钯催化下稳定磷叶立德与烯丙基醇的脱水偶联反应

引用本文: 马献涛, 于静, 马瑞甜, 燕然, 张振雷. 钯催化下稳定磷叶立德与烯丙基醇的脱水偶联反应[J]. 有机化学, 2019, 39(3): 830-835. doi: 10.6023/cjoc201812051 shu

Citation: Ma Xiantao, Yu Jing, Ma Ruitian, Yan Ran, Zhang Zhenlei. Palladium-Catalyzed Dehydrative Cross Couplings of Stabilized Phosphorus Ylides with Allylic Alcohols[J]. Chinese Journal of Organic Chemistry, 2019, 39(3): 830-835. doi: 10.6023/cjoc201812051 shu

钯催化下稳定磷叶立德与烯丙基醇的脱水偶联反应

马献涛 ^{a,
,} ,
于静 ^a, ,
马瑞甜 ^a, ,
燕然 ^a, ,
张振雷 ^{a,b,
,}

a.
信阳师范学院化学化工学院信阳 464000
b.
阜阳师范学院化学与材料工程学院阜阳 236037

通讯作者: Ma Xiantao, E-mail: xiantaoma@126.com; Zhang Zhenlei, E-mail: helenken@mail.ustc.edu.cn

基金项目:
河南省高等学校重点科研项目（No.19B150018）、信阳师范学院“南湖学者奖励计划”青年项目和信阳师范学院青年骨干教师资助计划（No.2018GGJS-05）资助项目

摘要: 报道了钯催化下酮基稳定的磷叶立德与烯丙基醇一锅法的烯丙化-Wittig反应.研究表明，在5 mol%四（三苯基膦）钯和20 mol%硼酸的共催化下，以52%~95%的收率得到官能化1，4-二烯化合物.该方法还可以进一步拓展到酯基以及氰基稳定的磷叶立德来合成对应的1，4-二烯化合物.

关键词:

English

Palladium-Catalyzed Dehydrative Cross Couplings of Stabilized Phosphorus Ylides with Allylic Alcohols

Ma Xiantao ^{a,
,} ,
Yu Jing ^a, ,
Ma Ruitian ^a, ,
Yan Ran ^a, ,
Zhang Zhenlei ^{a,b,
,}

a.
College of Chemistry and Chemical Engineering, Xinyang Normal University, Xinyang 464000
b.
School of Chemistry and Material Engineering, Fuyang Normal University, Fuyang 236037

Corresponding author: Ma Xiantao, xiantaoma@126.com; Zhang Zhenlei, helenken@mail.ustc.edu.cn

Received Date: 31 December 2018
Revised Date: 27 January 2019
Available Online: 25 March 2019
Fund Project:
Project supported by the Scientific Research Project of Henan Province (No. 19B150018), the Nanhu Scholars Program for Young Scholars of Xinyang Normal University and the Young Core Instructor Program of Xinyang Normal University (No. 2018GGJS-05)

Abstract: A dehydrative cross coupling of ketone-stabilized phosphorus ylides with the readily available allylic alcohols followed by an one-pot Wittig reaction is developed. A range of functional 1, 4-dienes could be obtained in 52%~95% isolated yields in the presence of 5 mol% Pd(PPh₃) ₄ and 20 mol% B(OH) ₃. The same method can be extended to ester or nitrile-stabi-lized phosphorus ylides, affording the corresponding 1, 4-dienes in moderate yields.

Key words:

1, 4-二烯结构广泛存在于天然产物及药物活性分子中^[1].目前, 文献中已有较多的1, 4-二烯的合成方法^[2~6], 如过渡金属催化下烯基金属试剂的烯丙基偶联反应^[3]、烯/炔烃的官能化反应等^{[4, 5]}.磷叶立德是一种重要的合成中间体, 被广泛应用于有机合成中.如磷叶立德与醛、酮的Wittig反应是制备取代烯烃的重要合成方法^[7]. 2010年, 游书力课题组^[8a]首次报道了钯催化下烯丙基酯与酯基稳定磷叶立德的一锅法烯丙化-Wittig反应, 用于酯基取代的1, 4-二烯化合物的合成(Scheme 1A); 2013年, 田仕凯课题组^[8b]发展了烯丙基一级胺与稳定磷叶立德的烯丙基偶联反应, 用于酮基、酯基以及氰基取代的1, 4-二烯化合物的合成(Scheme 1A).与烯丙基酯类化合物相比, 烯丙基醇具有廉价易得, 低毒稳定, 参与反应时离去基团小、原子经济性好等优点, 近年来得到了合成化学家们的青睐^[9].最近, 我们课题组^[10]报道了水相体系中烯丙基醇与稳定磷叶立德的脱水偶联反应, 然而该方法仅适用于酮基取代的1, 4-二烯化合物的合成(Scheme 1B).基于对醇的取代反应的兴趣^[11], 报道了四(三苯基膦)钯催化下烯丙基醇与稳定磷叶立德的一锅法脱水偶联反应, 用于酮基、酯基以及氰基取代的1, 4-二烯化合物的高效合成(Scheme 1C).

