锡粉促进“一锅法”合成芳基三氟甲基取代高烯丙基酰肼类化合物

引用本文: 王克虎, 王雅琳, 殷雪娇, 彭先沙, 黄丹凤, 苏瀛鹏, 胡雨来. 锡粉促进“一锅法”合成芳基三氟甲基取代高烯丙基酰肼类化合物[J]. 有机化学, 2017, 37(7): 1764-1773. doi: 10.6023/cjoc201612042 shu

Citation: Wang Kehu, Wang Yalin, Yin Xuejiao, Peng Xiansha, Huang Danfeng, Su Yingpeng, Hu Yulai. Tin-Promoted One-Pot Synthesis of Aryl/Trifluoromethyl Group Substituted Homoallylic N-Acylhydrazines[J]. Chinese Journal of Organic Chemistry, 2017, 37(7): 1764-1773. doi: 10.6023/cjoc201612042 shu

锡粉促进“一锅法”合成芳基三氟甲基取代高烯丙基酰肼类化合物

西北师范大学化学化工学院兰州 730070

通讯作者: 王克虎, wangkh@nwnu.edu.cn; 胡雨来, huyl@nwnu.edu.cn

基金项目:

国家自然科学基金（Nos.21262031，21462037）资助项目

摘要: 在三氟化硼乙醚（BF₃·OEt₂）促进下，以芳基三氟甲基酮、酰肼、烯丙基溴和锡粉为原料，"一锅法"合成了一系列含三氟甲基的高烯丙基酰肼类化合物.该方法具有收率高、适用范围广以及反应操作简便等优点.合成的三氟甲基高烯丙基酰肼类化合物是一类有效的三氟甲基合成砌块，可方便地转化为各类三氟甲基取代的含氮化合物.

关键词:

English

Tin-Promoted One-Pot Synthesis of Aryl/Trifluoromethyl Group Substituted Homoallylic N-Acylhydrazines

College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070

Corresponding author: Wang Kehu, E-mail: wangkh@nwnu.edu.cn; Hu Yulai, E-mail: huyl@nwnu.edu.cn

Received Date: 13 December 2016
Revised Date: 01 March 2017
Available Online: 25 July 2017
Fund Project:

Project supported by the National Natural Science Foundation of China (Nos. 21262031, 21462037)

Abstract: A series of trifluoromethylated homoallylic N-acylhydrazines were obtained from one-pot reaction of aryl trifluoroketones, acylhydrazines and allyl bromide promoted by tin powder in the presence of boron trifluoride diethyl etherate (BF₃·OEt₂). The features of this process include good yields, wide substrate scope, mild conditions and easy operation. Trifluoromethylated homoallylic N-acylhydrazines are useful trifluoromethyl building blocks. They can be easily transformed into trifluoromethylated nitrogen-containing compounds.

Key words:

one-pot
/ tin powder
/ aryl trifluoroketones
/ trifluoromethylated homoallylic N-acylhydrazines

近年来, 有机氟化学得到了迅速的发展, 其中含三氟甲基的有机化合物在医药^[1]、农药^[2]、染色工业及材料科学^[3]等诸多领域得到了广泛的应用, 备受化学家关注, 发展了各种有效的方法合成含三氟甲基的有机化合物.三氟甲基合成砌块法合成含三氟甲基的有机化合物是一种简便有效的方法^[4].含三氟甲基合成砌块法主要是利用含氟砌块上原有的官能团的转化从而合成结构复杂的含氟有机化合物.芳基三氟甲基酮是一类重要的亲电含氟有机合成砌块, 可以发生还原反应^[5]、1, 2-加成反应^[6]、Crossed-Tishchenko反应^[7]、Aldol反应^[8]、Micheal加成^[9]反应及Henry反应^[10], 简单高效地转化为一系列重要的三氟甲基有机化合物.

高烯丙基酰肼类化合物是一类有用的有机合成中间体, 可简单高效地转化为高烯丙基胺^[11]和吡唑及其它含氮衍生物^[12].高烯丙基酰肼一般可由酰腙类化合物与烯丙基化试剂(例如有机锡^[13]、有机铟^[14]及有机硅^{[11b, 15]}等)反应制备, 也可由酰腙类化合物与烯丙基卤在锡粉^[16]或铟粉^[17]促进下反应制备.本文报道在锡粉促进下, 以芳基三氟甲基酮为三氟甲基合成砌块, 与酰肼、烯丙基溴“一锅法”反应制备含三氟甲基的高烯丙基酰肼化合物, 为三氟甲基高烯丙基酰肼类化合物的合成提供了一种简便高效的方法, 三氟甲基高烯丙基酰肼可方便地转化为三氟甲基高烯丙基胺.

1 结果与讨论

1.1 反应条件的优化

首先我们以对甲苯磺酸(TsOH)为促进剂, 四氢呋喃(THF)为溶剂, 将2, 2, 2-三氟苯乙酮(1a)、苯甲酰肼(2a)、烯丙基溴(3a)和锡粉一次性加入反应容器中, 在四氢呋喃中回流条件下薄层色谱(TLC)监测反应48 h后, 发现有少量的目标产物5a生成, 反应主要生成了1a的烯丙基化产物高烯丙基醇.于是尝试改变实验操作过程, 先将1a与2a在TsOH (5 mol%)促进下四氢呋喃中加热回流, TLC检测中间体酰腙4很快生成, 然后加入烯丙基溴、锡粉和TsOH (10 mol%), 继续加热回流反应, 最终以71%的产率得到了目标化合物5a(表 1, Entry 10).实验结果表明, 对甲苯磺酸分次加入有利于反应的发生.

表 1 反应条件优化^a Table 1. Optimization of the reaction conditions

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Entry	Molar ratio of 1a/2a/3a/Sn	Additive	Isolated yield/%
1	1:1.5:2:2.5	—	0
2	1:1.5:2:2.5	TfOH	49
3	1:1.5:2:2.5	C₆H₅COOH	64
4	1:1.5:2:2.5	CF₃COOH	41
5	1:1.5:2:2.5	TMSCl	59
6	1:1.5:2:2.5	HCl	23
7	1:1.5:2:2.5	HBr	27
8	1:1.5:2:2.5	FeCl₃	56
9	1:1.5:2:2.5	ZnBr₂	37
10	1:1.5:2:2.5	TsOH	71
11^b	1:1.5:2:2.5	TsOH	75
12^c	1:1.5:2:2.5	TsOH	67
13	1:1.5:2:2.5	BF₃•OEt₂	70
14^d	1:1.5:2:2.5	BF₃•OEt₂	62
15^b	1:1.5:2:2.5	BF₃•OEt₂	78
16^c	1:1.5:2:2.5	BF₃•OEt₂	75
17^b	1:1.2:2:2.5	BF₃•OEt₂	64
18^b	1:1.5:1.5:2	BF₃•OEt₂	53
19^b	1:1.5:2.5:3	BF₃•OEt₂	75
20^b	1:1.5:3:2.5	BF₃•OEt₂	69
21^b^{, e}	1:1.5:2:2.5	BF₃•OEt₂	34
^aReaction conditions: The mixture of 1a (0.3 mmol), 2a (0.45 mmol), additive (5 mol%) and THF (3 mL) was reacted under reflux condition. After the formation of 4 detected by TLC, 3a (0.6 mmol), Sn (0.75 mmol), additive (10 mol%) and THF (3 mL) were added, and the mixture was reacted under reflux condition. ^bAdding 15 mol% additive for the second time. ^cAdding 20 mol% additive for the second time. ^d Adding 5 mol% additive for the second time. ^e At room temperature.

