Visible-light-driven Chlorotrifluoromethylative and ... - ACS Publications

Subscriber access provided by University of Rochester | River Campus & Miner Libraries

Note

Visible-light-driven Chlorotrifluoromethylative and Chlorotrichloromethylative Cyclizations of Enynes Hong Hou, Daliang Tang, Hengxue Li, Yue Xu, Chao-Guo Yan, Yao-Cheng Shi, Xiao-Yun Chen, and SHAOQUN ZHU J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00842 • Publication Date (Web): 16 May 2019 Downloaded from http://pubs.acs.org on May 16, 2019

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 11 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

The Journal of Organic Chemistry

Visible-light-driven Chlorotrifluoromethylative Chlorotrichloromethylative Cyclizations of Enynes

and

Hong Hou†,*, Daliang Tang†, Hengxue Li†, Yue Xu†, Chaoguo Yan†, Yaocheng Shi†, Xiaoyun Chen‡,*, and Shaoqun Zhu†,* †School

of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou, China

‡School

of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang, China

Supporting Information Placeholder R1

R1 R

+

CF3/Cl3SO2Cl

R

Cl

V isible light

CF3/Cl3

X

X

X = NSO2R, C(CO2Me)

53-89% yield

ABSTRACT: Described herein is a visible-light-driven chlorotrifluoromethylative and chlorotrichloromethylative cyclization reaction to synthesize chlorotrifluoromethylated and chlorotrichloromethylated cyclic compounds. Visible-light photochemistry was utilized to generate trifluoromethyl and trichloromethyl radicals and trigger radical addition/cyclization/chlorination sequences. The use of terminal alkene-derived enynes enables the regioselective and stereoselective synthesis of chlorotrifluoromethylated and chlorotrichloromethylated pyrrolidines, piperidines and cyclopentanes.

The radical addition and cyclization of substrates containing multiple unsaturated bonds represents a powerful and efficient synthetic strategy for the synthesis of complex organic compounds.[1-3] Various radical precursors have been reported for radical generation to trigger the cascade reactions that result in cyclic structures. [3,4] However, most of the reactions reported in the literature were ineffective, and only one atom or group was inserted into the final products. [4] Visible light photochemistry offers the unique ability of single electron transfer radical generation, which enables a redoxneutral radical addition and cyclization reaction without excess oxidant or reductant, leading to highly efficient and atomeconomical organic synthesis.[5] One example of this technique is the atom transfer radical cyclization (ATRC) reaction, which could provide final products with added chemical groups, with more than three new chemical bonds formed in one reaction step. [6,7] Due to the high efficiency and atom economy of the visiblelight-promoted ATRC reaction, this reaction has attracted our attention. Recently, we reported a visible-light-mediated chlorosulfonylative cyclization reaction of enynes, in which regioselective sulfonyl radical addition to the C≡C π bond of the enyne yielded a choro-alkyl-substituted cyclic alkenyl sulfone product.[8] To continue our research on heterocyclic compound synthesis, we report herein new visible-light-driven

chlorotrifluoromethylative and chlorotrichloromethylative cyclization reactions to generate various chlorotrifluoromethylated and chlorotrichloromethylated pyrrolidines, piperidines and cyclopentane using the readily accessible enynes, CF3SO2Cl and CCl3SO2Cl. Compared with perviously reported electrocatalytic chlorotrifluoromethylative cyclization reaction, both Acr+-Mes (9-Mesityl-10-methylacridinium perchlorate) and Ir(dtbbpy)(ppy)2PF6 could be used as the catalyst, which indicated that the transition metal was not essential for the present reaction system (Scheme 1).[9,10] Previous work: Electrocatalytic enyne chlorotrifluoromethylative cyclization (ref 9)

R2 TsN R1

Mn(OTf)2 (10 mol%) MgCl2 (3.0 equiv) NaSO2CF3 (2.0 equiv)

R2 R1

Cl

CF3

LiClO4 (0.2 M), HOAc/MeCN (1:10) C(+)/Pt(-), constant current

N Ts

This work: chlorotrifluoromethylative and chlorotrichloromethylative cyclization by visible light R1 X R

CF3/Cl3SO2Cl Acr+-Mes or Ir(dtbbpy(ppy)2PF6 Visible light

R1 Cl

R CF3/Cl3

X X = NSO2R2, C(CO2Me)

SCHEME 1. Electrocatalytic Enyne Chlorotrifluoromethylative Cyclizations and Visible-light-driven

ACS Paragon Plus Environment

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

Chlorotrifluoromethylative and Chlorotrichloromethylative Cyclizations of Enynes. Table 1: Reaction condition screening chlorotrifluoromethylative cyclizationsa

for

the

Ph Cl

Ph Ts N

+

CF3SO2Cl

Me 1a

Me

Catalyst

CF3

K2HPO4 (5.0 equiv.) Solvent (2.0 mL) 23 W fluorescent bulb

N Ts 3a

2

Loading

Solvent

Yield (%)b

1.0

MeCN

61

Ir(bpy)(ppy)2PF6

1.0

MeCN

65

3

Ru(bpy)3Cl2

1.0

MeCN

70

4

Acr+-Mes.ClO4

5.0

MeCN

80

5

Acr+-Mes.ClO4

5.0

DCM

88

6

Acr+-Mes.ClO4

5.0

DCE

78

7

Acr+-Mes.ClO4

5.0

Acetone

70

8

Acr+-Mes.ClO4

5.0

EtOAc

68

9c

Acr+-Mes.ClO4

5.0

DCM

18

10

-

-

DCM

trace

Entry

Catalyst

1

Ir(dtbbpy)(ppy)2PF6

2

(mol%)

aReactions were carried out with 0.4 mmol of 1a, 0.8 mmol of 2a, 2.0 mmol of K2HPO4, 1.0 mol% or 5.0 mmol% of catalyst, and 2.0 mL of solvent under an argon atmosphere. bYield of the isolated product. cThe reaction was performed in the dark. Acr+Mes.ClO4: 9-Mesityl-10-methylacridinium perchlorate

4-Methyl-N-(2-methylallyl)-N-(3-phenylprop-2-yn-1yl)benzenesulfonamide (1a, 0.40 mmol, 1.0 equiv.) and CF3SO2Cl (2, 0.8 mmol, 2.0 equiv.) were reacted in MeCN as the solvent. Under irradiation with a 23 W fluorescent bulb, different catalysts, including Ir(dtbbpy)(ppy)2PF6, Ir(bpy)(ppy)2PF6 and Ru(bpy)3Cl2 were tested, and all gave the desired product (Z)-4-(chloro(phenyl)methylene)-3-methyl-1tosyl-3-(2,2,2-trifluoroethyl)pyrrolidine 3a in moderate to good yield (61-70%). When the organic dye Acr+-Mes.ClO4 (9Mesityl-10-methylacridinium perchlorate) was used as catalyst (5.0 mol% catalyst loading), 3a was isolated in 88% yield. Different solvents were tested next, and acetone gave 3a in 70% isolated yield. When EtOAc was used, 3a was obtained in 68% yield. The background reactions were carefully investigated, and the reactions without a catalyst yielded trace amounts of 3a. When the reaction was performed in the dark, 3a was isolated in 18% yield (Table 1, entries 9-10). Notably, the E isomer of 3a were not observed in any of the reactions tested during the reaction condition screening process. Under the best reaction conditions established above, the enyne substrate scope was further investigated. First, different enynes with different electronic and steric aryl groups on the alkyne were introduced to react with CF3SO2Cl, and all proved to be compatible, giving the corresponding products 3a-3f in

Page 2 of 11

good yield (73-88%, entries 1-6 in Table 2). Electron-donating groups, such as MeO- and Me- at different positions were tested, and all gave the products 3b, 3c and 3d in good yield. 4-MethylN-(2-methylallyl)-N-(3-(o-tolyl)prop-2-yn-1yl)benzenesulfonamide 1d and 4-methyl-N-(2-methylallyl)-N(3-(naphthalen-1-yl)prop-2-yn-1-yl)benzenesulfonamide 1h also gave the desired products 3d and 3h in 83% and 77% isolated yield respectively, The highly steric nature of the substrate also led to the product formation (entries 4 and 8, Table 2). Electron-withdrawing groups, such as Cl- and CO2Me-, were compatible as well, and the corresponding products 3e and 3f were obtained in 76% and 82% yield, respectively. Heterocyclic aromatic groups were also suitable, and 2-thienyland 3-pyridinyl-containing enynes gave their corresponding products 3g and 3i in 63% and 78% yields respectively (entries 7 and 9, Table 2). Table 2: Scope of enynes for the chlorotrifluoromethylative cyclizationa R1 X

+

Acr+-Mes ClO4 (5.0 mol%)

CF3SO2Cl

R1 Cl

R

CF3 X

2

1a-1n

R

K2HPO4 (5.0 equiv.) DCM (2.0 mL) 23 W fluorescent bulb

3a-3n

Entry

R1

R

X

3

Yield [%]b

1

C6H5

Me

NTs

3a

88

2

4-MeOC6H4

Me

NTs

3b

78

3

3-MeOC6H4

Me

NTs

3c

73

4

2-MeC6H4

Me

NTs

3d

83

5

4-ClC6H4

Me

NTs

3e

76

6

4-CO2MeC6H4

Me

NTs

3f

82

7

2-Thienyl

Me

NTs

3g

63

8

1-Naphthyl

Me

NTs

3h

77

9

3-Pyridinyl

Me

NTs

3i

78

10

C6H5

H

NTs

3j

58

11

C6H5

CO2Me

NTs

3k

67

12

Me

Me

NTs

3l

64

13

C6H5

Me

C(CO2Me)2

3m

67

14

C6H5

Me

O

3n

0

aReactions

were carried out with 0.4 mmol of 1, 0.8 mmol of 2a, 2.0 mmol of K2HPO4, and 0.02 mmol of Acr+-Mes.ClO4 in dichloromethane (DCM) (2.0 mL) under an argon atmosphere. bYield of the isolated product. N-Allyl-4-methylbenzenesulfonamide derived enyne 1j was next subjected to the above reaction conditions, and the radical transformation successfully gave the desired product 3j in 58% yield (entry 10, Table 2). Compared to the reaction of 1a with 2, the reaction of 1j formed 3j in lower yield, which could be explained by the lower stability of the secondary carbon radical intermediate generated from 1j than of the tertiary carbon


Page 3 of 11 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


radical intermediate generated from 1a before the 5-exo cyclization step. Replacement of the methyl group with an ester was also possible, and the ester-containing pyrrolidine 3k was formed in 67% yield. When the N-(but-2-yn-1-yl)-4methylbenzenesulfonamide-derived substrate 1l was subjected to the above mentioned reaction conditions, (Z)-4(1-chloroethylidene)-3-methyl-1-tosyl-3-(2,2,2trifluoroethyl)pyrrolidine 3l was obtained in 64% yield. Some byproduct or isomer was observed by thin-layer chromatography (TLC), but we failed to isolate any other isomer or byproduct via column chromatography. The all-carbon cyclic compound (E)-dimethyl 4(chloro(phenyl)methylene)-3-methyl-3-(2,2,2trifluoroethyl)cyclopentane-1,1-dicarboxylate 3m was obtained in 67% yield. The propargyl alcohol-derived 1,6enyne was decomposed under the reaction conditions, the desired chlorotrifluoromethylated tetrahydrofuran product 3n was failed to obtained (entry 14, Table 2).