图式 1

图式 1. 稳定磷叶立德的烯丙基偶联反应

Scheme 1. Catalytic cross coupling of stabilized phosphorus ylides with allylic partners

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1. 结果与讨论

以肉桂醇(1a)与苯甲酰基稳定的磷叶立德(2a)作为模板反应对反应条件进行了筛选.根据已有经验, 反应初始条件设定为:肉桂醇(1a, 0.36 mmol)、苯甲酰基稳定的磷叶立德(2a, 0.30 mmol)、Pd(PPh₃)₄ (5 mol%)、硼酸(20 mol%)、乙腈(0.50 mL), 氮气保护下置于110 ℃加热搅拌反应12 h; 待反应液冷却至室温后, 加入甲醛水溶液(3 equiv.), 室温下继续搅拌6 h, 以84%的分离收率得到预期的1, 4-二烯产物3a(表 1, Entry 1).对照实验表明, 反应在没有钯催化剂或添加剂的条件下, 均不能顺利进行, 说明钯催化剂和添加剂在活化烯丙基醇C—O键断裂过程中起着至关重要的作用(Entries 2, 3).随后, 对反应的添加剂进行了筛选, 结果发现使用其他的添加剂时, 并不能得到更好的反应收率(Entries 4, 5), 因此, 选定硼酸作为最优添加剂.对反应溶剂的筛选发现, 乙腈是最优的反应溶剂(Entries 6~9).对反应温度筛选发现, 降低温度至60 ℃, 只能观测到少量产物的生成(Entry 10).

表 1

表 1 钯催化下肉桂醇与苯甲酰基稳定磷叶立德烯丙化反应的条件筛选^a

Table 1. Condition screening for Pd-catalyzed allylic cross coupling of phosphorus ylide 2awith cinnamyl alcohol 1a

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Entry	[Pd]	Additive	Solvent	Yield^b/%
1	Pd(PPh₃)₄	B(OH)₃	MeCN	84
2	Pd(PPh₃)₄	—	MeCN	0
3	—	B(OH)₃	MeCN	0
4	Pd(PPh₃)₄	ZnCl₂	MeCN	32
5	Pd(PPh₃)₄	TsOH	MeCN	51
6	Pd(PPh₃)₄	B(OH)₃	DMSO	28
7	Pd(PPh₃)₄	B(OH)₃	DMF	82
8	Pd(PPh₃)₄	B(OH)₃	Toluene	80
9	Pd(PPh₃)₄	B(OH)₃	Dioxane	75
10^c	Pd(PPh₃)₄	B(OH)₃	MeCN	Trace
^a Unless otherwise noted, the mixture of 1a (0.36 mmol, 1.2 equiv.), 2a (0.30 mmol), Pd catalyst (5 mol%), additive (20 mol%) and solvent (0.5 mL) was sealed under N₂, heated at 110 ℃ for 12 h, then HCHO (37% in water w/w, 3 equiv.) was added and stirred at room temperature for another 6 h and monitored by TLC and/or GC-MS. ^b Isolated yield based on 2a. ^c 60 ℃.

将以上优化的反应条件(表 1, Entry 1)用于各种取代的烯丙基醇与酮基稳定磷叶立德的偶联反应, 结果如表 2所示.对于取代的肉桂醇, 当苯环上带有供电子基时, 可以顺利地与磷叶立德(2a)发生反应, 更加高效地得到官能化1, 4-二烯产物3b (表 2, Entries 1, 2).与之相反, 当苯环上带有强吸电子基, 如硝基时, 可能是不利于π-烯丙基钯正离子中间体的稳定存在, 只能观测到少量产物3c生成(Entry 3).当苯环含有邻位位阻的取代基时, 仍可以高效地得到官能化1, 4-二烯产物3d (Entry 4).该方法也适用于脂肪型取代的烯丙基醇, 如(E)-2-己烯-1-醇, 以单一的区域选择性中等收率得到预期产物3e (Entry 5).对于简单的烯丙基醇, 也可以得到预期产物3f(Entry 6).对于α-取代的烯丙基二级醇, 可以顺利地发生反应, 专一选择性地得到直链型的烯丙基偶联产物3a和3g~3k (Entries 7~12).随后, 对磷叶立德的底物范围进行了初步探索, 结果发现:酮基相连的芳环上, 不论是供电子基还是吸电子基, 以及稠环、杂芳环取代基均可以以较高的收率得到预期产物3l~3q (Entries 13~18).对于吲哚或吡咯取代的酮基稳定磷叶立德, 可能由于吲哚、吡咯基比较活泼, 在标准条件下只能得到一个复杂的混合物, 不具备制备价值(Entries 19, 20).对于脂肪酮基稳定的磷叶立德, 在标准条件下收率较低; 但是, 将反应温度升高到125 ℃时, 也可以顺利地得到预期产物3t~3v (Entries 21~23).可能是由于α-酮酯稳定的磷叶立德过于活泼, 在标准反应条件下, 并不能得到预期产物3w (Entry 24).上述的合成方法可以很方便地应用于肉桂醇与酯基或氰基稳定磷叶立德的偶联反应, 只需将反应溶剂更换为N, N-二甲基甲酰胺, 将反应温度提高到125 ℃, 以中等到较高的收率得到官能化1, 4-二烯3x~3y (Entries 25, 26).然而, 该方法不能很好地应用于酰胺基稳定的磷叶立德, 在标准反应条件下不能得到预期产物3z (Entry 27).

