Cross dehydrogenative coupling strategy for allylation of benzylanilines promoted by DDQ

Journal Pre-proof Cross dehydrogenative coupling strategy for allylation of benzylanilines promoted by DDQ Ruimei Xiong, Muhammad Ijaz Hussain, Qing Liu, Wen Xia, Yan Xiong PII:

S0040-4020(19)31200-1

DOI:

https://doi.org/10.1016/j.tet.2019.130798

Reference:

TET 130798

To appear in:

Tetrahedron

Received Date: 3 September 2019 Revised Date:

9 November 2019

Accepted Date: 12 November 2019

Please cite this article as: Xiong R, Hussain MI, Liu Q, Xia W, Xiong Y, Cross dehydrogenative coupling strategy for allylation of benzylanilines promoted by DDQ, Tetrahedron (2019), doi: https:// doi.org/10.1016/j.tet.2019.130798. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Ltd.

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Cross Dehydrogenative Coupling Strategy for Allylation of N-Benzylanilines Promoted by DDQ Ruimei Xionga, Muhammad Ijaz Hussainb, Qing Liua, Wen Xiaa, Yan Xionga,∗

n Bu3Sn H N

DDQ

No products (with NMR evidence)

R2

H N

R1 DDQ

n Bu3Sn

R2

R1

R2 = aryl, styryl yields: up to 99%

1

Tetrahedron journal homepage: www.elsevier.com

Cross Dehydrogenative Coupling Strategy for Allylation of Benzylanilines Promoted by DDQ Ruimei Xionga, Muhammad Ijaz Hussainb, Qing Liua, Wen Xiaa, Yan Xionga,∗ a a

School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 401331, China Department of Chemistry, Ghazi University, Dera Gazi Khan, Punjab 32200, Pakistan

ARTICLE INFO

ABSTRACT

Article history: Received Received in revised form Accepted Available online

A cross dehydrogenative coupling strategy for allylation of benzylanilines promoted by DDQ is reported, which uses nonmetallic quinone DDQ as an oxidant in the allylation of N-benzylanilines under mild conditions. C-C bond with high selectivity and activity was constructed in this reaction and homoallylic amines were obtained with yields of up to 99% . 2019 Elsevier Ltd. All rights reserved.

Keywords: Allylation Benzyl aniline DDQ Dehydrogenative coupling Homoallylic amines

1.Introduction Homoallylic amines with extensive biological profile, especially in terms of antifungal effects, are key motifs in natural products and drug molecules[1-5]. Moreover, homoallylic amines are also important organic synthesis intermediates, which are often used to synthesize nitrogen-containing heterocyclic compounds[6-8]. Several previously reported synthetic methodologies to excess homoallylic amine-based compounds can be divided into the following three categories: 1) C–H bond oxidation of α-position of the amino group to generate iminium cation in situ, which is available to accept the nucleophilic attack[9-13]; 2) cooking reaction of three components of aldehydes, amines and allyl reagents[14-16]; 3) addition reaction of imine with allylic metal reagents [17-18]. Among these methods, for the reported α-C–H bond oxidation, transition metals such as silver and iron were indispensable. Therefore, the metal free synthetic way was highly expected to pursue. Recently our approaches to access phosphonation and cyanidation reactions of N-alkyl anilines through α-C–H oxidaiton by DDQ, as depicted in Scheme 1, have been successfully achieved[19]. Following our interests in the development of oxidation coupling reaction in a transition-metal free system[20], our group attempted to prepare homoallylic amine derivatives through direct allylation reactions of amine compounds. In view of the unique oxidability of DDQ, we continued to conduct an extended study on the coupling reaction ——— system between benzylaniline substrates and nucleophile

oxidized by DDQ, and hereby report DDQ promoted green and efficient direct cross dehydrogenative coupling strategy for allylation reactions of amines.

Scheme 1. Phosphonation, cyanidation and allylation oxidized by DDQ.

2. Results and discussion Preliminary endeavors were focused on product yield optimization. Considering further development of the reaction system and the excellent chemical selectivity of allyltin reagent[21], we first attempted to investigate the efficiency of allyltributyltin as allyl reagent and successfully obtained the corresponding allyl products. Initial screening with N-benzyl aniline and allyltributytin in THF afforded homoallylic amine 2a in a 27% yield in 2 hours. Encouraged by the preliminary results, we then investigated the effects of the types of oxidants and their amounts on the reaction yields, which are summarized in Table 1. Table 1. Screening of different oxidants and amounts.a

* Corresponding author. School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 401331, China. E-mail address: [email protected] (Y. Xiong)

2

Tetrahedron

Entry

Quinones

(x equiv)a

1 2 3 4 5 6 7 8 9

Q1 Q2 Q3 Q4 Q1 Q1 Q1 Q1 Q1

1.5 1.5 1.5 1.5 1.2 1.0 0.8 0.6 (+O2 baloon) 0.2 (+O2 baloon)

Yield (%)b 27 0 0 0 54 37 24 5 trace

a Reaction conditions: N-benzyl aniline (0.5 mmol), allyl tributyltin (0.6 mmol, 1.2 equiv) and quinone reagent (specified) in 2 mL tetrahydrofuran solvent at room temperature for 2 hours. b NMR yield.

