Palladium-Catalyzed Allylic Substitution Reaction of

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Palladium-Catalyzed Allylic Substitution Reaction of Benzothiazolylacetamide with Allylic Alcohols in Water Shulei Pan, Binqiang Wu, Jinjin Hu, Ruigang Xu, Min Jiang, Xiaofei Zeng, and Guofu Zhong J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01313 • Publication Date (Web): 25 Jul 2019 Downloaded from pubs.acs.org on July 25, 2019

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The Journal of Organic Chemistry

Palladium-Catalyzed Allylic Substitution Reaction of Benzothiazolylacetamide with Allylic Alcohols in Water Shulei Pan, Binqiang Wu, Jinjin Hu, Ruigang Xu, Min Jiang, Xiaofei Zeng* and Guofu Zhong* College of Materials, Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou 311121, China O Arhetero

OH N R1

R

2

R

Pd(PPh3)4 (PhO)2PO2H

Arhetero

H2O, 100 °C

O

Ph R2

N R1 34 examples up to 99% yield

Abstract. An efficient tetrakis(triphenylphosphine)palladium and Brønsted acid catalyzed allylic substitution reaction of benzothiazolylacetamide with allylic alcohols in water has been developed, and the corresponding allylated products were afforded in good to excellent (up to 99%) yields with high regioselectivities. This straightforward protocol exhibits good functional group tolerance and scalability.

Introduction The transition metal catalyzed allylic substitution reactions1 of various nucleophiles via a π-allyl metal intermediate are of great importance due to their wide applications and utility as a convenient and efficient tool for the formatting C-C, C-N and C-O bonds,2 which play a key role in organic chemistry. A variety of highly stereoselective allylic substitution reactions have been realized with various activated precursors of π-allyl fragments (allyl halides,3 esters,4 and carbonates,5,6 etc.) and nucleophiles. Since water is produced as the only by-product when the readily available allylic alcohols were used as the starting materials in the AAS (Asymmetric Allylic Substitution) reaction, the use of synthetically reliable alcohols instead of allyl carbonates have become more and more popular.7 Despite AAS reactions being atom-efficient and green transformations, a much greener process under water conditions remains a challenging task. Water is widely recognized as a perfect solvent in sustainable chemistry, owing to its safety (nontoxicity and nonflammability), cost-efficiency, abundance and readily availability,8 thus the development of water-based organic transformations is rapidly becoming an of importance area in organic chemistry. Indeed, water has been used as starting material9 or solvent in the allylic substitution reactions catalyzed by palladium catalysts10 and transition metal free conditions,11 however, only a few were able to perform with allylic alcohols. Kobayashi12 described a cooperative palladium and carboxylic acid catalyzed allylic substitution of allyl alcohols in water as a suspension medium, and various substrates turned out to be quite efficient in this catalytic system. Wang developed a calix[n]arene sulfonic acids catalyzed allylic alkylation of indoles with allyl alcohols in water, and the catalyst could be recycled seven times.13 Shimizu14a and Nájera14b independently reported direct allylic amination reactions of free allylic alcohols catalyzed by

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Brønsted or Lewis acids in water, and a wide variety of nitrogenated nucleophiles were well tolerated in these transformations. Although using water as solvent in organic reactions has drawn a great interest of chemists, the strategies out of green chemistry point still require extensive research. The benzathiazoles are found in a wide variety of bioactive molecules and natural products and they are accompanied with almost all the biological and pharmacological activities,15 like antibacterial, antiprotozoal, antimalarial, anticancer,16 treat allergies,17 genemodulating activities, antischizophrenia, antihypertension,18 anti-inflammation,19 anti-HIV infections20 and many more. From the perspective of synthetic simplicity and atom economy, the development of green methodologies for the construction of molecular diversified benzothiazoles is of great significant. Recently, we reported a palladium catalyzed mono- or di-selective allylic substitution reaction of benzothiazolylacetate and allylic alcohols, affording various mono- and diallylated products in good to excellent yields and selectivities.21b As a continuation of our efforts in chemoselective allylic substitution reactions,21 we report herein a palladium catalyzed highly efficient atom economic and environmentally friendly allylic substitution reaction of benzathiazole acetic amides with allylic alcohols by using H2O as solvent.

Results and discussion The

investigation

was

initiated

with

ethyl

2-(benzo[d]thiazol-2-yl)acetamide

(1a)

and

1-phenylprop-2-en-1-ol (2a) as representative substrates under the catalysis of Pd(PPh3)4 in water. At the outset, different acids (including Lewis acids and Brønsted acids) were screened as the hydroxyl group activator, and (PhO)2POOH provided the best result, which afforded the desired allyl substituted product 3a in 45 % yield (Table 1, entries 1-5). Then, different reaction temperature was tested, and it was found that the yield was increased when the temperature was increased from room temperature to 100 °C, the desired product 3a could be obtained in 92% yield (entries 6-8). Next, the effect of catalyst loading on the reaction was evaluated. The results revealed that 4 mol% of Pd(PPh3)4 and 8 mol% of (PhO)2POOH promote the reaction well, further decreasing or increasing the amount of catalysts would result in decreased yields (entries 9-12). Further optimization of the molar ratio of 1a and 2a was subsequently carried out (entries 13-14). Thus, the best yield of the allylated product 3a could be achieved with 1.2 equiv. of 2a in the presence of 4 mol% of Pd(PPh3)4 and 8 mol% of (PhO)2PO2H in water at 100 oC, in excellent yield of 92%. Table 1. Optimization of the reaction conditionsa OH CONMe2

N 1a

Ph

catalyst addictive H2O, T

S

S N 3a

2a

CONMe2

entry

catalyst

additive

T (oC)

yield (%)b

1

Pd(PPh3)4

FeCl3

rt

10

2

Pd(PPh3)4

Sc(OTf)3

rt

8

3

Pd(PPh3)4

Yb(OTf)3

rt

Trace

4

Pd(PPh3)4

CH3CO2H

rt

Trace

5

Pd(PPh3)4

rt

45

6

Pd(PPh3)4

(PhO)90 2POOH (PhO)2POOH

50

52

7

Pd(PPh3)4

(PhO)2POOH

75

64


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aUnless

8

Pd(PPh3)4

(PhO)2POOH

100

9c

92

Pd(PPh3)4

(PhO)2POOH

100

61

10d

Pd(PPh3)4

(PhO)2POOH

100

91

11e

Pd(PPh3)4

(PhO)2POOH

100

58

12f

Pd(PPh3)4

(PhO)2POOH

100

90

13g

Pd(PPh3)4

(PhO)2POOH

100

87

14h

Pd(PPh3)4

(PhO)2POOH

100

93

indicated otherwise, the reaction was carried out at a 0.2 mmol scale and catalyzed by 4 mol % of Pd(PPh3)4 in

H2O (2 mL) with 8 mol% of (PhO)2PO2H as additives for 12 h, and the molar ratio of 1a: 2a was 1:1.2. bYield of isolated product based on 1a. c 2 mol% of Pd(PPh3)4 was added. d8 mol% of Pd(PPh3)4 was added. e4 mol% of (PhO)2POOH was added. f12 mol% of (PhO)2POOH was added. gThe molar ratio of 1a : 2a was 1:1. hThe molar ratio of 1a : 2a was 1:2.

With the optimized condition in hand, the scope of allylic electrophiles was then explored. As show in Table 2, a wide range of allylic alcohols were evaluated and all reactions proceeded smoothly, with negligible or no byproducts. Allylic alcohols substituted with arenes bearing various electron-rich and electron-deficient groups on the ortho-, meta-, or para-positions were all well tolerated in this transformation, affording the corresponding products in good to excellent yields (57-99%). Notably, the halogen atoms such as bromide, chloride and fluoride at the ortho-, meta-, or para-position of the phenyl ring could survive in the reaction, and gave the desired alkylation products with excellent yields (3h-3n, 91-98%). Additionly, substrates possessing thienyl and fused-ring aryl groups also gave corresponding products 3w and 3x in 82 and 97% yields, respectively. The aliphatic aldehyde derived branched allylic alcohol 2z could also be utilized in the reaction, however, the allylated product 3z was furnished in lower yields. (entry 26). Furthermore, linear allylic alcohols such as simple cinnamyl alcohols and allylic alcohols can also react with 2-(benzo[d]thiazol-2-yl)-N,N-dimethylacetamide (1a) to afford desired products 3a and 3aa in good yields (89 and 92%, Scheme 1). In addition, the 1,3-disubstituted allylic alcohols could be well tolerated in the reaction. Interestingly, when (E)-1-phenylbut-2-en-1-ol (2ab) and (E)-4-phenylbut-3-en-2-ol (2ac) reacted with 1a under standard conditions, the same allylated product 3ab was afforded in high yields (89 and 93%) but with low diastereoselectivity (1.1:1). The results indicated that the two reactions might proceed through the same palladium π-allyl intermediate. Table 2. Substrate Scope of the Reactiona OH

