex may be realized by using ethanol as the hydrogen source. In the literature, although there are some transitionmetal-catalyzed examples for this kind of reductive cyclization, the hydrogen source usually comes from H2,11 hydrosilanes,8,12 or organozinc reagents.13 In 2007, Cheng reported a cobalt-catalyzed reductive cyclization of 1,6-enynes by using water as the hydrogen source. However, equivalents of Zn and a catalytic amount of ZnI2 must be added to the system for the reaction to proceed.14 Therefore, the use of ethanol is undoubtedly an environmentally benign and economical strategy.15 Herein, we report a mild and stereoselective reductive cyclization of cyclohexadienone© 2017 American Chemical Society

Received: October 17, 2017 Published: December 20, 2017 1033

DOI: 10.1021/acs.joc.7b02641 J. Org. Chem. 2018, 83, 1033−1040

Note

The Journal of Organic Chemistry Table 1. Screening the Reaction Conditions for the Reductive Cyclization of 1aa

entry

PdII catalyst

cosolvent

T (°C)

2a (%)b

1 2 3 4 5 6c 7 8 9 10 11 12

[(dppp)Pd(H2O)2](BF4)2 [(dppp)Pd(H2O)2](OTf)2 [(dppb)Pd(H2O)2](BF4)2 [(dppe)Pd(H2O)2](OTf)2 [(bpy)Pd(H2O)2](BF4)2 [(dppp)Pd(H2O)2](BF4)2 [(dppp)Pd(H2O)2](BF4)2 [(dppp)Pd(H2O)2](BF4)2 [(dppp)Pd(H2O)2](BF4)2 [(dppp)Pd(H2O)2](BF4)2 [(dppp)Pd(H2O)2](BF4)2 −

− − − − − dioxane − dioxane DCE THF toluene −

40 40 40 40 40 40 rt rt rt rt rt rt

76 54 56 18 trace nr 85 (85)d 79 72 68 54 nr

Scheme 1. Deuterium-Labeling Experiments

cationic palladium(II)-catalyzed reductive cyclization of 1,6enyne is illustrated in Scheme 2. The active catalytic species A is initially formed from the precatalyst [(dppp)Pd(H2O)2](BF4)2, which then reacts with ethanol to generate Pd ethoxide complex B. β-H elimination of B produces the key intermediate Pd hydride complex C. Insertion of the carbon− carbon triple bond in substrate 1a into the hydrogen− palladium bond in intermediate C affords vinylpalladium intermediate D. Addition of the carbon−palladium bond to the intramolecular conjugate alkene gives rise to intermediate E or enolate E′. Protonolysis of E or E′ by ethanol delivers product 2a and regenerates palladium(II) species to complete the catalytic cycle. From deuterium-labeling studies, it is obvious that the hydrogen in the exocyclic double bond comes from the α-H in ethanol and that OH provides the hydrogen source in the protonolysis step, which is different from the rhodium-catalyzed reductive cyclization of 1,6-enyne using ethanol as the hydrogen source.15 To demonstrate the synthetic utility of the present reaction, we transformed product 2a, as summarized in Scheme 3. The TMS group can be easily substituted by an iodine atom to give product 3a in 74% yield from treatment of 2a with N-iodosuccinimide in acetonitrile. In addition, 3a can be further transferred to compound 4a via Sonogashira coupling. In conclusion, we have developed a cationic palladium(II)catalyzed reductive cyclization of cyclohexadienone-containing 1,6-enynes to give access to fused heterocycles under mild reaction conditions by using ethanol as a hydrogen donor and solvent. This is the first example of using ethanol as the hydrogen source in palladium-catalyzed enyne cyclization. The reaction is initiated by hydropalladation of alkyne and is quenched by addition of the intramolecular conjugate alkene. This possible mechanism was preliminarily demonstrated by deuterium-labeling experiments. Studies on asymmetric versions of the reaction and the applications of this methodology are currently underway in our laboratory.

a

Reaction conditions: 1a (0.1 mmol, 1.0 equiv) and catalyst (5 mol %) were added to ethanol (1 mL)/cosolvent (0.2 mL) as shown in the table. The mixture was then stirred at 40 °C for 5 h (or at room temperature overnight). dppp = 1,3-bis(diphenylphosphino)propane, dppb = 1,4-bis(diphenylphosphino)butane, dppe = 1,2-bis(diphenylphosphino)ethane, bpy = bipyridine, rt = room temperature, nr = no reaction. bThe yield was determined by 1H NMR analysis using 1,3,5-trimethoxybenzene as an internal standard. cWithout ethanol. dThe yield in parentheses was the isolated yield.

mentioned above, and the results are summarized in Table 2. First, the substituent effect on the cyclohexadienone skeleton was examined. Substrates with alkyl groups involved (methyl, ethyl, and n-butyl (R1)) furnished the corresponding products in moderate to good yields (2a−2c). When R1 was a phenyl or substituted-phenyl group, the reaction also proceeded successfully to give the desired cyclization products. The result showed that chloro, fluoro, and trifluoromethyl groups were compatible with the procedure (2d−2i). Notably, the reaction was amenable with a naphthyl group on the cyclohexadienone skeleton (2j). Next, the influence of a substituent on the alkyne was investigated. It was found that TBS (tert-butyldimethylsilyl), DMPS (dimethylphenylsilyl), and TES (triethylsilyl) provided the products in yields lower than that of TMS (trimethylsilyl), which may be due to steric hindrance (2k−2m). A substrate with a methyl group on the alkyne produced 2n in 69% yield, and the substrate-bearing tertiary butyl group gave product 2o in only 51% yield. When a phenyl group was substituted on the alkyne, the reaction was disordered with the formation of unidentified products (2p). No reaction occurred for the substrates bearing a terminal alkyne or with oxygen and N-Boc tethered (2q−2s). To gain insight into the reaction mechanism, the reaction of 1a in deuterated ethanol under the standard conditions was carried out. The use of CH3CH2OD as a hydrogen source and solvent formed product d-2a with the deuterium on the cyclohexenone ring in 71% yield (Scheme 1, eq 1). On the other hand, the use of CH3CD2OH afforded d-2a′ deuterated at the exocyclic double bond in 64% yield (Scheme 1, eq 2). On the basis of the result mentioned above and according to our previous work, a proposed catalytic cycle for this novel

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EXPERIMENTAL SECTION

General Information. All solvents were dried and distilled using standard procedures. Unless otherwise noted, reagents were obtained from commercial sources and used without further purification. 1H NMR and 13C NMR were recorded in deuterated chloroform (CDCl3). Coupling constants are recorded in hertz, and chemical shifts are recorded as δ values in parts per million. The following abbreviations are used to describe multiplicities: s = 1034