Table 3: Scope of the sulfonylamide protected group for the chlorotrifluoromethylative cyclizationa

O O S N R2

Ph +

CF3SO2Cl

R


Table 4: Scope of enynes for the chlorotrichloromethylative cyclizationa Ar Me

+

N O S O R2 3o-3t

Entry

R2

R

3

Yield [%]b

1

C6H5

Me

3o

61

2

4-PhC6H4

Me

3p

73

3

2-Naphthyl

Me

3q

88

4

Benzyl

Me

3r

85

5

nBu

Me

3s

71

6

4-PhC6H4

H

3t

53

4

1

R CF3


CCl3SO2Cl

X

Ph Cl

2

1o-1t

To further expand the substrate scope, N-(3-phenylprop-2-yn1-yl)-N-tosylmethacrylamide 1u was subjected to the specified reaction conditions, the desired products 5g were obtained in 81% yield. (Scheme 2) The internal alkene derived enynes were suitable, affording the chlorotrifluoromethylated piperidines. However, two different products resulting from the different radical addition steps were formed and isolated when 6 was introduced to the reaction. The major component, 7’, was isolated in 48% yield, upon addition of the trifluoromethane carbon radical to the C=C π bond (site b, Scheme 2), and the minor product, 7, obtained in 40% yield, was generated from the addition of the trifluoromethane carbon radical addition to the C≡C π bond (site a, Scheme 2). Both 7 and 7’ were fully characterized, and the structure was defined by single-crystal X-ray single diffraction (see Supporting Information (SI) for details).[11]

were carried out with 0.4 mmol of 1, 0.8 mmol of 2a, 2.0 mmol of K2HPO4, and 0.02 mmol of Acr+-Mes.ClO4 in dichloromethane (DCM) (2.0 mL) under an argon atmosphere. bYield of the isolated product.

Ir(dtbbpy(ppy)2PF6 (1.0 mol%)

Ar Cl


Me CCl3 X 5a-5f

Entry

Ar

X

5

Yield [%]b

1

4-MeOC6H4

NTs

5a

89

2

2-Thienyl

NTs

5b

56

3

4-ClC6H4

NTs

5c

78

4

4-CO2Me C6H4

NTs

5d

70

5

Me

NTs

5e

79

6

C6H5

C(CO2Me)2

5f

82

aReactions

were carried out with 0.4 mmol of 1, 0.8 mmol of 4, 2.0 mmol of K2HPO4, and 0.02 mmol of Ir(dtbbpy)(ppy)2PF6 in dichloromethane (DCM) (2.0 mL) under an argon atmosphere. bYield of the isolated product.

aReactions

The protective group was investigated next, and different sulfonylamide groups were tested and proved to be suitable for this cyclization reaction. Both aromatic and aliphatic sulfonylamide groups were introduced to the reaction, and successfully generated the corresponding products 3o-3t in good yields (53-88%, Table 3). The relative configuration was confirmed to be Z by single-crystal x-ray diffraction of 3p.[11] Chlorotrichloromethylative cyclizations also attracted our attention, and we next investigated trichloromethanesulfonyl chloride 4. To our great delight, the reaction without the optimized condition afforded the desired chlorotrichloromethylated pyrrolidine products 5a-5f in good isolated yields and 1.0 mol% of Ir(dtbbpy)(ppy)2PF6 was used as the catalyst (56-89%, Table 4).

Ph Ts N

+

CCl3SO2Cl

Me

O

1u 0.4 mmol Ph b

4 0.8 mmol

a

Ph

N Ts 6

2

Cl

As above

F3C N Ts 7, 40%

Cl

Me Me

Me CCl3


Me Me + CF SO Cl 3 2

Ph

Ir(dtbbpy(ppy)2PF6 (1.0 mol%)

N O Ts 5g 81% yield Me Me Ph +

F3C

Cl N Ts 7', 48%

SCHEME 2. Reaction of N-(3-phenylprop-2-yn-1-yl)-Ntosylmethacrylamide, internal alkene derived 1,6-enynes with sulfonyl chloride. The reaction of 4.0 mmol 1u with 8.0 mmol of 2 at a concentration of 0.2 M was tested next and 1.39 g of (Z)-4(chloro(phenyl)methylene)-3-methyl-1-tosyl-3-(2,2,2-



trifluoroethyl)pyrrolidin-2-one 3u was isolated. (76% yield, Scheme 3)

Ts N O

+

CF3SO2Cl

Cl

2 8.0 mmol

Me

CF3 N O Ts 3u 1.39 g, 76% yield


Me

1u 1.41 g, 4.0 mmol

Ph


Ph

SCHEME 3. Large scale reaction. Based on literature reports and our previous report on the radical cyclization reaction using sulfonyl chloride, a possible mechanism for this chlorotrifluoromethylative cyclization reaction is presented in Scheme 4. The generation of CF3 radical 9 from CF3SO2Cl 2 is a well-established process, and the single electron transfer process between the photoexcited catalyst species and the sulfonyl chloride leads to the formation of sulfonyl radicals and chlorine anions. Fragmentation of the trifluoromethyl sulfonyl radical leads to CF3 radical 9 formation.[12] Addition of the CF3 radical to the C=C π bond of enyne 1a gives tertiary carbon radical intermediate 10, and subsequent intramolecular 5-exo radical cyclization results in vinyl radical 11 formation. The direct chlorine atom transfer reaction between the vinyl carbon radical 11 and CF3SO2Cl 2 affords the desired chlorotrifluoromethylated pyrrolidine product 3a, and results in sulfonyl radical 8 regeneration.[13] The sulfonyl radical would returns to the reaction cycle. In all cases, 6-endo-radical cyclization products were not observed, and the above reactions gave only Z-products. Ph

1a SO2

CF3SO2Cl 2

O O Photocatalyst Visible light F3C S 8 Ph Cl

Me

CF3SO2Cl 2 CF3

N

Ts

Me

CF3 9

CF3

N 10

Ts

Ph

5-exo cyclization

Me CF3

N

Ts

11

3a

SCHEME 4. Possible mechanisms. In conclusion, we have described a visible-light-driven chlorotrifluoromethylative and chlorotrichloromethylative cyclization approach. And a series of chlorotrifluoromethylated and chlorotrichloromethylated pyrrolidines, piperidines and cyclopentane in moderate to goods. Further application of this ATRC reaction is still underway in our laboratory.

EXPERIMENTAL SECTION General Methods. All experiments were conducted under an argon atmosphere. DCM, DCE, EtOAc, and acetonitrile were dried and distilled by the standard methods. Other commercially available reagents were purchased and used

Page 4 of 11

without further purification, unless otherwise stated. Flash chromatographic separations were carried out on 200−300 mesh silica gel. Reactions were monitored by TLC analysis of reaction aliquots. Melting points were measured on a Yanaco Micro Melting Point Apparatus. 1H NMR, 13C NMR and 19F NMR were recorded on a Variance VNMR 400 or Bruker AV-600 spectrometer. Chemical shifts (δ) are reported in ppm, and coupling constants (J) are in hertz (Hz). The following abbreviations were used to explain the multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, dd = doublet of doublets, m = multiplet, br = broad. IR spectra were recorded on a Perkin Elmer Spectrum 100 FTIR (KBr disc) and are reported in terms of frequency of absorption (cm-1). High resolution mass spectra (HRMS) were obtained on AB 5800 MALDI-TOF/TOF and are recorded using electrospray ionization (ESI). X-ray crystallographic data were collected using SMART APEX II X-ray diffractometer. For the light source in detail and the material of the irradiation vessel, see the Supporting Information. Compounds 1a-1n and 1u were prepared according to the previous reported procedures.[9] Citations to the references containing characterization data for these compounds: 1b,[9] 1c,[4e] 1d,[9] 1e,[9] 1f,[4g] 1g,[4h] 1h,[4g] 1i,[4e] 1j,[9] 1k,[14] 1l,[9] 1m,[15] 1n,[9], 1u[9]. 1o and 6 were prepared according to the previous reported procedures and the characterization data are consistent with the previous reports.[16,17] General procedure for the preparation of 1p-1t. A mixture of 3-phenylprop-2-yn-1-amine (11 mmol, 1.1 eq) in DCM (20 mL) was sequentially added RSO2Cl (10 mmol, 1.0 eq) and triethylamine (25 mmol, 2.5 eq). The reaction mixture was stirred overnight at room temperature. The resulting mixture was then extracted with DCM (2×20 mL), washed with a saturated aqueous solution of brine, dried over Na2SO4, and evaporated under reduced pressure gave the corresponding crude alkynyl sulfonamides. Then acetone (25 mL) was added as solvent, K2CO3 (15 mmol) and allyl bromide (15 mmol) were added. The reaction mixture was stirred at room temperature for 24 h. The resulting mixture was extracted with ethyl ether (2×20 mL), washed with saturated aqueous solution of brine, dried over Na2SO4, and evaporated under reduced pressure and purified by chromatography on silica gel to afford the corresponding compounds 1p-1t. N-(2-methylallyl)-N-(3-phenylprop-2-yn-1-yl)-[1,1'biphenyl]-4-sulfonamide (1p): 1H NMR (400 MHz, CDCl ) δ 7.96 (d, J = 8.1 Hz, 2H), 7.66 (d, J = 3 8.3 Hz, 2H), 7.45 (d, J = 6.8 Hz, 6H), 7.41 (d, J = 8.6 Hz, 1H), 7.19 (d, J = 7.4 Hz, 1H), 7.09 (t, J = 7.5 Hz, 2H), 6.98 (d, J = 7.5 Hz, 2H), 5.02 (s, 1H), 4.30 (s, 1H), 3.86 (s, 1H), 1.84 (s, 2H); 13C{1H} NMR (CDCl3, 100 MHz): 145.6, 139.3, 139.1, 137.5, 131.4, 128.9, 128.4, 128.3, 128.1, 127.5, 127.3, 122.0, 115.7, 85.8, 81.4, 52.8, 36.4, 19.7; IR (neat): ν = 3067, 2917, 1593, 1487, 1440, 1345, 1161, 1099, 904, 839, 760, 693 cm-1; HRMS (ESI) Exact mass calculated for [C25H23SO2NNa]+ [M+Na]+: 424.1342, found:424.1341. N-(2-methylallyl)-N-(3-phenylprop-2-yn-1yl)naphthalene-2-sulfonamide (1q):