S N 1a

entry

CONMe2

R

R


S

H2O, 100 °C

N 3

2

CONMe2

3

R

yield (%)b

1

3a

C6H5

92

2

3b

2-MeC6H4

86

3

3c

3-MeC6H4

63

4

3d

4-MeC6H4

88

5

3e

2-MeOC6H4

63

6

3f

3-MeOC6H4

89

7

3g

4-MeOC6H4

73

8

3h

4-BrC6H4

96

9

3i

2-ClC6H4

94



aUnless

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10

3j

3-ClC6H4

98

11

3k

4-ClC6H4

98

12

3l

2-FC6H4

91

13

3m

3-FC6H4

94

14

3n

4-FC6H4

97

15

3o

2,6-Cl2C6H4

83

16

3p

4-EtC6H4

93

17

3q

2,6-(MeO)2C6H4

57

18

3r

3-EtO-4-MeC6H4

63

19

3s

4-CF3C6H4

99

20

3t

4-NO2C6H4

93

21

3u

4-t-BuC6H4

91

22

3v

4-i-BuC6H4

90

23

3w

2-Thienyl

82

24

3x

2-Naphthyl

97

25

3y

4-PhC6H4

85

26

3z

Et

38

indicated otherwise, the reaction was carried out at a 0.2 mmol scale and catalyzed by 4 mol % of Pd(PPh3)4 in H2O (2

mL) with 8 mol% of (PhO)2PO2H as additives for 12 h at 100 oC, and the molar ratio of 1:2 was 1:1.2.

bYield

of isolated product

based on 1a. Scheme 1. The Reaction of Other Allylic Alcohols.

S N

CONMe2

OH

R

S

H2O, 100 °C

N

2

1a

R


OH

CONMe2 3 3aa: R = H, yield: 92% 3a: R = Ph, yield: 89% Ph

Ph

CH3 2ab 1.2 eq yield: 89% dr: 1.1:1 OH

Pd(PPh3)4 (PhO)2POOH

S CONMe2

N

H2O, 100 °C 12 h

Ph

1a 0.2 mmol

2ac 1.2 eq

CH3

S N O 3ab

Ph

CH3

CH3

S

yield: 93% dr 1.1:1

NMe2

N O 3ab

NMe2

Table 3. Scope of Heteroaryl Acetamides for the Allylationa,b O Arhetero

OH N R1

R2

1

Ph

Pd(PPh3)4 (PhO)2PO2H Arhetero H2O, 100 °C

2a

4

O

N O 4a yield: 51%

NMe2

O

N R1

NMe2

Ph O

Ph2 R2

Ph N

4b yield: 88%


N Me2N

Ph O

4c yield: 93%

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Ph

Me

N

Ph

F3C

S

N

NMe2

O

O

4d yield: 88%

aUnless

Ph S

S

N

N O 4f yield: 76%

NMe2

4e yield: 93%

O

indicated otherwise, the reaction was carried out at a 0.2 mmol scale and catalyzed by 4 mol % of

Pd(PPh3)4 in H2O (2 mL) with 8 mol% of (PhO)2PO2H as additives for 12 h at 100 oC. bYield of isolated product.

Scheme 2. The Reaction of 2-(Benzo[d]thiazol-2-yl)-N-methylacetamide (1g) with Allylic Alcohols.

CONHMe

N 1ag

Ph

Pd(PPh3)4 (PhO)2PO2H H2O, 100 °C 12 h

OH

S Ph

2

S N

CONHMe 4g yield: 55%

We then paid our attention to expanding the substrate scope of heteroaryl acetamides (Table 3). Various azaaryl substrates that bearing benzoxazolyl (1aa), isoquinolinyl (1ab), quinolinly (1ac) were all well tolerated in this allylation reaction to give product (4a, 4b, 4c) in moderate to excellent yield (51-93%). Apart from these substrates above, the methyl (1ad) and trifluoromethyl (1ae) substituted benzothiazolylacetamide were all suitable for this transformation, affording the products (4d and 4e) in high yields (88-93%). Of particular note, when the N,N-dimethylamino group of the amide was replaced by morpholine, the reaction proceeded smoothly to give the desired products 4f in 76% yield. It was noteworthy that the N-methyl amide 2-(benzo[d]thiazol-2-yl)-N-methylacetamide (1ag) was also good substrate for the reaction, the corresponding product 4g could be obtained in 55% yield (Scheme 2). In addition, this aquous reaction could be easily carried out on gram-scale (with 5.0 mmol of benzothiazolylacetamide 1a) and good yield (88%) was obtained. Furthermore, the resulting allylic alkylated benzothiazolylacetamide derivatives could undergo versatile transformations. For example, treating 3a with Pd/C catalyst under a hydrogen atomosphere at rt, the hydrogenated product 5 could be obtained in quantitative yield. When 3a was treated with LiAlH4 in THF under reflux condition, an unexpected deamidated product 6 was formed in 51% yield (Scheme 3). Scheme 3. Gram Scale Reaction and Synthetic Tunability of the Allylated Product. OH

S N 1a 5.0 mmol

S N

CONMe2

2a 1.2 eq Ph Pd/C, H2

S

MeOH, rt 12 h

N

CONMe2

5 yield: 99%

Ph

Ph


S

H2O, 100 °C 12 h

N

Ph

CONMe2 3a 1.48 g yield: 88% LiAlH4

THF CONMe2 reflux, 4 h 3a

Ph S N 6 yield: 51%

Conclusions In summary, we have described a palladium and Brønsted acid catalyzed allylic substitution reaction of benzothiazolylacetamide with allylic alcohols that proceeds in pure water as the solvent. The reactions occur in a highly selective manner with a broad substrate scope, both linear and branched allylic alcohols



as well as allyl alcohol could all be well tolerated in the reaction. This method, which represents an environmentally friendly alternative to methods previously reported employing organic solvents, provides the corresponding allylated products good to excellent yields. Further investigation on asymmetric allylic substitution is now in progress.

Experimental Section General Analytical thin layer chromatography (TLC) was performed using Merck 60 F254 precoated silica gel plate (0.2 mm thickness). Subsequent to elution, plates were visualized using UV radiation (254 nm) on Spectroline Model ENF-24061/F 254 nm. Further visualization was possible by staining with basic solution of potassium permanganate or acidic solution of ceric molybdate. Flash column chromatography was performed using Merck aluminium oxide 90 active neutral with freshly distilled solvents. Columns were typically packed as a slurry and equilibrated with the appropriate solvent system prior to use. Proton nuclear magnetic resonance spectra (1H NMR) were recorded on a Bruker AMX 500 spectrophotometer (CDCl3 as solvent). Chemical shifts for 1H NMR spectra are reported as δ in units of parts per million (ppm) downfield from SiMe4 (0.0) and relative to the signal of chloroform-d (7.26, singlet). Multiplicities were given as: s (singlet), d (doublet), t (triplet), dd (doublet of doublets) or m (multiplets). The number of protons (n) for a given resonance is indicated by nH. Coupling constants are reported as a J value in Hz. Carbon nuclear magnetic resonance spectra (13C NMR) are reported as δ in units of parts per million (ppm) downfield from SiMe4 (0.0) and relative to the signal of chloroform-d (77.0, triplet). High resolution mass spectrometry (HRMS) was recorded on QTOF Premier for ESI+. The starting materials 1a, 1af22 and 1aa23 were synthesized following published procedures. The allylic alcohols 2 were synthesized according to the literatures except allyl and cinnamyl alcohol, which were commercially available from TCI and used without further purification.24

Procedure for the synthesis of hetereoaryl N,N-dimethylacetamides.25 In a 100-mL round-bottom flask containing a magnetic stir bar were added the chloro-substituted heteroaromatic compounds (5.0 mmol, 1.0 equiv), dimethylacetamide (DMAc, 0.51 mL, 5.5 mmol, 1.1 equiv) and anhydrous THF (10 mL). The mixture was cooled to -78 C, LiHMDS (1.0 M solution in THF, 11.0 mL, 11.0 mmol, 2.2 equiv) was then added dropwise to the reaction mixture. Thereafter, the reaction mixture was slowly warmed to room temperature and stirred overnight. The reaction mixture was quenched with a saturated aqueous NH4Cl solution (20 mL) and then diluted with EtOAc (40 mL). The organic layer was separated and washed with brine (20 mL). After evaporation of the solvent under vacuum, the crude mixture was purified by flash column chromatography to give the desired 1ab-1ae. 2-(isoquinolin-1-yl)-N,N-dimethylacetamide (1ab). Yellow solid, 0.68 g, yield = 64%. 1H NMR (500 MHz, CDCl3) δ 8.44 (d, J = 5.7 Hz, 1H), 8.32 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 8.1 Hz, 1H), 7.67 (t, J = 7.5 Hz, 1H), 7.61 (t, J = 7.6 Hz, 1H), 7.56 (d, J = 5.7 Hz, 1H), 4.41 (s, 2H), 3.16 (s, 3H), 2.98 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 169.8, 156.0, 141.8, 136.4, 130.1, 127.9, 127.5, 127.1, 125.9, 120.1, 42.4, 38.0, 35.7. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C13H15N2O 215.1179; found 215.1172. N,N-dimethyl-2-(quinolin-2-yl)acetamide (1ac). Yellow solid, 0.60 g, yield = 56%. 1H NMR (500 MHz, CDCl3) δ 8.04 (d, J = 8.5 Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H), 7.72 (d, J = 8.0 Hz, 1H), 7.63-7.60 (m, 1H), 7.45-7.41 (m, 2H), 4.03 (s, 2H), 3.05 (s, 3H), 2.90 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 169.9, 156.3, 147.8, 136.5, 129.4, 129.0, 127.6, 127.1, 126.2, 121.7, 44.9, 37.8, 35.6. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C13H15N2O 215.1179; found 215.1175.


