1, 8-二氮杂二环十一碳-7-烯(DBU)立体选择性催化合成噁唑啉-2-(硫)酮衍生物

引用本文: 杨权力, 宋玉叶, 余平, 王龙, 刘明国, 黄年玉. 1, 8-二氮杂二环十一碳-7-烯(DBU)立体选择性催化合成噁唑啉-2-(硫)酮衍生物[J]. 有机化学, 2017, 37(12): 3177-3185. doi: 10.6023/cjoc201704036 shu

Citation: Yang Quanli, Song Yuye, Yu Ping, Wang Long, Liu Mingguo, Huang Nianyu. 1, 8-Diazabicyclo[5.4.0]undec-7-ene (DBU)-Promoted Stere-oselective Synthesis of Oxazolidin-2-(thi)one Derivatives[J]. Chinese Journal of Organic Chemistry, 2017, 37(12): 3177-3185. doi: 10.6023/cjoc201704036 shu

1, 8-二氮杂二环十一碳-7-烯(DBU)立体选择性催化合成噁唑啉-2-(硫)酮衍生物

杨权力 ^a, ,
宋玉叶 ^a, ,
余平 ^a, ,
王龙 ^b, ,
刘明国 ^a, ,
黄年玉 ^{a,
,}

a.
三峡大学生物与制药学院天然产物研究与利用湖北省重点实验室宜昌 443002
b.
三峡大学材料与化工学院宜昌 443002

通讯作者: 黄年玉, hny115@126.com

基金项目:

国家自然科学基金（No.21602123）及三峡大学青年拔尖人才项目和研究生创新基金（No.SDYC2016121）资助项目

摘要: 以1，8-二氮杂二环十一碳-7-烯（DBU）为催化剂，在无其它金属催化条件下，炔丙醇与异氰酸酯（或硫氰酸酯）进行亲核加成/环化反应，合成了一系列多取代的噁唑烷-2-（硫）酮衍生物，收率为75%~95%.该反应经5-exo-dig环化机制，高度立体选择性地得到Z-式芳亚甲基取代产物，为噁唑啉酮的骨架合成提供了简单快速的合成方法.

关键词:

English

1, 8-Diazabicyclo[5.4.0]undec-7-ene (DBU)-Promoted Stere-oselective Synthesis of Oxazolidin-2-(thi)one Derivatives

a.
Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002
b.
College of Materials and Chemical Engineering, China Three Gorges University, Yichang 443002

Corresponding author: Huang Nianyu, E-mail: hny115@126.com

Received Date: 21 April 2017
Revised Date: 10 August 2017
Available Online: 25 December 2017
Fund Project:

Project supported by the National Natural Science Foundation of China (No. 21602123), the Youth Talent Development Foundation and Scientific Foundation from Graduate School of China Three Gorges University (No. SDYC2016121)

Abstract: A series of multi-substituted oxazolidin-2-(thi)one derivatives were prepared via 1, 8-diazabicyclo[5.4.0]undec-7-ene (DBU) promoted nucleophilic addition/cyclization from alkynyl alcohol and isocynate or thiocynate in high yields of 75%~95%. This concise and efficient approach provides a facial access to a library of biological (Z)-arylmethylene substituted oxazolidin-2-(thi)one derivatives with high stereo-selectivities.

Key words:

oxazolidin-2-(thi)one
/ 1, 8-diazabicyclo[5.4.0]undec-7-ene (DBU)
/ stereo-selectivity

噁唑啉酮作为一类非常重要的含氮杂环化合物, 因其独特的作用机制、口服生物利用度以及良好的构效关系(SAR)^[1]而在农药、医药等精细化学品^[2]和聚合物材料^[3]中广泛应用.其中, 噁唑啉-2-酮衍生物代表了一类重要的合成试剂^[4]和活性药效团^[5], 例如商品化的Evans手性助剂因其良好的配位和手性诱导性能, 在形成新的碳-碳键、碳-杂原子键及光学活性的天然产物中广泛使用^[6]; 此外, 在抗生素类药物Linezolid^[7]和Tedizolid^[8]中均含有该结构单元, 可选择性作用于真菌蛋白合成酶而发挥抗菌作用, 并与其它抗菌药无交叉耐药现象.