表 2

表 2 钯催化下稳定磷叶立德与烯丙基醇的脱水偶联反应

Table 2. Palladium-catalyzed dehydrative allylic cross coupling of stabilized phosphorus ylides with allylic alcohols

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Entry	R¹	R²	R³	3	Yield/%
1	Ph	—	PhCO	3a	84
2	4-MeOC₆H₄	—	PhCO	3b	95
3	4-NO₂C₆H₄	—	PhCO	3c	Trace
4	2-MeOC₆H₄	—	PhCO	3d	94
5	n-C₃H₇	—	PhCO	3e	61^c
6	H	—	PhCO	3f	78
7	—	Ph	PhCO	3a	86
8	—	4-ClC₆H₄	PhCO	3g	68
9	—	2-Thienyl	PhCO	3h	80
10	—	1-Naphthyl	PhCO	3i	75
11	—	2-Naphthyl	PhCO	3j	80
12	—	Et	PhCO	3k	65^c
13	Ph	—	4-MeOC₆H₄CO	3l	86
14	Ph	—	4-FC₆H₄CO	3m	78
15	Ph	—	4-ClC₆H₄CO	3n	75
16	Ph	—	2-NaphthylCO	3o	84
17	Ph	—	2-FurylCO	3p	73
18	Ph	—	2-ThienylCO	3q	62
19	Ph	—	3-IndolylCO	3r	Complex
20	Ph	—	2-PyrrylCO	3s	Complex
21	Ph	—	t-BuCO	3t	52^c
22	Ph	—	MeCO	3u	65^c
23	Ph	—	CyclopropylCO	3v	58^c
24	Ph	—	COCO₂Et	3w	Complex
25	Ph	—	CO₂Et	3x	82^d
26	Ph	—	CN	3y	64^d
27	Ph	—	CONH₂	3z	0^e
^a See Table 1 Entry 1 for details. ^b Isolated yield based on 2a. ^c125 ℃. ^dN, N-dimethylformamide (DMF) as the solvent. ^e Ylide was decomposed under the reaction conditions.

根据相关的实验结果及文献调研^[8~10], 该反应可能的机理如Scheme 2所示.首先烯丙基醇在钯催化剂和硼酸的共同作用下, C—O键活化发生断裂, 生成π-烯丙基钯正离子中间体5; 磷叶立德2作为亲核试剂进攻π-烯丙基钯正离子中间体5, 进而生成膦盐中间体6, 然后转化为新的磷叶立德中间体7, 最后, 7与甲醛发生Wittig反应得到最终预期产物3.

图式 2

图式 2. 可能的反应路径

Scheme 2. Possible reaction paths

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2. 结论

发展了一种钯催化下酮基稳定的磷叶立德与烯丙基醇一锅法的烯丙化-Wittig反应.研究表明, 在5 mol%四(三苯基膦)钯和20 mol%硼酸的共催化下, 可以以52%~95%的收率得到官能化1, 4-二烯化合物.该方法还可以进一步拓展到酯基以及氰基稳定的磷叶立德来合成对应的1, 4-二烯化合物.

3. 实验部分

3.1 仪器与试剂

所用化学试剂和溶剂均为商业可得, 没有经过处理, 直接使用.使用薄层色谱(TLC)和/或气质色谱(GC- MS)技术跟踪反应(HSGF254高效板, 紫外灯检测波长254, 365 nm).产物的¹H NMR, ¹³C NMR用JNM-ECZ600R/S3 (Jeol, Japan) (600 MHz, 150 MHz)型核磁共振仪测定, CDCl₃作为氘代溶剂.低分辨质谱MS (EI)用Agient GC-MS-5890A/5975C Plus spectrometer (EI)测定.高分辨质谱使用LC-TOF (Xevo G2-XS QTof)高分辨质谱仪以ESI电离源测定.柱层析使用黄海300~400目硅胶.所有试剂均购于试剂公司, 未经进一步纯化.