From Table 1, 1.5 equivalents of DDQ (Q1) made the reaction take place smoothly, and produced the corresponding homoallyllic amine product in 27% yield (entry 1). When other quinone based oxidants instead of DDQ , such as benzoquinone (Q2), 2,5-di-hydroxy-3,6-dichlorobenzoquinone(Q3), 3,3',5,5'tetra-butyl-4,4' biphenyl quinone(Q4) were subjected to reaction conditions, no target products were generated (entries 2-4). After that the amount of DDQ was studied, we found that when DDQ was reduced to 1.2 equivalents, a significant increase in yield was up to 54% (entry 5). However, when the DDQ continued to decrease, the yield decreases accordingly (entries 6 and 7). In addition, the effect of green and environment friendly oxidant utilizing molecular oxygen by decreasing equivalency of DDQ resulted in a huge fall in yield of only 5% for the target product (entry 8). The reaction did not occur when only 0.2 equivalent of DDQ was added in an oxygen atmosphere (entry 9). Therefore, we speculate that this process is not a cycle of DDQ catalytic oxidation. After determining the type and dosage of oxidants, the reaction conditions were further optimized, and the experimental results are shown in Table 2. First, the solvent effect was investigated. When the solvent was replaced by acetonitrile from tetrahydrofuran, the yield was significantly amplified up to 74% (entry 1). Both cyclic and acyclic ethereal solvents, when subjected to this coupling strategy, demonstrated a dramatic change in the yield. This study of ethereal medium revealed that among tert-butyl ether, dibutyl ether and diethyl ether later one provides a better medium for reaction system, while 1,4-dioxane as solvent was not conducive to the reaction (entries 2-5). Besides, some common laboratory solvents were investigated one by one, such as toluene, dichloromethane, dichloroethane, dimethyl sulfoxide, N,N-dimethyl formamide, and ethanol. Although reactions proceeded in these solvents, the yield of the target product is far lower than that of ethyl ether as a solvent (entries 611). The reaction system was also capable to produce the product without solvent, but the yield was only 40% (entry 12). After determining ether as the best solvent for this reaction, we investigated the effects of equivalent of allyl reagent and reaction

time. A direct relation between allyl reagent uploading and yield of homoallylic amine have been observed. When the amount of allyl tributyltin reagent was reduced, the yield of the target product showed a decreasing trend (entries 13-14). When the dosage of allyltributyltin was increased, the yield of the target product showed a trend of first increasing and then decreasing. 1.5 Equivalents of allyltributyltin reagent were the best dosage, and the corresponding yield rate was 92% (entries 15-17). Finally, when examining the effect of reaction time on yield, it was found that 2 hours was the best reaction time at room temperature, and shortening and prolonging the reaction time both led to a decreased yield of the target product (entries 18-22). Therefore, the optimal conditions for the allylation were: N-benzyl aniline substrate (0.5 mmol), allyltributyltin (0.75 mmol, 1.5 equiv), oxidant DDQ (0.6 mmol, 1.2 equiv), solvent ether (2 mL)and room temperature for 2 hours. Table 2. Optimization of the reaction condition.a

Entry

Solvent

Allyltributyltin (x equiv)

t (h)

1

CH3CN

1.2

2

74

2

MTBE

1.2

2

66

3

Bu2O

1.2

2

44 82

Yield (%)b

4

Et2O

1.2

2

5

1,4Dioxane

1.2

2

27

6

Toluene

1.2

2

65

7

DCM

1.2

2

39

8

DCE

1.2

2

53

9

DMSO

1.2

2

39

10

DMF

1.2

2

45

11

EtOH

1.2

2

28

12

-[c]

1.2

2

40

13

Et2O

1.0

2

58

14

Et2O

0.8

2

49

15

Et2O

1.5

2

92

16

Et2O

1.8

2

89

17

Et2O

2.0

2

81

18

Et2O

1.5

1

89

19

Et2O

1.5

3

90

20

Et2O

1.5

4

88

21

Et2O

1.5

5

84

3 22

Et2O

1.5

6

78

Table 3. Investigation of substrate scope.a

a

Reaction conditions: N-benzylaniline (0.5 mmol), allyltributyltin (specified), DDQ (0.6 mmol, 1.2 equiv) in solvent (2 mL) at room temperature for reaction time (specified). MTBE = methyl tert-butyl ether. b NMR yield. c No solvent.