DOI: 10.1021/acs.joc.7b02641 J. Org. Chem. 2018, 83, 1033−1040

Note

The Journal of Organic Chemistry Table 2. Substrate Scopea,b

a

Reaction conditions: 1 (0.1 mmol, 1.0 equiv) and [(dppp)Pd(H2O)2](BF4)2 (5 mol %) were added to ethanol (1.2 mL). The mixture was then stirred at room temperature overnight. dppp = 1,3-bis(diphenylphosphino)propane. bIsolated yields of chromatographically pure products. cnd = not determined. pressure, and the residue was purified by flash chromatography (petroleum ether/ethyl acetate = 6:1) to give the products 1a−1q. 4-Methyl-N-(1-methyl-4-oxocyclohexa-2,5-dien-1-yl)-N-(3(trimethylsilyl)prop-2-yn-1-yl)benzenesulfonamide (1a). white solid (232 mg, 30% yield); mp 80−82 °C; 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.04 (d, J = 10.4 Hz, 2H), 6.14 (d, J = 10.0 Hz, 2H), 4.30 (s, 2H), 2.44 (s, 3H), 1.62 (s, 3H), 0.14 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 184.6, 151.6, 144.0, 138.5, 129.6, 128.1, 127.8, 102.0, 91.1, 60.1, 37.2, 26.1, 21.7, −0.3; IR (neat, cm−1) ν 2957, 1664, 1630, 1601, 1395, 1154, 808; HRMS calculated for C20H26NO3SSi [M + H]+ 388.1397, found 388.1395. N-(1-Ethyl-4-oxocyclohexa-2,5-dien-1-yl)-4-methyl-N-(3(trimethylsilyl)prop-2-yn-1-yl)benzenesulfonamide (1b). yellow solid (498 mg, 62% yield); mp 50−52 °C; 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 8.4 Hz, 2H), 7.26 (d, J = 7.6 Hz, 2H), 6.95

singlet, brs = broad singlet, d = doublet, dd = double doublet, t = triplet, and m = multiplet. High-resolution mass spectra were recorded on a mass spectrometer with a TOF analyzer (ESI). Infrared spectra were recorded on a FT-IR spectrometer. Melting points were determined by using a local hot-stage melting point apparatus and are uncorrected. For column chromatography, silica gel of 200−300 mesh size was used. General Procedure for the Preparation of Substrates 1a− 1q. K2CO3 (4.0 mmol, 2.0 equiv) and N-oxocyclohexa-2,5-dien-1-ylbenzenesulfonamide17 (2.0 mmol, 1.0 equiv) were added to 40 mL of acetonitrile, and the mixture was stirred at 60 °C for 15 min. Then, substituted 3-bromoprop-1-yne (2.6 mmol, 1.3 equiv) was added to the mixture, and the solution was stirred until the consumption of N-oxocyclohexa-2,5-dien-1-yl-benzenesulfonamide as monitored by TLC. The solvent was evaporated under reduced 1035

DOI: 10.1021/acs.joc.7b02641 J. Org. Chem. 2018, 83, 1033−1040

Note

The Journal of Organic Chemistry Scheme 2. A Proposed Catalytic Cycle

4-Methyl-N-(4-oxo-1,4-dihydro-(1,1′-biphenyl)-1-yl)-N-(3(trimethylsilyl)prop-2-yn-1-yl)benzenesulfonamide (1d). yellow solid (674 mg, 75% yield); mp 149−150 °C; 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 8.4 Hz, 2H), 7.43−7.33 (m, 7H), 7.21 (d, J = 8.0 Hz, 2H), 6.11 (dd, J = 8.4, 1.6 Hz, 2H), 4.19 (s, 2H), 2.42 (s, 3H), 0.15 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 184.6, 147.7, 144.2, 138.0, 137.3, 129.5, 129.3, 129.2, 128.6, 127.6, 126.8, 102.1, 91.0, 65.2, 37.6, 21.7, −0.3; IR (neat, cm−1) ν 2959, 1663, 1624, 1596, 1347, 847; HRMS calculated for C25H28NO3SSi [M + H]+ 450.1554, found 450.1550. 4-Methyl-N-(4′-methyl-4-oxo-1,4-dihydro-(1,1′-biphenyl)-1-yl)N-(3-(trimethylsilyl)prop-2-yn-1-yl)benzenesulfonamide (1e). yellow solid (306 mg, 33% yield); mp 96−98 °C; 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 10.4 Hz, 2H), 7.27−7.25 (m, 2H), 7.20 (d, J = 8.0 Hz, 2H), 7.14 (d, J = 8.0 Hz, 2H), 6.08 (dd, J = 8.8, 2.0 Hz, 2H), 4.18 (s, 2H), 2.41 (s, 3H), 2.34 (s, 3H), 0.15 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 184.7, 147.9, 144.1, 139.4, 137.3, 134.9, 130.2, 129.2, 128.7, 127.4, 126.8, 102.2, 90.9, 65.0, 37.5, 21.7, 21.2, −0.3; IR (neat, cm−1) ν 2958, 2924, 2251, 2177, 1668, 1629, 1599, 1398, 1159, 843; HRMS calculated for C26H30NO3SSi [M + H]+ 464.1710, found 464.1704. N-(4′-Methoxy-4-oxo-1,4-dihydro-(1,1′-biphenyl)-1-yl)-4-methyl-N-(3-(trimethylsilyl)prop-2-yn-1-yl)benzenesulfonamide (1f). yellow solid (613 mg, 64% yield); mp 46−48 °C; 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 7.6 Hz, 2H), 7.42 (d, J = 10.0 Hz, 2H), 7.30 (d, J = 8.8 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 6.85 (d, J = 8.4 Hz, 2H), 6.10 (d, J = 10.0 Hz, 2H), 4.19 (s, 2H), 3.79 (s, 3H), 2.42 (s, 3H), 0.17 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 184.5, 160.0, 147.9, 143.9, 137.2, 129.2, 129.0, 128.5, 128.1, 127.1, 114.6, 102.1, 90.6, 64.5, 55.3, 37.3, 21.5, −0.4; IR (neat, cm−1) ν 2957, 2901, 1667, 1629, 1602, 1506, 1157, 836; HRMS calculated for C26H30NO4SSi [M + H]+ 480.1659, found 480.1656. N-(4′-Fluoro-4-oxo-1,4-dihydro-(1,1′-biphenyl)-1-yl)-4-methylN-(3-(trimethylsilyl)prop-2-yn-1-yl)benzenesulfonamide (1g). yellow solid (613 mg, 66% yield); mp 42−43 °C; 1H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 8.4 Hz, 2H), 7.40−7.34 (m, 4H), 7.21 (d, J = 8.4 Hz, 2H), 7.01 (t, J = 8.8 Hz, 2H), 6.13 (d, J = 10.0 Hz, 2H),