3.2 实验方法

3.2.1 钯催化下稳定磷叶立德与烯丙基醇的脱水偶联反应

氮气保护下, 向10 mL的Schlenk反应管内依次加入肉桂醇1a (48.2 mg, 0.36 mmol), 磷叶立德2a (114.0 mg, 0.30 mmol), 硼酸(3.7 mg, 20 mol%), 四(三苯基膦)钯(17.3 mg, 5 mol%)和乙腈(0.5 mL), 加毕置于110 ℃油浴上加热搅拌反应12 h.待反应液冷却后, 加入甲醛水溶液(质量分数37% in water, 0.068 mL, 0.90 mmol), 室温下继续搅拌反应6 h, 柱层析分离[V(乙酸乙酯):V(石油醚)=0:100~1:30]得产物3a.

(E)-1-苯基-4-苯甲酰基-1, 4-戊二烯(3a)^[10]:无色油. ¹H NMR (600 MHz, CDCl₃) δ: 7.82~7.76 (m, 2H), 7.57~7.52 (m, 1H), 7.47~7.42 (m, 2H), 7.38 (d, J=7.8 Hz, 2H), 7.31 (t, J=7.8 Hz, 2H), 7.22 (t, J=7.2 Hz, 1H), 6.52 (d, J=15.8 Hz, 1H), 6.31 (dt, J=15.8, 7.2 Hz, 1H), 5.95 (s, 1H), 5.72 (s, 1H), 3.39 (d, J=7.2 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃) δ: 197.9, 146.6, 137.8, 137.4, 132.6, 132.4, 129.6, 128.7, 128.6, 127.4, 127.0, 126.7, 126.3, 35.5; MS (EI) m/z: 248.

(E)-1-(4-甲氧基苯基)-4-苯甲酰基-1, 4-戊二烯(3b)^[10]:无色油. ¹H NMR (600 MHz, CDCl₃) δ: 7.75 (dd, J=5.4, 3.6 Hz, 2H), 7.55~7.51 (m, 1H), 7.45~7.40 (m, 2H), 7.32~7.26 (m, 2H), 6.90~6.81 (m, 2H), 6.44 (d, J=15.6 Hz, 1H), 6.14 (dt, J=15.6, 7.2 Hz, 1H), 5.93 (s, 1H), 5.69 (s, 1H), 3.79 (s, 3H), 3.34 (d, J=7.2 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃) δ: 198.0, 159.1, 146.9, 137.8, 132.4, 132.0, 130.3, 129.6, 128.3, 127.4, 126.8, 124.4, 114.1, 55.4, 35.5; MS (EI) m/z: 278.

(E)-1-(2-甲氧基苯基)-4-苯甲酰基-1, 4-戊二烯(3d)^[10]:无色油. ¹H NMR (600 MHz, CDCl₃) δ: 7.84~7.71 (m, 2H), 7.58~7.52 (m, 1H), 7.47~7.42 (m, 3H), 7.23~7.16 (m, 1H), 6.94~6.88 (m, 3H), 6.30 (dt, J=15.6, 7.2 Hz, 1H), 5.95 (s, 1H), 5.70 (s, 1H), 3.83 (s, 3H), 3.40 (d, J=6.8 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃) δ: 198.0, 156.5, 146.9, 137.8, 132.3, 129.6, 128.3, 127.2, 126.7, 126.5, 120.7, 110.9, 55.6, 35.9; MS (EI) m/z: 278.

(E)-2-苯甲酰基-1, 4-辛二烯(3e)^[10]: 无色油. ¹H NMR (600 MHz, CDCl₃) δ: 7.73 (d, J=7.8 Hz, 2H), 7.55~7.51 (m, 1H), 7.45~7.41 (m, 2H), 5.84 (s, 1H), 5.61 (s, 1H), 5.57~5.37 (m, 2H), 3.14 (d, J=6.6 Hz, 2H), 2.06~1.89 (m, 2H), 1.43~1.35 (m, 2H), 0.86 (t, J=7.2 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 198.2, 147.4, 137.9, 133.6, 132.2, 129.6, 128.3, 126.2, 125.9, 35.2, 34.7, 22.6, 13.7; MS (EI) m/z: 214.