为了进一步提高收率, 我们对反应条件进行了优化, 考察了促进剂、溶剂、温度以及物料比等因素对反应产率的影响.首先对不同的促进剂进行了筛选(表 1), 结果表明一些布朗斯特酸(例如HCl、HBr、TfOH、C₆H₅COOH、CF₃COOH和TsOH)和路易斯酸(例如FeCl₃、ZnBr₂和BF₃•OEt₂)都可以促进该反应的发生, 其中TsOH和BF₃•OEt₂表现出较高的反应活性(表 1, Entries 10~15).但是当以TsOH为促进剂进行底物拓展时, 发现反应产率都比较低.因此, 最终选择BF₃•OEt₂为最佳促进剂.试验结果表明BF₃•OEt₂的用量对目标化合物5a的产率有影响.当中间体酰腙4生成以后进行烯丙基化反应时, BF₃•OEt₂用量减少到5 mol%, 反应产率为62%; BF₃•OEt₂用量增加到15 mol%, 反应产率达到78%;继续增加BF₃•OEt₂用量, 反应产率不再继续提高(表 1, Entries 14~16).因此, 反应促进剂的最佳用量确定两次总量为20 mol%.接着对反应的物料比进行了优化.由表 1可知, 其最佳物料比为n(1a):n(2b):n(3a):n(锡粉)＝1:1.5:2:2.5.减少烯丙基溴和锡粉的用量, 中间体酰腙有剩余, 反应产率下降了(表 1, Entry 18).增加烯丙基溴和锡粉的用量, 反应体系变得更为复杂, 反应产率反而下降了(表 1, Entries 19和20).室温条件下反应只能以34%收率得到目标产物(表 1, Entry 21).

在三氟化硼乙醚促进下, 对常用溶剂也进行了考察(表 2).该反应在甲醇、乙醇、乙腈、二氯甲烷(DCM)、N, N-二甲基甲酰胺(DMF)、二氧六环和甲苯中均能发生反应.在四氢呋喃中反应得到了较高的产率(表 2, Entry 1), 因此, 四氢呋喃被确定为最佳溶剂.

表 2 溶剂对反应的影响^a Table 2. Effect of solvent on the reaction

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Entry	Solvent	Isolated yield/%
1	THF	78
2	CH₃OH	33
3	EtOH	38
4	CH₃CN	16
5^b	Dioxane	15
6^b	Toluene	31
7^b	DMF	10
8	DCM	37
^aReaction conditions: The mixture of 1a (0.3 mmol), 2a (0.45 mmol), BF₃·OEt₂ (5 mol%) and THF (3 mL) was reacted under reflux condition. After the formation of 4 detected by TLC, 3a (0.6 mmol), Sn (0.75 mmol), BF₃·OEt₂ (15 mol%) and THF (3 mL) were added, and the mixture was reacted under reflux condition. ^b At 70 ℃.

至此, 我们最终确定反应最佳条件为: 1 equiv. 1a、1.5 equiv. 2a和BF₃•OEt₂ (5 mol%)在THF中加热回流, TLC检测酰腙生产后加入2 equiv.烯丙基溴、2.5 equiv.的锡粉与BF₃•OEt₂ (15 mol%)回流条件下反应.

1.2 底物的拓展

为了探索该反应的适应性, 在上述优化反应条件下, 对各种取代2, 2, 2-三氟芳基乙酮与取代芳基甲酰肼反应情况进行了考察, 结果列于表 3.我们首先对取代芳基甲酰肼进行了拓展, 发现芳环上取代基电子效应对该反应产率影响不大, 不管是吸电子取代基还是给电子取代基, 都能以中等以上的产率获得目标化合物, 但是芳环上取代基位置对该反应有一定的影响.例如对位和间位取代的芳基甲酰肼, 都能以不错的产率得到相应产物, 但邻位取代的芳基甲酰肼, 反应几乎没有发生, 回收得到原料(表 3, 5b和5f). 2-呋喃甲酰肼和2-萘甲酰肼反应活性较高, 分别以90%和84%的产率得到目标产物(表 3, 5k和5l).对于脂肪族酰肼如月桂酰肼和乙酰肼, 发现可以和2, 2, 2-三氟芳基乙酮反应生成酰腙, 但是中间体酰腙并没有发生烯丙基化反应(表 3, 5o和5p).接着对取代2, 2, 2-三氟芳基乙酮芳环上取代基性质及取代位置对该反应的影响进行了研究.发现底物1芳环上取代基的电子效应和空间位阻对反应产物3的产率有一定影响, 吸电子取代基且在对位取代的底物通常都能取得较好的反应产率(表 3, 5s), 邻位取代的底物反应活性很低, 回收得到原料. 2-萘基三氟甲基酮也可以顺利地发生反应, 以较高的产率得到目标产物(表 3, 5y, 5z和5aa).而对于脂肪族的三氟甲基酮, 则没有检测到目标产物的生成. α, β-不饱和肉桂基三氟甲基酮反应活性较低, 以45%的产率得到目标产物(表 3, 5ab).

表 3 反应底物范围^a.b Table 3. Substrate scope

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接下来, 我们考察了取代的烯丙基溴对反应产率的影响.由表 4可知, 肉桂基溴(3b)能顺利发生反应, 反应表现出区域选择性, 得到的产物均为α-加成产物(5ac~5ae)^[18]. 2-甲基-3-溴丙烯(3c)也能顺利进行反应, 加成产物5af、5ag和5ah分别以85%、88%和83%的收率获得.

表 4 烯丙基溴的适用范围^a^{, b} Table 4. Substrate scope of allyl bromides

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在该实验中合成的三氟甲基高烯丙基酰肼类化合物可以进一步处理为三氟甲基合成结构单元, 以提供其它三氟甲基化有机化合物.我们小组进行了文献调研和实验探究, 发现在SmI₂作用下, 三氟甲基高烯丙基酰肼(5a)可发生氮-氮键的断键反应^[11], 转化为有机合成中重要的中间体高烯丙基胺类化合物6 (Eq. 1).

2 结论

本文在原位生成烯丙基锡试剂以及原位生成三氟甲基酰腙的基础上, 高效简便地利用一锅法反应合成了一系列含三氟甲基高烯丙基酰肼类化合物.采用一锅法合成各种取代含三氟甲基高烯丙基酰肼类化合物的策略具有原料廉价易得、反应条件温和可控、收率高和后处理容易等特点, 是一种可广泛应用于各种含三氟甲基高烯丙基酰肼类化合物合成的方法.合成的三氟甲基高烯丙基酰肼类化合物作为一类有效的三氟甲基合成砌块可方便地转化为各类三氟甲基取代的杂环化合物, 它们在有机合成中的研究我们课题组正在进行中.

3 实验部分

3.1 仪器与试剂

核磁共振谱用BRUKER PT jxf790425AM 400MHz或Agilent DD2 600 MHz型核磁共振仪测定, 以氘代氯仿作为溶剂, TMS为内标; 高分辨质谱用Bruker APEX Ⅱ傅里叶变换离子回旋共振质谱仪测定, ESI源; 熔点测定用显微熔点测定仪测定, 温度未校正.实验中所用试剂均为国产分析纯级.所用溶剂均通过标准方法蒸馏干燥.