Under the optimal reaction conditions, we examined the scope of the reaction with the objective of identifying the structural and electronic parameters of the substrates that resulted in good yields and selectivities. We first investigated the compatibility of the substrates when the benzene rings of aniline and benzyl substrates were replaced by different functional groups, and the experimental results are shown in Table 3. When the paraposition of benzyl was replaced by fluorine atom, the corresponding substrate shows excellent reactivity with a yield of 99% (2b). The substrates of the substitution on the phenyl moieties also showed excellent reactivity, when para-position of the benzene ring is substituted by halogen atoms, and the corresponding products were obtained with a yield of 99% (2c to 2e). Both the meta-substituted benzyl substrates and metasubstituted phenyl substrates showed good reactivity, the reaction efficiency of the corresponding substrates was slightly lower than para-substituted substrates with yields of 81% and 89% (2f and 2g), respectively. When the para-position of benzyl was replaced by bromine atom, the corresponding substrate showed excellent reactivity with a yield of 95% (2h). While the ortho-position of benzyl was replaced by halogen atoms, the reaction hardly occurred. We speculate that steric hindrance is the main factor leading to the non-reaction (2i and 2j). In order to enrich the diversity of substrates, the substituted diphenyl ring of substrates were also investigated. 4-Bromo-n-(4-chloro-phenyl) aniline showed excellent reactivity with a yield of 84% (2k). Subsequently, when the benzene ring of benzyl part was replaced in substrates with different substituents, it was found that the methyl and methoxy substrates with electron-giving effects could proceeded well, and the corresponding homoallyllic amine products (2l and 2m) were obtained in 86% and 93% yields, respectively. When aniline counterpoint is replaced by electrondonating group methyl, the corresponding substrate showed low reactivity and selectivity under standard reaction conditions. TLC point plate analysis results showed that the reaction was very complex and nearly half of the raw materials did not react (2n). Similarly, the aniline counterpoint was replaced by electron-rich group methoxy, it was incompatible with the optimal conditions. When the benzene-ring counterpoint was replaced by strongly electron-withdrawing trifluoro methyl and cyano groups, the corresponding substrates showed only moderate reactivity, with yields of 55% and 46% (2o and 2p), respectively. In addition, the para-position of phenyl and benzyl moieties were replaced by nitro group showed good reactivity with yields of 71% and 76% (2q and 2r), respectively. Heterocyclic secondary amines such as N-(thiophene-2-methyl) aniline led to better yield (2s). Cinnamyl aniline also occurred successfully, but the yield is low, only in 32% (2t). However, N-(pyridine-3-methyl) aniline showed poor reactivity, and TLC analysis showed that only a trace amount of product was generated, while a large number of raw materials did not react (2u). When the ortho-position of the phenyl moieties was replaced by fluorine atom, the reaction also hardly occurs (2v). We speculate that it is caused by steric hindrance. Unfortunately, aliphatic substrates such as N-tert-butyl benzylamine, N-(cyclohexylmethyl)aniline, N(cyclopropylmethyl)aniline and N-octyl aniline did not react (2w to 2z). We speculate that it is caused by the poor stability of the imine intermediate after oxidative dehydrogenation.

2a, 92%b (90%)c

2b, 99% (99%)

2c, 99% (96%) HN

Br

2d, 99% (99%)

2e, 92% (89%)

2f, 81% (69%)

2g, 89% (85%)

2h, 95% (91%)

2i, 0%

2k, 84% (81%)

2l, 86% (79%)

2n, <10%b

2o, 55% (42%)

2j, trace

2m, 93% (89%)

N H O2N

2p, 46% (46%)

2q, 71% (70%)

2s, 66% (58%)

2t, 32% (28%)

2r, 76% (73%)

2u, trace HN

a

2v, 0%

2w, 0%

2y, 0%

2z, 0%

Ph

2x, 0%

Reaction conditions: secondary amine substrate (0.5 mmol), allyl tributyltin (0.75 mmol, 1.5 equiv) and oxidant DDQ (0.6 mmol, 1.2 equiv) in solvent ether (2 mL) at room temperature for 2 hours. b NMR yield.

4

Tetrahedron c

O

Isolated yield by silica-gel column.