Page 5 of 11 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

1H NMR (400 MHz, CDCl


3) δ 8.49 (s, 1H), 7.93 (d, J = 8.1 Hz, 1H), 7.89 (s, 2H), 7.84 (d, J = 8.2 Hz, 1H), 7.58 (dt, J = 14.9, 7.0 Hz, 2H), 7.15 (t, J = 7.5 Hz, 1H), 7.01 (t, J = 7.4 Hz, 2H), 6.64 (d, J = 7.7 Hz, 2H), 5.01 (s, 2H), 4.32 (s, 2H), 3.87 (s, 2H), 1.83 (s, 3H) ; 13C{1H} NMR (CDCl , 100 MHz): 139.2, 136.0, 134.9, 132.3, 3 131.2, 129.3, 129.1, 129.0, 128.6, 127.8, 127.3, 123.1, 121.8, 115.6, 85.7, 81.4, 52.8, 36.5, 19.8 ; IR (neat): ν = 3061, 2921, 2855, 1443, 1343, 1158, 904, 757, 695 cm-1; HRMS (ESI) Exact mass calculated for [C23H21SO2NNa]+ [M+Na]+:398.1185, found: 398.1186. N-(2-methylallyl)-1-phenyl-N-(3-phenylprop-2-yn-1yl)methanesulfonamide (1r): 1H NMR (400 MHz, CDCl ) δ 7.46 (dd, J = 17.9, 15.1 Hz, 5H), 7.36 3 (d, J = 8.3 Hz, 5H), 4.98 (s, 2H), 4.37 (d, J = 27.1 Hz, 2H), 4.31 – 4.19 (m, 2H), 3.58 (d, J = 20.9 Hz, 2H), 1.70 (d, J = 12.1 Hz, 3H); 13C{1H} NMR (CDCl , 100 MHz):139.4, 131.6, 130.9, 128.8, 3 128.64, 128.60, 128.5, 122.0, 115.2, 85.8, 83.1, 58.3, 53.3, 36.1, 19.4 ; IR (neat): ν = 3071, 2929, 1594, 1492, 1444, 1342, 1148, 1023, 760, 695 cm-1; HRMS (ESI) Exact mass calculated for [C20H21SO2NNa]+ [M+Na]+: 362.1185, found: 362.1185. N-(2-methylallyl)-N-(3-phenylprop-2-yn-1-yl)butane-1sulfonamide (1s): 1H NMR (400 MHz, CDCl ) δ 7.39 (d, J = 6.1 Hz, 1H), 7.32 (s, 1H), 3 5.03 (d, J = 16.6 Hz, 1H), 4.21 (s, 2H), 3.90 (s, 2H), 3.24 – 3.01 (m, 2H), 1.84 (dt, J = 15.1, 7.5 Hz, 1H), 1.77 (s, 1H), 1.39 (dt, J = 31.8, 15.8 Hz, 1H), 0.89 (t, J = 7.2 Hz, 2H) ; 13C{1H} NMR (CDCl3, 100 MHz):139.4, 131.5, 128.7, 128.4, 122.0, 115.2, 85.5, 82.7, 52.8, 51.8, 35.8, 25.0, 21.7, 19.5, 13.5 ; IR (neat): ν = 3062, 2951, 1589, 1455, 1334, 1145, 1023, 760, 698 cm-1; HRMS (ESI) Exact mass calculated for [C17H23SO2NNa]+ [M+Na]+: 328.1342, found: 328.1338. N-allyl-N-(3-phenylprop-2-yn-1-yl)-[1,1'-biphenyl]-4sulfonamide (1t): 1H NMR (400 MHz, CDCl ) δ 7.95 (d, J = 7.9 Hz, 2H), 7.66 (d, J = 3 7.6 Hz, 2H), 7.44 (dd, J = 17.4, 8.9 Hz, 5H), 7.20 (t, J = 7.0 Hz, 1H), 7.10 (t, J = 7.5 Hz, 2H), 7.00 (d, J = 7.5 Hz, 2H), 5.83 (td, J = 16.1, 6.5 Hz, 1H), 5.32 (dd, J = 25.6, 13.5 Hz, 2H), 4.35 (s, 2H), 3.94 (d, J = 6.1 Hz, 2H) ; 13C{1H} NMR (CDCl3, 100 MHz): 145.6, 139.3, 137.4, 131.9, 131.4, 128.9, 128.4, 128.3, 128.2, 127.5, 127.3, 122.0, 120.1, 85.9, 81.4, 49.3, 36.7 ; IR (neat): ν = 1484, 1334, 1163, 893, 763, 674 cm-1; HRMS (ESI) Exact mass calculated for [C24H21SO2NNa]+ [M+Na]+: 410.1185, found: 410.0879. General procedure for the chlorotrifluoromethylative cyclizations of enynes. An oven-dried reaction tube with a stirr bar was charged with enynes 1 (0.40 mmol, 1.0 equiv.), trifluoromethanesulfonyl chloride 2 (134.8 mg, 0.80 mmol), K2HPO4∙3H2O (456.4 mg, 2.00 mmol), Acr+-Mes·ClO4 (6.2 mg, 0.02 mmol) and was sealed with a rubber stopper, evacuated and backfilled with argon for three times, then dry DCM (4.0 mL) as solvent was added. The tube was then immersed sideways into a sand bath under the room temperature, and irradiated by 23 W fluorescent bulb for 5–12 h with stirring. After the enynes 1 was completely consumed (monitored by TLC), the crude mixture was directly purified by flash column chromatography on silica gel (EtOAc/petroleum ether 1:20) to give the desired products 3a-3u.

(Z)-4-(chloro(phenyl)methylene)-3-methyl-1-tosyl-3(2,2,2-trifluoroethyl)pyrrolidine (3a): White solid (157.2 mg, 88%); m.p. 75–77 oC; 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.1 Hz, 2H), 7.39 (dd, J = 7.3, 5.8 Hz, 5H), 7.22 (dd, J = 6.5, 2.8 Hz, 2H), 4.15 (d, J = 15.4 Hz, 1H), 3.91 (d, J = 15.4 Hz, 1H), 3.21 (s, 2H), 2.47 (s, 3H), 2.05 (dq, J = 15.2, 11.4 Hz, 1H), 1.86 (dq, J = 15.4, 11.3 Hz, 1H), 1.17 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) 144.1, 140.4, 137.0, 131.7, 129.9, 129.5, 128.8, 128.7, 128.1, 127.0, 125.7 (d, J = 277.4 Hz, CF3), 59.9 (d, J = 2.4 Hz), 53.1, 43.4 (d, J = 5.7 Hz), 40.4 (q, J = 27.3 Hz, CCF3), 24.4 (d, J = 1.2 Hz), 21.6; 19F NMR (376 MHz, CDCl3 ) δ –60.3 (t, J = 7.14 Hz, 3F); IR (neat): ν = 3009, 2885, 1663, 1592, 1483, 1355, 1240, 1168, 1098, 1025, 887, 812, 702 cm-1; HRMS (ESI) Exact mass calculated for [C21H21SO2ClNF3H]+ [M+H]+: 444.1006, found: 444.1012. (Z)-4-(chloro(4-methoxyphenyl)methylene)-3-methyl-1tosyl-3-(2,2,2-trifluoroethyl)pyrrolidine (3b): White solid (146.9 mg, 78 %); m.p. 121–123 oC; 1H NMR (400 MHz, CDCl3) δ 7.77–7.72 (m, 2H), 7.42–7.37 (m, 2H), 7.17–7.14 (m, 1H), 7.14 – 7.12 (m, 1H), 6.91–6.88 (m, 1H), 6.88 – 6.85 (m, 1H), 4.13 (d, J = 15.4 Hz, 1H), 3.87 (d, J = 15.4 Hz, 1H), 3.82 (s, 3H), 3.20 (s, 2H), 2.47 (s, 3H), 2.13–1.99 (m, 1H), 1.91 (dq, J = 15.3, 11.3 Hz, 1H), 1.18 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 160.2, 144.1, 140.4, 131.6, 130.2, 129.9, 129.2, 128.1, 127.2, 125.8 (d, J = 277.4 Hz, CF3) 114.0, 59.9 (d, J = 2.4 Hz), 55.3, 53.2, 43.4, 40.4 (q, J = 27.2 Hz, CCF3), 24.4, 21.6; 19F NMR (376 MHz, CDCl3 ) δ – 60.3 (t, J = 7.52 Hz, 3F); IR (neat): ν = 2960, 2836, 1606, 1509, 1464, 1375, 1293, 1163, 889, 810, 704 cm-1; HRMS (ESI) Exact mass calculated for [C22H23SO3ClNF3H]+ [M+H]+: 474.1112, found: 474.1120. (Z)-4-(chloro(3-methoxyphenyl)methylene)-3-methyl-1tosyl-3-(2,2,2-trifluoroethyl)pyrrolidine (3c): White solid (138.4 mg, 73%); m.p. 74–76 oC; 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.2 Hz, 2H), 7.40 (d, J = 8.0 Hz, 2H), 7.28 (dd, J = 12.7, 4.7 Hz, 1H), 6.93-6.90 (m, J = 8.4, 2.6, 0.8 Hz, 1H), 6.82–6.78 (m, 1H), 6.74 (dd, J = 2.4, 1.6 Hz, 1H), 4.14 (d, J = 15.4 Hz, 1H), 3.89 (d, J = 15.4 Hz, 1H), 3.79 (s, 3H), 3.22 (s, 2H), 2.47 (s, 3H), 2.08 (dq, J = 15.2, 11.4 Hz, 1H), 1.93 (dq, J = 15.3, 11.3 Hz, 1H), 1.20 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) 159.5, 144.1, 140.3, 138.1, 131.6, 129.9, 129.8, 128.0, 126.7, 125.8 (d, J = 277.4 Hz, CF3), 121.1, 115.0, 114.5, 59.9 (q, J = 2.3Hz), 55.3, 53.1, 43.4 (q, J = 1.7 Hz), 40.3 (q, J = 27.3 Hz, CCF3), 24.4 (d, J = 1.3Hz), 21.6; 19F NMR (376 MHz, CDCl ) δ –60.2 (t, J = 7.52 Hz, 3F); IR (neat): 3 ν = 2943, 2840, 1599, 1486, 1430, 1352, 1164, 1044, 879, 814, 707 cm-1; HRMS (ESI) Exact mass calculated for [C22H23SO3ClNF3H]+ [M+H]+: 474.1112, found: 474.1124. (Z)-4-(chloro(o-tolyl)methylene)-3-methyl-1-tosyl-3(2,2,2-trifluoroethyl)pyrrolidine (3d): White solid (151.7 mg, 83 %); m.p. 89–91 oC; 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.2 Hz, 2H), 7.40 (d, J = 8.0 Hz, 2H), 7.28 (dd, J = 12.7, 4.7 Hz, 1H), 6.92 (m, J = 8.4, 2.6, 0.8 Hz, 1H), 6.82–6.78 (m, 1H), 6.74 (dd, J = 2.4, 1.6 Hz, 1H), 4.14 (d, J = 15.4 Hz, 1H), 3.89 (d, J = 15.4 Hz, 1H), 3.79 (s, 3H), 3.22 (s, 2H), 2.47 (s, 3H), 2.08 (dq, J = 15.2, 11.4 Hz, 1H), 1.93 (dq, J = 15.3, 11.3 Hz, 1H), 1.20 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz) 159.5, 144.1, 140.3, 138.1, 131.6, 129.9, 129.8, 128.0, 126.7, 125.8 (d, J = 277.4 Hz, CF3), 121.1, 115.0, 114.5, 59.9 (q, J = 2.3Hz), 55.3, 53.1, 43.4 (q, J = 1.7 Hz), 40.3 (q,