3.2 实验方法

3.2.1 Weinreb酰胺的合成

Weinreb酰胺按照参考文献[19]合成.首先在100 mL干燥的三口瓶中依次加入3 g N-甲基-N-甲氧基胺盐酸盐、15 mL乙二醇和36 mL三乙胺, 然后加热收集47~50℃的馏份, 定量得1.86 g无色液体N-甲基-N-甲氧基胺.然后在冰水浴下向50 mL圆底烧瓶中加入羧酸(10 mmol)、N-甲基-N-甲氧基胺(30 mmol)溶于30 mL甲苯中, 在0 ℃下搅拌10 min后, 向混合物中缓慢滴加PCl₃ (5 mmol)的甲苯混合液, 滴加完毕后, 让其自然升至室温.混合物于60 ℃下继续加热30 min, 经TLC检测.原料反应完后, 冷却至室温, 加饱和NaHCO₃水溶液猝灭反应.用乙醚萃取, 无水MgSO₄干燥, 蒸发浓缩, 剩余物柱层析[V(石油醚):V(乙酸乙酯)＝4:1]分离得到产率为97%的纯Weinreb酰胺.

3.2.2 取代2, 2, 2-三氟甲基酮的合成

取代2, 2, 2-三氟甲基酮按照参考文献[20]合成.将氟化铯(1 mmol)加入50 mL圆底烧瓶, 加入3 mL甲苯, 搅拌溶解后, 再加入上述制备的Weinreb酰胺(5 mmol), 冰水浴冷却至0 ℃.将TMSCF₃缓慢滴入反应瓶, 搅拌10 min后撤去冰水浴, 室温搅拌过夜. TLC检测反应完全后加入5 mL水, 将四丁基氟化铵(4 mmol)溶于5 mL四氢呋喃后加入反应体系, 50 ℃回流2 h.冷却至室温, 用乙酸乙酯(10 mL×3) 萃取, 有机相用无水硫酸镁干燥, 蒸发浓缩, 剩余物柱层析[V(石油醚):V(乙酸乙酯)＝6:1]分离得取代2, 2, 2-三氟甲基酮.

3.2.3 取代酰肼的合成

取代酰肼按照参考文献[21]合成.在100 mL单口瓶中依次加入有机羧酸(0.045 mol)、乙醇(30 mL)、浓硫酸(1 mL), 加热回流, TLC检测反应完全后, 减压蒸除溶剂, 体系冷却至室温, 逐滴加入饱和碳酸钠至溶液呈中性, 乙酸乙酯萃取(30 mL×3), 合并有机相, 无水硫酸镁干燥有机相, 蒸发浓缩得酯粗产品.将新制的酯溶于乙醇(10 mL), 加入3 equiv.水合肼(80%水溶液), 加热回流, TLC检测酯完全反应后, 蒸去乙醇, 冷却结晶, 过滤, 粗产品用无水乙醇重结晶, 干燥得酰肼纯品.

3.2.4 高烯丙基酰肼类化合物合成

50 mL圆底烧瓶中依次加入三氟甲基酮(0.3 mmol)、酰肼(0.45 mmol)、BF₃•OEt₂ (5 mol%)、四氢呋喃(3 mL), 加热回流, TLC检测酰腙生成后, 反应体系中依次加入锡粉(0.75 mmol)、烯丙基溴(0.6 mmol)及BF₃•OEt₂ (15 mol%), 补加3 mL四氢呋喃, 继续加热回流, TLC检测反应完全后, 蒸发除去溶剂, 加入乙酸乙酯(10 mL)及饱和氯化铵溶液(3 mL)猝灭反应, 分液, 乙酸乙酯萃取(10 mL×3), 合并有机相, 有机相用无水硫酸镁干燥, 蒸发浓缩, 剩余物柱层析[V(石油醚):V(乙酸乙酯)＝4:1]分离得化合物5.

N'-(1, 1, 1-三氟-2-苯基戊-4-烯-2-基)苯甲酰肼(5a):得83 mg无色针晶, 产率83%. m.p. 124~125 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.67 (d, J＝7.8 Hz, 2H), 7.64 (d, J＝7.2 Hz, 2H), 7.51 (t, J＝7.2 Hz, 1H), 7.43~7.38 (m, 5H), 7.29 (d, J＝7.2 Hz, 1H), 5.98 (d, J＝7.8 Hz, 1H), 5.75~5.69 (m, 1H), 5.18 (d, J＝16.8 Hz, 1H), 5.10 (d, J＝10.2 Hz, 1H), 3.03 (dd, J＝15.0, 7.2 Hz, 1H), 2.95 (dd, J＝15.0, 7.2 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃) δ: 166.5, 134.7, 132.3, 132.0, 131.2, 128.8, 128.7, 128.6, 127.6, 126.8, 126.4 (q, J＝286.0 Hz), 119.6, 67.8 (q, J＝24.0 Hz), 36.9; ¹⁹F NMR (376 MHz, CDCl₃) δ: －72.45. HRMS calcd for C₁₈H₁₈F₃N₂O [M+H]⁺ 335.1366, found 335.1356.

3-甲基-N'-(1, 1, 1-三氟-2-苯基戊-4-烯-2-基)苯甲酰肼(5c):得82 mg无色针晶, 产率78%. m.p. 90~91 ℃; ¹H NMR (600 MHz, CDCl₃)δ: 7.67 (d, J＝7.8 Hz, 2H), 7.49 (s, 1H), 7.44~7.36 (m, 5H), 7.32~7.27 (m, 2H), 5.97 (d, J＝7.8 Hz, 1H), 5.76~5.69 (m, 1H), 5.17 (dd, J＝16.8, 1.2 Hz, 1H), 5.10 (dd, J＝10.2, 0.6 Hz, 1H), 3.03 (dd, J＝15.0, 7.2 Hz, 1H), 2.96 (dd, J＝15.0, 7.2 Hz, 1H), 2.37 (s, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 166.7, 138.6, 134.8, 132.7, 132.3, 131.2, 128.7, 128.6, 128.5, 127.6, 126.4 (q, J＝285.0 Hz), 123.7, 119.5, 67.8 (q, J＝24.0 Hz), 36.8, 21.3; ¹⁹F NMR (376 MHz, CDCl₃) δ: －72.49. HRMS calcd for C₁₉H₂₀F₃N₂O [M+H]⁺ 349.1522, found 349.1526.

4-甲基-N'-(1, 1, 1-三氟-2-苯基戊-4-烯-2-基)苯甲酰肼(5d):得88 mg无色针晶, 产率84%. m.p. 128~129 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.67 (d, J＝7.8 Hz, 2H), 7.54 (d, J＝8.4 Hz, 2H), 7.42~7.35 (m, 4H), 7.19 (d, J＝7.8 Hz, 2H), 5.97 (d, J＝7.8 Hz, 1H), 5.75~5.68 (m, 1H), 5.16 (dd, J＝17.4, 1.2 Hz, 1H), 5.08 (d, J＝10.2 Hz, 1H), 3.02 (dd, J＝15.6, 7.2 Hz, 1H), 2.94 (dd, J＝15.6, 7.2 Hz, 1H), 2.37 (s, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 166.5, 142.5, 134.8, 131.2, 129.4, 129.3, 128.6, 128.5, 127.6, 126.8, 126.4 (q, J＝286.0 Hz), 119.5, 67.8 (q, J＝24.0 Hz), 36.8, 21.4; ¹⁹F NMR (376 MHz, CDCl₃) δ: －72.53. HRMS calcd for C₁₉H₂₀F₃N₂O [M+H]⁺ 349.1522, found 349.1511.