Scheme 3. Transformations of Product 2a

(d, J = 10.4 Hz, 2H), 6.20 (d, J = 10.0 Hz, 2H), 4.34 (s, 2H), 2.43 (s, 3H), 2.03 (q, J = 7.6 Hz, 2H), 0.75 (t, J = 7.2 Hz, 3H), 0.14 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 185.1, 149.5, 144.0, 138.6, 129.5, 128.2, 102.2, 91.1, 77.5, 76.8, 64.5, 37.0, 29.7, 21.7, 8.6, −0.3; IR (neat, cm−1) ν 2960, 2177, 1667, 1630, 1599, 1349, 1158, 1089, 841; HRMS calculated for C21H28NO3SSi [M + H]+ 402.1554, found 402.1547. N-(1-Butyl-4-oxocyclohexa-2,5-dien-1-yl)-4-methyl-N-(3(trimethylsilyl)prop-2-yn-1-yl)benzenesulfonamide (1c). yellow solid (575 mg, 67% yield); mp 85−88 °C; 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 6.91 (d, J = 10.4 Hz, 2H), 6.11 (d, J = 10.0 Hz, 2H), 4.27 (s, 2H), 2.36 (s, 3H), 1.93−1.89 (m, 2H), 1.16−1.13 (m, 2H), 1.05−0.99 (m, 2H), 0.73 (t, J = 7.2 Hz, 3H), 0.08 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 184.9, 149.7, 143.8, 138.3, 129.3, 128.9, 128.0, 102.0, 90.8, 63.7, 36.7, 36.3, 25.9, 22.5, 21.5, 13.7, −0.5; IR (neat, cm−1) ν 2953, 2866, 1672, 1632, 1600, 1150, 842; HRMS calculated for C23H32NO3SSi [M + H]+ 430.1867, found 430.1864. 1036

DOI: 10.1021/acs.joc.7b02641 J. Org. Chem. 2018, 83, 1033−1040

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The Journal of Organic Chemistry

(neat, cm−1) ν 3045, 2876, 1703, 1665, 1630, 1600, 1329, 1155, 869; HRMS calculated for C23H32NO3SSi [M + H]+ 430.1867, found 430.1870. N-(But-2-yn-1-yl)-4-methyl-N-(1-methyl-4-oxocyclohexa-2,5dien-1-yl)benzenesulfonamide (1n).3b white solid (355 mg, 54% yield); mp 96−98 °C; 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H), 7.03 (d, J = 10.0 Hz, 2H), 6.14 (d, J = 10.0 Hz, 2H), 4.23 (d, J = 2.0 Hz, 2H), 2.43 (s, 3H), 1.77 (s, 3H), 1.61 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 184.6, 151.8, 143.9, 138.4, 129.4, 127.9, 127.6, 81.8, 75.5, 59.8, 36.8, 26.2, 21.6, 3.5; IR (neat, cm−1) ν 3009, 2926, 1664, 1629, 1599, 1328, 1153, 812; HRMS calculated for C18H20NO3S [M + H]+ 330.1158, found 330.1158. N-(4,4-Dimethylpent-2-yn-1-yl)-4-methyl-N-(1-methyl-4-oxocyclohexa-2,5-dien-1-yl)benzenesulfonamide (1o). white solid (613 mg, 83% yield); mp 46−48 °C; 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 7.6 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.05 (d, J = 9.6 Hz, 2H), 6.13 (d, J = 9.6 Hz, 2H), 4.30 (s, 2H), 2.43 (s, 3H), 1.62 (s, 3H), 1.15 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 184.6, 152.0, 143.8, 138.4, 129.4, 128.0, 127.4, 127.3, 94.2, 75.0, 59.8, 36.7, 30.6, 27.4, 26.1, 21.6; IR (neat, cm−1) ν 2968, 1709, 1671, 1631, 1601, 1150, 809; HRMS calculated for C21H26NO3S [M + H]+ 372.1628, found 372.1626. 4-Methyl-N-(1-methyl-4-oxocyclohexa-2,5-dien-1-yl)-N-(3-phenylprop-2-yn-1-yl)benzenesulfonamide (1p). white solid (563 mg, 72% yield); mp 96−97 °C; 1H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.4 Hz, 2H), 7.36−7.25 (m, 7H), 7.07 (d, J = 10.0 Hz, 2H), 6.17 (d, J = 10.4 Hz, 2H), 4.52 (s, 2H), 2.40 (s, 3H), 1.66 (s, 3H); 13 C{1H} NMR (100 MHz, CDCl3) δ 184.5, 151.6, 144.0, 138.2, 131.5, 129.6, 128.8, 128.4, 127.9, 127.7, 122.0, 85.5, 85.4, 60.0, 37.2, 26.2, 21.5; IR (neat, cm−1) ν 3045, 1706, 1668, 1319, 1150, 1088; HRMS calculated for C23H22NO3S [M + H]+ 392.1315, found 392.1316. 4-Methyl-N-(1-methyl-4-oxocyclohexa-2,5-dien-1-yl)-N-(prop-2yn-1-yl)benzenesulfonamide (1q). white solid (472 mg, 75% yield); mp 112−114 °C; 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 7.05 (d, J = 10.4 Hz, 2H), 6.17 (d, J = 10.0 Hz, 2H), 4.28 (d, J = 2.4 Hz, 2H), 2.45 (s, 3H), 2.40 (s, 1H), 1.62 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 184.4, 151.3, 144.1, 138.4, 129.6, 128.0, 127.8, 80.3, 73.9, 60.1, 36.3, 25.8, 21.6; IR (neat, cm−1) ν 3311, 3222, 1714, 1670, 1312, 1149, 815; HRMS calculated for C17H18NO3S [M + H]+ 316.1002, found 316.0997. Substrates 1r3a and 1s5 Were the Known Compounds, and They Were Prepared According to the Reported Procedures. 4-(But-2-yn-1-yloxy)-4-methylcyclohexa-2,5-dienone (1r). white solid; mp 68−70 °C; 1H NMR (400 MHz, CDCl3) δ 6.84 (d, J = 10.0 Hz, 2H), 6.30 (d, J = 10.0 Hz, 2H), 3.96 (d, J = 2.4 Hz, 2H), 1.85 (t, J = 2.4 Hz, 3H), 1.48 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 185.1, 151.1, 130.4, 83.4, 75.6, 73.0, 54.4, 26.5, 3.8; IR (neat, cm−1) ν 2974, 2926, 2865, 1664, 1629, 1379, 1078, 1030, 862; HRMS calculated for C11H13O2 [M + H]+ 177.0910, found 177.0910. tert-Butyl But-2-yn-1-yl(1-methyl-4-oxocyclohexa-2,5-dien-1-yl)carbamate (1s). oil; 1H NMR (400 MHz, CDCl3) δ 7.07 (d, J = 10.0 Hz, 2H), 6.16 (d, J = 10.0 Hz, 2H), 4.17 (d, J = 2.4 Hz, 2H), 1.84 (t, J = 2.4 Hz, 3H), 1.69 (s, 3H), 1.38 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 185.4, 155.0, 154.1, 126.7, 81.8, 79.6, 76.1, 57.5, 34.4, 28.2, 26.2, 3.7; IR (neat, cm−1) ν 2978, 2923, 1692, 1665, 1627, 1364, 1157, 852; HRMS calculated for C16H22NO3 [M + H]+ 276.1594, found 276.1594. General Procedure for Cationic Palladium(II)-Catalyzed Reductive Cyclization of Alkynyl Cyclohexadienones. To an oven-dried Schlenk tube were added alkynyl cyclohexadienone 1 (0.1 mmol), [(dppp)Pd(H2O)2](BF4)2 (3.6 mg, 0.005 mmol, 5 mol %), and 1.2 mL of ethanol. The resulting mixture was stirred at room temperature overnight. Then, the solvent was evaporated under reduced pressure, and the residue was purified by flash column chromatography (petroleum ether/ethyl acetate = 4:1) to give product 2.