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N,N-dimethyl-2-(6-methylbenzo[d]thiazol-2-yl)acetamide (1ad). Yellow solid, 1.21 g, yield = 48%. 1H NMR (500 MHz, CDCl3) δ 7.85 (d, J = 8.3 Hz, 1H), 7.66 (s, 1H), 7.27 (d, J = 4.2 Hz, 1H), 4.22 (s, 2H), 3.14 (s, 3H), 3.02 (s, 3H), 2.48 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 167.8, 163.4, 150.7, 136.1, 135.1, 127.5, 122.2, 121.3, 39.5, 37.8, 35.8, 21.5. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C22H15N2O 235.0900; found 235.0907. N,N-dimethyl-2-(6-(trifluoromethyl)benzo[d]thiazol-2-yl)acetamide (1ae). Yellow solid, 1.48 g, yield = 52%. 1H

NMR (500 MHz, CDCl3) δ 8.18 (s, 1H), 8.06 (d, J = 8.5 Hz, 1H), 7.69 (d, J = 8.4 Hz, 1H), 4.28 (s, 2H), 3.10

(d, J = 61.9 Hz, 6H). 13C{1H} NMR (125 MHz, CDCl3) δ 168.1, 167.3, 154.4, 136.1, 127. 2 (q, J = 34.8 Hz), 126.2 (q, J = 220.2 Hz), 123.1, 122.9 (q, J = 3.2 Hz), 119.2 (q, J = 4.1 Hz), 39.2, 37.7, 35.8. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C12H12F3N2OS 289.0617; found 289.0611.

Procedure for the synthesis of 2-(benzo[d]thiazol-2-yl)-N-methylacetamide (1ag). To a 100 ml round-botom flask 2-(benzo[d]thiazol-2-yl)acetic acid (5.0 mmol, 0.97 g, 1.0 equiv), methylamine (33 wt.% in absolute MeOH, 5.0 mmol, 1.0 equiv), anhydrous DMF (15 ml), EDCl (7.5 mmol, 1.44 g, 1.5 equiv), HOBT (7.5 mmol, 1.01 ml, 1.5 equiv) and DIPEA (7.5 mmol, 1.24 ml, 1.5 equiv) were added subsequently and stirred at rt overnight. The reaction was quenched with satutated aqueous NH4Cl solution (50 ml) and extracted with EtOAc (50 ml). The organic layer was dried over sodium sulfate and purified by column chromatography to give 1ag (0.47 g, 45%) as a white powder. 1H

NMR (500 MHz, CDCl3) δ 8.01 (d, J = 8.2 Hz, 1H), 7.88 (d, J = 8.0 Hz, 1H), 7.50 (t, J = 7.7 Hz, 1H), 7.41 (t, J

= 7.6 Hz, 1H), 7.19 (s, 1H), 4.06 (s, 2H), 2.87 (d, J = 4.8 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 167.1, 164.8, 153.0, 135.1, 126.3, 125.4, 122.8, 121.7, 40.9, 26.5. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C10H11N2OS 207.0587; found 207.0588.

General procedure for the allylic alkylation reaction: To a mixture of (PhO)2PO2H (0.016 mmol, 8 mol%), 2-(benzo[d]thiazol-2-yl)acetamide (1, 0.2 mmol, 1.0 equiv) in water (2 mL) in a 10 ml round-bottom flask were added allylic alcohol (2, 0.24 mmol, 1.2 equiv) and Pd(PPh3)4 (0.008 mmol, 4 mol%). Then, the reaction mixture was stirred at 100 oC until the completion of the reaction (monitored by TLC). The reaction mixture was quenched with water and extracted with ethyl acetate (5 mL × 3). The organic layer was dried over Na2SO4 and evaporated in vacuum. The residue was purified by silica gel column chromatography (petroleum ether/EtOAc = 50:1 to 10:1) to afford the desired product. (E)-2-(benzo[d]thiazol-2-yl)-N,N-dimethyl-5-phenylpent-4-enamide (3a). White solid, 61.7 mg, yield = 92%; mp. = 110.6-111.4 °C; 1H NMR (500 MHz, CDCl3) δ 7.99 (d, J = 8.1 Hz, 1H), 7.86 (d, J = 7.9 Hz, 1H), 7.46-7.43 (m, 1H), 7.37-7.34 (m, 1H), 7.31-7.25 (m, 4H), 7.20-7.17 (m, 1H), 6.51 (d, J = 15.8 Hz, 1H), 6.20 (dt, J = 15.7, 7.3 Hz, 1H), 4.67 (dd, J = 8.4, 6.5 Hz, 1H), 3.17-3.11 (m, 4H), 2.99 (s, 3H), 2.93-2.87 (m, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 170.1, 169.6, 152.4, 137.1, 135.6, 133.1, 128.5, 127.4, 126.3, 126.0, 126.0, 125.1, 122.9, 121.8, 48.5, 38.3, 37.7, 36.2. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C20H21N2OS 337.1369; found 337.1377. (E)-2-(benzo[d]thiazol-2-yl)-N,N-dimethyl-5-(o-tolyl)pent-4-enamide (3b). Yellow liquid, 60.1 mg, yield = 86%; 1H NMR (500 MHz, CDCl3) δ 7.98 (d, J = 8.1 Hz, 1H), 7.87 (d, J = 7.9 Hz, 1H), 7.47-7.44 (m, 1H), 7.38-7.33 (m, 2H), 7.12-7.09 (m, 3H), 6.69 (d, J = 15.6 Hz, 1H), 6.06 (dt, J = 15.6, 7.25 Hz, 1H), 4.70 (dd, J = 8.2, 6.7 Hz, 1H), 3.18-3.12 (m, 4H), 3.00 (s, 3H), 2.95-2.91 (m, 1H), 2.23 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 170.1, 169.6, 152.3, 136.3, 135.6, 135.2, 131.1, 130.2, 127.3, 127.3, 126.0, 126.0, 125.7, 125.1, 122.8, 121.8, 48.6, 38.6, 37.7, 36.2, 19.7. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C21H23N2OS 351.1526; found 351.1535. (E)-2-(benzo[d]thiazol-2-yl)-N,N-dimethyl-5-(m-tolyl)pent-4-enamide (3c). Yellow solid, 43.9 mg, yield = 63%; mp. = 101.0-102.4 °C; 1H NMR (500 MHz, CDCl3) δ 7.99 (d, J = 8.1 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.46 (dd, J = 11.2, 4.1 Hz, 1H), 7.38 (t, J = 7.6 Hz, 1H), 7.17 (t, J = 7.5 Hz, 1H), 7.12-7.10 (m, 2H), 7.02 (d, J = 7.3 Hz,



1H), 6.48 (d, J = 15.8 Hz, 1H), 6.19 (dt, J = 15.7, 7.3 Hz, 1H), 4.66 (dd, J = 8.4, 6.5 Hz, 1H), 3.15-3.10 (m, 4H), 3.00 (s, 3H), 2.91-2.86 (m, 1H), 2.31 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 170.1, 169.6, 152.3, 138.1, 137.0, 135.6, 133.1, 128.4, 128.2, 127.0, 126.0, 125.7, 125.1, 123.4, 122.9, 121.8, 48.6, 38.4, 37.7, 36.2, 21.4. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C21H23N2OS 351.1526; found 351.1531. (E)-2-(benzo[d]thiazol-2-yl)-N,N-dimethyl-5-(p-tolyl)pent-4-enamide (3d). White solid, 61.1 mg, yield = 88%; mp. = 126.1-127.2 °C; 1H NMR (500 MHz, CDCl3) δ 7.91 (d, J = 8.1 Hz, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.38 (t, J = 7.6 Hz, 1H), 7.29 (t, J = 7.6 Hz, 1H), 7.13 (d, J = 8.0 Hz, 2H), 7.00 (d, J = 7.9 Hz, 2H), 6.40 (d, J = 15.8 Hz, 1H), 6.07 (dt, J = 15.8, 7.2 Hz, 1H), 4.59 (dd, J = 8.3, 6.5 Hz, 1H), 3.07-3.01 (m, 4H), 2.91 (s, 3H), 2.83-2.78 (m, 1H), 2.23 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 170.2, 169.7, 152.3, 137.2, 135.6, 134.3, 132.9, 129.2, 126.1, 126.0, 125.1, 124.8, 122.9, 121.8, 48.6, 38.4, 37.7, 36.2, 21.2. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C21H23N2OS 351.1526; found 351.1532. (E)-2-(benzo[d]thiazol-2-yl)-5-(2-methoxyphenyl)-N,N-dimethylpent-4-enamide (3e). Yellow liquid, 45.9 mg, yield = 63%; 1H NMR (500 MHz, CDCl3) δ 7.98 (d, J = 8.1 Hz, 1H), 7.87 (d, J = 7.9 Hz, 1H), 7.46-7.44 (m, 1H), 7.39-7.34 (m, 2H), 7.20-7.17 (m, 1H), 6.88 (t, J = 7.5 Hz, 1H), 6.83 (dd, J = 12.2, 3.7 Hz, 2H), 6.18 (dt, J = 15.8, 7.2 Hz, 1H), 4.69 (dd, J = 8.4, 6.5 Hz, 1H), 3.79 (s, 3H), 3.16- 3.11 (m, 4H), 3.00 (s, 3H), 2.95-2.89 (m, 1H). 13C{1H}