4-甲氧基-N'-(1, 1, 1-三氟-2-苯基戊-4-烯-2-基)苯甲酰肼(5e):得83 mg无色针晶, 产率76%. m.p. 106~108 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.67 (d, J＝7.8 Hz, 2H), 7.62 (d, J＝8.4 Hz, 2H), 7.41 (t, J＝7.2 Hz, 2H), 7.36 (t, J＝7.2 Hz, 1H), 7.27 (d, J＝7.2 Hz, 1H), 6.89 (d, J＝9.0 Hz, 2H), 5.96 (d, J＝7.8 Hz, 1H), 5.75~5.68 (m, 1H), 5.16 (dd, J＝17.4, 1.8 Hz, 1H), 5.08 (d, J＝10.2 Hz, 1H), 3.82 (s, 3H), 3.02 (dd, J＝15.0, 7.2 Hz, 1H), 2.94 (dd, J＝15.0, 7.2 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃) δ: 166.3, 162.6, 134.9, 131.3, 128.7, 128.6, 128.5, 127.6, 126.4 (q, J＝286.5 Hz), 124.5, 119.5, 113.9, 67.8 (q, J＝24.0 Hz), 55.4, 36.8; ¹⁹F NMR (376 MHz, CDCl₃)δ:－72.56. HRMS calcd for C₁₉H₂₀F₃N₂O₂ [M+H]⁺ 365.1471, found 365.1459.

3-氯-N'-(1, 1, 1-三氟-2-苯基戊-4-烯-2-基)苯甲酰肼(5g):得96 mg无色针晶, 产率87%. m.p. 105~108 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.66 (d, J＝6.6 Hz, 2H), 7.62 (s, 1H), 7.48~7.40 (m, 5H), 7.38 (d, J＝7.2 Hz, 1H), 7.33~7.30 (m, 1H), 5.93 (d, J＝7.2 Hz, 1H), 5.72~5.68 (m, 1H), 5.17 (d, J＝17.4 Hz, 1H), 5.10 (d, J＝10.2 Hz, 1H), 3.00 (dd, J＝13.8, 6.0 Hz, 1H), 2.94 (dd, J＝13.8, 6.0 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃)δ: 165.2, 134.9, 134.6, 134.0, 132.0, 131.1, 130.0, 128.7, 128.6, 127.5, 127.3, 126.0 (q, J＝286.5 Hz), 124.8, 119.7, 67.8 (q, J＝24.0 Hz), 37.1; ¹⁹F NMR (376 MHz, CDCl₃)δ: －72.25. HRMS calcd for C₁₈H₁₆ClF₃N₂NaO [M+Na]⁺ 391.0795, found 391.0802.

4-氯-N'-(1, 1, 1-三氟-2-苯基戊-4-烯-2-基)苯甲酰肼(5h):得94 mg无色针晶, 产率85%. m.p. 110~113 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.66 (d, J＝7.8 Hz, 2H), 7.56 (d, J＝8.4 Hz, 2H), 7.43~7.35 (m, 6H), 5.95 (d, J＝6.0 Hz, 1H), 5.73~5.67 (m, 1H), 5.16 (dd, J＝16.8, 1.2 Hz, 1H), 5.09 (dd, J＝10.2, 1.2 Hz, 1H), 3.00 (dd, J＝15.6, 7.2 Hz, 1H), 2.93 (dd, J＝15.6, 7.2 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃)δ: 165.6, 138.3, 134.7, 131.1, 130.6, 129.0, 128.7, 128.6, 128.3, 127.5, 126.4 (q, J＝286.5 Hz), 119.7, 67.9 (q, J＝24.0 Hz), 37.1. ¹⁹F NMR (376 MHz, CDCl₃) δ: －72.24. HRMS calcd for C₁₈H₁₇ClF₃N₂O [M+H]⁺ 369.0976, found 369.0964.

N'-(1, 1, 1-三氟-2-苯基戊-4-烯-2-基)-4-(三氟甲基)苯甲酰肼(5i):得87 mg无色针晶, 产率72%. m.p. 95~97 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.72 (d, J＝8.4 Hz, 2H), 7.67~7.63 (m, 5H), 7.43~7.36 (m, 3H), 5.96 (d, J＝7.8 Hz, 1H), 5.74~5.67 (m, 1H), 5.17 (d, J＝17.4 Hz, 1H), 5.10 (d, J＝10.2 Hz, 1H), 3.01 (dd, J＝15.0, 6.6 Hz, 1H), 2.94 (dd, J＝15.2, 6.6 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃)δ: 165.2, 135.6, 134.6, 133.4 (q, J＝33.0 Hz), 131.0, 128.7, 128.6, 127.5, 127.4, 126.4 (q, J＝286.5 Hz), 125.7 (q, J＝3.0 Hz), 123.5 (q, J＝271.5 Hz), 119.7, 67.9 (q, J＝24.0 Hz), 37.3; ¹⁹F NMR (376 MHz, CDCl₃) δ: －63.56, －72.18. HRMS calcd for C₁₉H₁₇F₆N₂O[M+ H]⁺ 403.1240, found 403.1226.

3-溴-N'-(1, 1, 1-三氟-2-苯基戊-4-烯-2-基)苯甲酰肼(5j):得103 mg无色针晶, 产率83%. m.p. 99~100 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.78 (s, 1H), 7.66 (d, J＝7.2 Hz, 2H), 7.59 (d, J＝7.2 Hz, 1H), 7.51 (d, J＝7.8 Hz, 2H), 7.42~7.36 (m, 3H), 7.25~7.22 (m, 1H), 5.93 (d, J＝7.8 Hz, 1H), 5.71~5.65 (m, 1H), 5.16 (dd, J＝16.8, 1.2 Hz, 1H), 5.09 (d, J＝10.2 Hz, 1H), 3.00 (dd, J＝15.0, 7.2 Hz, 1H), 2.94 (dd, J＝15.0, 7.2 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃)δ: 165.1, 134.8, 134.6, 134.2, 131.0, 130.2, 130.1, 128.7, 128.6, 127.5, 126.3 (q, J＝285.0 Hz), 125.3, 122.8, 119.6, 67.8 (q, J＝24.0 Hz), 37.0; ¹⁹F NMR (376 MHz, CDCl₃) δ: －72.25. HRMS calcd for C₁₈H₁₆BrF₃N₂NaO[M+Na]⁺ 437.0270, found 437.0276.

N'-(1, 1, 1-三氟-2-苯基戊-4-烯-2-基)呋喃-2-碳酰肼(5k):得88 mg无色针晶, 产率90%. m.p. 118~119 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 7.68~7.62 (m, 3H), 7.43~7.35 (m, 4H), 7.12~7.11 (m, 1H), 6.48~6.47 (m, 1H), 5.77~5.66 (m, 2H), 5.18 (d, J＝16.8 Hz, 1H), 5.10 (d, J＝10.4 Hz, 1H), 3.01 (dd, J＝15.2, 7.2 Hz, 1H), 2.92 (dd, J＝15.2, 7.2 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃)δ: 157.0, 146.1, 144.3, 134.6, 131.1, 128.6, 128.5, 127.6, 126.3 (q, J＝286.0 Hz), 119.7, 115.1, 112.0, 67.7 (q, J＝24.0 Hz), 36.8; ¹⁹F NMR (376 MHz, CDCl₃) δ: －72.53. HRMS calcd for C₁₆H₁₆F₃N₂O₂[M+H]⁺ 325.1158, found 325.1147.

