Cationic Palladium(II)-Catalyzed Reductive Cyclization of Alkynyl

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Cationic Palladium(II)-Catalyzed Reductive Cyclization of Alkynyl Cyclohexadienones Weiming Wu, tianyu chen, Junjie Chen, and Xiuling Han J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02641 • Publication Date (Web): 20 Dec 2017 Downloaded from http://pubs.acs.org on December 21, 2017

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The Journal of Organic Chemistry

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

School of Metallurgy and Chemical Engineering, Jiangxi University of Science and Technology, Ganzhou 341000, China b

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

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 offered a convenient access to cyclohexenone-annulated heterocycles under mild reaction conditions. The reaction is initiated by hydropalladation of alkyne and quenched by addition to the intramolecular conjugate alkene and this possible mechanism was preliminarily demonstrated by deuterium-labeling experiments.

Transition-metal-catalyzed cyclization reactions of enynes have emerged as useful methods for efficient synthesis of functionalized cyclic and heterocyclic compounds.1

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The Journal of Organic Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

In the past two decades, the cyclization of cyclohexadienone-containing 1,6-enynes with different nucleophiles catalyzed by transition-metals provided versatile way for the access of cyclohexenone-annulated systems in a highly selective, atom- and 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 group7 employed a palladium(0)-catalyzed reductive cyclization (developed by Trost8) of cyclohexadienone-containing 1,6-enynes 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 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 quenched by addition to the carbonyl groups. Based on these previous work, we envisioned that a reductive cyclization of 1,6-enynes catalyzed by palladium(II) complex may be realized by using ethanol as the hydrogen source. In the literature, although there are some transition-metal catalyzed examples for this kind of reductive cyclization, the hydrogen source usually comes from H2,11 hydrosilanes8,12 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 should be added in the system.14 Therefore, the use of ethanol is undoubtedly an environmentally benign and economical strategy.15 Herein, we report a mild and stereoselective reductive


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cyclization of cyclohexadienone-containing 1,6-enynes catalyzed by 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 give good results. Therefore, we focused on employing some cationic palladium complexes in the evaluation of reaction of 1a in ethanol. It was pleased to see that the cyclization can be realized to give product 2a smoothly at 40 oC when the catalysts bearing diphosphine ligand such as dppp, dppb and dppe were used (entries 1-4)16. Among which,

[(dppp)Pd(H2O)2](BF4)2

gave

the

best

yield

(76%).

In

contrast,

[(bpy)Pd(H2O)2](BF4)2 has no catalytic activity for the procedure (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 the cosolvent such as dioxane, DCE, THF and toluene did not improve the cyclization, which only gave lower yields (entries 8-11). Further investigation showed that no reaction occurred without the catalyst (entry 12). From the series of detailed screening mentioned above, the combination of 1.0 equiv of 1a and 5 mol % of [(dppp)Pd(H2O)2](BF4)2 in ethanol at room temperature overnight was determined as the optimum reaction conditions for our new procedure.



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Table 1. Screening the Reaction Conditions for the Reductive Cyclization of 1aa

a

entry

PdII catalyst

cosolvent

T (oC)

2a (%)b

1


-

40

76

2

[(dppp)Pd(H2O)2](OTf)2

-

40

54

3

[(dppb)Pd(H2O)2](BF4)2

-

40

56

4

[(dppe)Pd(H2O)2](OTf)2

-

40

18

5

[(bpy)Pd(H2O)2](BF4)2

-

40

trace

6

c


dioxane

40

nr

7


-

rt

85 (85)d

8


dioxane

rt

79

9


DCE

rt

72

10


THF

rt

68

11


toluene

rt

54

12

-

-

rt

nr

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 oC for 5 h (or room temperature overnight). bThe yield was determined by 1

HNMR analysis using 1,3,5-trimethoxybenzene as an internal standard. CWithout

ethanol.

d

The

yield

in

parentheses

was

isolated

yield,

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. To investigate the generality and the scope of this reductive cyclization, various cyclohexadienone-containing 1,6-enynes were subjected to the above-mentioned


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optimum conditions and the result was summarized in Table 2. Firstly, the substituent effect on 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, 2b and 2c). When R1 was a phenyl or substituted phenyl group, the reaction also proceeded successfully to give the desired cyclization products and 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). Then, the influence of substituent

on

the

alkyne

was

investigated.