NMR (125 MHz, CDCl3) δ 170.3, 169.8, 156.5, 152.3, 135.7, 128.4, 127.8, 126.7, 126.5, 126.2, 125.9, 125.0,

122.8, 121.7, 120.6, 110.8, 55.4, 48.6, 38.8, 37.7, 36.2. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C21H23N2O2S 367.1475; found 367.1482. (E)-2-(benzo[d]thiazol-2-yl)-5-(3-methoxyphenyl)-N,N-dimethylpent-4-enamide (3f). Yellow solid, 64.6 mg, yield = 89%; mp. = 104.5-105.4 °C; 1H NMR (500 MHz, CDCl3) δ 7.98 (d, J = 8.1 Hz, 1H), 7.86 (d, J = 7.9 Hz, 1H), 7.46-7.44 (m, 1H), 7.38-7.35 (m, 1H), 7.18 (t, J = 7.9 Hz, 1H), 6.90 (d, J = 7.7 Hz, 1H), 6.854-6.83 (m, 1H), 6.75 (dd, J = 8.0, 2.3 Hz, 1H), 6.48 (d, J = 15.8 Hz, 1H), 6.20 (dt, J = 15.8, 7.2 Hz, 1H), 4.66 (dd, J = 8.4, 6.4 Hz, 1H), 3.78 (s, 3H), 3.18-3.11 (m, 4H), 2.99 (s, 3H), 2.92-2.86 (m, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 170.0, 169.5, 159.8, 152.4, 138.6, 135.6, 133.0, 129.5, 126.3, 126.0, 125.1, 122.9, 121.7, 118.9, 113.0, 111.6, 55.2, 48.5, 38.3, 37.7, 36.2. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C21H23N2O2S 367.1475; found 367.1484. (E)-2-(benzo[d]thiazol-2-yl)-5-(4-methoxyphenyl)-N,N-dimethylpent-4-enamide (3g). Yellow solid, 53.3 mg, yield = 73%; mp. = 93.3-93.6 °C; 1H NMR (500 MHz, CDCl3) δ 7.98 (d, J = 8.1 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.47-7.44 (m, 1H), 7.38-7.35 (m, 1H), 7.24 (d, J = 8.7 Hz, 2H), 6.81 (d, J = 8.7 Hz, 2H), 6.45 (d, J = 15.8 Hz, 1H), 6.05 (dt, J = 15.8, 7.2 Hz, 1H), 4.66 (dd, J = 8.3, 6.5 Hz, 1H), 3.78 (s, 3H), 3.14-3.08 (m, 4H), 2.99 (d, J = 5.5 Hz, 3H), 2.90-2.84 (m, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 170.2, 169.7, 159.0, 152.3, 135.6, 132.4, 129.9, 127.4, 126.0, 125.1, 123.6, 122.8, 121.7, 113.9, 55.3, 48.6, 38.4, 37.7, 36.2. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C21H23N2O2S 367.1475; found 367.1484. (E)-2-(benzo[d]thiazol-2-yl)-5-(4-bromophenyl)-N,N-dimethylpent-4-enamide (3h). White solid, 79.3 mg, yield = 96%; mp. = 174.3-176.4 °C; 1H NMR (500 MHz, CDCl3) δ 7.98 (d, J = 8.1 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.46 (dd, J = 8.0, 7.3 Hz, 1H), 7.38-7.36 (m, 3H), 7.15 (d, J = 8.4 Hz, 2H), 6.43 (d, J = 15.8 Hz, 1H), 6.19 (dt, J = 15.8, 7.2 Hz, 1H), 4.65 (dd, J = 8.1, 6.7 Hz, 1H), 3.14-3.09 (m, 4H), 2.99 (s, 3H), 2.92-2.86 (m, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 169.9, 169.3, 152.3, 136.0, 135.6, 131.9, 131.6, 127.8, 126.9, 126.0, 125.2, 122.9, 121.8, 121.1, 48.4, 38.2, 37.6, 36.2. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C20H20BrN2OS 415.0474; found 415.0479. (E)-2-(benzo[d]thiazol-2-yl)-5-(2-chlorophenyl)-N,N-dimethylpent-4-enamide (3i). White solid, 69.4 mg, yield = 94%; mp. = 95.4-96.9 °C; 1H NMR (500 MHz, CDCl3) δ 7.99 (d, J = 8.1 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.47-7.42 (m, 2H), 7.37 (t, J = 7.6 Hz, 1H), 7.30-7.27 (m, 1H), 7.17-7.10 (m, 2H), 6.86 (d, J = 15.8 Hz, 1H), 6.19 (dt, J = 15.7, 7.1 Hz, 1H), 4.70 (dd, J = 8.3, 6.6 Hz, 1H), 3.22-3.15 (m, 4H), 3.01 (s, 3H), 2.98-2.92 (m, 1H). 13C{1H}

NMR (125 MHz, CDCl3) δ 169.9, 169.4, 152.4, 135.6, 135.3, 132.8, 129.6, 129.2, 129.1, 128.4, 126.9, 126.8,

126.0, 125.2, 122.9, 121.8, 48.4, 38.2, 37.7, 36.2. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C20H20ClN2OS


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371.0979; found 371.0983. (E)-2-(benzo[d]thiazol-2-yl)-5-(3-chlorophenyl)-N,N-dimethylpent-4-enamide (3j). White solid, 72.5 mg, yield = 98%; mp. = 132.6-133.0 °C; 1H NMR (500 MHz, CDCl3) δ7.99 (d, J = 8.1 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.48-7.45 (m, 1H), 7.39-3.36 (m, 1H), 7.28 (s, 1H), 7.18-7.14 (m, 3H), 6.43 (d, J = 15.8 Hz, 1H), 6.21 (dt, J = 15.7, 7.2 Hz, 1H), 4.66 (dd, J = 8.2, 6.6 Hz, 1H), 3.17-3.11 (m, 4H), 3.00 (s, 3H), 2.93-2.87 (m, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 169.8, 169.3, 152.3, 139.0, 135.6, 134.4, 131.8, 129.7, 127.6, 127.3, 126.1, 126.2, 125.2, 124.5, 122.9, 121.8, 48.4, 38.1, 37.7, 36.2. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C20H20ClN2OS 371.0979; found 371.0984. (E)-2-(benzo[d]thiazol-2-yl)-5-(4-chlorophenyl)-N,N-dimethylpent-4-enamide (3k). White solid, 72.2 mg, yield = 98%; mp. = 166.3-167.5 °C; 1H NMR (500 MHz, CDCl3) δ7.90 (d, J = 8.1 Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.37 (dd, J = 11.2, 4.1 Hz, 1H), 7.28 (dd, J = 11.1, 4.1 Hz, 1H), 7.15 – 7.11 (m, 4H), 6.36 (d, J = 15.8 Hz, 1H), 6.08 (dt, J = 15.7, 7.2 Hz, 1H), 4.57 (dd, J = 8.0, 6.7 Hz, 1H), 3.07-3.01 (m, 4H), 2.91 (s, 3H), 2.84-2.78 (m, 1H). 13C{1H}

NMR (125 MHz, CDCl3) δ 168.9, 168.3, 151.3, 134.5, 131.9, 130.8, 127.6, 126.4, 125.6, 125.0, 124.1, 121.8,