N'-(1, 1, 1-三氟-2-苯基戊-4-烯-2-基)-2-萘甲酰肼(5l):得97 mg无色针晶, 产率84%. m.p. 117~120 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.16 (s, 1H), 7.87~7.82 (m, 3H), 7.71~7.65 (m, 3H), 7.57~7.50 (m, 3H), 7.45~7.36 (m, 3H), 6.05 (d, J＝7.6 Hz, 1H), 5.21~5.10 (m, 1H), 5.19 (d, J＝16.8 Hz, 1H), 5.11 (d, J＝10.0 Hz, 1H), 3.07 (dd, J＝15.2, 7.2 Hz, 1H), 2.98 (dd, J＝15.2, 7.2 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃)δ: 166.6, 134.9, 134.8, 132.5, 131.2, 129.4, 128.9, 128.7, 128.6, 127.9, 127.7, 127.6, 126.9, 126.4 (q, J＝285.0 Hz), 123.0, 119.6, 67.8 (q, J＝24.0 Hz), 36.9; ¹⁹F NMR (376 MHz, CDCl₃)δ: －72.38. HRMS calcd for C₂₂H₁₉F₃N₂NaO[M+Na]⁺ 407.1342, found 407.1350.

N'-(1, 1, 1-三氟-2-苯基戊-4-烯-2-基)-3, 5-双(三氟甲基)苯甲酰肼(5m):得121 mg无色针晶, 产率86%. m.p. 92~93 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 8.04 (s, 2H), 8.00 (s, 1H), 7.67~7.65 (m, 3H), 7.43~7.39 (m, 3H), 5.94 (d, J＝6.6 Hz, 1H), 5.72~5.69 (m, 1H), 5.20 (d, J＝16.8 Hz, 1H), 5.13 (d, J＝10.2 Hz, 1H), 3.03~2.95 (m, 2H); ¹³C NMR (150 MHz, CDCl₃) δ: 163.7, 134.4, 134.3, 132.4 (q, J＝34.0 Hz), 131.0, 128.9, 128.8, 127.5, 127.2, 126.3 (q, J＝286.0 Hz), 125.5, 122.7 (q, J＝272.0 Hz), 119.9, 68.0 (q, J＝24.0 Hz), 37.5; ¹⁹F NMR (376 MHz, CDCl₃)δ: －63.52, －72.13. HRMS calcd for C₂₀H₁₅F₉N₂NaO[M+Na]⁺ 493.0933, found 493.0941.

3, 5-二氯-N'-(1, 1, 1-三氟-2-苯基戊-4-烯-2-基)苯甲酰肼(5n):得99 mg无色针晶, 产率82%. m.p. 118~119 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 7.65 (d, J＝7.2 Hz, 2H), 7.47~7.38 (m, 6H), 5.91 (d, J＝7.6 Hz, 1H), 5.74~5.64 (m, 1H), 5.18 (d, J＝17.2 Hz, 1H), 5.11 (d, J＝10.0 Hz, 1H), 3.02~2.90 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 163.9, 135.6, 135.1, 134.5, 131.8, 130.9, 128.8, 128.7, 127.5, 126.3 (q, J＝286.5 Hz), 125.5, 119.8, 67.9 (q, J＝24.0 Hz), 37.2; ¹⁹F NMR (376 MHz, CDCl₃) δ: －72.20. HRMS calcd for C₁₈H₁₅Cl₂F₃N₂NaO[M+Na]⁺ 425.0406, found 425.0413.

N'-(2-(3-氯苯基)-1, 1, 1-三氟戊-4-烯-2-基)苯甲酰肼(5r):得94 mg无色针晶, 产率85%. m.p. 90~93 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 7.69~7.64 (m, 3H), 7.56~7.49 (m, 2H), 7.43~7.35 (m, 5H), 5.93 (d, J＝7.6 Hz, 1H), 5.75~5.65 (m, 1H), 5.18 (dd, J＝16.8, 1.2 Hz, 1H), 5.13 (d, J＝10.0 Hz, 1H), 3.01 (dd, J＝15.2, 7.2 Hz, 1H), 2.89 (dd, J＝15.2, 7.2 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃)δ: 166.8, 137.0, 134.7, 132.1, 130.7, 129.8, 128.9, 128.7, 128.0, 126.9, 126.2 (q, J＝286.0 Hz), 125.9, 120.1, 67.7 (q, J＝24.0 Hz), 37.0; ¹⁹F NMR (376 MHz, CDCl₃) δ: －72.26. HRMS calcd for C₁₈H₁₇ClF₃N₂O [M+H]⁺ 369.0976, found 369.0965.

N'-(2-(4-氯苯基)-1, 1, 1-三氟戊-4-烯-2-基)苯甲酰肼(5s):得97 mg无色针晶, 产率88%. m.p. 131~133 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.65 (d, J＝7.2 Hz, 2H), 7.61 (d, J＝8.4 Hz, 2H), 7.51 (t, J＝7.8 Hz, 1H), 7.43~7.38 (m, 4H), 7.29 (d, J＝6.0 Hz, 1H), 5.89 (d, J＝7.2 Hz, 1H), 5.73~5.66 (m, 1H), 5.17 (d, J＝17.4 Hz, 1H), 5.12 (d, J＝10.2 Hz, 1H), 3.00 (dd, J＝15.0, 7.2 Hz, 1H), 2.90 (dd, J＝15.0, 7.2 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃)δ: 166.7, 134.8, 133.4, 132.2, 132.1, 130.8, 129.2, 129.1, 128.8, 126.9, 126.2 (q, J＝286.5 Hz), 120.1, 67.6 (q, J＝24.0 Hz), 36.9; ¹⁹F NMR (376 MHz, CDCl₃) δ: －72.53. HRMS calcd for C₁₈H₁₆ClF₃N₂NaO[M+Na]⁺ 391.0795, found 391.0805.

N'-(1, 1, 1-三氟-2-间甲苯基戊-4-烯-2-基)苯甲酰肼(5t):得77 mg无色针晶, 产率74%. m.p. 96~98 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 7.65 (d, J＝7.2 Hz, 2H), 7.48~7.45 (m, 4H), 7.39 (t, J＝8.0 Hz, 2H), 7.30 (t, J＝7.6 Hz, 1H), 7.18 (d, J＝7.6 Hz, 1H), 5.99 (d, J＝8.0 Hz, 1H), 5.75~5.67 (m, 1H), 5.17 (dd, J＝16.8, 1.2 Hz, 1H), 5.09 (dd, J＝10.0, 1.2 Hz, 1H), 3.02 (dd, J＝15.2, 6.8 Hz, 1H), 2.94 (dd, J＝15.2, 6.8 Hz, 1H), 2.38 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 166.4, 138.2, 134.7, 132.3, 131.9, 131.3, 129.4, 128.6, 128.4, 128.1, 126.8, 126.4 (q, J＝286.0 Hz), 124.6, 119.4, 67.6 (q, J＝24.0 Hz), 36.7, 21.6; ¹⁹F NMR (376 MHz, CDCl₃)δ: －72.47. HRMS calcd for C₁₉H₂₀F₃N₂O [M+H]⁺349.1522, found 349.1513.

N'-(1, 1, 1-三氟-2-对甲苯基戊-4-烯-2-基)苯甲酰肼5u:得89 mg无色针晶, 产率86%. m.p. 105~107 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.65 (d, J＝7.2 Hz, 2H), 7.55 (d, J＝8.4 Hz, 2H), 7.50 (t, J＝7.2 Hz, 1H), 7.41 (t, J＝7.8 Hz, 2H), 7.36 (d, J＝7.2 Hz, 1H), 7.23 (d, J＝7.8 Hz, 2H), 5.97 (d, J＝7.8 Hz, 1H), 5.78~5.67 (m, 1H), 5.17 (d, J＝18.6 Hz, 1H), 5.10 (d, J＝10.2 Hz, 1H), 3.02 (dd, J＝15.0, 7.2 Hz, 1H), 2.94 (dd, J＝15.6, 7.2 Hz, 1H), 2.36 (s, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 166.4, 138.5, 132.4, 132.0, 131.7, 131.3, 129.3, 128.7, 127.5, 126.8, 126.4 (q, J＝286.9 Hz), 119.5, 67.6 (q, J＝22.6 Hz), 36.7, 21.0; ¹⁹F NMR (376 MHz, CDCl₃) δ: －72.82. HRMS calcd for C₁₉H₁₉F₃N₂NaO[M+Na]⁺ 371.1342, found 371.1337.