4.18 (s, 2H), 2.42 (s, 3H), 0.16 (s, 9H); 13C{1H}NMR (100 MHz, CDCl3) δ 184.3, 162.9 (d, J = 249.0 Hz), 147.4, 144.2, 137.3, 133.8, 129.2, 128.8 (d, J = 8.4 Hz), 128.4, 127.7, 116.4 (d, J = 22.0 Hz), 101.9, 91.0, 64.6, 37.6, 21.6, −0.4; 19F NMR (376 MHz, CDCl3) δ −111.7; IR (neat, cm−1) ν 2959, 2926, 2253, 2178, 1669, 1630, 1599, 1503, 1398, 1344, 1185, 838; HRMS calculated for C25H27FNO3SSi [M + H]+ 468.1459, found 468.1454. N-(4′-Chloro-4-oxo-1,4-dihydro-(1,1′-biphenyl)-1-yl)-4-methylN-(3-(trimethylsilyl)prop-2-yn-1-yl)benzenesulfonamide (1h). yellow oil (455 mg, 47% yield); 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 10.4 Hz, 2H), 7.31−7.27 (m, 4H), 7.21 (d, J = 8.0 Hz, 2H), 6.14 (d, J = 10.0 Hz, 2H), 4.18 (s, 2H), 2.42 (s, 3H), 0.15 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 184.3, 147.1, 144.3, 137.3, 136.7, 135.3, 129.5, 129.3, 128.5, 128.3, 128.0, 101.8, 91.2, 64.7, 37.7, 21.7, −0.3; IR (neat, cm−1) ν 2959, 2177, 1669, 1630, 1597, 1346, 1159, 839; HRMS calculated for C25H27ClNO3SSi [M + H]+ 484.1164, found 484.1158. 4-Methyl-N-(4-oxo-4′-(trifluoromethyl)-1,4-dihydro-(1,1′-biphenyl)-1-yl)-N-(3-(trimethylsilyl)prop-2-yn-1-yl)benzenesulfonamide (1i). yellow solid (538 mg, 52% yield); mp 62−64 °C; 1H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 8.0 Hz, 2H), 7.61−7.54 (m, 4H), 7.46 (d, J = 10.0 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 6.24 (d, J = 10.0 Hz, 2H), 4.24 (s, 2H), 2.46 (s, 3H), 0.19 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 184.1, 146.7, 144.3, 142.2, 137.2, 131.1 (q, J = 32.6 Hz), 129.3, 128.4, 128.3, 127.3, 126.2 (q, J = 3.8 Hz), 123.7 (q, J = 271.0 Hz), 101.5, 91.2, 64.9, 37.9, 21.6, −0.4; 19F NMR (376 MHz, CDCl3) δ −62.8; IR (neat, cm−1) ν 2960, 1671, 1613, 1324, 1160, 840; HRMS calculated for C26H30F3N2O3SSi [M + NH4]+ 535.1693, found 535.1696. 4-Methyl-N-(1-(naphthalen-2-yl)-4-oxocyclohexa-2,5-dien-1-yl)N-(3-(trimethylsilyl)prop-2-yn-1-yl)benzenesulfonamide (1j). yellow solid (709 mg, 71% yield); mp 71−73 °C; 1H NMR (400 MHz, CDCl3) δ 7.85−7.81 (m, 2H), 7.76−7.72 (m, 4H), 7.57−7.49 (m, 5H), 7.17 (d, J = 8.0 Hz, 2H), 6.17 (d, J = 9.6 Hz, 2H), 4.22 (s, 2H), 2.40 (s, 3H), 0.16 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 164.6, 147.5, 144.1, 137.2, 135.0, 133.2, 133.1, 129.4, 129.1, 128.6, 128.2, 127.7, 127.2, 126.9, 125.9, 124.1, 102.0, 90.9, 65.1, 37.6, 21.6, −0.4; IR (neat, cm−1) ν 3055, 2958, 1735, 1668, 1630, 1597, 1342, 1158, 841; HRMS calculated for C29H30NO3SSi [M + H]+ 500.1710, found 500.1705. N-(3-(tert-Butyldimethylsilyl)prop-2-yn-1-yl)-4-methyl-N-(1methyl-4-oxocyclohexa-2,5-dien-1-yl)benzenesulfonamide (1k). yellow solid (317 mg, 37% yield); mp 108−110 °C; 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.06 (d, J = 10.0 Hz, 2H), 6.14 (d, J = 10.4 Hz, 2H), 4.32 (s, 2H), 2.43 (s, 3H), 1.61 (s, 3H), 0.91 (s, 9H), 0.08 (s, 6H); 13 C{1H} NMR (100 MHz, CDCl3) δ 184.6, 151.6, 144.0, 138.6, 129.7, 128.0, 127.8, 102.8, 89.4, 60.1, 37.2, 26.1, 26.0, 21.7, 16.6, −4.7; IR (neat, cm−1) ν 2947, 2927, 2853, 1671, 1630, 1318, 1150, 862; HRMS calculated for C23H32NO3SSi [M + H]+ 430.1867, found 430.1861. N-(3-(Dimethyl(phenyl)silyl)prop-2-yn-1-yl)-4-methyl-N-(1-methyl-4-oxocyclohexa-2,5-dien-1-yl)benzenesulfonamide (1l). white solid (334 mg, 37% yield); mp 85−87 °C; 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.4 Hz, 2H), 7.52 (d, J = 7.6 Hz, 2H), 7.42− 7.36 (m, 3H), 7.15 (d, J = 7.6 Hz, 2H), 6.99 (d, J = 10.4 Hz, 2H), 6.07 (d, J = 10.0 Hz, 2H), 4.36 (s, 2H), 2.38 (s, 3H), 1.59 (s, 3H), 0.39 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 184.5, 151.6, 144.0, 138.2, 136.0, 133.6, 129.8, 129.5, 128.1, 128.0, 127.7, 103.5, 89.3, 60.0, 37.2, 26.1, 21.6, −1.3; IR (neat, cm−1) ν 3048, 2965, 1664, 1630, 1600, 1154, 811; HRMS calculated for C25H28NO3SSi [M + H]+ 450.1554, found 450.1563. 4-Methyl-N-(1-methyl-4-oxocyclohexa-2,5-dien-1-yl)-N-(3(triethylsilyl)prop-2-yn-1-yl)benzenesulfonamide (1m). yellow solid (275 mg, 32% yield); mp 72−73 °C; 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.4 Hz, 2H), 7.07 (d, J = 9.6 Hz, 2H), 6.13 (d, J = 10.0 Hz, 2H), 4.34 (s, 2H), 2.43 (s, 3H), 1.63 (s, 3H), 0.96 (t, J = 8.0 Hz, 9H), 0.57 (q, J = 8.0 Hz, 6H); 13 C{1H} NMR (100 MHz, CDCl3) δ 184.4, 151.6, 143.9, 138.4, 129.5, 127.9, 127.6, 102.9, 88.5, 60.0, 37.1, 25.9, 21.5, 7.4, 4.1; IR 1037