It

was

found

that

TBS

(tert-butyldimethylsilyl), DMPS (dimethylphenylsilyl) and TES (triethylsilyl) provided the products in lower yields than TMS (trimethylsilyl), which may be due to the steric hinderance (2k, 2l and 2m). Substrate with methyl group on the alkyne produced 2n in 69% yield and the substrate bearing tertiary butyl group only gave product 2o in 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, 2r and 2s).



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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.

b

Isolated yields of chromatographically pure products.

determined.


C

nd = not

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To gain insight into the reaction mechanism, the reaction of 1a in deuterated ethanol in the standard conditions was carried out. The use of CH3CH2OD as a hydrogen source and solvent formed product d-2a with the deuterium on cyclohexenone ring in 71% yield (Scheme 1, equation 1). On the other hand, the use of CH3CD2OH afforded d-2a’ deuterated at the exocyclic double bond in 64% yield (Scheme 1, equation 2). Scheme 1. Deuterium-Labeling Experiments

On the basis of the above result and according to our previous work, a proposed catalytic cycle for this novel cationic palladium(II)-catalyzed reductive cyclization of 1,6-enyne is illustrated in Scheme 2. The active catalytic species A is initially formed from the pre-catalyst [(dppp)Pd(H2O)2](BF4)2, which then reacts with ethanol to generate Pd ethoxide complex B. -H elimination of B produces the key intermediate Pd hydride complex C. Insertion of the carbon-carbon triple bond in substrate 1a into hydrogen-palladium bond in intermediate C affords a 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 to see that the hydrogen in exocyclic double bond comes from the -H in ethanol and OH provides the hydrogen source in protonolysis step, which is different from the rhodium-catalyzed reductive cyclization of 1,6-enyne using ethanol as the hydrogen source.15 Scheme 2. A Proposed Catalytic Cycle

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 iodine atom to give product 3a in 74% yield when treatment of 2a with N-iodosuccinimide in acetonitrile. In addition, 3a can be further transferred to compound 4a via


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Sonogashira coupling. Scheme 3. Transformations of Product 2a

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 by using ethanol as the hydrogen source in palladium-catalyzed enyne cyclization. The reaction is initiated by hydropalladation of alkyne and quenched by addition to the intramolecular conjugate alkene and this possible mechanism

was

preliminarily demonstrated by

deuterium-labeling

experiments. Studies on asymmetric version of the reaction and the application of this methodology are currently underway in our laborotary.

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


13

C NMR were recorded in


deuterated chloroform (CDCl3). Coupling constants are recorded in hertz, and chemical shifts are recorded as δ values in ppm. The following abbreviations are used to describe multiplicities: s = singlet, brs = broad singlet, d = doublet, dd = double doublet, t = triplet, m = multiplet. High-resolution mass spectra were carried out 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-yl-

benzenesulfonamide17 (2.0 mmol, 1.0 equiv) were added to 40 mL of acetonitrile and the mixture was stirred at 60 oC for 15 minutes. Then substituted 3-bromoprop-1-yne (2.6 mmol, 1.3 equiv) was added 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 pressure and the residue was purified by flash chromatography (petroleum ether : ethyl acetate = 6:1 ) to give the products 1a-1o. 4-Methyl-N-(1-methyl-4-oxocyclohexa-2,5-dien-1-yl)-N-(3-(trimethylsilyl)prop-2-yn1-yl)benzenesulfonamide (1a). white solid; (232 mg; 30% yield); m.p.: 80-82 oC; 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): 2957, 1664,