(E)-2-苯甲酰基-1, 4-戊二烯(3f)^[12]:无色油. ¹H NMR (600 MHz, CDCl₃) δ: 7.75~7.64 (m, 2H), 7.52~7.40 (m, 1H), 7.35 (dd, J=10.8, 4.8 Hz, 2H), 5.92~5.73 (m, 2H), 5.59 (s, 1H), 5.12~4.99 (m, 2H), 3.15 (d, J=6.6 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃) δ: 196.7, 145.4, 136.7, 133.9, 131.2, 128.5, 127.2, 125.4, 116.1, 35.2; MS (EI) m/z: 172.

(E)-1-(4-氯苯基)-4-苯甲酰基-1, 4-戊二烯(3g):无色固体. m.p. 70~72 ℃(文献值^[10] 72~73 ℃); ¹H NMR (600 MHz, CDCl₃) δ: 7.76 (dd, J=7.8, 1.2 Hz, 2H), 7.58~7.40 (m, 3H), 7.38~7.21 (m, 4H), 6.45 (d, J=15.6 Hz, 1H), 6.27 (dt, J=15.6, 7.2 Hz, 1H), 5.94 (s, 1H), 5.72 (s, 1H), 3.37 (d, J=6.6 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃) δ: 197.7, 146.4, 137.7, 135.9, 132.9, 132.4, 131.3, 129.6, 128.8, 128.4, 127.5, 127.1, 35.6; MS (EI) m/z: 282

(E)-1-(2-噻吩基)-4-苯甲酰基-1, 4-戊二烯(3h)^[10]:无色油. ¹H NMR (600 MHz, CDCl₃) δ: 7.75 (dd, J=5.4, 3.6 Hz, 2H) 7.55~7.50 (m, 1H), 7.43 (t, J=7.8 Hz, 2H), 7.10 (d, J=5.4 Hz, 1H), 6.97~6.84 (m, 2H), 6.63 (d, J=15.6 Hz, 1H), 6.13 (dt, J=15.6, 7.2 Hz, 1H), 5.94 (s, 1H), 5.71 (s, 1H), 3.34 (d, J=7.2 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃) δ: 197.7, 146.3, 142.5, 137.7, 132.4, 129.6, 128.3, 127.4, 127.1, 126.4, 126.2, 125.1, 123.8, 35.3; MS (EI) m/z: 254.

(E)-1-(1-萘基)-4-苯甲酰基-1, 4-戊二烯(3i):无色固体, m.p. 65~66 ℃(文献值^[10] m.p. 68~69 ℃); ¹H NMR (600 MHz, CDCl₃) δ: 8.10~8.05 (m, 1H), 7.83~7.77 (m, 3H), 7.73 (d, J=8.2 Hz, 1H), 7.60~7.40 (m, 7H), 7.24 (d, J=15.6 Hz, 1H), 6.29 (dt, J=15.6, 7.2 Hz, 1H), 5.98 (s, 1H), 5.73 (s, 1H), 3.49 (d, J=6.6 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃) δ: 197.8, 171.2, 146.6, 137.7, 135.2, 133.7, 132.4, 131.2, 129.9, 129.6, 128.5, 128.3, 127.7, 126.8, 126.0, 125.8, 125.7, 123.9, 123.8, 35.2; MS (EI) m/z: 298.

(E)-1-(2-萘基)-4-苯甲酰基-1, 4-戊二烯(3j):无色固体, m.p. 73~74 ℃(文献值^[10] m.p. 76~77 ℃); ¹H NMR (600 MHz, CDCl₃) δ: 8.10 (d, J=7.8 Hz, 1H), 7.86~7.80 (m, 3H), 7.77 (d, J=7.8 Hz), 7.59~7.40 (m, 7H), 7.27 (d, J=15.6 Hz, 1H), 6.48~6.19 (dt, J=15.6, 7.2 Hz, 1H), 6.02 (s, 1H), 5.76 (s, 1H), 3.52 (d, J=7.2 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃) δ: 197.9, 146.7, 137.8, 135.3, 133.7, 132.4, 131.2, 129.9, 129.7, 128.6, 128.4, 127.8, 127.0, 126.1, 125.9, 125.8, 124.0, 123.9, 35.9; MS (EI) m/z: 298.

(E)-2-苯甲酰基-1, 4-庚二烯(3k)^[10]:无色油. ¹H NMR (600 MHz, CDCl₃) δ: 7.74 (d, J=7.8 Hz, 2H), 7.59~7.47 (m, 1H), 7.42 (t, J=7.8 Hz, 2H), 5.84 (d, J=1.0 Hz, 1H), 5.61 (s, 1H), 5.60~5.55 (m, 1H), 5.48~5.41 (m, 1H), 3.13 (d, J=6.5 Hz, 2H), 2.06~2.00 (m, 2H), 0.96 (t, J=7.2 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 198.2, 147.4, 137.9, 135.3, 132.2, 129.6, 128.3, 126.0, 125.1, 35.1, 25.7, 13.9; MS (EI) m/z: 200.