噁唑啉酮的合成方法研究是有机合成领域的研究热点之一, 目前有多种合成该母核的方法^[9].例如, 金、钯或银等过渡金属^[10]可催化炔丙基胺或醇和CO₂发生分子间环化得到噁唑啉酮; 碳酸酯与氨基醇的反应^[11]也可以用于构建噁唑啉酮; 卤化酮、醋酸银等过渡金属盐^[12]亦可催化异氰酸酯和炔丙醇环化生成噁唑啉酮.为进一步拓展杂环化合物的合成方法^[13], 本文报道了在无金属催化条件, 1, 8-二氮杂二环十一碳-7-烯(DBU)催化促进炔丙醇与异(硫)氰酸酯发生环化反应, 高收率立体选择性地合成了一系列(Z)-4-芳亚甲基取代噁唑啉-2-(硫)酮衍生物, 丰富了噁唑啉酮骨架的制备方法.

1 结果与讨论

为筛选噁唑啉-2-(硫)酮衍生物的最佳合成条件, 本工作首先通过苯乙炔(1a)和3-戊酮(2a)制备得了炔丙醇中间体3a, 将其作为模型反应底物与4-甲基苯基异氰酸酯(4a)进行条件实验(Eq. 1), 以筛选合适的催化剂、溶剂和反应温度及时间(表 1).

表 1 模型反应的条件优化 Table 1. Optimization of reaction conditions for the model reaction

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Entry	Catalyst^a	Solvent	Temp./ ℃	Time/ h	Yield^b/%
Entry	Catalyst^a	Solvent	Temp./ ℃	Time/ h	Carbamate ester	5a
1	AgNO₃	Toluene	30	24	0	0
2	PdCl₂	CH₃CN	30	24	0	0
3	CuI	CH₃CN	30	24	0	0
4	I₂	Toluene	30	24	0	0
5	DMAP	DMF	50	24	80	0
6	DBU	CH₂Cl₂	30	12	70	30
7	DBU	CH₂Cl₂	30	24	5	85
8	DBU	Toluene	30	24	0	0
9	DBU	CHCl₃	30	24	90	0
10	DBU	Et₂O	30	24	0	0
11	DBU	EtOAc	30	24	0	0
12	DBU	CH₃OH	30	24	0	0
13	DBU	CH₃CN	30	12	0	90
14	K₂CO₃	CH₃CN	30	24	0	40
15	Morpholine	CH₃CN	30	24	0	0
16	Et₃N	CH₃CN	30	24	0	30
17	NaOH	CH₃CN	30	24	0	0
18	DBU^c	CH₃CN	30	24	0	60
19	DBU^d	CH₃CN	30	12	0	90
20	DBU^e	CH₃CN	30	12	0	80
21	DBU	CH₃CN	40	8	0	90
22	DBU	CH₃CN	50	8	0	60
23	DBU	CH₃CN	20	24	40	60
^aGeneral conditions: catalyst (20 mol%) was added into the mixture of 3a (95 mg, 0.5 mmol) and 4a (67 mg, 0.5 mmol) in corresponding solvent (2.0 mL). ^b Isolated yield. ^c10 mol% of DBU was used. ^d30 mol% of DBU was used. ^e40 mol% of DBU was used.

首先考察了文献报道的催化剂如AgNO₃^[12b]、PdCl₂^[14]、CuI^[15]等的催化效果, 但经24 h反应后没有观察到氨基甲酸酯中间体或产物(表 1, Entries 1~4).当使用4-二甲基氨基吡啶(DMAP)时^[12b], 将温度加热至50 ℃发现氨基甲酸酯中间体是唯一的产物(Entry 5).有文献^[12c]报道DBU可以促进炔丙醇和苯基异氰酸酯在二氯甲烷回流条件下的反应, 经证实该反应在30 ℃下可进行, 但反应12 h后仅得到30%的环化产物5a (Entry 6);当延长时间至24 h后环化产物产率可以达到85% (Entry 7);采用甲苯、氯仿、乙醚、乙酸乙酯或甲醇为溶剂时, 该反应却不能进行(Entries 8~12);而当溶剂为乙腈时, 12 h后环化产率可达到90% (Entry 13).以乙腈为溶剂时, K₂CO₃和Et₃N的催化效果较差, 其它有机或无机碱^[28]对该反应没有催化作用(Entries 14~17).鉴于此, DBU被确定为最合适的催化剂, 接下来我们对其用量进行了筛选.减少DBU的用量到10 mol%后, 反应24 h后5a的收率仅为60% (Entry 18); 30 mol% DBU的催化效果与20 mol%用量时相同(Entries 13, 19);增加到40 mol%用量时产物的收率降到80% (Entry 20);因此20 mol% DBU被确定为最佳用量.通过对反应温度的筛选发现, 当升高温度至40 ℃时产物收率与30 ℃时相当, 但反应时间可由12 h缩短至8 h (Entries 13, 21);进一步升高反应温度至50 ℃时产物收率明显降低(Entry 20), 可能为高温下反应过于剧烈所致; 反应温度为20 ℃时, 24 h后仍有较多中间体存在, 反应不完全(Entry 23).综上所述, 该模型反应的最佳条件确定为:催化剂DBU的用量为20 mol%, 使用乙腈作溶剂, 在40 ℃下反应8 h.