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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-1yl)benzenesulfonamide (1b). yellow solid; (498 mg; 62% yield); m.p.: 50-52 oC; 1H NMR (400 MHz, CDCl3): δ 7.8 (d, J = 8.4 Hz, 2H), 7.26 (d, J = 7.6 Hz, 2H), 6.95 (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):  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-1yl)benzenesulfonamide (1c). yellow solid; (575 mg; 67% yield); m.p.: 85-88 oC; 1H NMR (400 MHz, CDCl3): δ 7.7 (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); 13

C{1H} NMR (100 MHz, CDCl3): δ 18, 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): 2953, 2866, 1672, 1632, 1600, 1150, 842; HRMS calculated for C23H32NO3SSi (M+H)+: 430.1867; Found: 430.1864. 4-Methyl-N-(4-oxo-1,4-dihydro-(1,1'-biphenyl)-1-yl)-N-(3-(trimethylsilyl)prop-2-yn-1yl)benzenesulfonamide (1d). yellow solid (674 mg; 75% yield); m.p.: 149-150 oC; 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); 13

C{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): 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); m.p.: 96-98 oC; 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):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); m.p.: 46-48 oC; 1H NMR (400 MHz, CDCl3): δ 7.7 (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): 2957, 2901, 1667, 1629, 1602, 1506, 1157, 836; HRMS calculated for C26H30NO4SSi


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(M+H)+: 480.1659; Found: 480.1656. N-(4'-Fluoro-4-oxo-1,4-dihydro-(1,1'-biphenyl)-1-yl)-4-methyl-N-(3-(trimethylsilyl)prop-2-yn-1-yl)benzenesulfonamide (1g). yellow solid; (613 mg; 66% yield); m.p.: 42-43 oC; 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), 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;

19

F NMR (376 MHz,

CDCl3): δ -111.7; IR (neat, cm-1):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-methyl-N-(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): 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); m.p.: 62-64 oC; 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):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); m.p.: 71-73 oC; 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):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-(1-methyl-4-oxocyclohexa2,5-dien-1-yl)benzenesulfonamide (1k). yellow solid; (317 mg; 37% yield); m.p.: 108-110 oC; 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); 13C{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,


Page 14 of 29

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21.7, 16.6, -4.7; IR (neat,cm-1):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); m.p.: 85-87 o

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):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-1yl)benzenesulfonamide (1m). yellow solid; (275 mg; 32% yield); m.p.: 72-73 oC; 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); 13C{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 (neat, cm-1):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-2,5-dien-1-yl)benzenesulfonamide (1n).3b white solid; (355 mg; 54% yield); m.p.: 96-98 oC; 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



Page 16 of 29

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):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); m.p.: 46-48 oC; 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);

13

C{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): 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); m.p.: 96-97 oC; 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): 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-2-yn-1-yl)benzenesul-


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fonamide (1q). white solid; (472 mg; 75% yield); m.p.: 112-114 oC; 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): 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; m.p.: 68-70 oC; 1

H 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);

13

C{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): , 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; 1

H 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): , 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. (Z)-7a-Methyl-1-tosyl-3-((trimethylsilyl)methylene)-2,3,3a,4-tetrahydro-1H-indol-5(7aH)-one (2a). white solid; (33 mg; 85% yield); m.p.: 98-100 oC; 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); 13

C{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): 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); 1H 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,


Page 18 of 29

Page 19 of 29 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


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):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-indol5(7aH)-one (2c). yellow oil; (29 mg; 68% yield); 1H NMR (400 MHz, CDCl3): δ 7.7 (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),(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);

13

C{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): 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-indol5(7aH)-one (2d). white solid; (37 mg; 82% yield); m.p.: 120-122 oC; 1H NMR (400 MHz, CDCl3): δ 7.67 (d, J = 8.4 Hz, 2H), 7.61 (dd, J = 10.4 Hz, 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): 2955, 1688, 1638, 1599, 1336, 1153, 839;HRMS calculated