3-甲基-N'-(1, 1, 1-三氟-2-间甲苯基戊-4-烯-2-基)苯甲酰肼(5v):得76 mg无色针晶, 产率70%. m.p. 115~116 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.49 (s, 2H), 7.46~7.40 (m, 3H), 7.30~7.24 (m, 3H), 7.17 (d, J＝7.2 Hz, 1H), 5.98 (d, J＝7.8 Hz, 1H), 5.75~5.68 (m, 1H), 5.16 (d, J＝16.8 Hz, 1H), 5.08 (d, J＝10.2 Hz, 1H), 3.02 (dd, J＝15.0, 7.2 Hz, 1H), 2.94 (dd, J＝15.2, 7.2 Hz, 1H), 2.37 (s, 3H), 2.34 (s, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 166.6, 138.5, 138.2, 134.7, 132.6, 132.2, 131.3, 129.3, 128.5, 128.4, 128.2, 127.6, 126.4 (q, J＝286.0 Hz), 124.7, 123.7, 119.3, 67.6 (q, J＝24.0 Hz), 36.6, 21.6, 21.2; ¹⁹F NMR (376 MHz, CDCl₃)δ: －72.49. HRMS calcd for C₂₀H₂₂F₃N₂O [M+H]⁺ 363.1679, found 363.1671.

3-溴-N'-(1, 1, 1-三氟-2-间甲苯基戊-4-烯-2-基)苯甲酰肼(5w):得100 mg无色针晶, 产率78%. m.p. 108~111 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.77 (s, 1H), 7.62 (d, J＝7.2 Hz, 1H), 7.57 (d, J＝7.8 Hz, 1H), 7.51 (d, J＝7.2 Hz, 1H), 7.47 (s, 1H), 7.44 (d, J＝7.8 Hz, 1H), 7.29 (t, J＝7.2 Hz, 1H), 7.21 (t, J＝7.2 Hz, 1H), 7.17 (d, J＝7.2 Hz, 1H), 5.94 (d, J＝7.8 Hz, 1H), 5.73~5.66 (m, 1H), 5.16 (d, J＝17.4 Hz, 1H), 5.08 (d, J＝10.2 Hz, 1H), 2.99 (dd, J＝15.0, 6.6 Hz, 1H), 2.93 (dd, J＝15.0, 6.6 Hz, 1H), 2.37 (s, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 165.0, 138.2, 134.8, 134.5, 134.2, 131.2, 130.2, 130.1, 129.4, 128.4, 128.1, 126.3 (q, J＝286.5 Hz), 125.3, 124.6, 122.7, 119.4, 67.7 (q, J＝24.0 Hz), 36.9, 21.6; ¹⁹F NMR (376 MHz, CDCl₃)δ: －72.22. HRMS calcd for C₁₉H₁₈BrF₃N₂NaO [M+Na]⁺ 450.2109, found 450.2115.

3-溴-N'-(2-(3-氯苯基)-1, 1, 1-三氟戊-4-烯-2-基)苯甲酰肼(5x):得110 mg无色针晶, 产率82%. m.p. 103~104 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.77~7.75 (m, 2H), 7.69 (s, 1H), 7.58~7.54 (m, 2H), 7.50 (d, J＝7.8 Hz, 1H), 7.33 (s, 2H), 7.21 (t, J＝7.8 Hz, 1H), 5.88 (d, J＝7.2 Hz, 1H), 5.71~5.64 (m, 1H), 5.16 (d, J＝17.4 Hz, 1H), 5.10 (d, J＝10.2 Hz, 1H), 2.98 (dd, J＝15.0, 7.2 Hz, 1H), 2.88 (dd, J＝15.2, 7.2 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃)δ: 165.5, 136.8, 134.9, 134.6, 133.9, 130.5, 130.2, 130.1, 129.7, 128.9, 128.0, 126.0 (q, J＝286.5 Hz), 125.9, 125.3, 122.7, 120.0, 67.6 (q, J＝24.0 Hz), 37.0; ¹⁹F NMR (376 MHz, CDCl₃)δ: －71.99. HRMS calcd for C₁₈H₁₅BrClF₃N₂NaO [M+Na]⁺ 470.9879, found 470.9887.

N'-(1, 1, 1-三氟-2-(萘-2-基)戊-4-烯-2-基)苯甲酰肼(5y):得68 mg无色针晶, 产率59%. m.p. 151~153 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.18 (s, 1H), 7.90~7.83 (m, 3H), 7.77 (d, J＝7.6 Hz, 1H), 7.64~7.62 (m, 2H), 7.52~7.44 (m, 4H), 7.36 (t, J＝7.6 Hz, 2H), 6.11 (d, J＝7.6 Hz, 1H), 5.80~5.70 (m, 1H), 5.20 (dd, J＝16.8, 1.2 Hz, 1H), 5.09 (d, J＝10.4 Hz, 1H), 3.11 (dd, J＝14.4, 6.6 Hz, 1H), 3.05 (dd, J＝14.4, 6.6 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃)δ: 166.6, 132.8, 132.3, 132.2, 131.9, 131.1, 128.6, 128.5, 128.3, 127.5, 127.4, 126.9, 126.8, 126.7, 126.5 (q, J＝288.4 Hz), 126.4, 124.7, 119.6, 68.0 (q, J＝24.0 Hz), 37.1; ¹⁹F NMR (376 MHz, CDCl₃)δ: －72.02. HRMS calcd for C₂₂H₁₉F₃N₂NaO [M+Na]⁺ 407.1342, found 407.1349.

4-甲氧基-N'-[1, 1, 1-三氟-2-(萘-2-基)戊-4-烯-2-基]苯甲酰肼(5z):得109 mg无色针晶, 产率88%. m.p. 110~112 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 8.17 (s, 1H), 8.03~7.68 (m, 5H), 7.61 (d, J＝9.0 Hz, 2H), 7.56~7.46 (m, 2H), 6.86 (d, J＝8.4 Hz, 2H), 6.10 (d, J＝6.6 Hz, 1H), 5.75~5.68 (m, 1H), 5.19 (d, J＝16.8 Hz, 1H), 5.08 (d, J＝9.6 Hz, 1H), 3.79 (s, 3H), 3.10 (dd, J＝15.6, 7.2Hz, 1H), 3.04 (dd, J＝15.6, 7.2 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ: 166.4, 162.5, 132.9, 132.8, 132.3, 131.3, 128.7, 128.5, 128.3, 127.5, 127.4, 126.8, 126.5 (q, J＝286.0 Hz), 126.4, 124.8, 124.4, 119.6, 113.9, 67.9 (q, J＝24.0 Hz), 55.3, 36.9; ¹⁹F NMR (376 MHz, CDCl₃) δ: －72.12. HRMS calcd for C₂₃H₂₁F₃N₂NaO₂[M+Na]⁺ 437.1447, found 437.1454.