120.7, 47.4, 37.1, 36.6, 35.2. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C20H20ClN2OS 371.0979; found 371.0986. (E)-2-(benzo[d]thiazol-2-yl)-5-(2-fluorophenyl)-N,N-dimethylpent-4-enamide (3l). White solid, 64.3 mg, yield = 91%; mp. = 107.3-109.1 °C; 1H NMR (500 MHz, CDCl3) δ 7.99 (d, J = 8.1 Hz, 1H), 7.87 (d, J = 7.7 Hz, 1H), 7.47-7.44 (m, 1H), 7.38-7.34 (m 2H), 7.17-7.13 (m, 1H), 7.03 (t, J = 7.5 Hz, 1H), 6.98 (dd, J = 10.1, 8.9 Hz, 1H), 6.65 (d, J = 16.0 Hz, 1H), 6.28 (dt, J = 15.9, 7.2 Hz, 1H), 4.69 (dd, J = 8.3, 6.6 Hz, 1H), 3.19-3.13 (m, 4H), 3.00 (s, 3H), 2.96-2.90 (m 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 170.0, 169.4, 160.0 (d, J = 247.4 Hz), 152.4, 135.6, 128.7 (d, J = 4.6), 128.6 (d, J = 8.3), 127.4 (d, J = 3.8 Hz), 126.0, 125.4 (d, J = 3.5 Hz), 125.1, 124.9 (d, J = 12.2 Hz), 124.0 (d, J = 3.5 Hz), 122.9, 121.7, 115.6 (d, J = 22.0 Hz), 48.4, 38.6, 37.7, 36.2. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C20H20FN2OS 355.1275; found 355.1281. (E)-2-(benzo[d]thiazol-2-yl)-5-(3-fluorophenyl)-N,N-dimethylpent-4-enamide (3m). White solid, 66.7 mg, yield = 94%; mp. = 113.7-114.0 °C; 1H NMR (500 MHz, CDCl3) δ 7.99 (d, J = 8.1 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.46 (t, J = 7.3 Hz, 1H), 7.37 (t, J = 7.6 Hz, 1H), 7.21 (m, 1H), 7.05 (d, J = 7.7 Hz, 1H), 7.00 (d, J = 10.2 Hz, 1H), 6.88 (td, J = 8.3, 1.9 Hz, 1H), 6.46 (d, J = 15.8 Hz, 1H), 6.21 (dt, J = 15.8, 7.3 Hz, 1H), 4.66 (dd, J = 8.1, 6.7 Hz, 1H), 3.17-3.11 (m, 4H), 3.00 (s, 3H), 2.93-2.89 (m, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 169.9, 169.3, 163.0 (d, J =243.6 Hz), 152.4, 139.5 (d, J = 7.6 Hz), 135.6, 132.0 (d, J = 2.4 Hz), 130.9 (d, J = 8.3 Hz), 127.5, 126.5, 125.2, 122.9, 122.2 (d, J = 2.7 Hz), 121.8, 114.1(d, J = 21.2 Hz), 112.6 (d, J = 21.6 Hz), 48.4, 38.1, 37.6, 36.2. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C20H20FN2OS 355.1275; found 355.1283. (E)-2-(benzo[d]thiazol-2-yl)-5-(4-fluorophenyl)-N,N-dimethylpent-4-enamide (3n). White solid, 68.4 mg, yield = 97%; mp. = 99.1-104.0 °C; 1H NMR (500 MHz, CDCl3) δ 7.99 (d, J = 8.1 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.48-7.45 (m, 1H), 7.39-7.36 (m, 1H), 7.27-7.24 (m, 2H), 6.97-6.93 (m, 2H), 6.46 (d, J = 15.8 Hz, 1H), 6.11 (dt, J = 15.8, 7.2 Hz, 1H), 4.66 (dd, J = 8.1, 6.7 Hz, 1H), 3.15-3.09 (m, 4H), 3.00 (s, 3H), 2.92-2.86 (m, 1H). 13C{1H}

NMR (125 MHz, CDCl3) δ 170.0, 169.5, 162.1 (d, J = 245.0 Hz), 152.3, 135.6, 133.2 (d, J = 3.2 Hz), 131.9,

127.7 (d, J = 7.9 Hz), 126.0, 125.7 (d, J = 2.1 Hz), 125.2, 122.9, 121.8, 115.3 (d, J = 21.4 Hz), 48.5, 38.2, 37.7, 36.2. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C20H20FN2OS 355.1275; found 355.1284. (E)-2-(benzo[d]thiazol-2-yl)-5-(2,6-dichlorophenyl)-N,N-dimethylpent-4-enamide (3o).Yellow liquid, 66.3 mg, yield = 83%; 1H NMR (500 MHz, CDCl3) δ 7.98 (d, J = 8.1 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.46 (t, J = 7.7 Hz, 1H), 7.37 (t, J = 7.6 Hz, 1H), 7.24 (d, J = 8.0 Hz, 2H), 7.03 (t, J = 8.0 Hz, 1H), 6.46 (d, J = 16.1 Hz, 1H), 6.18 (dt, J = 16.0, 7.2 Hz, 1H), 4.76 (dd, J = 8.3, 6.7 Hz, 1H), 3.25-3.17 (m, 4H), 3.01-2.94 (m, 4H). 13C{1H} NMR (125 MHz, CDCl3) δ 169.9, 169.4, 152.3, 135.7, 134.7, 134.6, 134.3, 128.3, 128.0, 126.8, 126.0, 125.1, 122.8, 121.7, 48.1, 38.5, 37.8, 36.2. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C20H19Cl2N2OS 405.0590; found 405.0597.