O

Cl

To explore the potential value of this reaction in industrial application, we conducted an appropriately scaled-up study on it, and the experimental results are shown in Scheme 2. Taking 10 mmol of N-benzyl aniline and 15 mmol of allyl tributyltin as raw materials in 10 mL of ethyl ether as a solvent, and 12 mmol of DDQ was subjected slowly under constant agitation at room temperature. After two hours of reaction, 1.965g of allylated product was obtained, with a yield of 88%. In this experiment, the yield of homoallylic amines decreased slightly, which indicated that the preparation of homoallylic amines by this method has certain practicability.

n Bu3Sn

CN

+ Cl

CN O

-e

nBu3 Sn +

Et2O rt 25%

Cl

CN

Cl

CN OSnnBu3

+e O Cl

CN

+ Cl

CN O

Scheme 4. Reaction of DDQ with allyltributyltin.

Scheme 2. Gram-scale experiment of allylation.

To testify this conjecture and acquire forthright proof, chemical quenching of radicals was investigated by adding 3 equivalents of TEMPO (2,2,6,6-tetramethylpiperidine oxide, Scheme 3), a well-known radical-trapping reagent, to the standard reaction. The surveillance was persistent with conjecture that the reaction may have radical process. Fig. 1. Comparison of allyltributyltin and allylated phenol intermediate.

Scheme 3. Radical trapping experiment.

The sequence of adding starting materials was found crucial for this transformation as well. When adding the allyltributyltin before DDQ, the reaction failed to generate the allylation product with N-benzyl aniline recovered in above 99%. Therefore, nuclear magnetic hydrogen spectrum analysis of allyltributyltin reagent was used as a reference standard in interpreting our hypotheses and exploring the formation of intermediate in the reaction process. 1H NMR shows that methylene in allyltributyltin has double peaks, and its chemical displacement is 1.77 ppm. One hydrogen on the inner side of the olefinic double bond has multiple peaks, and its chemical displacement is 5.985.89 ppm. The chemical displacements for terminal sp2 hybridized hydrogens appeared at 4.78 ppm and 4.64 ppm, respectively. When mixing 0.75 mmol of allyltributyltin reagent and DDQ (1.2 eq.) at room temperature for half an hour, allylated phenol intermediate was formed in 25% NMR yield (Scheme 4). 1 H NMR spectrum showed that the allyltributyltin reagent was oxidized directly and the peak of methylene downshifted to 4.66 ppm (Fig. 1). Consequently, we speculated that DDQ did oxidize allyltributyltin reagent into allylic radical by single electron transfer and DDQ was converted into radical anion after acquiring one electron, both of which resulted in generation of the coupling product. Even when mixing N-benzylamine, allyltributyltin and DDQ in CDCl3, the oxidation of allyltributyltin was observed from mixture NMR spectrum, which indicates that oxidative process of allyltributyltin was unable to be neglected, especially in changing of addition sequence.

In addition, the reaction effect of N-benzyl aniline with DDQ was investigated. To the mixture of N-benzyl aniline and excessive DDQ was added CDCl3, and the resulting solution was transferred into NMR tube for nuclear magnetic characterization at room temperature. The experimental results are shown in Fig. 2 below. The chemical displacement of N-H in N-benzyl aniline is 4.03 ppm before the reaction with DDQ. After the reaction with DDQ, the signal peak of N-H is almost disappeared, and a new peak appears at 8.46 ppm. It can be seen that in the reaction process, DDQ firstly oxidized N-benzyl aniline into imine intermediate. In another case of N-(2-bromobenzyl) aniline (2j) which was inactive in this allylation, the N-H signal likewise demonstrated the imine formation. So the reason of inactivity might exist in the later nucleophilic addition stage.

Fig. 2. The reaction of DDQ with N-benzyl aniline

Based on the above experimental results, we proposed the possible mechanism of allylation reaction, as shown in Fig. 3. Firstly the single electron transfer process takes place, and DDQ oxidizes N-benzyl aniline to imine intermediate, and then allyl tin reagent attacks it via nucleophilic addition, and allyl C-C bond formation occurs when tributyltin groups are removed, and corresponding homoallylic amine products are generated. When

5 ortho-halogen substitution is on the benzene ring, no products (2i, 2j and 2v) were obtained in spite of the observed imine formation in NMR tests. The inactivity probably resulted from steric repulsion between allyl and halogen.

residue was purified by column chromatography on silica gel column using EtOAc−petroleum ether solution as eluent to afford secondary amine. 4.3 General procedure for synthesizing the homoallylic amines (2a-z) Secondary amine (0.5 mmol), ether (2 mL), DDQ (0.6 mmol, 1.2 equiv), allyl tributyltin (0.75 mmol, 1.5 equiv) were added successively to the 10 mL test tube at room temperature for 2 hours. The reaction was monitored by TLC point plate. After the reaction, saturated sodium thiosulfate solution (10 mL) was added to quench the reaction, and organic phase was extracted by dichloroform, dried by anhydrous magnesium sulfate, filtered and vapored to get the oil residue, which was separated by column chromatography to afford pure allylated products. 4.3.1 N-(1-phenylbut-3-en-1-yl)aniline (2a) [12]

Fig. 3. Possible mechanism of allylation.