鉴于此, 我们根据模型反应的最佳条件制备了25个(Z)-4-芳亚甲基取代的噁唑啉-2-(硫)酮衍生物(Scheme 1), 并且该反应表现出良好的立体选择性和官能团兼容性(表 2).所合成的目标化合物都通过核磁共振(NMR)、红外光谱(IR)和高分辨质谱(HR-ESI-MS)表征.在 ¹H NMR光谱中, 5i和5j的噁唑啉-2-酮骨架的环外双键的烯烃质子信号分别位于δ 4.36和4.24, 而其余化合物的环外烯基质子在δ 5.53~5.69处出现单峰.在¹³C NMR中, 化合物噁唑啉-2-酮5a~5q的羰基碳化学位移在δ 153.9~157.2处, 而噁唑啉-2-硫酮5r~5t的羰基碳在δ 187.6~188.9处出现共振信号, 其中化合物5s还通过了单晶X射线衍射分析进行了进一步确证(CCDC号码1545013), 其晶体结构见图 1.在红外光谱中, 目标化合物中羰基的强红外吸收峰位于1745~1777 cm^-¹处.在HRMS谱中, 所有化合物都可以观察到(M+H)⁺或(M+Na)⁺的离子加合物离子峰.

图式1 噁唑啉-2-(硫)酮衍生物5的合成路线 Scheme1. Synthetic routes for the oxazolidin-2-(thi)one derivatives 5

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表 2 噁唑啉-2-(硫)酮衍生物5衍生物 Table 2. Oxazolidin-2-(thi)one derivatives 5

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Entry	Product	Substitution					Isolated yield/%
Entry	Product	R¹	R²	R³	R⁴	X	Isolated yield/%
1	5a	C₆H₅	Me	Et	p-MeC₆H₄	O	91
2	5b	C₆H₅	Et	Et	p-MeC₆H₄	O	90
3	5c	C₆H₅	Me	i-Pr	p-MeC₆H₄	O	86
4	5d	C₆H₅	Me	i-Bu	p-MeC₆H₄	O	85
5	5e	C₆H₅	Me	Cyclopropyl	p-MeC₆H₄	O	80
6	5f	p-MeC₆H₄		Cyclopentyl	p-MeC₆H₄	O	78
7	5g	C₆H₅	Me	i-Bu	p-FC₆H₄	O	87
8	5h	C₆H₅	Me	Cyclopropyl	p-FC₆H₄	O	86
9	5i	TMS	Et	C₆H₅	p-FC₆H₄	O	75
10	5j	H	Et	C₆H₅	p-FC₆H₄	O	91
11	5k	C₆H₅	Et	Et	Naphthyl	O	85
12	5l	C₆H₅	Et	Et	i-Pr	O	87
13	5m	C₆H₅	Me	i-Bu	i-Pr	O	86
14	5n	C₆H₅	Me	Cyclopropyl	i-Pr	O	87
15	5o	C₆H₅		Cyclopentyl	i-Pr	O	88
16	5p	C₆H₅	Et	Et	Et	O	86
17	5q	C₆H₅	Me	Cyclopropyl	Et	O	84
18	5r	C₆H₅	Et	Et	C₆H₅	S	83
19	5s	C₆H₅	Et	Et	Et	S	87
20	5t	C₆H₅	Me	i-Bu	C₆H₅	S	80
21	5u	p-FC₆H₄	Me	Et	p-MeC₆H₄	O	90
22	5v	p-MeOC₆H₄	Me	Et	p-MeC₆H₄	O	80
23	5w	p-CNC₆H₄	Et	Et	p-MeC₆H₄	O	91
24	5x	n-Bu	Et	Et	p-MeC₆H₄	O	65
25	5y	Cyclopropyl	Et	Et	p-MeC₆H₄	O	62