(E)-2-(benzo[d]thiazol-2-yl)-5-(4-ethylphenyl)-N,N-dimethylpent-4-enamide (3p). Yellow solid, 67.8 mg, yield = 93%; mp. = 102.4-103.2 °C; 1H NMR (500 MHz, CDCl3) δ 7.98 (d, J = 8.1 Hz, 1H), 7.86 (d, J = 7.9 Hz, 1H), 7.47-7.43 (m, 1H), 7.38-7.34 (m, 1H), 7.23 (d, J = 8.1 Hz, 2H), 7.10 (d, J = 8.1 Hz, 2H), 6.49 (d, J = 15.8 Hz, 1H), 6.15 (dt, J = 15.7, 7.3 Hz, 1H), 4.66 (dd, J = 8.4, 6.4 Hz, 1H), 3.16 -3.09 (m, 4H), 2.99 (s, 3H), 2.91-2.85 (m, 1H), 2.60 (q, J = 7.6 Hz, 2H), 1.20 (t, J = 7.6 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 170.1, 169.2, 152.3, 143.6, 135.6, 134.6, 133.0, 128.0, 126.2, 126.0, 125.1, 124.9, 122.9, 121.8, 48.6, 38.4, 37.7, 36.2, 28.6, 15.6. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C22H25N2OS 365.1682; found 365.1689. (E)-2-(benzo[d]thiazol-2-yl)-5-(2,6-dimethoxyphenyl)-N,N-dimethylpent-4-enamide (3q). Yellow liquid, 45.1 mg, yield = 57%; 1H NMR (500 MHz, CDCl3) δ7.91 (d, J = 8.1 Hz, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.38 (t, J = 7.6 Hz, 1H), 7.29 (t, J = 7.6 Hz, 1H), 7.13 (d, J = 8.0 Hz, 2H), 7.00 (d, J = 7.9 Hz, 2H), 6.40 (d, J = 15.8 Hz, 1H), 6.56 (dt, J = 15, 10 Hz 1H), 6.51 (d, J = 10.0 Hz, 2H), 4.59 (dd, J = 8.3, 6.5 Hz, 1H), 3.08 – 3.01 (m, 4H), 2.91 (d, J = 6.3 Hz, 3H), 2.95 – 2.98 (m, 1H), 2.23 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 170.7, 170.3, 158.3, 152.3, 135.8, 130.0, 127.8, 125.8, 124.9, 123.4, 122.7, 121.7, 114.4, 103.9, 55.7, 48.7, 40.4, 37.8, 36.2. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C22H25N2O3S 397.1580; found 397.1574. (E)-2-(benzo[d]thiazol-2-yl)-5-(3-ethoxy-4-methylphenyl)-N,N-dimethylpent-4-enamide (3r). Yellow liquid, 49.6 mg, yield = 63%; mp. = 102.4-103.2 °C; 1H NMR (500 MHz, CDCl3) δ 7.99-7.97 (m, 1H), 7.88-7.86 (m, 1H), 7.48-7.45 (m, 1H), 7.37-7.36 (m, 1H), 6.86-6.83 (m, 2H), 6.78 (d, J = 8.1 Hz, 1H), 6.43 (d, J = 15.8 Hz, 1H), 6.05 (dt, J = 15.6, 7.3 Hz, 1H), 4.66 (dd, J = 8.4, 6.5 Hz, 1H), 4.08 (q, J = 7.0 Hz, 2H), 3.85 (s, 3H), 3.16-3.09 (m, 4H), 3.00 (s, 3H), 2.90-2.84 (m, 1H), 1.46 (t, J = 7.0 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 170.1, 169.6, 152.3, 148.9, 148.3, 135.6, 132.8, 130.2, 126.0, 125.1, 123.9, 122.8, 121.7, 119.2, 111.3, 110.3, 64.3, 56.0, 48.7, 38.3, 37.7, 36.2, 14.8. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C23H27N2O2S 394.1701; found 394.1706. (E)-2-(benzo[d]thiazol-2-yl)-N,N-dimethyl-5-(4-(trifluoromethyl)phenyl)pent-4-enamide (3s) Yellow solid, 79.7 mg, yield = 99%; mp. = 147.7-148.3 °C; 1H NMR (500 MHz, CDCl3) δ 7.99 (d, J = 8.1 Hz, 1H), 7.88 (d, J = 8.0 Hz, 1H), 7.51 (d, J = 8.2 Hz, 2H), 7.49-7.45 (m, 1H), 7.40-7.37 (m, 3H), 6.53 (d, J = 15.8 Hz, 1H), 6.31 (dt, J = 15.8, 7.3 Hz, 1H), 4.67 (dd, J = 8.0, 6.8 Hz, 1H), 3.19-3.14 (m, 4H), 3.01 (s, 3H), 2.96-2.90 (m, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 169.8, 169.2, 152.3, 140.5, 135.5, 131.8, 129.1 (q, J = 32.3 Hz), 128.9, 126.4, 126.1, 125.5 (q, J = 3.7 Hz), 125.2, 124.2 (q, J = 270.2 Hz), 122.9, 121.8, 48.3, 38.1, 37.6, 36.2. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C21H20F3N2OS 405.1243; found 405.1236. (E)-2-(benzo[d]thiazol-2-yl)-N,N-dimethyl-5-(4-nitrophenyl)pent-4-enamide (3t). Yellow solid, 70.8 mg, yield = 93%; mp. = 196.4-198.2 °C; 1H NMR (500 MHz, CDCl3) δ 8.04 (d, J = 8.8 Hz, 2H), 7.91 (d, J = 8.1 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.42-7.38 (m, 1H), 7.34-7.30 (m, 3H), 6.48 (d, J = 15.8 Hz, 1H), 6.32 (dt, J = 15.7, 7.2 Hz, 1H), 4.60 (dd, J = 7.7, 7.2 Hz, 1H), 3.14-3.06 (m, 4H), 2.94 (s, 3H), 2.91-2.86 (m, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 169.6, 168.9, 152.3, 146.8, 143.5, 135.5, 131.4, 131.2, 126.7, 126.2, 125.3, 124.0, 122.9, 121.8, 48.2, 38.1, 37.6, 36.3. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C20H20N3O3S 382.1220; found 382.1214. (E)-2-(benzo[d]thiazol-2-yl)-5-(4-(tert-butyl)phenyl)-N,N-dimethylpent-4-enamide (3u). Yellow liquid, 71.2 mg, yield = 91%; 1H NMR (500 MHz, CDCl3) δ 7.98 (d, J = 8.1 Hz, 1H), 7.86 (d, J = 7.9 Hz, 1H), 7.47-7.44 (m, 1H), 7.38-7.34 (m, 1H), 7.31-7.24 (m, 4H), 6.50 (d, J = 15.8 Hz, 1H), 6.16 (dt, J = 15.8, 7.4 Hz, 1H), 4.66 (dd, J = 8.5, 6.4 Hz, 1H), 3.16-3.09 (m, 4H), 2.99 (s, 3H), 2.91-2.85 (m, 1H), 1.29 (s, 9H). 13C{1H} NMR (125 MHz, CDCl3) δ 170.1, 169.7, 152.3, 150.5, 135.6, 134.4, 132.8, 126.0, 125.4, 125.1, 125.1, 122.9, 121.8, 48.6, 38.4, 37.7, 36.2, 34.6, 31.3. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C24H29N2OS 393.1995; found 393.2000. (E)-2-(benzo[d]thiazol-2-yl)-5-(4-isobutylphenyl)-N,N-dimethylpent-4-enamide (3v). Yellow solid, 70.4 mg, yield = 90%; mp. = 99.1-100.5 °C; 1H NMR (500 MHz, CDCl3) δ 7.98 (d, J = 8.1 Hz, 1H), 7.86 (d, J = 7.9 Hz, 1H), 7.47-7.44 (m, 1H), 7.38-7.35 (m, 1H), 7.22 (d, J = 8.0 Hz, 2H), 7.05 (d, J = 8.0 Hz, 2H), 6.49 (d, J = 15.8 Hz, 1H), 6.16 (dt, J = 15.8, 7.3 Hz, 1H), 4.66 (dd, J = 8.4, 6.4 Hz, 1H), 3.16-3.10 (m, 4H), 2.99 (s, 3H), 2.91-2.85


Page 10 of 18

Page 11 of 18 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


(m, 1H), 2.42 (d, J = 7.2 Hz, 2H), 1.82 (dt, J = 13.5, 6.8 Hz, 1H), 0.88 (d, J = 6.6 Hz, 6H). 13C{1H} NMR (125 MHz, CDCl3) δ 170.1, 169.7, 152.3, 141.1, 135.6, 134.6, 133.0, 129.3, 126.0, 126.0, 125.1, 124.9, 122.7, 121.6, 48.6, 45.1, 38.4, 37.7, 36.2, 30.2, 22.4. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C24H29N2OS 393.1995; found 393.1992. (E)-2-(benzo[d]thiazol-2-yl)-N,N-dimethyl-5-(thiophen-2-yl)pent-4-enamide (3w). Yellow solid, 55.7 mg, yield = 82%; mp. = 63.9-74.9 °C; 1H NMR (500 MHz, CDCl3) δ 7.98 (d, J = 8.1 Hz, 1H), 7.86 (d, J = 8.0 Hz, 1H), 7.45 (t, J = 7.6 Hz, 1H), 7.37 (t, J = 7.5 Hz, 1H), 7.09 (d, J = 5.0 Hz, 1H), 6.92-6.90 (m, 1H), 6.86 (d, J = 3.3 Hz, 1H), 6.63 (d, J = 15.7 Hz, 1H), 6.02 (dt, J = 15.6, 7.4 Hz, 1H), 4.65 (dd, J = 8.4, 6.4 Hz, 1H), 3.16-3.07 (m, 4H), 2.99 (d, J = 7.2 Hz, 3H), 2.88-2.82 (m, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 170.0, 169.4, 152.3, 142.1, 135.6, 127.3, 126.3, 126.0, 125.6, 125.3, 125.1, 123.9, 122.9, 121.8, 48.3, 38.2, 37.7, 36.2. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C18H19N2OS2 343.0933; found 343.0927. (E)-2-(benzo[d]thiazol-2-yl)-N,N-dimethyl-5-(naphthalen-2-yl)pent-4-enamide (3x). Yellow solid, 74.7 mg, yield = 97%; mp. = 188.7-190.0 °C; 1H NMR (500 MHz, CDCl3) δ 7.92 (d, J = 8.1 Hz, 1H), 7.80 (d, J = 7.9 Hz, 1H), 7.68 (d, J = 9.1 Hz, 2H), 7.65 (d, J = 8.5 Hz, 1H), 7.57 (s, 1H), 7.44 (dd, J = 8.6, 1.5 Hz, 1H), 7.40-7.27 (m, 4H), 6.58 (d, J = 15.8 Hz, 1H), 6.25 (dt, J = 15.8, 7.3 Hz, 1H), 4.63 (dd, J = 8.3, 6.5 Hz, 1H), 3.15-3.08 (m, 1H), 3.07 (s, 3H), 2.92 (s, 3H), 2.90-2.85 (m, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 169.0, 168.5, 151.3, 134.6, 133.5, 132.5, 132.1, 131.8, 127.1, 126.9, 126.6, 125.3, 125.2, 125.0, 124.7, 124.1, 122.5, 121.8, 120.7, 47.5, 37.4, 36.6, 35.2. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C24H23N2OS 387.1523; found 387.1529. (E)-5-([1,1'-biphenyl]-4-yl)-2-(benzo[d]thiazol-2-yl)-N,N-dimethylpent-4-enamide (3y). Yellow solid, 73.3 mg, yield = 85%; mp. = 78.1-78.9°C; 1H NMR (500 MHz, CDCl3) δ 7.99 (d, J = 8.1 Hz, 1H), 7.87 (d, J = 7.9 Hz, 1H), 7.56 (d, J = 7.3 Hz, 2H), 7.51 (d, J = 8.2 Hz, 2H), 7.48-7.44 (m, 1H), 7.41 (t, J = 7.7 Hz, 2H), 7.37 (d, J = 8.2 Hz, 3H), 7.32 (t, J = 7.4 Hz, 1H), 6.54 (d, J = 15.8 Hz, 1H), 6.25 (dt, J = 15.8, 7.3 Hz, 1H), 4.68 (dd, J = 8.3, 6.5 Hz, 1H), 3.21-3.14 (m, 4H), 3.00 (s, 3H), 2.95-2.89 (m, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 170.1, 169.6, 152.4, 140.7, 140.2, 136.2, 135.6, 132.6, 128.8, 127.3, 127.2, 126.9, 126.7, 126.1, 126.0, 125.2, 122.9, 121.8, 48.6, 38.4, 37.7, 36.2. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C26H25N2OS 413.1682; found 413.1682. (E)-2-(benzo[d]thiazol-2-yl)-N,N-dimethylhept-4-enamide (3z). Colorless liquid, 22 mg, yield = 38%; 1H NMR (500 MHz, CDCl3) δ7.97 (d, J = 8.2 Hz, 1H), 7.86 (d, J = 8.0 Hz, 1H), 7.45 (t, J = 7.7 Hz, 1H), 7.36 (t, J = 7.6 Hz, 1H), 5.61-5.55 (m, 1H), 5.42-5.36 (m, 1H), 4.57 (t, J = 7.1 Hz, 1H), 3.16 (s, 3H), 2.99 (s, 3H), 2.91-2.85 (m, 1H), 2.71-2.66 (m, 1H), 1.98-1.93 (m, 2H), 1.69 (s, 2H), 0.89 (t, J = 7.4 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 170.5, 170.0, 152.3, 135.9, 135.7, 125.8, 124.9, 124.5, 122.8, 121.7, 48.6, 38.1, 37.7, 36.1, 25.5, 13.6. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C16H21N2OS 289.1369; found 289.1370. 2-(benzo[d]thiazol-2-yl)-N,N-dimethylpent-4-enamide (3aa). Yellow liquid, 47.7 mg, yield = 92%; 1H NMR (500 MHz, CDCl3) δ 7.98 (d, J = 7.9 Hz, 1H), 7.87 (dd, J = 8.0, 0.4 Hz, 1H), 7.47-7.44 (m, 1H), 7.38-7.35 (m, 1H), 5.84-5.76 (m, 1H), 5.14 (dd, J = 17.1, 1.5 Hz, 1H), 5.06-5.03 (m, 1H), 4.62 (dd, J = 8.0, 7.0 Hz, 1H), 3.16 (s, 3H), 3.00-2.94 (m, 4H), 2.78-2.73 (m, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 170.1, 169.7, 152.3, 135.6, 134.3, 126.0, 125.1, 122.8, 121.7, 117.9, 48.1, 38.9, 37.7, 36.2. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C14H17N2OS 261.1056; found 261.1056. (E)-2-(benzo[d]thiazol-2-yl)-N,N,3-trimethyl-5-phenylpent-4-enamide (3ab). 62.4 mg, yield = 89%, dr (1.1:1); Major diastereomer: white solid, mp. = 147.3-147.7 °C; 1H NMR (500 MHz, CDCl3) δ 8.00 (d, J = 8.1 Hz, 1H), 7.88 (d, J = 8.0 Hz, 1H), 7.46 (t, J = 7.6 Hz, 1H), 7.39-7.35 (m, 3H), 7.31 (t, J = 7.6 Hz, 2H), 7.22 (t, J = 7.2 Hz, 1H), 6.55 (d, J = 15.9 Hz, 1H), 6.21 (dd, J = 15.9, 8.0 Hz, 1H), 4.48 (d, J = 10.2 Hz, 1H), 3.34-3.26 (m, 1H), 3.12 (s, 3H), 2.92 (s, 3H), 1.06 (d, J = 6.8 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 170.5, 169.1, 152.0, 137.2, 136.0, 131.7, 131.0, 128.6, 127.4, 126.3, 125.9, 125.1, 122.8, 121.7, 54.4, 42.6, 37.8, 36.1, 17.8. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C21H23N2OS 351.1526; found 351.1522. Minor diastereomer: white solid, mp. = 147.3-147.7 °C; 1H NMR (500 MHz, CDCl3) δ 7.92 (d, J = 8.1 Hz, 1H),