(E)-1-苯基-4-(4-甲氧基苯甲酰基)-1, 4-戊二烯(3l):无色固体, m.p. 38~39 ℃(文献值^[10] m.p. 38~39 ℃); ¹H NMR (600 MHz, CDCl₃) δ: 7.82 (d, J=9.0 Hz, 2H), 7.34 (d, J=7.8 Hz, 2H), 7.28 (t, J=7.8 Hz, 2H), 7.19 (t, J=7.8 Hz, 1H), 6.97~6.91 (m, 2H), 6.49 (d, J=15.6 Hz, 1H), 6.27 (dt, J=15.6, 7.2 Hz, 1H), 5.82 (s, 1H), 5.61 (s, 1H), 3.84 (s, 3H), 3.36 (d, J=7.2 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃) δ: 196.5, 163.2, 146.8, 137.4, 132.4, 132.0, 130.1, 128.5, 127.3, 126.7, 126.2, 124.5, 113.6, 55.5, 35.9; MS (EI) m/z: 278.

(E)-1-苯基-4-(4-氟苯甲酰基)-1, 4-戊二烯(3m)^[10]:无色油. ¹H NMR (600 MHz, CDCl₃) δ: 7.84~7.79 (m, 2H), 7.36 (d, J=7.2 Hz, 2H), 7.30 (t, J=7.8 Hz, 2H), 7.22 (d, J=7.2 Hz, 1H), 7.14~7.08 (m, 2H), 6.50 (d, J=15.6 Hz, 1H), 6.28 (dt, J=15.6, 7.2 Hz, 1H), 5.93 (s, 1H), 5.67 (s, 1H), 3.36 (d, J=7.2 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃) δ: 196.4, 165.4 (d, J=253.7 Hz), 146.6, 137.3, 133.8, 132.7, 132.2 (d, J=9.3 Hz), 128.6, 127.4, 126.4 (d, J=10.2 Hz), 126.3, 115.5 (d, J=21.8 Hz), 35.6; MS (EI) m/z: 266.

(E)-1-苯基-4-(4-氯苯甲酰基)-1, 4-戊二烯(3n):无色固体, m.p. 52~53 ℃ (文献值^[10] m.p. 51~52 ℃); ¹H NMR (600 MHz, CDCl₃) δ: 7.72 (dd, J=8.4, 2.4 Hz, 2H), 7.45~7.41 (m, 2H), 7.36 (d, J=7.2 Hz, 2H), 7.33~7.28 (m, 2H), 7.22 (t, J=7.2 Hz, 1H), 6.51 (d, J=15.6 Hz, 1H), 6.28 (dt, J=15.6, 7.2 Hz, 1H), 5.95 (s, 1H), 5.68 (s, 1H), 3.37 (d, J=7.2 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃) δ: 196.6, 146.5, 138.8, 137.3, 136.0, 132.8, 131.0, 128.7, 128.6, 127.4, 127.0, 126.3, 126.2, 35.5; MS (EI) m/z: 282.

(E)-1-苯基-4-(2-萘甲酰基)-1, 4-戊二烯(3o):无色固体, m.p. 53~54 ℃(文献值^[10] m.p. 56~57 ℃); ¹H NMR (600 MHz, CDCl₃) δ: 8.30 (s, 1H), 7.96~7.86 (m, 4H), 7.62~7.53 (m, 2H), 7.44~7.38 (m, 2H), 7.34~7.28 (m, 2H), 7.25~7.17(m, 1H), 6.57 (d, J=15.6 Hz, 1H), 6.37 (dt, J=15.6, 7.2 Hz, 1H), 6.00 (s, 1H), 5.79 (s, 1H), 3.46 (d, J=7.2 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃) δ: 197.9, 146.8, 137.4, 135.3, 135.0, 132.7, 132.4, 131.3, 129.5, 128.7, 128.4, 128.3, 127.9, 127.4, 126.9, 126.8, 126.7, 126.3, 125.6, 35.8; MS (EI) m/z: 298.

(E)-1-苯基-4-(2-呋喃甲酰基)-1, 4-戊二烯(3p)^[10]:无色油. ¹H NMR (600 MHz, CDCl₃) δ: 7.62 (s, 1H), 7.37~7.24 (m, 4H), 7.20 (t, J=7.2 Hz, 1H), 7.21~7.12 (m, 1H), 6.50 (dd, J=3.6, 1.8 Hz, 1H), 6.45 (d, J=15.6 Hz, 1H), 6.22 (dt, J=15.6, 7.2 Hz, 1H), 6.03 (s, 1H), 5.82 (s, 1H), 3.32 (d, J=7.2 Hz, 2H); ¹³C NMR (150 MHz, CDCl₃) δ: 183.5, 151.8, 147.0, 146.1, 137.1, 132.4, 128.4, 127.1, 126.2, 126.0, 124.6, 119.9, 111.9, 35.2; MS (EI) m/z: 238.