J = 27.3 Hz, CCF3), 24.4 (d, J = 1.3Hz), 21.6; 19F NMR (376 MHz, CDCl3 ) δ –60.2; IR (neat): ν = 2981, 2894, 1624, 1548, 1453, 1341, 1243, 1013, 981, 782, 679 cm-1; HRMS (ESI) Exact mass calculated for [C22H23SO2ClNF3H]+ [M+H]+: 458.1163, found: 458.1151. (Z)-4-(chloro(4-chlorophenyl)methylene)-3-methyl-1tosyl-3-(2,2,2-trifluoroethyl)pyrrolidine (3e): White solid (146.2 mg, 76 %); m.p. 103–105 oC; 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 8.2 Hz, 2H), 7.40 (s, 1H), 7.37 (t, J = 2.4 Hz, 2H), 7.36–7.33 (m, 1H), 7.19–7.16 (m, 1H), 7.16–7.14 (m, 1H), 4.12 (d, J = 15.5 Hz, 1H), 3.91 (d, J = 15.6 Hz, 1H), 3.26 (d, J = 9.7 Hz, 1H), 3.17 (d, J = 9.7 Hz, 1H), 2.47 (s, 3H), 2.09 (dq, J = 15.2, 11.3 Hz, 1H), 1.90 (dq, J = 15.3, 11.1 Hz, 1H), 1.15 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 144.2, 141.3, 135.6, 135.4, 131.7, 130.2, 129.9, 129.1, 128.0, 125.8, 125.6 (d, J = 277.4 Hz, CF3), 59.8 (d, J = 2.3 Hz), 55.2, 43.5 (q, J = 1.7 Hz), 40.5 (q, J = 27.4 Hz, CCF3), 24.4 (d, J = 1.4 Hz), 21.6; 19F NMR (376 MHz, CDCl3 ) δ – 60.2 (t, J = 7.14 Hz, 3F); IR (neat): ν = 2925, 2869, 1594, 1487, 1348, 1314, 1161, 1043, 895, 832, 664 cm-1; HRMS (ESI) Exact mass calculated for [C21H20SO2Cl2NF3H]+ [M+H]+: 478.0617, found: 478.0621. (Z)-methyl 4-(chloro(4-methyl-1-tosyl-4-(2,2,2trifluoroethyl)pyrrolidin-3-ylidene)methyl)benzoate (3f): White solid (165.0 mg, 82 %); m.p. 125–127 oC; 1H NMR (400 MHz, CDCl3) δ 8.09–7.99 (m, 2H), 7.77–7.71 (m, 2H), 7.39 (d, J = 7.9 Hz, 2H), 7.34–7.27 (m, 2H), 4.13 (d, J = 15.6 Hz, 1H), 3.96– 3.89 (m, 4H), 3.25 (d, J = 9.6 Hz, 1H), 3.17 (d, J = 9.7 Hz, 1H), 2.47 (s, 3H), 2.08 (dq, J = 15.3, 11.3 Hz, 1H), 1.86 (dq, J = 15.3, 11.1 Hz, 1H), 1.14 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) 166.0, 144.2, 141.3, 141.2, 131.6, 131.0, 129.9, 129.8, 129.0, 128.0, 125.6, 125.5 (d, J = 277.5 Hz, CF3), 59.8 (d, J = 2.3 Hz), 53.2, 52.4, 43.5 (d, J = 1.7 Hz), 40.5 (q, J = 27.3 Hz, CCF3), 24.3 (d, J = 1.2 Hz), 21.6; 19F NMR (376 MHz, CDCl3 ) δ –60.2 (t, J = 7.52 Hz, 3F); IR (neat): ν = 2957, 2849, 1722, 1603, 1440, 1375, 1261, 1184, 1137, 1042, 897, 808, 704, 667 cm-1; HRMS (ESI) Exact mass calculated for [C23H23SO4ClNF3H]+ [M+H]+: 502.1061, found: 502.1067. (Z)-4-(chloro(thiophen-2-yl)methylene)-3-methyl-1tosyl-3-(2,2,2-trifluoroethyl)pyrrolidine (3g): White solid (112.9 mg, 63 %); m.p. 107–109 oC; 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 7.8 Hz, 2H), 7.39 (d, J = 7.9 Hz, 3H), 7.12–6.93 (m, 2H), 4.14 (d, J = 16.0 Hz, 1H), 3.88 (d, J = 16.0 Hz, 1H), 3.23 (s, 2H), 2.47 (s, 3H), 2.24–1.97 (m, 2H), 1.27 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) 144.6, 144.2, 137.3, 131.6, 129.9, 129.3, 128.3, 128.0, 126.8, 125.8 (d, J = 277.3 Hz, CF3), 119.9, 59.9 (d, J = 2.3 Hz), 53.6, 43.8 (d, J = 1.7 Hz), 39.7 (d, J = 27.5 Hz, CCF3), 24.0, 21.6; 19F NMR (376 MHz, CDCl3 ) δ –60.2 (t, J = 7.52 Hz, 3F); IR (neat): ν = 2964, 1651, 1540, 1454, 1261, 1093, 1021, 800, 703 cm-1; HRMS (ESI) Exact mass calculated for [C19H19S2O2ClNF3H]+ [M+H]+: 450.0571, found: 450.0576. (Z)-4-(chloro(naphthalen-1-yl)methylene)-3-methyl-1tosyl-3-(2,2,2-trifluoroethyl)pyrrolidine (3h): White solid (152.7mg, 77 %); m.p. 170–172 oC; 1H NMR (400 MHz, CDCl3) δ 7.78–7.72 (m, 2H), 7.42–7.32 (m, 5H), 7.28–7.23 (m, 2H), 4.09 (dd, J = 15.6, 1.7 Hz, 1H), 3.90 (d, J = 15.6 Hz, 1H), 3.40 (dd, J = 10.1, 3.2 Hz, 1H), 3.30 (dd, J = 10.1, 6.3 Hz, 1H), 3.18 (d, J = 8.1 Hz, 1H), 2.46 (s, 3H), 2.17–1.97 (m, 1H), 1.90–1.75 (m, 1H).

13C{1H}

Page 6 of 11

NMR (CDCl3, 100 MHz): 144.2, 136.4, 135.9, 131.9, 129.9, 129.4, 128.8, 128.0, 127.9, 127.2, 125.6 (d, J = 274.3 Hz, CF3), 53.6, 52.4, 36.1 (d, J = 2.7Hz), 35.8 (d, J = 28.0 Hz, CCF3), 21.6; 19F NMR (376 MHz, CDCl3 ) δ: –65.2; IR (neat): ν = 2989, 2894, 1662, 1594, 1363, 1261, 1163, 1094 cm-1; HRMS (ESI) Exact mass calculated for [C25H23SO2ClNF3H]+ [M+H]+: 494.1163, found: 494.1173. (Z)-3-(chloro(4-methyl-1-tosyl-4-(2,2,2trifluoroethyl)pyrrolidin-3-ylidene)methyl)pyridine (3i): White solid (139.4 mg, 78 %); m.p. 124–126 oC; 1H NMR (400 MHz, CDCl3) δ: 8.63 (dd, J = 4.9, 1.7 Hz, 1H), 8.49 (dd, J = 2.2, 0.7 Hz, 1H), 7.77–7.71 (m, 2H), 7.60–7.52 (m, 1H), 7.39 (d, J = 7.9 Hz, 2H), 7.36–7.33 (m, 1H), 4.13 (d, J = 15.7 Hz, 1H), 3.97 (d, J = 15.7 Hz, 1H), 3.30 (d, J = 9.7 Hz, 1H), 3.15 (d, J = 9.7 Hz, 1H), 2.47 (s, 3H), 2.13 (dq, J = 15.2, 11.2 Hz, 1H), 1.87 (dq, J = 15.3, 11.0 Hz, 1H), 1.13 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz): 150.5, 149.4, 144.3, 142.9, 136.8, 133.2, 131.6, 129.9, 128.0, 125.4 (d, J = 277.4 Hz, CF3), 123.6, 123.4, 59.7 (q, J = 2.3 Hz), 53.3, 43.6 (q, J = 1.7 Hz), 40.8 (q, J = 27.5 Hz, CCF3), 24.4 (d, J = 1.3 Hz), 21.6; 19F NMR (376 MHz, CDCl3 ) δ: –60.2 (t, J = 7.52 Hz, 3F); IR (neat): ν = 2979, 1669, 1595, 1352, 1258, 1161, 1090, 787, 711, 663 cm-1; HRMS (ESI) Exact mass calculated for [C20H20SO2ClN2F3H]+ [M+H]+: 445.0959, found: 445.0975. (Z)-3-(chloro(phenyl)methylene)-1-tosyl-4-(2,2,2trifluoroethyl)pyrrolidine (3j): Colorless gum (99.3 mg, 58 %); 1H NMR (400 MHz, CDCl3) δ 7.78–7.72 (m, 2H), 7.42–7.32 (m, 5H), 7.28–7.23 (m, 2H), 4.09 (dd, J = 15.6, 1.7 Hz, 1H), 3.90 (d, J = 15.6 Hz, 1H), 3.40 (dd, J = 10.1, 3.2 Hz, 1H), 3.30 (dd, J = 10.1, 6.3 Hz, 1H), 3.18 (d, J = 8.1 Hz, 1H), 2.46 (s, 3H), 2.17–1.97 (m, 1H), 1.90–1.75 (m, 1H); 13C{1H} NMR (CDCl3, 100 MHz): 144.2, 136.4, 135.9, 131.9, 129.9, 129.4, 128.8, 128.0, 127.9, 127.2, 125.6 (d, J = 274.3 Hz, CF3), 53.6, 52.4, 36.1 (d, J = 2.7Hz), 35.8 (d, J = 28.0 Hz, CCF3), 21.6; 19F NMR (376 MHz, CDCl3 ) δ – 65.2 (t, J = 6.77 Hz, 3F); IR (neat): ν = 2945, 1596, 1568, 1453, 1324, 1136, 804, 763 cm-1; HRMS (ESI) Exact mass calculated for [C20H19SO2ClNF3H]+ [M+H]+: 430.0850, found: 430.0867. (Z)-methyl 4-(chloro(phenyl)methylene)-1-tosyl-3-(2,2,2trifluoroethyl)pyrrolidine-3-carboxylate (3k): White solid (130.1mg, 67 %); m.p. 153–155 oC; 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.3 Hz, 2H), 7.43–7.32 (m, 5H), 7.20–7.12 (m, 2H), 4.14 (q, J = 15.1 Hz, 2H), 3.78 (d, J = 10.1 Hz, 1H), 3.55 (d, J = 10.1 Hz, 1H), 3.47 (s, 3H), 2.55 (dq, J = 15.6, 10.7 Hz, 1H), 2.47 (s, 3H), 2.24 (dq, J = 15.5, 10.6 Hz, 1H); 13C{1H} NMR (CDCl3, 100 MHz) 170.3, 144.2, 136.0, 135.1, 129.9, 129.7, 129.5, 128.61, 128.59, 128.0, 127.9, 125.0 (d, J = 277.1 Hz, CF3), 56.2 (d, J = 2.0 Hz), 53.12, 53.05, 52.4 (d, J = 2.1 Hz), 37.7 (q, J = 28.8 Hz, CCF3), 21.6; 19F NMR (376 MHz, CDCl3 ) δ –59.9 (t, J = 6.77 Hz, 3F); IR (neat): ν = 2923, 1736, 1592, 1447, 1352, 1261, 1162, 1052, 826, 763 cm-1; HRMS (ESI) Exact mass calculated for [C22H21SO4ClNF3H]+ [M+H]+: 488.0905, found: 488.0922. (Z)-4-(1-chloroethylidene)-3-methyl-1-tosyl-3-(2,2,2trifluoroethyl)pyrrolidine (3l): Colorless gum (98.1 mg, 64 %); 1H NMR (400 MHz, CDCl3) δ: 7.70 (d, J = 8.2 Hz, 2H), 7.36 (d, J = 8.0 Hz, 2H), 3.88 (dd, J = 14.7, 1.9 Hz, 1H), 3.77 (dd, J = 14.7, 1.9 Hz, 1H), 3.42 (d, J = 9.7 Hz, 1H), 2.92 (d, J = 9.7 Hz, 1H), 2.45 (s, 3H), 2.40 (d, J = 11.2 Hz, 2H), 2.13 (t, J = 1.9 Hz, 3H), 1.36 (s, 3H); 13C{1H} (CDCl3, 100 MHz): 144.1, 137.1, 131.3, 129.8,