7.81 (d, J = 8.0 Hz, 1H), 7.41-7.38 (m, 1H), 7.31 (t, J = 7.6 Hz, 1H), 7.19-7.09 (m, 5H), 6.34 (d, J = 15.8 Hz, 1H), 6.05 (dd, J = 15.8, 8.5 Hz, 1H), 4.53 (d, J = 10.0 Hz, 1H), 3.38-3.30 (m, 1H), 3.22 (s, 3H), 3.01 (s, 3H), 1.25 (d, J = 6.6 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 170.2, 169.1, 152.0, 137.2, 135.8, 131.6, 131.0, 128.3, 127.1, 126.2, 125.8, 125.0, 122.7, 121.7, 54.0, 42.62, 37.9, 36.2, 19.5. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C21H23N2OS 351.1526; found 351.1524. (E)-2-(benzo[d]oxazol-2-yl)-N,N-dimethyl-5-phenylpent-4-enamide (4a). Yellow liquid, 32.5 mg, yield = 51%; 1H

NMR (500 MHz, CDCl3) δ 7.71 (dd, J = 6.1, 2.9 Hz, 1H), 7.53 (dd, J = 6.1, 3.0 Hz, 1H), 7.35-7.31 (m, 2H),

7.30-7.25 (m, 4H), 7.19 (t, J = 7.1 Hz, 1H), 6.52 (d, J = 15.8 Hz, 1H), 6.23 (dt, J = 15.8, 7.2 Hz, 1H), 4.40 (t, J = 7.4 Hz, 1H), 3.20-3.15 (m, 4H), 3.09-3.01 (m, 4H). 13C{1H} NMR (125 MHz, CDCl3) δ 167.9, 163.4, 150.9, 140.9, 137.1, 132.9, 128.5, 127.4, 126.2, 126.2, 125.1, 124.4, 120.0, 110.8, 43.9, 37.6, 36.3, 34.1. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C20H21N2O2 321.1598; found 321.1593. (E)-2-(isoquinolin-1-yl)-N,N-dimethyl-5-phenylpent-4-enamide (4b). Yellow liquid, 57.9 mg, yield (88%); 1H NMR (500 MHz, CDCl3) δ 8.42 (d, J = 5.7 Hz, 1H), 8.23 (d, J = 8.4 Hz, 1H), 7.77 (d, J = 8.0 Hz, 1H), 7.61 (t, J = 7.5 Hz, 1H), 7.55 (t, J = 7.5 Hz, 1H), 7.47 (d, J = 5.6 Hz, 1H), 7.19-7.14 (m, 4H), 7.07 (t, J = 6.9 Hz, 1H), 6.33 (d, J = 15.9 Hz, 1H), 6.28-6.23 (m, 1H), 4.65 (dd, J = 8.4, 5.7 Hz, 1H), 3.25-3.20 (m, 1H), 2.91 (s, 3H), 2.75-2.69 (m, 1H), 2.60 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 171.5, 159.1, 142.3, 137.5, 136.8, 131.5, 130.1, 129.0, 128.4, 127.9, 127.7, 127.0, 126.4, 126.1, 124.5, 120.0, 50.5, 37.0, 36.6, 36.1. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C22H23N2O 331.1805; found 331.1803. (E)-2-(1l4-quinolin-1-yl)-N,N-dimethyl-5-phenylpent-4-enamide (4c). Colorless liquid, 61.4 mg, yield = 93%; 1H

NMR (500 MHz, CDCl3) δ 8.13 (d, J = 8.6 Hz, 1H), 8.06 (d, J = 8.5 Hz, 1H), 7.80 (d, J = 8.1 Hz, 1H), 7.70 (t,