图1 噁唑啉-2-硫酮5s的晶体结构 Figure1. Crystal structure of the oxazolidin-2-thione 5s

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为进一步研究化合物的光谱性质和环化机理, 使用三甲基甲硅烷基保护的炔丙醇(3i)在DBU的催化作用下与4-氟苯基异氰酸酯(4i)反应(Scheme 2), 然后脱去三甲硅烷基保护基后分离反应产物, 经鉴定产物为五元环噁唑啉-2-酮骨架, 从其¹³C NMR谱中没有观察到经6-endo-dig机制得到的六元环产物(5j')的特征信号峰, 而在化合物5j的DEPT-135光谱得到末端烯键的特征信号δ 84.0, HSQC谱分析表明该碳分别与δ 4.25 (d, J＝3.0 Hz, 1H)和4.23 (d, J＝3.0 Hz, 1H)处的质子相关.因此可以证明化合物5i和5j的噁唑啉-2-酮的骨架均通过5-exo-dig环化机制^[16]得到.

图式 2 反应选择性研究 Scheme2. Planned synthesis for selectivity study

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经文献调研^[17], DBU促进亲核加成/环化反应的可能机理如Scheme 3所示.首先, 将炔丙醇中间体3经DBU去质子化得到烷氧基阴离子A, 再亲核进攻异氰酸酯4得到氨基甲酸酯中间体B; 然后氨基甲酸酯B中的N作为亲核中心与DBU活化的炔键加成, 经5-exo-dig环化机制得到DBU复合物C; 最后, DBU离去得到相应的目标化合物噁唑啉-2-(硫)酮衍生物5.

图式 3 可能的反应机理 Scheme3. Possible reaction mechanism

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2 结论

在无金属催化剂的条件下, 通过DBU促进炔醇与异氰酸酯亲核加成/5-exo-dig环化合成了一系列(Z)-4-芳亚甲基取代的噁唑啉-2-(硫)酮衍生物, 该反应具有高度立体选择性、反应条件温和、后处理简单及产率高等优点, 适合于快速构建化合物库并用于生物活性筛选.由于其无金属性质, 该反应亦可满足生物和药物化学的特定纯度要求, 其在活性天然产物结构修饰中的应用已在本实验室展开.

3 实验部分

3.1 仪器与试剂

核磁共振谱(NMR)用Bruker AVANCE Ⅲ 400 MHz Plus NMR光谱仪测试, 使用TMS为内标, CDCl₃为溶剂.质谱(MS)使用MALDI TOF/TOF 5800测量.红外辐射光谱(IR)在PE-983红外光谱仪上记录, 吸收值为cm^-1.熔点由X-4数字显示显微熔点测定仪测定, 温度计未校正.减压蒸发溶剂使用EYELA SB-1100旋转蒸发仪在50 ℃下进行.

所有试剂均为分析纯, 乙腈、二氯甲烷和乙酸乙酯用CaCl₂干燥并蒸馏后使用, 四氢呋喃用钠丝干燥并在氮气氛下蒸馏后使用.

3.2 实验方法

3.2.1 炔丙醇3的合成

在-78 ℃及氩气氛的条件下, 将正丁基锂(2.0 mol•L^-1, n-C₆H₁₄, 3.0 mL)缓慢滴加到炔(5.0 mmol)的无水四氢呋喃(THF) (20.0 mL)溶液中. 30 min后, 加入醛或酮2 (5.0 mmol), 将混合物温热至室温, 搅拌2 h.反应完成后, 加入饱和NaHCO₃水溶液淬灭反应, 并用乙酸乙酯萃取有机相.将合并的有机萃取物用盐水洗涤, 用无水Na₂SO₄干燥并真空浓缩, 通过柱色谱纯化, 得到炔丙醇3.