Page 7 of 11 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


128.1, 126.1, 125.8 (d, J = 277.4 Hz, CF3), 60.6 (d, J = 2.1Hz), 53.3, 42.7 (d, J = 1.6 Hz), 40.2 (q, J = 26.9 Hz, CH2CF3), 22.8, 22.4 (d, J = 1.4 Hz), 21.5; 19F NMR (376 MHz, CDCl3 ) δ : –60.5 (t, J = 7.52 Hz, 3F); IR (neat): ν = 2925, 2869, 1664, 1591, 1353, 1259, 1165, 1092, 799, 706 cm-1; HRMS (ESI) Exact mass calculated for [C16H19SO2ClNF3H]+ [M+H]+: 382.0850, found: 382.0861. (Z)-dimethyl(E)-4-(chloro(phenyl)methylene)-3-methyl3-(2,2,2-trichloroethyl)cyclopentane-1,1-dicarboxylate (3m): Colorless gum (108.5 mg, 67 %); 1H NMR (400 MHz, CDCl3) δ 7.29 (s, 3H), 7.18 (d, J = 6.3 Hz, 2H), 3.72 (s, 3H), 3.69 (s, 3H), 3.50 (d, J = 18.5 Hz, 1H), 3.17 (d, J = 18.5 Hz, 1H), 2.66 (d, J = 14.1 Hz, 1H), 2.45 (d, J = 14.1 Hz, 1H), 2.05 – 1.86 (m, 1H), 1.90 – 1.67 (m, 1H), 0.98 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) 179.94, 179.93, 144.2, 137.9, 131.5, 129.2, 129.0, 128.5, 126.1 (d, J = 277.6 Hz, CF3), 56.6, 53.1, 53.0, 52.7, 41.7, 42.6 (q, J = 26.3 Hz, CCF3), 41.6, 27.0; 19F NMR (565 MHz, CDCl3 ) δ – 59.8 (t, J = 7.52 Hz, 3F); IR (neat): ν = 2964, 1739, 1576, 1432, 1262, 1075, 949, 819, 781 cm-1; HRMS (ESI) Exact mass calculated for [C19H20O4ClF3Na]+ [M+Na]+: 427.0894, found: 427.0881. (Z)-4-(chloro(phenyl)methylene)-3-methyl-1(phenylsulfonyl)-3-(2,2,2-trifluoroethyl)pyrrolidine (3o): White solid (104.3 mg, 61 %); m.p. 65–67 oC; 1H NMR (400 MHz, CDCl3) δ 7.90–7.85 (m, 2H), 7.71–7.65 (m, 1H), 7.64–7.58 (m, 2H), 7.42–7.34 (m, 3H), 7.25–7.19 (m, 2H), 4.18 (d, J = 15.5 Hz, 1H), 3.93 (d, J = 15.5 Hz, 1H), 3.24 (s, 2H), 2.05 (dq, J = 15.3, 11.4 Hz, 1H), 1.86 (dq, J = 15.3, 11.2 Hz, 1H), 1.17 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 140.3, 136.9, 134.9, 133.2, 129.5, 129.2, 128.8, 128.7, 128.0, 127.1, 124.3 (d, J = 277.5 Hz, CF3), 59.8 (q, J = 2.4 Hz), 53.1, 43.5 (q, J = 1.7 Hz), 40.4 (q, J = 27.3 Hz), 24.3 (d, J = 1.4 Hz); 19F NMR (376 MHz, CDCl3 ) δ –60.3 (t, J = 7.52 Hz, 3F); IR (neat): ν = 3069, 2924, 2854, 1654, 1446, 1351, 1262, 1165, 1124, 1043, 893, 753 cm-1; HRMS (ESI) Exact mass calculated for [C20H19SO2ClNF3H]+ [M+H]+: 430.0850, found: 430.0862. (Z)-1-([1,1'-biphenyl]-4-ylsulfonyl)-4(chloro(phenyl)methylene)-3-methyl-3-(2,2,2trifluoroethyl)pyrrolidine (3p): White solid (148.0 mg, 73 %); m.p. 108–110 oC; 1H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.4 Hz, 2H), 7.73 (d, J = 8.4 Hz, 2H), 7.60 – 7.54 (m, 2H), 7.43 (t, J = 7.4 Hz, 2H), 7.36 (t, J = 7.3 Hz, 1H), 7.33–7.26 (m, 3H), 7.19–7.11 (m, 2H), 4.13 (d, J = 15.5 Hz, 1H), 3.90 (d, J = 15.5 Hz, 1H), 3.20 (s, 2H), 2.01 (dq, J = 15.1, 11.4 Hz, 1H), 1.80 (dq, J = 15.3, 11.3 Hz, 1H), 1.11 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) 146.1, 140.4, 139.1, 136.9, 133.2, 129.5, 129.1, 128.8, 128.73, 128.65, 128.5, 127.8, 127.3, 127.1, 125.7 (d, J = 277.0 Hz, CF3), 59.9 (d, J = 2.5 Hz), 53.2, 43.5 (d, J = 1.7 Hz ), 40.4 (q, J = 27.2 Hz, CCF3), 24.4 (d, J = 1.2 Hz); 19F NMR (376 MHz, CDCl3 ) δ –60.3 (t, J = 6.77 Hz, 3F); IR (neat): ν = 3062, 2925, 2854, 1594, 1960, 1480, 1350, 1260, 1162, 1128, 1002, 827, 719 cm-1; HRMS (ESI) Exact mass calculated for [C26H23SO2ClNF3H]+ [M+H]+: 506.1163, found:506.1171. (Z)-4-(chloro(phenyl)methylene)-3-methyl-1(naphthalen-2-ylsulfonyl)-3-(2,2,2trifluoroethyl)pyrrolidine (3q): White solid (168.5 mg, 88 %); m.p. 97–98 oC; 1H NMR (400 MHz, CDCl3) δ 8.46 (s, 1H), 8.05 (d, J = 8.3 Hz, 2H), 7.97 (d, J = 7.9 Hz, 1H), 7.87 (dd, J = 8.6, 1.7 Hz, 1H), 7.75–7.62 (m, 2H), 7.40–7.33 (m, 3H), 7.20 (dt, J =

7.5, 3.7 Hz, 2H), 4.23 (d, J = 15.5 Hz, 1H), 4.02 (d, J = 15.5 Hz, 1H), 3.32 (q, J = 9.7 Hz, 2H), 2.07 (dq, J = 15.7, 11.4 Hz, 1H), 1.87 (dq, J = 15.3, 11.3 Hz, 1H), 1.17 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) 140.2, 136.8, 135.0, 132.2, 131.8, 129.43, 129.42, 129.34, 129.33, 129.0, 128.7, 128.6, 127.9, 127.7, 127.0, 125.7 (d, J = 277.3 Hz, CF3), 123.1, 59.9 (q, J = 2.3 Hz), 53.2, 43.5 (q, J = 1.7 Hz), 40.4 (q, J = 27.3 Hz, CCF3), 24.2 (d, J = 1.2 Hz); 19F NMR (376 MHz, CDCl3 ) δ –60.3 (t, J = 7.14 Hz, 3F); IR (neat): ν = 3056, 2925, 2830, 1627, 1591, 1485, 1373, 1314, 1190, 1042, 894, 750 cm-1; HRMS (ESI) Exact mass calculated for [C24H21SO2ClNF3H]+ [M+H]+: 480.1006, found: 480.1007. (Z)-1-(benzylsulfonyl)-4-(chloro(phenyl)methylene)-3methyl-3-(2,2,2-trifluoroethyl)pyrrolidine (3r): White solid (161.2 mg, 85 %); m.p. 123–125 oC; 1H NMR (400 MHz, CDCl3) δ 7.51–7.35 (m, 8H), 7.24 (dd, J = 6.6, 2.7 Hz, 2H), 4.33 (s, 2H), 4.29–4.16 (m, 1H), 4.02 (d, J = 15.8 Hz, 1H), 3.31 (d, J = 10.3 Hz, 1H), 3.22 (d, J = 10.3 Hz, 1H), 2.00 (dq, J = 15.2, 11.4 Hz, 1H), 1.83 (dq, J = 15.4, 11.2 Hz, 1H), 1.10 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) 140.5, 137.0, 130.6, 129.5, 128.93, 128.87, 128.8, 128.7, 128.6, 126.7,125.7 (d, J = 277.5 Hz, CF3), 59.9 (q, J = 2.4 Hz), 57.7, 53.2, 43.6 (q, J = 1.7 Hz), 40.3 (q, J = 27.5 Hz), 24.3 (d, J = 1.3 Hz); 19F NMR (376 MHz, CDCl3 ) δ –60.2 (t, J = 7.14 Hz, 3F); IR (neat): ν = 2924, 2854, 1493, 1457, 1341, 1261, 1045, 891, 779 cm-1; HRMS (ESI) Exact mass calculated for [C21H21SO2ClNF3H]+ [M+H]+: 444.1006, found: 444.1020. (Z)-1-(butylsulfonyl)-3-(chloro(phenyl)methylene)-4(2,2,2-trifluoroethyl)pyrrolidine (3s): Colorless gum (116.2 mg, 71 %); 1H NMR (400 MHz, CDCl3) δ 7.49–7.39 (m, 3H), 7.36–7.22 (m, 2H), 4.37 (d, J = 15.7 Hz, 1H), 4.22 (d, J = 15.7 Hz, 1H), 3.53 (d, J = 10.1 Hz, 1H), 3.41 (d, J = 10.1 Hz, 1H), 3.10–3.01 (m, 2H), 2.24–2.09 (m, 1H), 1.95 (dt, J = 11.3, 9.2 Hz, 1H), 1.90– 1.81 (m, 2H), 1.49 (dd, J = 14.9, 7.4 Hz, 2H), 1.20 (s, 3H), 0.98 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (CDCl3, 100 MHz) 140.6, 137.0, 129.5, 128.9, 128.7, 127.0, 125.8 (d, J = 277.3 Hz, CF3), 59.5 (d, J = 2.3Hz), 53.0, 50.2, 43.7 (q, J = 1.7 Hz), 40.5 (q, J = 27.3 Hz, CCF3), 25.1, 24.4 (d, J =1.1 Hz), 21.6, 13.6; 19F NMR (565 MHz, CDCl3 ) δ –60.3 (t, J = 7.52 Hz, 3F); IR (neat): ν = 2962, 2928, 2875, 1630, 1597, 1489, 1462, 1370, 1260, 1145, 1046, 893, 754 cm-1; HRMS (ESI) Exact mass calculated for [C18H23SO2ClNF3H]+ [M+H]+: 410.1163, found: 410.1168. (Z)-1-([1,1'-biphenyl]-4-ylsulfonyl)-3(chloro(phenyl)methylene)-4-(2,2,2trifluoroethyl)pyrrolidine (3t): White solid (105.1 mg, 53%); m.p. 112–114 oC; 1H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 8.4 Hz, 2H), 7.84–7.76 (m, 2H), 7.63 (dd, J = 5.2, 3.3 Hz, 2H), 7.53–7.46 (m, 2H), 7.46–7.40 (m, 1H), 7.38–7.31 (m, 3H), 7.30– 7.22 (m, 2H), 4.15 (dd, J = 15.6, 1.6 Hz, 1H), 3.99 (d, J = 15.6 Hz, 1H), 3.49 – 3.45 (m, 1H), 3.41 – 3.36 (m, 1H), 3.20 (s, 1H), 2.15– 2.01 (m, 1H), 1.97–1.75 (m, 1H); 13C{1H} NMR (CDCl3, 100 MHz): 146.2, 139.0, 136.3, 135.8, 133.5, 129.5, 129.1, 128.8, 128.7, 128.5, 127.93, 127.89, 127.3, 125.7 (d, J = 276.2 Hz, CF3), 53.7, 52.4, 36.1 (q, J = 2.7 Hz), 35.8 (d, J = 27.7 Hz, CCF3); 19F NMR (376 MHz, CDCl3 ) δ – 65.2 (t, J = 7.14 Hz, 3F). IR (neat): ν = 3060, 1479, 1443, 1390, 1316, 1159, 1131, 830, 763 cm-1; HRMS (ESI) Exact mass calculated for [C25H21SO2ClNF3H]+ [M+H]+:492.1006, found: 492.1003.