(E)-1-苯基-4-(2-噻吩甲酰基)-1, 4-戊二烯(3p)^[10]:无色油. ¹H NMR (400 MHz, CDCl₃) δ: 7.72~7.64 (m, 2H), 7.37~7.19 (m, 5H), 7.13~7.10 (m, 1H), 6.48 (d, J=15.6 Hz, 1H), 6.27 (dt, J=15.6, 7.2 Hz, 1H), 5.89 (d, J=0.6 Hz, 1H), 5.81 (d, J=0.6 Hz, 1H), 3.36 (dd, J=7.2, 0.6 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 189.1, 147.0, 143.4, 137.3, 134.1, 133.9, 132.6, 128.5, 127.9, 127.3, 126.3, 126.2, 123.9, 35.8; MS (EI) m/z: 254.

(E)-1-苯基-4-(叔丁基甲酰基)-1, 4-戊二烯(3t)^[10]:无色油. ¹H NMR (600 MHz, CDCl₃) δ: 7.35 (d, J=7.2 Hz, 2H), 7.30 (t, J=7.2 Hz, 2H), 7.23~7.17 (m, 1H), 6.42 (d, J=15.6 Hz, 1H), 6.18 (dt, J=15.6, 7.2 Hz, 1H), 5.54 (s, 1H), 5.49 (d, J=1.2 Hz, 1H), 3.14 (dd, J=7.2, 1.2 Hz, 2H), 1.25 (s, 9H); ¹³C NMR (150 MHz, CDCl₃) δ: 211.0, 146.9, 137.4, 132.5, 128.6, 127.4, 126.7, 126.2, 118.6, 44.2, 37.6, 27.9; MS (EI) m/z: 228.

(E)-1-苯基-4-(乙酰基)-1, 4-戊二烯(3u)^[10]:无色油. ¹H NMR (600 MHz, CDCl₃) δ: 7.40~7.31 (m), 7.31~7.23 (m), 7.20 (t, J=7.4 Hz), 6.42 (d, J=15.8 Hz), 6.21 (dt, J=15.7, 7.0 Hz), 6.08 (s), 5.85 (d, J=1.2 Hz), 3.17 (d, J=6.9 Hz), 2.36 (s); ¹³C NMR (150 MHz, CDCl₃) δ: 199.4, 147.7, 137.4, 132.1, 128.6, 127.3, 127.2, 126.2, 126.1, 34.0, 26.0; MS (EI) m/z: 186.

(E)-1-苯基-4-(环丙甲酰基)-1, 4-戊二烯(3v):无色油. ¹H NMR (600 MHz, CDCl₃) δ: 7.47~7.16 (m, 5H), 6.43 (d, J=15.8 Hz, 1H), 6.29~6.15 (m, 2H), 5.83 (s, 1H), 3.21 (d, J=7.2 Hz, 2H), 2.54~2.39 (m, 1H), 1.11~1.07 (m, 2H), 0.95~0.90 (m, 3H); ¹³C NMR (150 MHz, CDCl₃) δ: 201.42 (s), 148.16 (s), 137.50 (s), 132.08 (s), 128.59 (s), 127.28 (d, J=11.8 Hz), 126.19 (s), 124.50 (s), 34.53 (s), 16.51 (s), 11.34 (s); MS (EI) m/z: 212. HRMS (ESI) calcd for C₁₅H₁₇O (M+H)⁺ 213.1279, found 213.1295

2-肉桂基-丙烯酸乙酯(3x)^[8a]:无色油. ¹H NMR (600 MHz, CDCl₃) δ: 7.37~7.34 (m, 2H), 7.31~7.27 (m, 2H), 7.22~7.18 (m, 1H), 6.44 (d, J=15.6 Hz, 1H), 6.27~6.21 (m, 2H), 5.61 (d, J=1.2 Hz), 4.22 (q, J=7.2 Hz), 3.20 (d, J=7.2 Hz), 1.30 (t, J=7.2 Hz); ¹³C NMR (150 MHz, CDCl₃) δ: 171.2, 139.5, 137.4, 132.1, 128.6, 127.3, 126.9, 125.5, 60.8, 35.2, 14.3; MS (EI) m/z: 216.