1-(苯基乙炔基)环戊烷基-1-醇(3a)^[18a]:无色油状, 产率90%. ¹H NMR (CDCl₃, 400 MHz) δ: 7.43~7.41 (m, 2H), 7.31~7.28 (m, 3H), 2.08~2.02 (m, 4H), 1.95 (s, 1H), 1.89~1.80 (m, 2H), 1.79~1.63 (m, 2H); ¹³C NMR (CDCl₃, 100 MHz) δ: 131.6, 128.3, 128.2, 122.9, 92.9, 83.1, 74.9, 42.5, 23.5.

3-乙基-1-苯基-1-炔-3-戊醇(3b)^[18b]:无色油状, 产率92%. ¹H NMR (CDCl₃, 400 MHz) δ: 7.44~7.41 (m, 2H), 7.31~7.29 (m, 3H), 2.04 (s, 1H), 1.82~1.71 (m, 4H), 1.16 (t, J＝7.4 Hz, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ: 131.7, 128.3, 128.2, 122.9, 91.7, 84.5, 72.6, 34.5, 8.7.

2-环丙基-4-苯基-3-炔-2-丁醇(3c)^[18c]:无色油状, 产率91%. ¹H NMR (CDCl₃, 400 MHz) δ: 7.41~7.37 (m, 2H), 7.30~7.28 (m, 3H), 2.23 (s, 1H), 1.67 (s, 3H), 1.24~1.21 (m, 1H), 0.56~0.53 (m, 4H); ¹³C NMR (CDCl₃, 100 MHz) δ: 131.7, 128.3, 128.2, 122.5, 89.9, 83.8, 70.5, 29.8, 22.1, 2.6, 1.7.

3, 4-二甲基-1-苯基-1-炔-3-戊醇(3d):白色固体, 产率90%. m.p. 42~43 ℃(文献值^[18d]: 42~43 ℃); ¹H NMR (CDCl₃, 400 MHz) δ: 7.43~7.41 (m, 2H), 7.30~7.29 (m, 3H), 2.05 (s, 1H), 1.93~1.87 (m, 1H), 1.54 (s, 3H), 1.11~1.06 (m, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ: 131.7, 128.3, 128.2, 122.9, 92.0, 84.0, 72.1, 39.1, 27.2, 18.0, 17.5.

3-甲基-1-苯基-1-炔-3-戊醇(3e):无色油状物, 产率94%. b.p. 151~153 ℃(文献值^[18d]: 151~154 ℃); ¹H NMR (CDCl₃, 400 MHz) δ: 7.43~7.41 (m, 2H), 7.30~7.29 (m, 3H), 2.07 (s, 1H), 1.82~1.76 (m, 2H), 1.57 (s, 3H), 1.11 (t, J＝7.4 Hz, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ: 131.6, 128.3, 128.2, 122.8, 92.6, 83.4, 69.1, 36.6, 29.3, 9.1.

3, 5-二甲基-1-苯基-1-炔-3-己醇(3f)^[18c]:无色油状, 产率93%. ¹H NMR (CDCl₃, 400 MHz) δ: 7.42~7.40 (m, 2H), 7.31~7.29 (m, 3H), 2.05~1.97 (m, 2H), 1.70 (s, 1H), 1.68 (s, 1H), 1.58 (s, 3H), 1.07~1.05 (m, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ: 131.5, 128.3, 128.2, 122.9, 93.3, 83.5, 68.5, 51.9, 30.9, 25.2, 24.3, 24.1.

3-苯基-1-三甲基硅烷-1-炔-3-戊醇(3g)^[18e]:无色油状, 产率84%. ¹H NMR (CDCl₃, 400 MHz) δ: 7.62~7.60 (m, 2H), 7.37~7.34 (m, 2H), 7.30~7.28 (m, 1H), 2.37 (s, 1H), 1.97~1.88 (m, 2H), 0.94 (t, J＝7.4 Hz, 3H), 0.22 (s, 9H); ¹³C NMR (CDCl₃, 100 MHz) δ: 144.2, 128.1, 127.6, 125.5, 107.6, 90.7, 74.2, 38.3, 9.1, 0.0.