3. Conclusion In summary, based on the previous work of phosphonation and cyanidation, we continued to develop the application of DDQ-promoted oxidation coupling system in C-C construction, and effectively prepared a series of homoallylic amine compounds. The reaction conditions were mild and free of transition metals, and the operation was simple, which provided a convenient and feasible way for the preparation of homoallylic amine compounds. In the mechanism study experiment, the specific oxidation effect of DDQ in this process was demonstrated through the comparison experiment and imine intermediate capture, and the single electron transfer process mediated by DDQ was proposed. The gram scale experiment is progressing smoothly, provides the potential industrial application value. 4. Experimental section 4.1 General Information 1

13

The H and C NMR spectra were recorded in CDCl3 solution on a Bruker Avance 500/125 MHz spectrometer at 20-25 oC. 1H NMR chemical shifts were reported in ppm using tetramethylsilane (TMS, δ = 0.00 ppm) as the internal standard. The data of 1H NMR was reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet), coupling constant (J value) in Hz and integration. 13C NMR spectra were reported in parts per million using solvent CDCl3 (δ = 77.2 ppm) as an internal standard. All the reagents used were of analytical grade, purchased locally and used without any purification unless otherwise specified. Solvents purchased from chemical supplier were firstly dried over 4Å molecular sieve for one week. Column chromatographys were performed using silica gel, and analytical thin-layer chromatography (TLC) was used to monitor the reactions, performed on silica gel plates. 4.2 General procedure for synthesis of substrates(1a-u) To a 100 mL round flask that was equipped with a stirring bar, corresponding aniline (10.0 mmol), corresponding aldehyde (11.0 mmol), NaOEt (1.36 g, 20.0 mmol) and methanol (20 mL) were added successively. The resulting mixture was stirred at 80 o C in atmosphere and monitored by TLC. When aniline was converted completely, the mixture was cooled to room temperature, and NaBH4 (0.416 g, 11.0 mmol) was added to the reaction mixture in portions. The continuous stirring was kept for additional 1-4 hours at 80 oC. TLC monitored the completion of the reaction. The solvent was evaporated and the resulting

Light yellow viscous liquid; 90% yield, 100 mg; 1H NMR (500 MHz, CDCl3) δ 7.30-7.28 (m, 2H), 7.26-7.23 (t, J = 7.5 Hz, 2H), 7.17-7.14 (m, 1H), 7.02-6.98 (t, J = 7.5 Hz, 2H), 6.58-6.55 (t, J = 7.0 Hz, 1H), 6.43-6.41 (d, J = 7.5 Hz, 2H), 5.73-5.64 (m, 1H), 5.13-5.06 (m, 2H), 4.32- 4.29 (m, 1H), 4.10 (s, 1H), 2.562.51 (m, 1H), 2.45-2.39 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 147.5, 143.7, 134.8, 129.2, 128.8, 127.2, 126.5, 118.5, 117.6, 113.7, 57.3, 43.5. 4.3.2 N-(1-(4-fluorophenyl)but-3-en-1-yl)aniline (2b) [12] Light yellow viscous liquid; 99% yield, 119 mg; 1H NMR (500 MHz, CDCl3) δ 7.31-7.29 (m, 2H), 7.08-7.05 (t, J = 8.5 Hz, 2H), 6.70-6.96 (t, J = 8.5 Hz, 2H), 6.65-6.63 (t, J = 7.0 Hz, 1H), 6.47-6.45 (d, J = 8.5 Hz, 2H), 5.77-5.68 (m, 1H), 5.18-5.12 (m, 2H), 4.36-4.34 (t, J = 7.0 Hz, 1H), 4.12 (s, 1H), 2.58-2.53 (m, 1H), 2.48-2.42 (m,1H). 13C NMR (125 MHz, CDCl3) δ 162.0 (d, J = 243.75 Hz), 147.3, 139.3 (d, J = 2.5 Hz), 134.5, 129.2, 127.9 (d, J = 7.5 Hz), 118.7, 117.7, 115.5 (d, J = 20.0 Hz), 113.6, 56.7, 43.5. 4.3.3 4-fluoro-N-(1-phenylbut-3-en-1-yl)aniline (2c) [12] Light yellow viscous liquid; 96% yield, 116 mg; 1H NMR (500 MHz, CDCl3) δ 7.34-7.29 (m, 4H), 7.23-7.21 (m, 1H), 6.786.74 (t, J = 9.0 Hz, 2H), 6.41-6.39 (m, 2H), 5,79-5,71 (m, 1H), 5.18-5.13 (m, 2H), 4.31-4.29 (m, 1H), 4.04 (s, 1H), 2.61-2,56 (m, 1H), 2.49-2.43 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 155.9 (d, J = 233.75 Hz), 143.9, 143.5, 134.8, 128.8, 127.3, 126.4, 118.5, 115.6 (d, J = 22.5 Hz), 114.4 (d, J = 7.5 Hz), 57.9, 43.5. 4.3.4 4-chloro-N-(1-phenylbut-3-en-1-yl)aniline (2d) [12] Light yellow viscous liquid; 99% yield, 127 mg; 1H NMR (500 MHz, CDCl3) δ 7.31-7.29 (m, 4H), 7.24-7.21 (m, 1H), 7.06.98 (d, J = 8.5 Hz, 2H), 6.40-6.34 (d, J = 9.0 Hz, 2H), 5.78-5.69 (m, 1H), 5.18-5.13 (m, 2H), 4.33 (s, 1H), 4.16 (s, 1H), 2.62-2.57 (m, 1H), 2.50-2.44 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 146.0, 143.1, 134.5, 129.0, 128.8, 127.3, 126.4, 122.1, 118.7, 114.7, 57.3, 43.3. 4.3.5 4-bromo-N-(1-phenylbut-3-en-1-yl)aniline (2e) [12] Light yellow viscous liquid; 89% yield, 135 mg; 1H NMR (500 MHz, CDCl3) δ 7.24-7.23 (m, 4H), 7.17-7.15 (m, 1H), 7.077.05 (d, J = 8.5 Hz, 2H), 6.29-6.27 (d, J = 8.5 Hz, 2H), 5.70-5.62 (m, 1H), 5.12-5.06 (m, 2H), 4.27-4.24 (m, 1H), 4.15 (s, 1H), 2.55-2.51 (m, 1H), 2.44-2.38 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 146.3, 143.0, 134.5, 131.9, 128.9, 127.4, 126.4, 118.7, 115.3, 109.3, 57.3, 43.3. 4.3.6 3-bromo-N-(1-phenylbut-3-en-1-yl)aniline (2f) [12]