2-肉桂基-丙烯腈(3y)^[13]:无色油. ¹H NMR (600 MHz, CDCl₃) δ: 7.40~7.20 (m, 5H), 6.53 (d, J=15.6 Hz, 1H), 6.16 (dt, J=15.6, 6.6 Hz, 1H), 5.92 (s, 1H), 5.80 (d, J=1.8 Hz, 1H), 3.18~3.12 (m, 2H); ¹³C NMR (150 MHz, CDCl₃) δ: 136.6, 134.2, 130.9, 128.6, 127.8, 126.4, 123.2, 121.8, 118.5, 37.7; MS (EI) m/z: 169.

辅助材料(Supporting Information) 所有产物的¹H NMR和¹³C NMR谱图.对酯基稳定磷叶立德的反应条件进一步考察及结果.这些材料可以免费从本刊网站(http://sioc-journal.cn/)上下载.

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图式 1 稳定磷叶立德的烯丙基偶联反应

Scheme 1 Catalytic cross coupling of stabilized phosphorus ylides with allylic partners

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图式 2 可能的反应路径

Scheme 2 Possible reaction paths

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表 1 钯催化下肉桂醇与苯甲酰基稳定磷叶立德烯丙化反应的条件筛选^a

Table 1. Condition screening for Pd-catalyzed allylic cross coupling of phosphorus ylide 2awith cinnamyl alcohol 1a


Entry	[Pd]	Additive	Solvent	Yield^b/%
1	Pd(PPh₃)₄	B(OH)₃	MeCN	84
2	Pd(PPh₃)₄	—	MeCN	0
3	—	B(OH)₃	MeCN	0
4	Pd(PPh₃)₄	ZnCl₂	MeCN	32
5	Pd(PPh₃)₄	TsOH	MeCN	51
6	Pd(PPh₃)₄	B(OH)₃	DMSO	28
7	Pd(PPh₃)₄	B(OH)₃	DMF	82
8	Pd(PPh₃)₄	B(OH)₃	Toluene	80
9	Pd(PPh₃)₄	B(OH)₃	Dioxane	75
10^c	Pd(PPh₃)₄	B(OH)₃	MeCN	Trace
^a Unless otherwise noted, the mixture of 1a (0.36 mmol, 1.2 equiv.), 2a (0.30 mmol), Pd catalyst (5 mol%), additive (20 mol%) and solvent (0.5 mL) was sealed under N₂, heated at 110 ℃ for 12 h, then HCHO (37% in water w/w, 3 equiv.) was added and stirred at room temperature for another 6 h and monitored by TLC and/or GC-MS. ^b Isolated yield based on 2a. ^c 60 ℃.

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表 2 钯催化下稳定磷叶立德与烯丙基醇的脱水偶联反应

Table 2. Palladium-catalyzed dehydrative allylic cross coupling of stabilized phosphorus ylides with allylic alcohols


Entry	R¹	R²	R³	3	Yield/%
1	Ph	—	PhCO	3a	84
2	4-MeOC₆H₄	—	PhCO	3b	95
3	4-NO₂C₆H₄	—	PhCO	3c	Trace
4	2-MeOC₆H₄	—	PhCO	3d	94
5	n-C₃H₇	—	PhCO	3e	61^c
6	H	—	PhCO	3f	78
7	—	Ph	PhCO	3a	86
8	—	4-ClC₆H₄	PhCO	3g	68
9	—	2-Thienyl	PhCO	3h	80
10	—	1-Naphthyl	PhCO	3i	75
11	—	2-Naphthyl	PhCO	3j	80
12	—	Et	PhCO	3k	65^c
13	Ph	—	4-MeOC₆H₄CO	3l	86
14	Ph	—	4-FC₆H₄CO	3m	78
15	Ph	—	4-ClC₆H₄CO	3n	75
16	Ph	—	2-NaphthylCO	3o	84
17	Ph	—	2-FurylCO	3p	73
18	Ph	—	2-ThienylCO	3q	62
19	Ph	—	3-IndolylCO	3r	Complex
20	Ph	—	2-PyrrylCO	3s	Complex
21	Ph	—	t-BuCO	3t	52^c
22	Ph	—	MeCO	3u	65^c
23	Ph	—	CyclopropylCO	3v	58^c
24	Ph	—	COCO₂Et	3w	Complex
25	Ph	—	CO₂Et	3x	82^d
26	Ph	—	CN	3y	64^d
27	Ph	—	CONH₂	3z	0^e
^a See Table 1 Entry 1 for details. ^b Isolated yield based on 2a. ^c125 ℃. ^dN, N-dimethylformamide (DMF) as the solvent. ^e Ylide was decomposed under the reaction conditions.

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沈阳化工大学材料科学与工程学院沈阳 110142