1-(4-甲基苯基乙炔基)环戊烷基-1-醇(3h):白色固体, 产率95%. m.p. 55~57 ℃(文献值^[18f]: 55~57 ℃); ¹H NMR (CDCl₃, 400 MHz) δ: 7.32~7.30 (m, 2H), 7.11~7.09 (m, 2H), 2.34 (s, 3H), 2.07~2.01 (m, 4H), 1.92 (s, 1H), 1.89~1.76 (m, 4H); ¹³C NMR (CDCl₃, 100 MHz) δ: 138.2, 131.5, 129.0, 119.8, 92.1, 83.2, 74.9, 42.5, 23.5, 21.4.

1-(4-氟苯基)-3-甲基-1-炔-3-戊醇(3i):无色油状, 产率90%. ¹H NMR (CDCl₃, 400 MHz) δ: 7.41~7.37 (m, 2H), 7.01~6.97 (m, 2H), 2.15 (s, 1H), 1.79~1.77 (m, 2H), 1.56 (s, 3H), 1.10 (t, J＝7.4 Hz, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ: 163.7, 161.2, 133.6, 133.5, 118.9, 118.8, 115.6, 155.4, 92.3, 82.3, 69.1, 36.6, 29.3, 9.1; IR (KBr) ν: 3406, 2973, 2366, 1603, 1509, 1463, 1369, 1232, 1152, 832 cm^-1; HRMS (ESI) calcd for C₁₂H₁₃FONa [M+Na]⁺ 215.0848, found 215.0849.

3-乙基-1-(4-氰基苯基)-1-炔-3-戊醇(3j):无色油状, 产率90%. ¹H NMR (CDCl₃, 400 MHz) δ: 7.61~7.59 (m, 2H), 7.51~7.49 (m, 2H), 2.01 (s, 1H), 1.80~1.75 (m, 4H), 1.10 (t, J＝7.4 Hz, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ: 132.2, 132.0, 127.8, 118.4, 111.6, 96.3, 82.9, 72.6, 34.3, 8.6; IR (KBr) ν: 3446, 2986, 2373, 2280, 1606, 1496, 1456, 1409, 1279, 1142, 836 cm^-1; HRMS (ESI) calcd for C₁₄H₁₅NONa [M+Na]⁺ 236.1051, found 236.1044.

4-(4-甲氧基苯基)-2-甲基-3-炔-2-丁醇(3k):白色固体, 产率94%. m.p. 175~176 ℃(文献值:^[18d] 175~176 ℃); ¹H NMR (CDCl₃, 400 MHz) δ: 7.36~7.33 (m, 2H), 6.84~6.81(m, 2H), 3.79 (s, 3H), 2.23 (s, 1H), 1.79~1.76 (m, 2H), 1.55 (s, 3H), 1.10 (t, J＝7.4 Hz, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ: 159.5, 133.1, 114.9, 113.8, 91.2, 83.2, 69.2, 55.3, 36.7, 29.4, 9.1.

3-乙基-4-炔-3-壬醇(3l)^[18g]:无色油状, 产率87%. ¹H NMR (CDCl₃, 400 MHz) δ: 2.22~2.19 (m, 2H), 1.68~1.60 (m, 4H), 1.58~1.38 (m, 4H), 1.01 (t, J＝6.8 Hz, 6H), 0.91 (t, J＝7.2 Hz, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ: 84.8, 82.5, 72.2, 34.6, 30.9, 21.9, 18.3, 13.6, 8.6.

1-环丙基-3-乙基-1-炔-3-戊醇(3m):无色油状, 产率86%. ¹H NMR (CDCl₃, 400 MHz) δ: 1.81 (s, 1H), 1.65~1.59 (m, 4H), 1.26~1.23 (m, 1H), 1.01 (t, J＝7.4 Hz, 6H), 0.98~0.74 (m, 2H), 0.67~0.64 (m, 2H); ¹³C NMR (CDCl₃, 100 MHz) δ: 88.0, 77.7, 72.1, 34.5, 8.5, 8.3, 0.6; IR (KBr) ν: 3453, 2920, 1739, 1549, 1509, 1463, 1082, 809, 669 cm^-1; HRMS (ESI) calcd for C₁₀H₁₇O [M+H]⁺ 153.1279, found 153.1272.