6

Tetrahedron

Light yellow viscous liquid; 79% yield, 120 mg; 1H NMR (500 MHz, CDCl3) δ 7.26-7.25 (m, 3H), 7.19-7.17 (m, 2H), 6.856.82 (t, J = 8.0 Hz, 1H), 6.69-6.68 (d, J = 7.5 Hz, 1H), 6.60 (s, 1H), 6.33-6.31 (d, J = 6.5 Hz, 1H), 5.70-5.62 (m, 1H), 5.13-5.07 (m, 2H), 4.30-4.16 (m, 2H), 2.56-2.54 (m, 1H), 2.44-2.40 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 146.3, 143.0, 134.5, 131.9, 128.9, 127.4, 126.4, 118.7, 115.3, 109.3, 57.3, 43.3.

White solid; 46% yield, 57 mg; 1H NMR (500 MHz, CDCl3) δ 7.61-7.60 (d, J = 8.0 Hz, 2H), 7.49-7.47 (d, J = 8.0 Hz, 2H), 7.09-7.06 (t, J = 8.5 Hz, 2H), 6.69-6.66 (t, J = 7.5 Hz, 1H), 6.436.41 (d, J = 7.5 Hz, 2H), 5.76-5.68 (m, 1H), 5.21-5.17 (m, 2H), 4.43-4.40 (m, 1H), 4.17 (s, 1H), 2.62-2.57 (m, 1H), 2.50-2.44 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 149.5, 146.8, 133.7, 132.7, 129.3, 127.3, 119.4, 119.0, 118.2, 113.6, 111.1, 57.1, 43.1.

4.3.7 N-(1-(3-bromophenyl)but-3-en-1-yl)aniline(2g) [12]

4.3.14 4-nitro-N-(1-phenylbut-3-en-1-yl)aniline (2q)[22]

Light yellow viscous liquid; 85% yield, 129 mg; 1H NMR (500 MHz, CDCl3) δ 7.32-7.31 (d, J = 5.0 Hz, 4H), 7.25-7.23 (m, 2H), 6.91-6.87 (t, J = 10.0 Hz, 1H), 6.74-6.73 (d, J = 5.0 Hz, 1H), 6.65 (s, 1H), 6.37-6.36 (d, J = 5.0 Hz, 1H), 5.77-5.69 (m, 1H), 5.19-5.13 (m, 2H), 4.35 (s, 1H), 4.21 (s, 1H), 2.62-2.57 (m, 1H), 2.50-2.44 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 148.7, 143.0, 134.5, 130.5, 128.9, 127.4, 126.4, 123.2, 118.7, 112.1, 57.1, 43.3.