DOI: 10.1021/acs.joc.7b02641 J. Org. Chem. 2018, 83, 1033−1040

Note

The Journal of Organic Chemistry

−0.6; IR (neat, cm−1) ν 2955, 2920, 2851, 1690, 1648, 1606, 1511, 1332, 1152, 836, 808; HRMS calculated for C26H35N2O4SSi [M + NH4]+ 499.2081, found 499.2080. (Z)-7a-(4-Fluorophenyl)-1-tosyl-3-((trimethylsilyl)methylene)2,3,3a,4-tetrahydro-1H-indol-5(7aH)-one (2g). yellow oil (38 mg, 81% yield); 1H NMR (400 MHz, CDCl3) δ 7.50 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 10.4 Hz, 1H), 7.31−7.25 (m, 4H), 6.98 (t, J = 8.8 Hz, 2H), 6.19 (d, J = 10.4 Hz, 1H), 5.44 (d, J = 2.0 Hz, 1H), 4.28 (d, J = 14.4 Hz, 1H), 4.21 (d, J = 14.0 Hz, 1H), 3.20 (brs, 1H), 2.59 (dd, J = 17.2, 4.0 Hz, 1H), 2.44 (s, 3H), 2.31 (dd, J = 17.2, 4.8 Hz, 1H), 0.08 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 196.0, 162.5 (d, J = 246.7 Hz), 149.7, 146.8, 144.0, 137.6, 135.7 (d, J = 3.8 Hz), 130.7, 129.5, 128.5 (d, J = 8.3 Hz), 127.3, 122.2, 115.5 (d, J = 21.2 Hz), 70.3, 56.2, 52.3, 35.7, 29.8, 21.7, −0.6; 19F NMR (376 MHz, CDCl3) δ −113.8; IR (neat, cm−1) ν 2953, 2921, 2851, 1693, 1638, 1602, 1507, 1328, 1151, 839, 809; HRMS calculated for C25H32FN2O3SSi [M + NH4]+ 487.1881, found 487.1876. (Z)-7a-(4-Chlorophenyl)-1-tosyl-3-((trimethylsilyl)methylene)2,3,3a,4-tetrahydro-1H-indol-5(7aH)-one (2h). yellow oil (29 mg, 60% yield); 1H NMR (400 MHz, CDCl3) δ 7.51 (d, J = 7.2 Hz, 2H), 7.40 (d, J = 10.4 Hz, 1H), 7.27−7.26 (m, 6H), 6.19 (d, J = 10.0 Hz, 1H), 5.44 (s, 1H), 4.27 (d, J = 14.0 Hz, 1H), 4.19 (d, J = 14.4 Hz, 1H), 3.18 (brs, 1H), 2.58 (dd, J = 15.2, 3.2 Hz, 1H), 2.44 (s, 3H), 2.30 (dd, J = 17.2, 4.0 Hz, 1H), 0.08 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 196.0, 149.6, 146.5, 144.1, 138.6, 137.5, 134.3, 130.9, 129.7, 128.7, 128.1, 127.3, 122.3, 70.4, 56.1, 52.3, 35.7, 21.7, −0.6; IR (neat, cm−1) ν 2953, 2921, 2852, 1690, 1640, 1597, 1490, 1325, 1150, 866, 839, 805; HRMS calculated for C25H32ClN2O3SSi [M + NH4]+ 503.1586, found 503.1581. (Z)-1-Tosyl-7a-(4-(trifluoromethyl)phenyl)-3-((trimethylsilyl)methylene)-2,3,3a,4-tetrahydro-1H-indol-5(7aH)-one (2i). yellow oil (32 mg, 62% yield); 1H NMR (400 MHz, CDCl3) δ 7.56− 7.42 (m, 7H), 7.26 (d, J = 7.6 Hz, 2H), 6.24 (d, J = 10.0 Hz, 1H), 5.46 (s, 1H), 4.29 (d, J = 14.0 Hz, 1H), 4.23 (d, J = 14.0 Hz, 1H), 3.21 (brs, 1H), 2.60 (dd, J = 17.2, 2.8 Hz, 1H), 2.44 (s, 3H), 2.30 (dd, J = 16.8, 4.4 Hz, 1H), 0.09 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 195.7, 149.4, 145.9, 144.2, 137.3, 131.2, 130.5 (q, J = 32.2 Hz), 129.7, 127.3, 127.1, 125.5 (q, J = 3.2 Hz), 124.0 (q, J = 270.8 Hz), 122.5, 70.4, 56.1, 52.3, 35.6, 21.7, −0.7; 19F NMR (376 MHz, CDCl3) δ −62.6; IR (neat, cm−1) ν 2953, 1691, 1641, 1619, 1597, 1324, 1109, 838; HRMS calculated for C26H32F3N2O3SSi [M + NH4]+ 537.1850, found 537.1842. (Z)-7a-(Naphthalen-2-yl)-1-tosyl-3-((trimethylsilyl)methylene)2,3,3a,4-tetrahydro-1H-indol-5(7aH)-one (2j). white solid (40 mg, 80% yield); mp 131−133 °C; 1H NMR (400 MHz, CDCl3) δ 7.84−7.82 (m, 1H), 7.76−7.71 (m, 3H), 7.57−7.41 (m, 6H), 7.16 (d, J = 8.4 Hz, 2H), 6.27 (d, J = 10.4 Hz, 1H), 5.46 (s, 1H), 4.35 (dt, J = 14.4, 2.0 Hz, 1H), 4.28 (d, J = 14.0 Hz, 1H), 3.35 (brs, 1H), 2.60 (dd, J = 17.2, 4.0 Hz, 1H), 2.40 (s, 3H), 2.34 (dd, J = 16.8, 4.8 Hz, 1H), 0.10 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 196.4, 150.1, 147.1, 143.8, 137.6, 137.0, 133.1, 132.9, 130.8, 129.5, 128.5, 128.3, 127.7, 127.3, 126.7, 126.6, 126.1, 124.2, 121.9, 71.1, 55.8, 52.4, 35.7, 21.7, −0.6; IR (neat, cm−1) ν 2954, 2920, 2851, 1690, 1645, 1596, 1330, 840, 808; HRMS calculated for C29H35N2O3SSi [M + NH4]+ 519.2132, found 519.2129. (Z)-3-((tert-Butyldimethylsilyl)methylene)-7a-methyl-1-tosyl2,3,3a,4-tetrahydro-1H-indol-5(7aH)-one (2k). yellow solid (31 mg, 72% yield); mp 111−113 °C; 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 6.95 (dd, J = 10.4, 1.6 Hz, 1H), 5.83 (d, J = 10.4 Hz, 1H), 5.47 (d, J = 2.4 Hz, 1H), 4.09 (d, J = 15.2 Hz, 1H), 4.05 (d, J = 12.4 Hz, 1H), 2.91 (brs, 1H), 2.71 (dd, J = 16.8, 4.4 Hz, 1H), 2.57 (dd, J = 16.8, 5.2 Hz, 1H), 2.43 (s, 3H), 1.70 (s, 3H), 0.80 (s, 9H), 0.04 (s, 3H), 0.02 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 196.1, 151.1, 149.6, 143.8, 138.4, 129.9, 128.3, 127.1, 120.0, 65.0, 53.1, 52.5, 37.0, 23.7, 21.7, 20.4, 17.4, −4.9, −5.0; IR (neat, cm−1) ν 2951, 2927, 2854, 1687, 1639, 1598, 1334, 1157, 816; HRMS calculated for C23H37N2O3SSi [M + NH4]+ 449.2289, found 449.2280. (Z)-3-((Dimethyl(phenyl)silyl)methylene)-7a-methyl-1-tosyl2,3,3a,4-tetrahydro-1H-indol-5(7aH)-one (2l). white solid (32 mg,