J = 7.7 Hz, 1H), 7.58 (d, J = 8.6 Hz, 1H), 7.52 (t, J = 7.5 Hz, 1H), 7.29-7.23 (m, 4H), 7.16 (t, J = 7.1 Hz, 1H), 6.46 (d, J = 15.8 Hz, 1H), 6.24 (dt, J = 15.8, 7.1 Hz, 1H), 4.41 (dd, J = 8.5, 6.3 Hz, 1H), 3.19-3.14 (m, 1H), 3.06 (s, 3H), 2.95 (s, 3H), 2.82-2.76 (m, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 171.4, 159.8, 147.7, 137.5, 137.1, 132.1, 129.6, 129.0, 128.4, 127.7, 127.6, 127.3, 127.1, 126.3, 126.2, 119.6, 53.0, 37.4, 37.0, 36.0. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C22H23N2O 331.1805; found 331.1810. (E)-N,N-dimethyl-2-(6-methylbenzo[d]thiazol-2-yl)-5-phenylpent-4-enamide (4d). Yellow solid, 40.4 mg, yield = 58%; mp. = 106.7-106.8 °C; 1H NMR (500 MHz, CDCl3) δ 7.85 (d, J = 8.3 Hz, 1H), 7.65 (s, 1H), 7.30-7.25 (m, 5H), 7.20-7.17 (m, 1H), 6.50 (d, J = 15.8 Hz, 1H), 6.19 (dt, J = 15, 10 Hz, 1H), 4.63 (dd, J = 8.3, 6.5 Hz, 1H), 3.17-3.09 (m, 4H), 2.99 (s, 3H), 2.91-2.85 (m, 1H), 2.47 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ 170.1, 168.4, 150.5, 137.2, 135.8, 135.2, 133.0, 128.5, 127.6, 127.4, 126.2, 126.1, 122.3, 121.5, 48.5, 38.3, 37.6, 36.2, 21.5. HRMS (ESI+TOF) calcd for C21H23N2OS (M+H)+, m/z 351.1526, found 351.1525. (E)-N,N-dimethyl-5-phenyl-2-(6-(trifluoromethyl)benzo[d]thiazol-2-yl)pent-4-enamide (4e). Yellow solid, 75.1 mg, yield = 93%; 1H NMR (500 MHz, CDCl3) δ 8.16 (s, 1H), 8.06 (d, J = 8.5 Hz, 1H), 7.69 (dd, J = 8.5, 1.2 Hz, 1H), 7.31-7.26 (m, 4H), 7.21-7.19 (m, 1H), 6.51 (d, J = 15.8 Hz, 1H), 6.18 (dt, J = 15.5 Hz, 1H), 4.74-4.71 (m, 1H), 3.16-3.10 (m, 4H), 3.01 (s, 3H), 2.95-2.89 (m, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 173.0, 169.8, 154.3, 136.9, 135.8, 133.4, 128.6, 127.5,127.3 (q, J = 32.4 Hz), 126.2, 125.3, 124.2 (q, J = 270.7 Hz), 123.3, 123.0 (q, J = 3.4 Hz), 119.4 (q, J = 4.2 Hz), 48.5, 38.5, 37.7, 36.2. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C21H20F3N2OS 405.1243; found 405.1238. (E)-2-(benzo[d]thiazol-2-yl)-1-morpholino-5-phenylpent-4-en-1-one (4f). Yellow solid, 57.2 mg, yield = 76%; mp. = 99.0-99.6 °C; 1H NMR (500 MHz, CDCl3) δ 7.98 (d, J = 8.1 Hz, 1H), 7.88 (d, J = 7.9 Hz, 1H), 7.49-7.46 (m, 1H), 7.41-7.38 (m, 1H), 7.31-7.28 (m, 4H), 7.22-7.19 (m, 1H), 6.52 (d, J = 15.8 Hz, 1H), 6.20 (dt, J = 15.8, 7.3 Hz, 1H), 4.61 (dd, J = 8.3, 6.5 Hz, 1H), 3.81-3.71 (m, 2H), 3.65-3.55 (m, 5H), 3.41-3.37 (m, 1H), 3.20-3.14 (m, 1H), 2.95-2.89 (m, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 169.2, 168.5, 152.4, 137.0, 135.5, 133.3, 128.6, 127.5, 126.2, 126.1, 125.8, 125.3, 122.9, 121.8, 66.7, 66.6, 48.2, 46.5, 42.8, 37.9. HRMS (ESI+TOF) m/z: [M+H]+ calcd


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for C22H23N2O2S 379.1475; found 379.1466. (E)-2-(benzo[d]thiazol-2-yl)-N-methyl-5-phenylpent-4-enamide (4g). Yellow solid, 35 mg, yield = 55%; mp. = 117.9-119.2 °C; 1H NMR (500 MHz, CDCl3) δ 7.97 (d, J = 8.1 Hz, 1H), 7.86 (d, J = 7.9 Hz, 1H), 7.47-7.44 (m, 1H), 7.39-7.36 (m, 1H), 7.27-7.22 (m, 4H), 7.19-7.16 (m, 1H), 7.07 (d, J = 4.4 Hz, 1H), 6.47 (d, J = 15.8 Hz, 1H), 6.15 (dt, J = 15.7, 7.2 Hz, 1H), 4.17 (t, J = 7.3 Hz, 1H), 3.17-3.12 (m, 1H), 3.01-2.95 (m, 1H), 2.81 (d, J = 4.8 Hz, 3H). 13C{1H}

NMR (125 MHz, CDCl3) δ 170.1, 169.8, 152.6, 137.0, 135.1, 133.2, 128.5, 127.4, 126.2, 125.6, 125.3, 122.8,

121.8, 52.4, 37.6, 26.6. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C19H19N2OS 323.1213; found 323.1217.

Procedure for gram-scale reaction: To a mixture of (PhO)2PO2H (0.4 mmol, 0.25 g, 8 mol%), 2-(benzo[d]thiazol-2-yl)acetamide (1, 5.0 mmol, 1.10 g, 1.0 equiv) in water (50 mL) in a 100 ml round-bottom flask were added allylic alcohol (2, 6.0 mmol, 0.81 g, 1.2 equiv) and Pd(PPh3)4 (0.2 mmol, 0.23 g, 4 mol%). Then, the reaction mixture was stirred at 100 oC

until the completion of the reaction (monitored by TLC). The reaction mixture was quenched with

water and extracted with ethyl acetate (50 mL × 3). The organic layer was dried over Na2SO4 and evaporated in vacuum. The residue was purified by silica gel column chromatography (petroleum ether/EtOAc = 50:1 to 10:1) to afford the desired product 3a (1.48 g, 88%) as white solid.

Experimental Procedure for the hydrogenation of 3a with Pd/C and H2. To a 10 mL oven falsk, (E)-2-(benzo[d]thiazol-2-yl)-N,N-dimethyl-5-phenylpent-4-enamide (3ª, 0.2 mmol) and MeOH (4.0 mL) were added, floowed by carefully addition of Pd/C (20 mg) at rt. The reaction mixture was allowed to stir at rt for 12 h under a hydrogen atomosphere with a hydrogen ballom. The reaction was filtered and concentrated under vacuo, and the crude product was purified by flash column chromatography (5:1 petroleum ether/ethyl acetate, visualized with UV) to afford product 5 (67 mg, 99% yield). 2-(benzo[d]thiazol-2-yl)-N,N-dimethyl-5-phenylpentanamide (5). Colorless liquid, 67 mg, yield = 99%; 1H NMR (500 MHz, CDCl3) δ 7.96 (d, J = 8.2 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.43 (t, J = 7.7 Hz, 1H), 7.34 (t, J = 7.6 Hz, 1H), 7.23 (t, J = 7.2 Hz, 2H), 7.16-7.13 (m, 3H), 4.52 (t, J = 7.3 Hz, 1H), 3.11 (d, J = 1.1 Hz, 3H), 2.96 (d, J = 1.1 Hz, 3H), 2.71-2.58 (m, 2H), 2.29-2.22 (m, 1H), 2.09-2.02 (m, 1H), 1.76-1.58 (m, 2H). 13C{1H} NMR (125 MHz, CDCl3) δ 170.6, 170.3, 152.3, 141.8, 135.6, 128.4, 128.4, 125.9, 125.9, 125.0, 122.8, 121.7, 48.1, 37.6, 36.1, 35.6, 34.5, 29.2. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C20H23N2OS 339.1526; found 339.1529.

Experimental Procedure for the reduction of 3a with LiAlH4. To a 10 mL oven falsk, (E)-2-(benzo[d]thiazol-2-yl)-N,N-dimethyl-5-phenylpent-4-enamide (3ª, 0.2 mmol) and anhydrous THF (4.0 mL) were added, floowed by carefully addition of LiAlH4 (0.2 mmol) at 0 oC. The reaction mixture was then warm to rt and allowed to stir at 100 oC for 4 h. The reaction was quenched with water and extracted with EtOAc, combied orgainc mixture was dried with Na2SO4 and concentrated in vacuo, and the crude product was purified by flash column chromatography (5:1 petroleum ether/ethyl acetate, visualized with UV) to afford product 6 (27 mg, 51% yield). (E)-2-(4-phenylbut-3-en-1-yl)benzo[d]thiazole (6). Yellow solid, 27 mg, yield = 51%; mp. = 74.7-76.6 °C; 1H NMR (500 MHz, Chloroform-d) δ 7.98 (d, J = 8.2 Hz, 1H), 7.84 (dd, J = 8.0, 1.1 Hz, 1H), 7.46 (t, J = 7.7 Hz, 1H), 7.37-7.33 (m, 3H), 7.29 (t, J = 7.7 Hz, 2H), 7.20 (t, J = 7.2 Hz, 1H), 6.50 (d, J = 16.0 Hz, 1H), 6.29 (dt, J = 15.7, 6.8 Hz, 1H), 3.30 (t, J = 7.9 Hz, 2H), 2.84 (m, 2H). 13C{1H} NMR (125 MHz, CDCl3) δ 171.0, 153.2, 137.3, 135.2, 131.6, 128.5, 128.1, 127.2, 126.1, 125.9, 124.7, 122.6, 121.5, 34.2, 32.7. HRMS (ESI+TOF) m/z: [M+H]+ calcd for C17H16NS 266.0998; found 266.1003.



ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc. Copies of 1H, 19F, and 13C NMR spectra of all new compounds.

AUTHOR INFORMATION Corresponding Author *E-mail: [email protected] (X.-F. Zeng) *E-mail: [email protected] (G.-F. Zhong)

ORCID Xiaofei Zeng: 0000-0003-4222-1365 Guofu Zhong: 0000-0001-9497-9069

Notes The authors declare no competing financial interest

Aknowlegdements We gratefully acknowledge the Natural Science Foundation of China (No. 21672048), the Natural Science Foundation of Zhejiang Province (LY18B020015), and Hangzhou Normal Uni-versity for financial support. X.Z. acknowledges a Xihu Scholar award from Hangzhou City, and G.Z. acknowledges a Qianjiang Scholar from Zhejiang Province in China.

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Palladium-Catalyzed Allylic Substitution Reaction of

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