Light yellow viscous liquid; 70% yield, 94 mg; 1H NMR (500 MHz, CDCl3) δ 8.19-8.17 (d, J = 10.0 Hz, 2H), 7.55-7.53 (d, J = 10.0 Hz, 2H), 7.10-7.06 (t, J = 10.0 Hz, 2H), 6.69-6.66 (t, J = 7.5 Hz, 1H), 6.44-6.42 (d, J = 10.0 Hz, 2H), 5.77-5.69 (m, 1H), 5.225.19 (m, 2H), 4.48-4.47 (m, 1H), 4.21 (s, 1H), 2.65-2.60 (m, 1H), 2.52-2.46 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 151.7, 147.3, 146.7.5, 133.6, 129.4, 127.4, 124.2, 119.5, 118.3, 113.7, 57.0, 43.1.

4.3.8 N-(1-(4-bromophenyl)but-3-en-1-yl)aniline(2h) [12] Light yellow viscous liquid; 91% yield, 138 mg; 1H NMR (500 MHz, CDCl3) δ 7.44-7.42 (d, J = 10.0 Hz, 2H), 7.24-7.23 (d, J = 5.0 Hz, 2H), 7.09-7.06 (t, J = 7.5 Hz, 2H), 6.67-6.64 (t, J = 7.5 Hz, 1H), 6.46-6.44 (d, J = 10.0 Hz, 2H), 5.75-5.70 (m,1H), 5.195.14 (m, 2H), 4.33 (s, 1H), 4.12 (s, 1H) 2.58-2.54 (m, 1H), 2.482.43 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 147.2, 142.9, 134.3, 131.9, 129.3, 128.3, 120.8, 118.9, 117.9, 113.7,77.5, 56.8, 43.3. 4.3.9 4-bromo-N-(1-(4-chlorophenyl)but-3-en-1-yl)aniline(2k) [12] Light yellow viscous liquid; 81% yield, 136 mg; 1H NMR (500 MHz, CDCl3) δ 7.37-7.35 (d, J = 8.5 Hz, 2H), 7.13-7.11 (d, J = 8.5 Hz, 2H), 6.94-6.92 (d, J = 9.0 Hz, 2H), 6.30-6.28 (d, J = 9.0 Hz, 2H), 5.67-5.59 (m, 1H), 5.12-5.07 (m, 2H), 4.22-4.20 (m, 1H), 4.11 (s, 1H), 2.51-2.46 (m, 1H), 2.40-2.34 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 145.7, 142.3, 134.1, 132.0, 129.1, 128.2, 122.5, 121.0, 119.1, 114.8, 56.9, 43.2. 4.3.10 N-(1-(p-tolyl)but-3-en-1-yl)aniline (2l) [12] Light yellow viscous liquid; 79% yield, 94 mg; 1H NMR (500 MHz, CDCl3) δ 7.25-7.23 (d, J = 7.5 Hz, 2H), 7.13-7.11 (d, J = 7.5 Hz, 2H), 7.08-7.05 (t, J = 8.0 Hz, 2H), 6.64-6.61 (t, J = 7.5 Hz, 1H), 6.50-6.48 (d, J = 8.0 Hz, 2H), 5.78-5.71 (m, 1H), 5.195.12 (m, 2H), 4.36-4.33 (t, J = 7.0 Hz, 1H), 4.13 (s, 1H), 2.602.56 (m, 1H), 2.50-2.46 (m, 1H), 2.32 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 147.6, 140.7, 136.7, 135.0, 129.4, 129.2, 126.4, 118.4, 117.4, 113.6, 57.0, 43.5, 21.2. 4.3.11 N-(1-(4-methoxyphenyl)but-3-en-1-yl)aniline (2m) [12] Light yellow viscous liquid; 89% yield, 113 mg; 1H NMR (500 MHz, CDCl3) δ 7.27-7.26 (d, J = 8.5 Hz, 2H), 7.09-7.05 (t, J = 7.5 Hz, 2H), 6.86-6.84 (d, J = 8.5 Hz, 2H), 6.65-6.62 (t, J = 7.0 Hz, 1H), 6.50-6.48 (d, J = 8.0 Hz, 2H), 5.79-5.71 (m, 1H), 5.18-5.12 (m, 2H), 4.34-4.32 (t, J = 7.0 Hz, 1H), 4.12 (s, 1H), 3.77 (s, 3H), 2.59-2.54 (m, 1H), 2.49-2.44 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 158.7, 147.6, 135.7, 134.9, 129.2, 127.5, 118.4, 117.5, 114.1, 113.7, 56.7, 55.4, 43.6. 4.3.12 N-(1-(4-(trifluoromethyl)phenyl)but-3-en-1-yl)aniline (2o) [12]