Page 20 of 29

for C25H33N2O3SSi (M+NH4)+: 469.1976; Found: 469.1970. (Z)-7a-(p-Tolyl)-1-tosyl-3-((trimethylsilyl)methylene)-2,3,3a,4-tetrahydro-1H-indol5-(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): 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-tetrahydro1H-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);

13

C

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, -0.6; IR (neat, cm-1): 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):


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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;

19

F NMR (376 MHz, CDCl3): δ -113.8; IR (neat,

cm-1):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): 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,4tetrahydro-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),



Page 22 of 29

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;

19

F NMR (376 MHz, CDCl3): δ -62.6; IR

(neat, cm-1): 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-tetrahydro1H-indol-5(7aH)-one (2j). white solid; (40 mg; 80% yield); m.p.: 131-133 oC; 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);

13

C 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): 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-tosyl-2,3,3a,4-tetrahydro-1Hindol-5(7aH)-one (2k). yellow solid; (31 mg; 72% yield); m.p.: 111-113 oC; 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,


Page 23 of 29 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


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): 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-tosyl-2,3,3a,4-tetrahydro-1Hindol-5(7aH)-one (2l). white solid; (32 mg; 70% yield); m.p.: 105-106 oC; 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); 13

C{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): 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-indol5(7aH)-one (2m). white solid; (23 mg; 53% yield); m.p.: 107-109 oC; 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):2950, 2910, 2871, 1690, 1639, 1595, 1335,



Page 24 of 29

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-1H-indol-5(7aH)-one

(2n).

white solid; (23 mg; 69% yield); m.p.: 103-105 oC; 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): 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-indol5(7aH)-one (2o). yellow solid; (19 mg; 51% yield); m.p.: 106-108 oC; 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): 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

Page 25 of 29 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


experiments were similar to the reaction as 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. Compound 3a and 4a was synthesized following published procedures with appropriate modifications.10a (Z)-3-(Iodomethylene)-7a-methyl-1-tosyl-2,3,3a,4-tetrahydro-1H-indol-5(7aH)-one (3a). white solid; (33 mg; 74% yield from 0.1 mmol of 2a); m.p.: 145-148 oC; 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):  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,4-tetrahydro-1H-indol -5(7aH)-one (4a). yellow solid; (33 mg; 79% yield from 0.1 mmol of 3a); m.p.: 61-63



o

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): 3052, 2923, 2251, 1685, 1596, 1491, 1333, 1153; HRMS calculated for C25H27N2O3S (M+NH4)+: 435.1737; Found: 435.1733. ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website at DOI: Copies of 1H, 13C NMR spectra data for all compounds Copies of 19F NMR spectra data for compounds 1g, 1i, 2g and 2i X-ray crystallographic data for 2a (CIF)

AUTHOR INFORMATION Corresponding Author *E-mail: [email protected]. Notes The authors declare no competing financial interest. ACKNOWLEDGMENTS We thank the National Natural Science Foundation of China (21232006, 21642002) and Chinese Academy of Sciences for financial support.


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References (1) For the reviews on cyclizations of enynes, see: (a) Aubert, C.; Buisine, O.; Malacria, M. Chem. Rev. 2002, 102, 813. (b) Zhang, Z.; Zhu, G.; Tong, X.; Wang, F.; Xie, X.; Wang, J.; Jiang, L. Curr. Org. Chem. 2006, 10, 1457. (c) Zhang, L.; Sun, J.; Kozmin, S. A. Adv. Synth. Catal. 2006, 348, 2271. (d) Michelet, V.; Toullec, P. Y.; Genêt, J.-P. Angew. Chem. Int. Ed. 2008, 47, 4268. (e) Carlotta, R.; Stefano, P.; Davide, R.; Maurizio, F. Chem. Soc. Rev. 2016, 45, 4364. (f) Harris, R. J.; Widenhoefer, R. A. Chem. Soc. Rev. 2016, 45, 4533. (g) Xuan, J.; Studer, A. Chem. Soc. Rev. 2017, 46, 4329. (2) For the reviews, see: (a) Kalstabakken, K. A.; Harned, A. M. Tetrahedron 2014, 70, 9571. (b)