Procedure for large scale reaction of N-(3-phenylprop-2yn-1-yl)-N-tosylmethacrylamide 1u with trifluoromethanesulfonyl chloride 2: An oven-dried flask with a stirr bar was charged with enynes 1u (4.0 mmol, 1.41 g), trifluoromethanesulfonyl chloride 2 (1.35 mg, 8.0 mmol), K2HPO4∙3H2O (4.56 g, 20.0 mmol), Acr+-Mes·ClO4 (62.0 mg, 0.02 mmol) and was sealed with a rubber stopper, evacuated and backfilled with argon for three times, then dry DCM (20.0 mL) as solvent was added. The tube was then irradiated by 23 W fluorescent bulb for 12 h under the room temperature, and with stirring. After the enynes 1u was completely consumed (monitored by TLC), the reaction mixture was evaporated under reduced pressure, then purified by flash column chromatography on silica gel (EtOAc/petroleum ether 1:20) and 1.39 g (76 % yield) of (Z)-4-(chloro(phenyl)methylene)3-methyl-1-tosyl-3-(2,2,2-trifluoroethyl)pyrrolidin-2-one (3u): White solid; m.p. 108–110 oC; 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 8.3 Hz, 2H), 7.44–7.38 (m, 3H), 7.36 (d, J = 8.2 Hz, 2H), 7.28 (dd, J = 6.6, 2.9 Hz, 2H), 4.82 (d, J = 15.4 Hz, 1H), 4.46 (d, J = 15.4 Hz, 1H), 2.45 (s, 3H), 2.41–2.26 (m, 1H), 2.06–1.89 (m, 1H), 1.10 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ: 173.8, 145.7, 136.4, 133.9, 130.8, 130.0, 129.7, 129.6, 128.9, 128.7, 128.3, 124.9 (d, J = 277.0 Hz, CF3), 50.3, 46.5 (d, J = 2.3 Hz), 41.2 (d, J = 27.3 Hz, CH2CF3), 25.7, 21.7; 19F NMR (376 MHz, CDCl3 ) δ –62.3 (t, J = 6.34 Hz, 3F); IR (neat): ν = 2963, 1745, 1651, 1558, 1507, 1457, 1261, 1090, 1022, 802, 704 cm-1; HRMS (ESI) Exact mass calculated for [C21H19SO3ClNF3H]+ [M+H]+: 458.0799, found: 458.0798. General procedure for the Chlorotrichloromethylative cyclizations of enynes: An oven-dried reaction tube with a stirr bar was charged with enynes 1 (0.40 mmol, 1.0 equiv.), trichloromethanesulfonyl chloride 4 (174.3 mg, 0.80 mmol), K2HPO4∙3H2O (456.4 mg, 2.00 mmol), Ir(dtbbpy)(ppy)2PF6 (3.7 mg, 0.004 mmol) and was sealed with a rubber stopper, evacuated and backfilled with argon for three times, then dry DCM (4.0 mL) as solvent was added. The tube was then immersed sideways into a sand bath under the room temperature, and irradiated by 23 W fluorescent bulb for 5–12 h with stirring. After the enynes 1 was completely consumed (monitored by TLC), the crude mixture was directly purified by flash column chromatography on silica gel (EtOAc/petroleum ether 1:20) to give the desired products 5a-5f. (Z)-4-(chloro(4-methoxyphenyl)methylene)-3-methyl-1tosyl-3-(2,2,2-trichloroethyl)pyrrolidine (5a): Colorless gum (186.1 mg, 89%); 1H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 7.5 Hz, 2H), 7.31 (d, J = 7.7 Hz, 2H), 7.11 (d, J = 7.6 Hz, 2H), 6.81 (d, J = 7.7 Hz, 2H), 4.01 (d, J = 14.8 Hz, 1H), 3.81 (d, J = 15.3 Hz, 1H), 3.73 (s, 3H), 3.65 (d, J = 9.5 Hz, 1H), 3.14 (d, J = 9.5 Hz, 1H), 2.81 (d, J = 15.6 Hz, 1H), 2.66 (d, J = 15.7 Hz, 1H), 2.39 (s, 3H), 1.18 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) 160.0, 144.0, 140.5, 131.2, 130.2, 129.8, 129.1, 128.0, 126.9, 113.9, 96.6, 59.4, 59.0, 55.3, 53.4, 47.0, 25.6, 21.6; IR (neat): ν = 2934, 1605, 1509, 1458, 1351, 1292, 1251, 1163, 1094, 1033, 834, 800 cm-1; HRMS (ESI) Exact mass calculated for [C22H23SO3Cl4NH]+ [M+H]+: 524.0196, found: 524.0205. (Z)-4-(chloro(thiophen-2-yl)methylene)-3-methyl-1tosyl-3-(2,2,2-trichloroethyl)pyrrolidine (5b): Colorless

Page 8 of 11

gum (111.3 mg, 56 %); 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 7.5 Hz, 2H), 7.45 – 7.31 (m, 3H), 7.10 – 6.93 (m, 2H), 4.12 (d, J = 15.8 Hz, 1H), 3.87 (d, J = 15.8 Hz, 1H), 3.71 (d, J = 9.5 Hz, 1H), 3.30 (d, J = 9.5 Hz, 1H), 2.96 (d, J = 15.6 Hz, 1H), 2.86 (d, J = 15.8 Hz, 1H), 2.47 (s, 3H), 1.38 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) 144.7, 144.2, 137.4, 131.2, 129.9, 129.4, 128.3, 128.1, 126.8, 119.7, 96.6, 59.7, 58.4, 53.8, 47.6, 25.4, 21.6; IR (neat): ν =1597, 1452, 1351, 1236, 1163, 1093, 1044, 908, 864, 814 cm-1; HRMS (ESI) Exact mass calculated for [C19H19S2O2Cl4NH]+ [M+H]+: 499.9655, found: 499.9679. (Z)-4-(chloro(4-chlorophenyl)methylene)-3-methyl-1tosyl-3-(2,2,2-trichloroethyl)pyrrolidine (5c): Colorless gum (164.1 mg, 78%); 1H NMR (400 MHz, CDCl3) δ 1H NMR δ 7.75 (d, J = 7.7 Hz, 2H), 7.39 (t, J = 8.5 Hz, 4H), 7.22 (d, J = 7.7 Hz, 2H), 4.09 (d, J = 15.4 Hz, 1H), 3.92 (d, J = 15.4 Hz, 1H), 3.78 (d, J = 9.6 Hz, 1H), 3.19 (d, J = 9.6 Hz, 1H), 2.89 (d, J = 15.7 Hz, 1H), 2.72 (d, J = 15.7 Hz, 1H), 2.47 (s, 3H), 1.24 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) 144.2, 141.4, 135.5, 135.4, 131.2, 129.8, 129.0, 128.1, 125.4, 96.3, 59.3, 59.1, 53.5, 47.1, 25.7, 21.6; IR (neat): ν = 1593, 1488, 1351, 1163, 1092, 1047, 896, 798 cm-1; HRMS (ESI) Exact mass calculated for [C21H20SO2Cl5NH]+ [M+H]+: 527.9701, found: 527.9734. (Z)-methyl 4-(chloro(4-methyl-1-tosyl-4-(2,2,2trichloroethyl)pyrrolidin-3-ylidene)methyl)benzoate (5d): Colorless gum (151.6 mg, 70%); 1H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 7.8 Hz, 2H), 7.68 (d, J = 7.7 Hz, 2H), 7.31 (dd, J = 13.7, 7.9 Hz, 4H), 4.08 – 3.94 (m, 1H), 3.87 (d, J = 15.2 Hz, 4H), 3.70 (d, J = 9.7 Hz, 1H), 3.12 (d, J = 9.6 Hz, 1H), 2.80 (d, J = 15.7 Hz, 1H), 2.63 (d, J = 15.7 Hz, 1H), 2.40 (s, 3H), 1.17 (d, J = 7.0 Hz, 3H); 13C{1H} NMR (CDCl3, 100 MHz) 166.0, 141.4, 135.5, 135.4, 131.2, 129.8, 129.0, 128.1, 125.4, 96.3, 59.3, 59.1, 53.5, 47.1, 25.7, 21.6; IR (neat): ν = 2952, 1726, 1601, 1438, 1352, 1278, 1163, 1097, 1048, 815, 757 cm-1; HRMS (ESI) Exact mass calculated for [C23H23SO4Cl4NH]+ [M+H]+: 550.0175, found: 549.9541. (Z)-4-(1-chloroethylidene)-3-methyl-1-tosyl-3-(2,2,2trichloroethyl)pyrrolidine (5e): Colorless gum (134.2 mg, 79%); 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 7.2 Hz, 2H), 7.38 (d, J = 7.5 Hz, 2H), 3.89 (d, J = 14.5 Hz, 1H), 3.83 (d, J = 9.7 Hz, 1H), 3.77 (d, J = 13.5 Hz, 1H), 3.11 (s, 2H), 3.00 (d, J = 9.8 Hz, 1H), 2.46 (s, 3H), 2.20 (s, 3H), 1.53 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) 144.1, 138.0, 131.2, 129.8, 128.1, 126.3, 96.9, 61.4, 59.2, 53.3, 46.6, 23.0, 22.5, 21.6; IR (neat): ν =2927, 1597, 1455, 1351, 1164, 1094, 1049, 815, 706 cm-1; HRMS (ESI) Exact mass calculated for [C16H19SO2Cl4NH]+ [M+H]+:431.9934, found: 431.9934 (Z)-dimethyl(E)-4-(chloro(phenyl)methylene)-3-methyl3-(2,2,2-trichloroethyl)cyclopentane-1,1-dicarboxylate (5f): Colorless gum (149.0 mg, 82 %); 1H NMR (400 MHz, CDCl3) δ 7.36 (d, J = 6.2 Hz, 3H), 7.30 (d, J = 6.6 Hz, 2H), 3.78 (s, 3H), 3.76 (s, 3H), 3.65 (d, J = 18.2 Hz, 1H), 3.22 (d, J = 13.9 Hz, 1H), 3.13 (d, J = 18.2 Hz, 1H), 2.78 (d, J = 15.7 Hz, 1H), 2.68 (d, J = 15.7 Hz, 1H), 2.57 (d, J = 14.0 Hz, 1H), 1.16 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) 172.1, 171.9, 144.3, 138.0, 129.3, 128.9, 128.5, 126.3, 97.2, 60.7, 56.9, 53.2, 53.0, 47.4, 47.0, 41.8, 28.1; IR (neat): ν = 2954, 1738, 1573, 1437, 1262, 1203, 1071, 948,