Light yellow viscous liquid; 42% yield, 61 mg; 1H NMR (500 MHz, CDCl3) δ 7.59-7.57 (d, J = 8.5 Hz, 2H), 7.49-7.48 (d, J = 8.5 Hz, 2H), 7.10-7.07 (t, J = 8.5 Hz, 2H), 6.68-6.66 (t, J = 7.0 Hz, 1H), 6.46-6.44 (d, J = 7.5 Hz, 2H), 5.76-5.71 (m, 1H), 5.225.17 (m, 2H), 4.44-4.43 (m, 1H), 4.18 (s, 1H), 2.63-2.59 (m, 1H), 2.51-2.46 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 148.0, 147.1, 134.1, 129.3, 126.8, 125.8, 119.2, 118.0, 113.7, 57.0, 43.3. 4.3.13 4-(1-(phenylamino)but-3-en-1-yl)benzonitrile (2p) [12]

4.3.15 N-(1-(4-nitrophenyl)but-3-en-1-yl)aniline(2r)[22] Light yellow viscous liquid; 73% yield, 98 mg; 1H NMR (500 MHz, CDCl3) δ 8.24 (s, 1H), 8.10-8.08 (d, J = 10.0 Hz 1H), 7.727.70 (d, J = 10.0 Hz, 1H), 7.50-7.47 (t, J = 7.5 Hz, 2H), 6.69-6.66 (t, J = 7.5 Hz 1H), 6.46-6.45 (d, J = 5.0 Hz, 2H), 5.76-5.71 (m, 1H), 5.22-5.18 (m, 2H), 4.48 (s, 1H), 4.22 (s, 1H), 2.65-2.60 (m, 1H), 2.53-2.47 (m, 1H). 13C NMR (125 MHz, CDCl3) δ 148.9, 146.8, 133.7, 132.8, 129.8, 129.4, 122.4, 121.5, 118.2, 113.7, 59.9, 43.2. 4.3.16 N-(1-(thiophen-2-yl)but-3-en-1-yl)aniline (2s) [12] Yellow viscous liquid; 68% yield, 78 mg; 1H NMR (500 MHz, CDCl3) δ 7.16-7.10 (m, 3H), 6.97-6.96 (m, 1H), 6.94-6.92 (m, 1H), 6.71-6.68 (t, J = 7.5 Hz, 1H), 6.60-6.59 (d, J = 8.0 Hz, 2H), 5.84-5.76 (m, 1H), 5.21-5.14 (m, 2H), 4.70 (s, 1H), 4.12 (s, 1H), 2.69-2.62 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 148.9, 147.2, 134.2, 129.3, 127.0, 123.9, 123.6, 118.9, 118.1, 113.8, 53.6, 43.3. 4.3.17 N-(1-phenylhexa-1,5-dien-3-yl)aniline (2t) Light yellow viscous liquid; 28% yield, 31mg; 1H NMR (500 MHz, CDCl3) δ 7.35-7.34 (m, 2H), 7.30-7.27 (t, J = 7.5 Hz, 2H), 7.22-7.19 (m, 1H), 7.16-7.13 (t, J = 8.5 Hz, 2H), 6.70-6.67 (t, J = 7.0 Hz, 1H), 6.65-6.63 (d, J = 7.5 Hz, 2H), 6.61-6.58 (m, 1H), 6.21-6.17 (m, 1H), 5.89-5.81 (m, 1H), 5.20-5.14 (m, 2H), 4.064.05 (m, 1H), 3.83 (s, 1H), 2.52-2.42 (m, 2H). 13C NMR (125 MHz, CDCl3) δ 147.7, 137.1, 134.6, 131.7, 130.5, 129.3, 128.7, 127.6, 126.5, 118.5,117.5,113.7, 54.9, 40.7. Notes The authors declare no competing financial interest. Acknowledgments We gratefully acknowledge funding from the National Natural Science Foundation of China (No. 21372265) and the Natural Science Foundation Project of CQ CSTC (cstc2018jcyjAX0155) for financial support. Supplementary Material Supplementary data associated with this article can be found, in the online version, at References 1.

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Highlights In this work, we have developed DDQ-promoted allyl reaction approach towards various N-benzyl anilines from N-benzyl aniline as raw material, allyltributyltin as allyl reagent and DDQ as oxidant. Detailed optimization of various parameters including screening of solvents, concentration effect of allyl tributyltin and solvent, temperature and reaction time was performed and a series of N-benzyl anilines carrying variety of functional groups such as halides, alkyl groups and cyanogroups were also scoped with yields of up to 99%. This protocol works smoothly on preparative scale synthesis and also presents an alternative access to the concise synthesis of homoallylic amines. Moreover, in the last part of our research, we explored the mechanism of the reaction.

Declaration of Interest Statement

All the authors declare no competing financial interest.