(Z)-7a-Methyl-1-tosyl-3-((trimethylsilyl)methylene)-2,3,3a,4-tetrahydro-1H-indol-5(7-aH)-one (2a). white solid (33 mg, 85% yield); mp 98−100 °C; 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 10.4 Hz, 1H), 5.82 (d, J = 10.4 Hz, 1H), 5.46 (s, 1H), 4.06 (s, 2H), 2.87 (brs, 1H), 2.66 (dd, J = 16.8, 4.0 Hz, 1H), 2.54 (dd, J = 17.2, 5.6 Hz, 1H), 2.42 (s, 3H), 1.68 (s, 3H), 0.04 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 196.0, 150.1, 149.6, 143.8, 138.4, 129.9, 128.3, 127.0, 122.2, 64.9, 52.7, 52.0, 36.7, 23.8, 21.6, −0.7; IR (neat, cm−1) ν 2953, 2869, 1691, 1641, 1598, 836, 814; HRMS calculated for C20H31N2O3SSi [M + NH4]+ 407.1819, found 407.1816. (Z)-7a-Ethyl-1-tosyl-3-((trimethylsilyl)methylene)-2,3,3a,4-tetrahydro-1H-indol-5-(7aH)-one (2b). yellow oil (23 mg, 57% yield); 1 H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 7.07 (d, J = 10.4 Hz, 1H), 5.93 (d, J = 10.0 Hz, 1H), 5.48 (s, 1H), 4.01 (s, 2H), 3.07 (t, J = 5.2 Hz, 1H), 2.44 (d, J = 6.0 Hz, 2H), 2.43 (s, 3H), 2.23 (q, J = 7.2 Hz, 1H), 1.93 (q, J = 7.6 Hz, 1H), 0.98 (t, J = 7.6 Hz, 3H), 0.05 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 196.7, 150.8, 148.8, 143.9, 137.4, 129.8, 129.2, 127.3, 122.5, 68.5, 51.8, 48.8, 37.9, 29.5, 21.7, 8.9, −0.6; IR (neat, cm−1) ν 2955, 2925, 1687, 1639, 1597, 1158, 836; HRMS calculated for C21H33N2O3SSi [M + NH4]+ 421.1976, found 421.1970. (Z)-7a-Butyl-1-tosyl-3-((trimethylsilyl)methylene)-2,3,3a,4-tetrahydro-1H-indol-5(7aH)-one (2c). yellow oil (29 mg, 68% yield); 1H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H), 7.06 (d, J = 10.4 Hz, 1H), 5.90 (d, J = 10.4 Hz, 1H), 5.46 (d, J = 2.0 Hz, 1H), 4.05−3.96 (m, 2H), 3.06 (t, J = 5.6 Hz, 1H), 2.43 (d, J = 6.4 Hz, 2H), 2.42 (s, 3H), 2.15−2.12 (m, 1H), 1.89−1.85 (m, 1H), 1.35−1.25 (m, 4H), 0.88 (t, J = 6.8 Hz, 3H), 0.04 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 196.7, 150.8, 149.0, 143.9, 137.4, 129.8, 129.0, 127.2, 122.4, 68.1, 51.8, 49.3, 37.9, 36.4, 26.6, 23.0, 21.7, 14.1, −0.6; IR (neat, cm−1) ν 2955, 2866, 1688, 1639, 1598, 1158, 836; HRMS calculated for C23H37N2O3SSi [M + NH4]+ 449.2289, found 449.2288. (Z)-7a-Phenyl-1-tosyl-3-((trimethylsilyl)methylene)-2,3,3a,4-tetrahydro-1H-indol-5(7aH)-one (2d). white solid (37 mg, 82% yield); mp 120−122 °C; 1H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 8.4 Hz, 2H), 7.61 (dd, J = 10.4, 1.6 Hz, 1H), 7.49−7.47 (m, 5H), 7.41 (d, J = 8.4 Hz, 2H), 6.37 (d, J = 10.4 Hz, 1H), 5.60 (dd, J = 4.4, 2.0 Hz, 1H), 4.48 (dt, J = 14.0, 2.0 Hz, 1H), 4.39 (d, J = 14.0 Hz, 1H), 3.41 (brs, 1H), 2.74 (dd, J = 17.2, 4.0 Hz, 1H), 2.60 (s, 3H), 2.50 (dd, J = 17.2, 4.8 Hz, 1H), 0.26 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 196.4, 150.1, 147.3, 143.8, 139.9, 137.7, 130.5, 129.6, 128.5, 128.3, 127.3, 126.7, 121.9, 70.9, 56.2, 52.3, 35.8, 21.7, −0.6; IR (neat, cm−1) ν 2955, 1688, 1638, 1599, 1336, 1153, 839; HRMS calculated for C25H33N2O3SSi [M + NH4]+ 469.1976, found 469.1970. (Z)-7a-(p-Tolyl)-1-tosyl-3-((trimethylsilyl)methylene)-2,3,3a,4tetrahydro-1H-indol-5-(7aH)-one (2e). yellow oil (26 mg, 56% yield); 1H NMR (400 MHz, CDCl3) δ 7.50 (d, J = 7.2 Hz, 2H), 7.42 (d, J = 10.4 Hz, 1H), 7.26−7.18 (m, 4H), 7.09 (d, J = 7.6 Hz, 2H), 6.17 (d, J = 10.4 Hz, 1H), 5.42 (s, 1H), 4.27 (d, J = 13.6 Hz, 1H), 4.19 (d, J = 14.8 Hz, 1H), 3.22 (s, 1H), 2.56 (dd, J = 16.8, 3.2 Hz, 1H), 2.43 (s, 3H), 2.35−2.30 (m, 4H), 0.08 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 196.5, 150.2, 147.5, 143.7, 138.1, 137.7, 136.8, 130.4, 129.5, 129.2, 127.4, 126.6, 121.8, 70.8, 56.1, 52.3, 35.8, 21.7, 21.3, −0.6; IR (neat, cm−1) ν 2954, 2924, 1688, 1638, 1598, 1383, 1336, 1156, 838; HRMS calculated for C26H35N2O3SSi [M + NH4]+ 483.2132, found 483.2128. (Z)-7a-(4-Methoxyphenyl)-1-tosyl-3-((trimethylsilyl)methylene)2,3,3a,4-tetrahydro-1H-indol-5(7aH)-one (2f). yellow oil (30 mg, 62% yield); 1H NMR (400 MHz, CDCl3) δ 7.47 (d, J = 8.4 Hz, 2H), 7.43 (dd, J = 10.0, 2.0 Hz, 1H), 7.23−7.19 (m, 4H), 6.78 (d, J = 8.8 Hz, 2H), 6.16 (d, J = 10.4 Hz, 1H), 5.43 (d, J = 2 Hz, 1H), 4.28 (d, J = 14.4 Hz, 1H), 4.20 (d, J = 14.0 Hz, 1H), 3.81 (s, 3H), 3.22 (brs, 1H), 2.56 (dd, J = 16.8, 3.6 Hz, 1H), 2.42 (s, 3H), 2.31 (dd, J = 16.8, 4.4 Hz, 1H), 0.08 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 194.4, 159.4, 150.1, 147.6, 143.6, 137.9, 131.3, 130.3, 129.5, 128.1, 127.3, 121.8, 113.8, 70.4, 55.9, 55.4, 52.3, 35.8, 21.7, 1038