N'-(1, 1, 1-三氟-2-(萘-2-基)戊-4-烯-2-基)-3, 5-双(三氟甲基)苯甲酰肼(5aa):得116 mg无色针晶, 产率74%. m.p. 100~103 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 8.17 (s, 1H), 8.08~8.05 (m, 2H), 7.97 (s, 1H), 7.89~7.83 (m, 3H), 7.74 (d, J＝7.8 Hz, 2H), 7.53~7.51 (m, 2H), 6.11~6.09 (m, 1H), 5.76~5.71(m, 1H), 5.22 (d, J＝16.8 Hz, 1H), 5.12 (d, J＝10.2 Hz, 1H), 3.10~3.00 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 163.7, 134.3, 133.0, 132.9, 132.2 (q, J＝34.0 Hz), 131.9, 131.0, 128.5, 128.4, 127.5, 127.4, 127.3, 127.0, 126.5, 126.4 (q, J＝286.0 Hz), 125.3, 124.6, 122.7 (q, J＝272 Hz), 119.9, 68.1 (q, J＝24.0 Hz), 37.7; ¹⁹F NMR (376 MHz, CDCl₃) δ: －63.50, －71.54. HRMS calcd for C₂₄H₁₇F₉N₂NaO[M+Na]⁺ 543.1089, found 543.1098.

(E)-N'-(1-(4-甲氧基苯基)-3-(三氟甲基)己-1, 5-二烯-3-基)苯甲酰肼(5ab):得53 mg无色针晶, 产率45%. m.p. 113~116 ℃; ¹H NMR (600 MHz, CDCl₃) δ: 7.70 (d, J＝7.8 Hz, 2H), 7.51 (t, J＝7.2 Hz, 1H), 7.43~7.41 (m, 3H), 7.31 (d, J＝8.4 Hz, 2H), 6.85~6.82 (m, 3H), 6.04 (d, J＝16.8 Hz, 1H), 5.99~5.92 (m, 1H), 5.62 (d, J＝7.2 Hz, 1H), 5.29~5.24 (m, 2H), 3.79 (s, 3H), 2.77 (dd, J＝14.4, 6.6 Hz, 1H), 2.71 (dd, J＝14.4, 6.6 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃)δ: 167.1, 159.8, 133.8, 132.3, 132.0, 131.1, 128.8, 128.7, 127.9, 126.8, 126.4 (q, J＝286.0 Hz), 120.4, 120.2, 114.0, 65.7 (q, J＝24.0 Hz), 55.3, 36.7; ¹⁹F NMR (376 MHz, CDCl₃) δ: －75.09. HRMS calcd for C₂₁H₂₁F₃N₂NaO₂ [M+Na]⁺ 413.1447, found 413.1453.

(E)-N'-(1, 1, 1-三氟-2, 3-二苯基戊-4-烯-2-基)苯甲酰肼(5ac):无色粘稠油状物; 90 mg, 产率73%. ¹H NMR (600 MHz, CDCl₃) δ 7.72 (d, J＝7.8 Hz, 2H), 7.62 (d, J＝7.8 Hz, 2H), 7.48 (t, J＝7.8 Hz, 1H), 7.44 (t, J＝7.2 Hz, 2H), 7.41~7.32 (m, 4H), 7.24 (d, J＝4.2 Hz, 4H), 7.21~7.15 (m, 1H), 6.50 (d, J＝15.6 Hz, 1H), 6.15~6.07 (m, 1H), 6.02 (d, J＝7.8 Hz, 1H), 3.18 (dd, J＝15.6, 7.2 Hz, 1H), 3.11 (dd, J＝15.6, 7.2 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃) δ: 166.5, 136.9, 134.8, 134.4, 132.3, 132.0, 128.8, 128.7, 128.6, 128.4, 127.7, 127.4, 126.8, 126.4 (q, J＝285.0 Hz), 126.2, 122.6, 68.2 (q, J＝24.0 Hz), 36.4; ¹⁹F NMR (376 MHz, CDCl₃) δ: －72.32. HRMS calcd for C₂₄H₂₂F₃N₂O [M+H]⁺ 411.1679, found 411.1682.

(E)-4-氯-N'-(1, 1, 1-三氟-2, 3-二苯基戊-4-烯-2-基)苯甲酰肼(5ad):无色粘稠油状物; 103 mg, 产率78%. ¹H NMR (600 MHz, CDCl₃) δ: 7.71 (d, J＝7.8 Hz, 2H), 7.53 (d, J＝8.4 Hz, 2H), 7.44 (t, J＝7.8 Hz, 2H), 7.38 (t, J＝7.2 Hz, 1H), 7.33 (t, J＝8.4 Hz, 3H), 7.28~7.21 (m, 4H), 7.19 (t, J＝6.6 Hz, 1H), 6.48 (d, J＝15.6 Hz, 1H), 6.13~6.04 (m, 1H), 5.99 (d, J＝7.2 Hz, 1H), 3.15 (dd, J＝15.6, 7.2 Hz, 1H), 3.11 (dd, J＝15.0, 7.2 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃) δ: 165.5, 138.3, 136.8, 134.6, 134.4, 130.6, 129.0, 128.8, 128.7, 128.5, 128.3, 127.6, 127.5, 126.4 (q, J＝285.0 Hz), 126.2, 122.5, 68.2 (q, J＝24.0 Hz), 36.5; ¹⁹F NMR (376 MHz, CDCl₃) δ: －72.27. HRMS calcd for C₂₄H₂₁F₃N₂OCl [M+H]⁺ 445.1289, found 445.1283.

(E)-4-甲基-N'-(1, 1, 1-三氟-2, 3-二苯基戊-4-烯-2-基)苯甲酰肼(5ae):无色粘稠油状物; 99 mg, 产率76%. ¹H NMR (600 MHz, CDCl₃) δ: 7.73 (d, J＝7.8 Hz, 2H), 7.54 (d, J＝7.8 Hz, 2H), 7.44 (t, J＝7.8 Hz, 2H), 7.42~7.33 (m, 2H), 7.25 (d, J＝4.8 Hz, 4H), 7.22~7.14 (m, 3H), 6.50 (d, J＝15.6 Hz, 1H), 6.15~6.08 (m, 1H), 6.03 (d, J＝7.2 Hz, 1H), 3.19 (dd, J＝15.0, 6.6 Hz, 1H), 3.12 (dd, J＝15.0, 7.2 Hz, 1H), 2.37 (s, 1H); ¹³C NMR (150 MHz, CDCl₃) δ: 166.5, 142.5, 136.9, 134.8, 134.3, 129.4, 129.3, 128.7, 128.6, 128.4, 127.7, 127.4, 126.8, 126.4 (q, J＝286.0 Hz), 126.2, 122.7, 68.2 (q, J＝24.0 Hz), 36.3, 21.4; ¹⁹F NMR (376 MHz, CDCl₃) δ: －72.37. HRMS calcd for C₂₅H₂₄F₃N₂O [M+H]⁺ 425.1835, found 425.1831.

N'-(1, 1, 1-三氟-4-甲基-2-苯基戊-4-烯-2-基)苯甲酰肼(5af):无色粘稠油状物; 89 mg, 产率85%. ¹H NMR (600 MHz, CDCl₃) δ: 7.68 (d, J＝7.8 Hz, 2H), 7.61 (d, J＝7.8 Hz, 2H), 7.47 (t, J＝8.4 Hz, 1H), 7.44 (s, 1H), 7.43~7.32 (m, 5H), 7.25 (d, J＝4.8 Hz, 4H), 6.15 (d, J＝6.6 Hz, 1H), 4.91 (s, 1H), 4.80 (s, 1H), 2.95~2.84 (m, 2H), 1.49 (s, 1H); ¹³C NMR (150 MHz, CDCl₃) δ: 166.2, 139.4, 135.5, 132.4, 131.8, 128.6, 128.5, 128.4, 127.1, 126.8, 126.6 (q, J＝286.5 Hz), 117.0, 67.9 (q, J＝24.0 Hz), 41.9, 23.9; ¹⁹F NMR (376 MHz, CDCl₃) δ: －71.01. HRMS calcd for C₁₉H₂₀F₃N₂O [M+H]⁺ 349.1522, found 349.1516.