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Soc. 2014, 136, 15607. (7) He, C.; Zhu, C.; Dai, Z.; Tseng, C.-C.; Ding, H. Angew. Chem. Int. Ed. 2013, 52, 13256. (8) Trost, B. M.; Rise, F. J. Am. Chem. Soc. 1987, 109, 3161. (9) For the review, see: (a) Lu, X. Top. Catal. 2005, 35, 73. For selected work published recently, see: (b) Xia, G.; Han, X.; Lu, X. Adv. Synth. Catal. 2012, 354, 2701. (c) Xia, G.; Han, X.; Lu, X. Org. Lett. 2014, 16, 6184. (d) Xia, G.; Han, X.; Lu, X. Org. Lett. 2014, 16, 2058. (e) Zhang, J.; Han, X.; Lu, X. Synlett 2015, 26, 1744. (f) Zhang, J.; Han, X.; Lu, X. J. Org. Chem. 2016, 81, 3423. (g) Chen, J.; Han, X.; Lu, X. J. Org. Chem. 2017, 82, 1977. (10) (a) Shen, K.; Han, X.; Lu, X. Org. Lett. 2013, 15, 1732. (b) Shen, K.; Han, X.; Xia, G.; Lu, X. Org. Chem. Front. 2015, 2, 145. (c) Zhang, X.; Han, X.; Hu, Z.; Lu, X. Synthesis 2017, 49, 4687. (11) (a) Jang, H.-Y.; Krische, M. J. J. Am. Chem. Soc. 2004, 126, 7875. (b) Jang, H.-Y.; Hughes, F. W.; Gong, H. Zhang, J.; Brodbelt, J. S.; Kriche, M. J. J. Am. Chem. Soc. 2005, 127, 6174. (c) Jung, I. G.; Seo, J.; Lee, S. I.; Chung, Y. K. Organometallics 2006, 25, 4240. (d) Jang, M.-S.; Wang, X.; Jang, W.-Y.; Jang, H.-Y. Organometallics 2009, 28, 4841. (e) Sylvester, K. T.; Chirik, P. J. J. Am. Chem. Soc. 2009, 131, 8772. (f) Hoyt, J.; Sylvester, K. T.; Semproni, S. P.; Chirik, P. J. J. Am. Chem. Soc. 2013, 135, 4862. (12) (a) Trost, B. M.; Rise, F. J. Am. Chem. Soc. 1987, 109, 3161. (b) Yamada, H.; Aoyagi, S.; Kibayashi, C. Tetrahedron Lett. 1996, 37, 8787. (13) (a) Montgomery, J.; Savchenko, A. V.; J. Am. Chem. Soc. 1996, 118, 2099. (b)


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Chen, M.; Weng, Y.; Guo, M.; Zhang, H.; Lei, A. Angew. Chem. Int. Ed. 2008, 47, 2279. (c) Lin, A.; Zhang, Z.-W.; Yang, J. Org. Lett. 2014, 16, 386. (14) Chang, H. -T.; Jayanth, T. T.; Wang, C.-C.; Cheng, C.-H.; J J. Am. Chem. Soc. 2007, 129, 12032. (15) In the literature, there is only one example on enyne reductive cyclization using alcohol as the hydrogen source (catalyzed by rhodium): Park, J. H.; Kim, S. M.; Chung, Y. K. Chem. Eur. J. 2011, 17, 10852. (16) The relative stereochemistry of 2a was assigned as cis-version on the basis of X-ray diffraction (see the Supporting Information). (17) Jia, P.; Zhang, Q.; Jin, H.; Huang, Y. Org. Lett. 2017, 19, 412.


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