DOI: 10.1021/acs.joc.7b02641 J. Org. Chem. 2018, 83, 1033−1040

Note

The Journal of Organic Chemistry 70% yield); mp 105−106 °C; 1H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 8.4 Hz, 2H), 7.43−7.25 (m, 7H), 6.88 (d, J = 10.0, 1.2 Hz, 1H), 5.84 (d, J = 10.4 Hz, 1H), 5.62 (d, J = 2.4 Hz, 1H), 3.82 (d, J = 16.4 Hz, 1H), 3.78 (d, J = 14.8 Hz, 1H), 2.91 (brs, 1H), 2.71 (dd, J = 17.2, 4.4 Hz, 1H), 2.69 (dd, J = 16.8, 5.2 Hz, 1H), 2.43 (s, 3H), 1.69 (s, 3H), 0.33 (d, J = 2.8 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 196.0, 152.2, 149.5, 143.7, 138.1, 137.8, 133.8, 129.8, 129.4, 128.4, 128.1, 127.1, 120.3, 65.0, 52.9, 52.2, 36.8, 23.8, 21.7, −1.8, −1.9; IR (neat, cm−1) ν 2957, 1685, 1636, 1597, 1333, 1156, 814; HRMS calculated for C25H33N2O3SSi [M + NH4]+ 469.1976, found 469.1969. (Z)-7a-Methyl-1-tosyl-3-((triethylsilyl)methylene)-2,3,3a,4-tetrahydro-1H-indol-5(7aH)-one (2m). white solid (23 mg, 53% yield); mp 107−109 °C; 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 6.96 (dd, J = 10.0, 1.2 Hz, 1H), 5.83 (d, J = 10.4 Hz, 1H), 5.43 (s, 1H), 4.07 (s, 2H), 2.93 (s, 1H), 2.71 (dd, J = 16.8, 4.4 Hz, 1H), 2.57 (dd, J = 16.8, 5.2 Hz, 1H), 2.44 (s, 3H), 1.70 (s, 3H), 0.86 (t, J = 8.0 Hz, 9H), 0.56 (q, J = 8.0 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 196.1, 151.3, 149.6, 143.8, 138.5, 129.9, 128.3, 127.1, 119.4, 65.0, 52.9, 52.4, 36.9, 23.8, 21.7, 7.5, 3.9; IR (neat, cm−1) ν 2950, 2910, 2871, 1690, 1639, 1595, 1335, 1157, 1008; HRMS calculated for C23H37N2O3SSi [M + NH4]+ 449.2289, found 449.2288. (Z)-3-Ethylidene-7a-methyl-1-tosyl-2,3,3a,4-tetrahydro-1Hindol-5(7aH)-one (2n). white solid (23 mg, 69% yield); mp 103− 105 °C; 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H), 6.96 (d, J = 10.4 Hz, 1H), 5.84 (d, J = 10.4 Hz, 1H), 5.39−5.33 (m, 1H), 4.06 (d, J = 16.4 Hz, 1H), 4.01 (d, J = 16.4 Hz, 1H), 2.88 (brs, 1H), 2.61 (dd, J = 16.8, 4.4 Hz, 1H), 2.53 (dd, J = 17.2, 5.2 Hz, 1H), 2.43 (s, 3H), 1.67 (s, 3H), 1.56 (dd, J = 6.8, 1.2 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 196.5, 149.7, 143.7, 138.6, 134.4, 129.9, 128.3, 127.1, 118.3, 65.5, 50.3, 50.2, 37.2, 23.6, 21.7, 14.4; IR (neat, cm−1) ν 2920, 2852, 1683, 1597, 1494, 1330, 1153, 815; HRMS calculated for C18H25N2O3S [M + NH4]+ 349.1580, found 349.1573. (Z)-3-(2,2-Dimethylpropylidene)-7a-methyl-1-tosyl-2,3,3a,4-tetrahydro-1H-indol-5(7aH)-one (2o). yellow solid (19 mg, 51% yield); mp 106−108 °C; 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 6.97 (dd, J = 10.4, 0.8 Hz, 1H), 5.86 (d, J = 10.4 Hz, 1H), 5.25 (s, 1H), 4.20 (d, J = 1.6 Hz, 2H), 2.84 (brs, 1H), 2.59−2.43 (m, 2H), 2.43 (s, 3H), 1.65 (s, 3H), 1.02 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 196.6, 149.5, 143.7, 138.4, 134.7, 130.2, 129.9, 128.5, 127.0, 64.0, 52.1, 49.6, 38.0, 33.3, 30.2, 23.8, 21.7; IR (neat, cm−1) ν 2960, 2867, 1685, 1598, 1494, 1330, 1155, 814; HRMS calculated for C21H31N2O3S [M + NH4]+ 391.2050, found 391.2041. Deuterium-Labeling Experiments. The procedures for deuterium-labeling experiments were