Page 9 of 11 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


879, 781 cm-1; HRMS (ESI) Exact mass calculated for [C19H20O4Cl4H]+ [M+H]+:455.0159, found: 455.0142. (Z)-4-(chloro(phenyl)methylene)-3-methyl-1-tosyl-3(2,2,2-trichloroethyl)pyrrolidin-2-one (5g): Colorless gum (163.9 mg, 81%); 1H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 7.5 Hz, 2H), 7.31 (d, J = 7.7 Hz, 2H), 7.11 (d, J = 7.6 Hz, 2H), 6.81 (d, J = 7.7 Hz, 2H), 4.01 (d, J = 14.8 Hz, 1H), 3.81 (d, J = 15.3 Hz, 1H), 3.73 (s, 3H), 3.65 (d, J = 9.5 Hz, 1H), 3.14 (d, J = 9.5 Hz, 1H), 2.81 (d, J = 15.6 Hz, 1H), 2.66 (d, J = 15.7 Hz, 1H), 2.39 (s, 3H), 1.18 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) 173.3, 145.8, 136.8, 133.6, 130.4, 130.2, 129.7, 129.6, 128.8, 128.7, 128.6, 95.4, 60.8, 51.2, 50.0, 26.3, 21.8; IR (neat): ν = 1742, 1596, 1459, 1372, 1296, 1235, 1176, 1115, 849, 791, 760 cm-1; HRMS (ESI) Exact mass calculated for [C21H19SO3Cl4NH]+ [M+H]+: 507.9883, found: 507.9896. Procedure for the Chlorotrifluormethylative cyclizations of 4-methyl-N-(3-methylbut-2-en-1-yl)-N-(3phenylprop-2-yn-1-yl)benzenesulfonamide: An oven-dried reaction tube with a stirr bar was charged with 4-methyl-N(3-methylbut-2-en-1-yl)-N-(3-phenylprop-2-yn-1yl)benzenesulfonamide 6 (0.40 mmol, 1.0 equiv.), trifluoromethanesulfonyl chloride 2 (134.8 mg, 0.80 mmol), K2HPO4∙3H2O (456.4 mg, 2.00 mmol), Acr+-Mes·ClO4 (6.2 mg, 0.02 mmol) was sealed with a rubber stopper, evacuated and backfilled with argon for three times, then dry DCM (4.0 mL) as solvent was added. The tube was then immersed sideways into a sand bath under the room temperature, and irradiated by 23 W fluorescent bulb for 12 h with stirring. After the enyne 6 was completely consumed (monitored by TLC), the crude mixture was directly purified by flash column chromatography on silica gel (EtOAc/petroleum ether 1:20) to give the desired products 7 and 7’. 3-(2-chloropropan-2-yl)-4-phenyl-1-tosyl-5(trifluoromethyl)-1,2,3,6-tetrahydropyridine (7): White solid (62.3 mg, 34%); m.p. 155–157 oC; 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.0 Hz, 2H), 7.37 (d, J = 7.9 Hz, 2H), 7.30 (s, 3H), 7.13 (s, 2H), 4.48 (d, J = 12.2 Hz, 1H), 4.24 (d, J = 17.1 Hz, 1H), 3.31 (d, J = 17.1 Hz, 1H), 3.03 (s, 1H), 2.55 (dd, J = 12.3, 3.5 Hz, 1H), 2.44 (s, 3H), 1.68 (s, 3H), 1.42 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) 144.3, 143.8 (d, J = 3.1 Hz), 139.4, 131.6, 129.9, 128.3, 128.0, 127.9, 124.9 (q, J = 27.3 Hz, CH2CF3), 122.6 (q, J = 274.7 Hz, CF3), 72.3, 53.2, 45.9, 44.2 (q, J = 4.5 Hz), 33.6, 31.4, 21.5; 19 F NMR (376 MHz, CDCl3 ) δ –57.8 (s, 3F); IR (neat): ν = 2924, 2851, 1660, 1594, 1455, 1336, 1177, 1105, 944, 826, 672 cm-1; HRMS (ESI) Exact mass calculated for [C22H23SO2ClNF3H]+ [M+H]+: 458.1163, found: 458.1184. (Z)-3-(chloro(phenyl)methylene)-4,4-dimethyl-1-tosyl-5(trifluoromethyl)piperidine (7’): White solid (99.2 mg, 54%); m.p. 161–163 oC; 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.3 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 7.32 (dd, J = 6.1, 2.8 Hz, 3H), 7.18 (s, 2H), 4.55 (dt, J = 14.6, 3.3 Hz, 1H), 3.90 (dd, J = 14.6, 6.8 Hz, 1H), 3.67–3.54 (m, 1H), 3.36 (dd, J = 12.7, 4.5 Hz, 1H), 2.47 (s, 3H), 2.28–2.13 (m, 1H), 1.09 (s, 3H), 0.87 (d, J = 1.4 Hz, 3H); 13C{1H} NMR (CDCl , 100 MHz) 144.0, 140.3, 133.9, 133.2, 3 129.9, 129.8, 128.2, 128.48, 128.1, 127.7,126.2 (d, J = 281.8 Hz, CF3), 49.6 (q, J = 23.4 Hz, CH2CF3), 47.2, 41.8 (q, J = 4.4 Hz), 38.6, 29.7, 26.7, 21.5; 19 F NMR (376 MHz, CDCl3 ) δ –61.7 (d, J = 3.76

Hz, 3F); IR (neat): ν = 2942, 2862, 1643, 1548, 1440, 1261, 1021, 967, 843 cm-1; HRMS (ESI) Exact mass calculated for [C22H23SO2ClNF3H]+ [M+H]+: 458.1163, found: 458.1162.

ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website. NMR Spectra and X-ray data were included (PDF). AUTHOR INFORMATION Corresponding Author [email protected] (H. Hou) [email protected] (X. Chen) [email protected] (S. Zhu) Notes The authors declare no competing financial interest.

ACKNOWLEDGMENTS This project was supported by the National Natural Science Foundation of China (21602085 and 21702179); the National Natural Science Foundation of Jiangsu Province (BK20160551); and the Priority Academic Program Development of Jiangsu Higher Education Institutions and Project supported by the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (17KJB150042), We also thank the Testing Centre of Yangzhou University for the sample analysis.

REFERENCES (1) For selected recent books and chapters, see (a) Hata, S. Sibi, M. P. in Addition of Free Radicals to Carbon-Carbon Multiple Bonds. In Stereoselective Synthesis, ed. De Vries, J. G. Molander, G. A. Evans, P. A. Science of Synthesis, Georg Thieme Verlag, Stuttgart, Germany, 2011, vol. 1, p 873. (b) Bertrand, M. P. Ferreri, C. in Radicals in Organic Synthesis, Vol. 2 (Eds.: Renaud, P.; Sibi, M.), Wiley-VCH, Weinheim, 2001, p 485. (2) For representative reviews, see (a) Jasperse, C. P. Curran, D. P. Fevig, T. L. Radical reactions in natural product synthesis. Chem. Rev. 1991, 91, 1237–1286. (b) Giese, B. Kopping, B. Gobel, T. Dickhaut, J. Thoma, G. Kulicke, K. J. Trach, F. Radical Cyclization Reactions. Org. React. 1996, 48, 301–361. (c) Clark, A. J. Atom transfer radical cyclisation reactions mediated by copper complexes. Chem. Soc. Rev., 2002, 31, 1–11. (d) Wille, U. Radical Cascades Initiated by Intermolecular Radical Addition to Alkynes and Related Triple Bond Systems. Chem. Rev. 2013, 113, 813–853. (3) For selected recent reviews, see (a) Chen, J.-R. Yan, D.-M. Wei, Q. Xiao, W.-J. Photocascade Catalysis: A New Strategy for Cascade Reactions. ChemPhotoChem 2017, 1, 148–158. (b) Xuan, J. Studer, A. Radical cascade cyclization of 1,n-enynes and diynes for the synthesis of carbocycles and heterocycles. Chem. Soc. Rev. 2017, 46, 4329–4346. (c) Xie, J. Jin, H. Hashmi, A. S K. The Recent Achievements of Redox-Neutral Radical C-C Cross-Coupling Enabled by Visible-Light. Chem. Soc. Rev. 2017, 46, 5193–5203. (d) Chen, J.-R. Hu, X.-Q. Lu, L.-Q. Xiao, W.-J. Visible light photoredoxcontrolled reactions of N-radicals and radical ions. Chem. Soc. Rev. 2016, 45, 2044–2056. (e) Shi, L. Xia. W, Photoredox