4-氯-N'-(1, 1, 1-三氟-4-甲基-2-苯基戊-4-烯-2-基)苯甲酰肼(5ag):无色粘稠油状物; 101 mg, 产率88%. ¹H NMR (600 MHz, CDCl₃) δ: 7.65 (d, J＝7.8 Hz, 2H), 7.55~7.44 (m, 3H), 7.39 (t, J＝7.8 Hz, 2H), 7.37~7.30 (m, 3H), 6.10 (d, J＝7.2 Hz, 1H), 4.90 (s, 1H), 4.78 (s, 1H), 2.93~2.81 (m, 2H), 1.47 (s, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 165.2, 139.4, 135.4, 130.2, 128.9, 128.6, 128.5, 128.4, 128.2, 127.0, 126.6 (q, J＝288.0 Hz), 117.1, 68.0 (q, J＝22.5 Hz), 42.0, 23.9; ¹⁹F NMR (376 MHz, CDCl₃) δ: －70.85. HRMS calcd for C₁₉H₁₉F₃N₂OCl [M+H]⁺ 383.1133, found 383.1125.

4-甲基-N'-(1, 1, 1-三氟-4-甲基-2-苯基戊-4-烯-2-基)苯甲酰肼(5ah):无色粘稠油状物; 90 mg, 产率83%. ¹H NMR (600 MHz, CDCl₃) δ: 7.67 (d, J＝7.8 Hz, 2H), 7.52 (d, J＝7.8 Hz, 2H), 7.40 (t, J＝7.8 Hz, 3H), 7.35 (t, J＝7.2 Hz, 1H), 7.18 (d, J＝7.8 Hz, 2H), 6.14 (d, J＝7.2 Hz, 1H), 4.91 (s, 1H), 4.79 (s, 1H), 2.94~2.83 (m, 2H), 2.36 (s, 3H), 1.48 (s, 1H); ¹³C NMR (150 MHz, CDCl₃) δ: 166.2, 142.4, 139.5, 135.6, 129.6, 129.3, 128.5, 128.4, 127.1, 126.8, 126.6 (q, J＝288.0 Hz), 116.9, 67.9 (q, J＝22.5 Hz), 41.8, 23.9, 21.4; ¹⁹F NMR (376 MHz, CDCl₃) δ: －71.12. HRMS calcd for C₂₀H₂₂F₃N₂O [M+H]⁺ 363.1679, found 363.1674.

3.2.5 高烯丙基胺类化合物6合成

钐粉(1.5 mmol)置于干燥的50 mL烧瓶中, 抽真空充氩气, 反复3次, 加入碘单质(1.5 mmol)的THF (20 mL)溶液, 100 ℃下回流搅拌3 h后, 溶液变为深蓝色.冷却至室温后, 继续在无水无氧条件下, 向该制备好的SmI₂-THF溶液中加入5a (0.5 mmol)的CH₃OH (3 mL)溶液, 室温下搅拌约30 min后, 5a完全被消耗.通过快速柱色谱法纯化, 得到目标产物1, 1, 1-三氟-2-苯基戊-4-烯-2-胺(6)^[11] 89 mg, 产率83%. ¹H NMR (600 MHz, CDCl₃) δ: 7.61 (d, J＝7.2 Hz, 2H), 7.41 (t, J＝7.8 Hz, 2H), 7.35 (t, J＝7.2 Hz, 1H), 5.62~5.49 (m, 1H), 5.16 (d, J＝16.8 Hz, 1H), 5.12 (d, J＝10.2 Hz, 1H), 2.97 (dd, J＝13.8, 5.4 Hz, 1H), 2.68 (dd, J＝14.4, 7.8 Hz, 1H), 1.80 (s, 2H); ¹³C NMR (150 MHz, CDCl₃) δ: 137.5, 131.2, 128.3, 128.1, 127.0 (q, J＝286.5 Hz), 126.8, 120.1, 61.0 (q, J＝27.0 Hz), 40.8; ¹⁹F NMR (376 MHz, CDCl₃) δ: －83.52. HRMS calcd for C₁₁H₁₃F₃N[M+H]⁺ 216.0995, found 216.0992.

辅助材料(Supporting Information) 化合物5和6的¹H NMR、¹³C NMR及¹⁹F NMR谱图及化合物的高分辨质谱.这些材料可以免费从本刊网站(http://sioc-jour-nal.cn/)上下载.

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表 1 反应条件优化^a

Table 1. Optimization of the reaction conditions


Entry	Molar ratio of 1a/2a/3a/Sn	Additive	Isolated yield/%
1	1:1.5:2:2.5	—	0
2	1:1.5:2:2.5	TfOH	49
3	1:1.5:2:2.5	C₆H₅COOH	64
4	1:1.5:2:2.5	CF₃COOH	41
5	1:1.5:2:2.5	TMSCl	59
6	1:1.5:2:2.5	HCl	23
7	1:1.5:2:2.5	HBr	27
8	1:1.5:2:2.5	FeCl₃	56
9	1:1.5:2:2.5	ZnBr₂	37
10	1:1.5:2:2.5	TsOH	71
11^b	1:1.5:2:2.5	TsOH	75
12^c	1:1.5:2:2.5	TsOH	67
13	1:1.5:2:2.5	BF₃•OEt₂	70
14^d	1:1.5:2:2.5	BF₃•OEt₂	62
15^b	1:1.5:2:2.5	BF₃•OEt₂	78
16^c	1:1.5:2:2.5	BF₃•OEt₂	75
17^b	1:1.2:2:2.5	BF₃•OEt₂	64
18^b	1:1.5:1.5:2	BF₃•OEt₂	53
19^b	1:1.5:2.5:3	BF₃•OEt₂	75
20^b	1:1.5:3:2.5	BF₃•OEt₂	69
21^b^{, e}	1:1.5:2:2.5	BF₃•OEt₂	34
^aReaction conditions: The mixture of 1a (0.3 mmol), 2a (0.45 mmol), additive (5 mol%) and THF (3 mL) was reacted under reflux condition. After the formation of 4 detected by TLC, 3a (0.6 mmol), Sn (0.75 mmol), additive (10 mol%) and THF (3 mL) were added, and the mixture was reacted under reflux condition. ^bAdding 15 mol% additive for the second time. ^cAdding 20 mol% additive for the second time. ^d Adding 5 mol% additive for the second time. ^e At room temperature.

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表 2 溶剂对反应的影响^a

Table 2. Effect of solvent on the reaction

Entry	Solvent	Isolated yield/%
1	THF	78
2	CH₃OH	33
3	EtOH	38
4	CH₃CN	16
5^b	Dioxane	15
6^b	Toluene	31
7^b	DMF	10
8	DCM	37
^aReaction conditions: The mixture of 1a (0.3 mmol), 2a (0.45 mmol), BF₃·OEt₂ (5 mol%) and THF (3 mL) was reacted under reflux condition. After the formation of 4 detected by TLC, 3a (0.6 mmol), Sn (0.75 mmol), BF₃·OEt₂ (15 mol%) and THF (3 mL) were added, and the mixture was reacted under reflux condition. ^b At 70 ℃.

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表 3 反应底物范围^a.b

Table 3. Substrate scope

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表 4 烯丙基溴的适用范围^a^{, b}

Table 4. Substrate scope of allyl bromides

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