similar to those for the reaction shown in Table 2 by using CH3CH2OD and CH3CD2OH as the solvents. d-2a: 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 6.97 (dt, J = 10.0, 1.6 Hz, 1H), 5.84 (dd, J = 10.0, 0.8 Hz, 1H), 5.47 (t, J = 2.0 Hz, 1H), 4.07 (s, 2H), 2.89 (brs, 1H), 2.65 (d, J = 4.0 Hz, 0.58H), 2.54 (d, J = 4.8 Hz, 0.54H), 2.44 (s, 3H), 1.70 (s, 3H), 0.06 (s, 9H). d-2a′: 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 6.97 (dd, J = 10.4, 0.8 Hz, 1H), 5.84 (d, J = 10.4 Hz, 1H), 5.47 (t, J = 2.4 Hz, 0.03H), 4.08 (s, 2H), 2.89 (brs, 1H), 2.68 (dd, J = 17.2, 4.4 Hz, 1H), 2.56 (dd, J = 16.8, 5.2 Hz, 1H), 2.44 (s, 3H), 1.70 (s, 3H), 0.06 (s, 9H). Transformation of Product 2a to Compounds 3a and 4a. Compounds 3a and 4a were synthesized following published procedures with appropriate modifications.10a (Z)-3-(Iodomethylene)-7a-methyl-1-tosyl-2,3,3a,4-tetrahydro1H-indol-5(7aH)-one (3a). white solid (33 mg, 74% yield from 0.1 mmol of 2a); mp 145−148 °C; 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.0 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 6.96 (d, J = 10.0 Hz, 1H), 6.15 (q, J = 2.4 Hz, 1H), 5.90 (d, J = 10.0 Hz, 1H), 4.03− 3.92 (m, 2H), 2.93 (brs, 1H), 2.66−2.54 (m, 2H), 2.43 (s, 3H), 1.68 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 195.1, 149.2,

146.8, 144.1, 138.1, 130.0, 128.7, 127.1, 72.6, 66.5, 57.0, 52.3, 36.8, 23.8, 21.7; IR (neat, cm−1) ν 3571, 3119, 3056, 2921, 2852, 1597, 1493, 1315, 1149, 1093, 839; HRMS calculated for C17H22IN2O3S [M + NH4]+ 461.0390, found 461.0384. (Z)-7a-Methyl-3-(3-phenylprop-2-yn-1-ylidene)-1-tosyl-2,3,3a,4tetrahydro-1H-indol-5(7aH)-one (4a). yellow solid (33 mg, 79% yield from 0.1 mmol of 3a); mp 61−63 °C; 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.0 Hz, 2H), 7.42−7.40 (m, 2H), 7.34−7.31 (m, 5H), 6.99 (dd, J = 10.4, 0.8 Hz, 1H), 5.91 (d, J = 10.4 Hz, 1H), 5.64 (q, J = 2.4 Hz, 1H), 4.34 (t, J = 2.0 Hz, 2H), 3.07 (d, J = 1.6 Hz, 1H), 2.64 (d, J = 5.2 Hz, 2H), 2.44 (s, 3H), 1.72 (s, 3H); 13 C{1H} NMR (100 MHz, CDCl3) δ 195.4, 149.4, 148.3, 144.0, 138.4, 131.6, 130.0, 128.7, 128.6, 128.5, 127.1, 122.9, 103.9, 96.4, 84.7, 65.8, 52.1, 50.7, 36.9, 23.7, 21.7; IR (neat, cm−1) ν 3052, 2923, 2251, 1685, 1596, 1491, 1333, 1153; HRMS calculated for C25H27N2O3S [M + NH4]+ 435.1737, found 435.1733.

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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.7b02641.

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Copies of 1H and 13C NMR spectra for all compounds and copies of 19F NMR spectra for compounds 1g, 1i, 2g, and 2i (PDF) X-ray crystallographic data for 2a (CIF)

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Xiuling Han: 0000-0001-5946-0296 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank the National Natural Science Foundation of China (21232006, 21642002) and the Chinese Academy of Sciences for financial support.

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REFERENCES

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