functionalization of C–H bonds adjacent to a nitrogen atom. Chem. Soc. Rev. 2012, 41, 7687–7697. (4) For selected recent examples of radical cyclization of enynes, see (a) Tucker, J. W. Nguyen, J. D. Narayanam, J. M. R. Krabbe, S. W. Stephenson, C. R. J. Tin-free radical cyclization reactions initiated by visible light photoredox catalysis. Chem. Commun. 2010, 46, 4985–4987. (b) Gao, P. Yan, X.-B Tao, T. Yang, F. He, T. Song, X.-R. Liu, X.-Y. Liang, Y.-M. Copper-Catalyzed Trifluoromethylation– Cyclization of Enynes: Highly Regioselective Construction of Trifluoromethylated Carbocycles and Heterocycles. Chem. Eur. J. 2013, 19, 14420–14424. (c) He, Y.-T. Li, L.-H. Zhou, Z.-Z. Hua, H.- L. Qiu, Y.-F. Liu, X.-Y. Liang, Y.-M. Copper-Catalyzed ThreeComponent Cyanotrifluoromethylation/Azidotrifluoromethylation and Carbocyclization of 1,6-Enynes. Org. Lett. 2014, 16, 3896–3899. (d) Zhang, L. Li, Z. Liu, Z.-Q. A Free-Radical Cascade Trifluoromethylation/Cyclization of N-Arylmethacrylamides and Enynes with Sodium Trifluoromethanesulfinate and Iodine Pentoxide. Org. Lett. 2014, 16, 3688–3691. (e) Wang, Y.-Q. He, Y.-T. Zhang, L.-L. Wu, X.-X. Liu, X.-Y. Liang, Y.-M. Palladium-Catalyzed Radical Cascade Iododifluoromethylation/Cyclization of 1,6Enynes with Ethyl Difluoroiodoacetate. Org. Lett. 2015, 17, 4280– 4283; (f) An, Y. Zhang, J. Xia, H. Wu, J. Radical cyclization of benzene-tethered 1,7-enynes with aryldiazonium tetrafluoroborates: a facile route to benzo[j]phenanthridines. Org. Chem. Front. 2017, 4, 1318–1321. (g) He, Y.-T. Wang, Q. Zhao, J. Wang, X.-Z. Qiu, Y.-F. Yang, Y.-C. Hu, J.-Y. Liu, X.-Y. Liang, Y.-M. Copper-Catalyzed Cascade Cyclization for the Synthesis of Trifluoromethyl-Substituted Spiro-2H-azirines from 1,6-Enynes. Adv. Synth. Catal., 2015, 357, 3069–3075. (h) Zheng, L. Zhou, Z.-Z. He, Y.-T. Li, L.-H. Ma, J.-W. Qiu, Y.-F. Zhou, P.-X. Liu, X.-Y. Xu, P.-F. Liang, Y.-M. Iodine-Promoted Radical Cyclization in Water: A Selective Reaction of 1, 6-Enynes with Sulfonyl Hydrazides. J. Org. Chem., 2016, 81, 66–76. (i) Shang, X.-J. Liu, D. Liu, Z.-Q. A NaSO2CF3/NaBrO3-mediated bromotrifluoromethylation of enyne via free-radical cascade processes. Org. Chem. Front., 2018, 5, 2856–2859. (5) (a) Shaw, M. H. Twilton, J. MacMillan, D. W. C. Photoredox Catalysis in Organic Chemistry. J. Org. Chem. 2016, 81, 6898–6926. (b) Prier, C. K. Rankic, D. A. MacMillan, D. W. C. Visible Light Photoredox Catalysis with Transition Metal Complexes: Applications in Organic Synthesis. Chem. Rev., 2013, 113, 5322– 5363. (6) For selected recent examples of atom-transfer radical addition across C=C and C≡C π bonds, see (a) Wallentin, C.-J. Nguyen, J. D. Finkbeiner, P. Stephenson, C. R. J. Visible LightMediated Atom Transfer Radical Addition via Oxidative and Reductive Quenching of Photocatalysts. J. Am. Chem. Soc., 2012, 134, 8875–8884. (b) Bagal, D. B. Kachkovskyi, G. Knorn, M. Rawner, T. Bhanage, B. M. Reiser, O. Trifluoromethylchlorosulfonylation of alkenes: evidence for an inner-sphere mechanism by a copper phenanthroline photoredox catalyst. Angew. Chem. Int. Ed. 2015, 54, 6999–7002. (c) Pagire, S. K. Paria, S. Reiser, O. Synthesis of βHydroxysulfones from Sulfonyl Chlorides and Alkenes Utilizing Visible Light Photocatalytic Sequences. Org. Lett., 2016, 18, 2106– 2109. (d) Li, H. Shan, C. Tung, C.-H. Xu, Z. Dual gold and photoredox catalysis: visible light-mediated intermolecular atom transfer thiosulfonylation of alkenes. Chem. Sci. 2017, 8, 2610–2615. (e) Yang, M.-N. Yan, D.-M. Zhao, Q.-Q. Chen, J.-R. Xiao, W.-J. Synthesis of Dihydropyrazoles via Ligand-Free Pd-Catalyzed Alkene Aminoarylation of Unsaturated Hydrazones with Diaryliodonium Salts. Org. Lett., 2017, 19, 5208–5211. (f) Iqbal, N. Jung, J. Park, S. Cho, E. J. Controlled Trifluoromethylation Reactions of Alkynes through Visible-Light Photoredox Catalysis. Angew. Chem., Int. Ed. 2014, 53, 539–542. (g) Tomita, R. Koike, T. Akita, M. PhotoredoxCatalyzed Stereoselective Conversion of Alkynes into Tetrasubstituted Trifluoromethylated Alkenes. Angew. Chem. Int. Ed., 2015, 54, 12923–12927. (h) Arai, Y. Tomita, R. Ando, G. Koike, T. Akita, M. Oxydifluoromethylation of Alkenes by Photoredox

Page 10 of 11

Catalysis: Simple Synthesis of CF2H-Containing Alcohols. Chem. Eur. J. 2016, 22, 1262–1265. (i) Qin, Q. Han, Y.-Y. Jiao, Y.-Y. He, Y. Yu, S. Photoredox-Catalyzed Diamidation and Oxidative Amidation of Alkenes: Solvent-Enabled Synthesis of 1,2-Diamides and α-Amino Ketones. Org. Lett. 2017, 19, 2909–2912. (j) Wei, Q. Chen, J.-R. Hu, X.-Q. Yang, X.-C. Lu, B. Xiao, W.-J. Photocatalytic Radical Trifluoromethylation/Cyclization Cascade: Synthesis of CF3Containing Pyrazolines and Isoxazolines. Org. Lett., 2015, 17, 4464–4467. (k) Geng, X. Lin, F. Wang, X. Jiao, N. Azidofluoroalkylation of Alkenes with Simple Fluoroalkyl Iodides Enabled by Photoredox Catalysis. Org. Lett. 2017, 19, 4738–4741. (7) For selected recent examples of atom-transfer radical cyclization of enynes, see (a) Zeng, X. Ilies, L. Nakamura, E. IronCatalyzed Regio- and Stereoselective Chlorosulfonylation of Terminal Alkynes with Aromatic Sulfonyl Chlorides. Org. Lett., 2012, 14, 954–956. (b) Zhu, S. Pathigoolla, A. Lowe, G. Walsh, D. A. Cooper, M. Lewis, W. Lam, H. W. Sulfonylative and Azidosulfonylative Cyclizations by Visible-LightPhotosensitization of Sulfonyl Azides in THF. Chem. Eur. J. 2017, 23, 17598–17604. (c) Li, H. Cheng, Z. Tung, C.-H. Xu, Z. Atom Transfer Radical Addition to Alkynes and Enynes: A Versatile Gold/Photoredox Approach to Thio-Functionalized Vinylsulfones. ACS Catal., 2018, 8, 8237–8243. (8) Hou, H. Li, H. Xu, Y. Song, C. Wang, C. Shi, Y. Han, Y. Yan, C. Zhu, S. Visible-Light-Mediated Chlorosulfonylative Cyclizations of 1,6-Enynes. Adv. Synth. Catal. 2018, 360, 4325–4329. (9) Ye, K.-Y. Song, Z. Sauer, G. S. Harenberg, J. H. Fu, N. Lin, S. Synthesis of Chlorotrifluoromethylated Pyrrolidines by Electrocatalytic Radical Ene-Yne Cyclization. Chem. Eu. J. 2018, 24, 12274–12279. (10) For representative reviews on Acr+-Mes as a photocatalyst, see: (a) Margrey, K. A.; Nicewicz, D. A. A General Approach to Catalytic Alkene Anti-Markovnikov Hydrofunctionalization Reactions via Acridinium Photoredox Catalysis. Acc. Chem. Res. 2016, 49, 1997–2006. (b) Romero, N. A.; Nicewicz, D. A. Organic Photoredox Catalysis. Chem Rev., 2016, 116, 10075–10166. (c) Noto, N. Tanaka, Y. Koike, T. Akita, M. Strongly Reducing (Diarylamino)anthracene Catalyst for Metal-Free Visible-Light Photocatalytic Fluoroalkylation. ACS Catal., 2018, 8, 9408–9419. (d) Koike, T. Akita, M. Fine Design of Photoredox Systems for Catalytic Fluoromethylation of Carbon–Carbon Multiple Bonds. Acc. Chem. Res., 2016, 49, 1937–1945. (11) CCDC 1891564 (3p), CCDC 1891562 (7) and CCDC 1891563 (7’) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif. (12) (a) Chen, L. Wu, L. Duan, W. Wang, T. Li, L. Zhang, K. Zhu, J. Peng, Z. Xiong, F. Photoredox-Catalyzed Cascade Radical Cyclization of Ester Arylpropiolates with CF3SO2Cl To Construct 3Trifluoromethyl Coumarin Derivatives. J. Org. Chem., 2018, 83, 8607–8614. (b) Oh, S. H. Malpani, Y. R. Ha, N. Jung, Y.-S. Han, S. B. Vicinal Difunctionalization of Alkenes: Chlorotrifluoromethylation with CF3SO2Cl by Photoredox Catalysis. Org. Lett., 2014, 16, 1310– 1313. (c) Nagib, D. A. MacMillan, D. W. C. Trifluoromethylation of arenes and heteroarenes by means of photoredox catalysis. Nature, 2011, 480, 224–228. (13) Gloor, C. S. Dénés, F. Renaud, P. Hydrosulfonylation Reaction with Arenesulfonyl Chlorides and Tetrahydrofuran: Conversion of Terminal Alkynes into Cyclopentylmethyl Sulfones. Angew. Chem. Int. Ed. 2017, 56, 13329–13332. (14) Xuan, J. Daniliuc, C. G. Studer, A. Construction of polycyclic γ-lactams and related heterocycles via electron catalysis. Org. Lett., 2016, 18, 6372–6375. (15) Gryparis, C. Efe, C. Raptis, C. Lykakis, I. N. Stratakis, M. Cyclization of 1,6-Enynes Catalyzed by Gold Nanoparticles Supported on TiO2: Significant Changes in Selectivity and Mechanism, as Compared to Homogeneous Au-Catalysis. Org. Lett., 2012, 14, 2956–2959.


Page 11 of 11 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


(16) Liu, B. Song, R.-J. Ouyang, X.-H. Li, Y. Hu, M. Li, J.-H. Palladium-catalyzed oxidative 6-exo-trig cyclization of 1,6-enynes: facile synthesis of bicyclo[4.1.0]heptan-5-ones. Chem. Commun., 2015, 51, 12819–12822.

(17) Nieto-Oberhuber, Pérez-Galán, C. P. Herrero-Gómez, E. Lauterbach, T. Rodríguez, C. López, S. Bour, C. Rosellón, A. Cárdenas, D. J. Echavarren, A. M. Gold(I)-Catalyzed Intramolecular [4+2] Cycloadditions of Arylalkynes or 1,3-Enynes with Alkenes: Scope and Mechanism. J. Am. Chem. Soc. 2008, 130, 269.


Visible-light-driven Chlorotrifluoromethylative and ... - ACS Publications

Recommend Documents