3.2.2 噁唑啉酮衍生物5的合成

在氮气氛的条件下, 将异氰酸酯或异硫氰酸酯4 (1.0 mmol)加入到炔丙醇3 (1.0 mmol)和无水乙腈(5.0 mL)混合液中, 然后滴加DBU (30.5 μL, 0.2 mmol), 并在30 ℃下搅拌24 h.然后将反应用水(15.0 mL)淬灭, EtOAc (10.0 mL×3)萃取, 将合并的有机层用盐水洗涤, 用Na₂SO₄干燥.除去溶剂后, 残余物通过¹H NMR分析E/Z选择性.通过柱色谱进一步纯化(洗脱液:己烷/ EtOAc, V:V＝50:1), 得到相应的噁唑啉酮衍生物5.

(Z)-4-芳亚甲基-5-乙基-5-甲基-3-(对甲苯基)噁唑啉-2-酮(5a):白色固体, 产率91%. m.p. 101~103 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 6.90~6.82 (m, 7H), 6.67~6.65 (m, 2H), 5.53 (s, 1H), 2.19 (s, 3H), 2.07~1.98 (m, 1H), 1.95~1.85 (m, 1H), 1.68 (s, 3H), 1.08 (t, J＝7.2 Hz, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ: 155.7, 141.2, 136.9, 133.4, 132.4, 128.7, 128.4, 126.9, 125.7, 125.5, 99.4, 85.4, 34.2, 26.9, 20.8, 7.5; IR (KBr) ν: 3413, 2927, 1777, 1661, 1511, 1319, 1229, 1130, 809, 701 cm^-1; HRMS (ESI) calcd for C₂₀H₂₁NO₂Na [M+Na]⁺ 330.1473, found 330.1470.

(Z)-4-芳亚甲基-5, 5-二乙基-3-(对甲苯基)噁唑啉-2-酮(5b):白色固体, 产率90%. m.p. 71~73 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 6.92~6.81 (m, 7H, ), 6.68~6.65 (m, 2H), 5.50 (s, 1H), 2.19 (s, 3H), 2.09~2.00 (m, 2H), 1.88~1.80 (m, 2H), 1.09 (t, J＝7.2 Hz, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ: 156.2, 139.4, 137.0, 133.5, 132.4, 128.7, 128.4, 126.9, 125.8, 125.4, 99.3, 88.3, 33.1, 20.8, 7.2; IR (KBr) ν: 3436, 2965, 1754, 1665, 1344, 1232, 1123, 950, 701, 624 cm^-1; HRMS (ESI) calcd for C₂₁H₂₄NO₂ [M+ H]⁺ 322.1807, found 322.1810.

(Z)-4-芳亚甲基-5-异丙基-5-甲基-3-(对甲苯基)噁唑啉-2-酮(5c):白色固体, 产率86%. m.p. 93~95 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 6.90~6.81 (m, 7H), 6.67~6.64 (m, 2H), 5.55 (s, 1H), 2.18 (s, 3H), 2.10~2.03 (m, 1H), 1.85~1.79 (m, 1H), 1.68 (s, 3H), 1.16 (d, J＝6.8 Hz, 3H), 1.12 (d, J＝6.8 Hz, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ: 156.0, 141.6, 136.9, 133.5, 132.3, 128.7, 128.4, 126.9, 125.6, 125.4, 99.5, 87.3, 38.0, 25.2, 20.8, 16.5, 16.4; IR (KBr) ν: 3445, 2971, 1761, 1665, 1514, 1399, 1251, 1136, 1030, 816, 704 cm^-1; HRMS (ESI) calcd for C₂₁H₂₃NO₂Na [M+Na]⁺ 344.1626, found 344.1623.

(Z)-4-芳亚甲基-5-异丁基-5-甲基-3-(对甲苯基)噁唑啉-2-酮(5d):白色固体, 产率85%. m.p. 97~99 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 6.90~6.82 (m, 7H), 6.66~6.64 (m, 2H), 5.53 (s, 1H), 2.19 (s, 3H), 2.04~1.90 (m, 2H), 1.85~1.81 (m, 1H), 1.68 (s, 3H), 1.06 (d, J＝6.4 Hz, 3H), 1.04 (d, J＝6.4 Hz, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ: 155.6, 141.9, 136.9, 133.4, 132.3, 128.7, 128.3, 126.9, 125.7, 125.4, 99.5, 85.4, 49.2, 28.1, 24.4, 24.1, 20.9; IR (KBr) ν: 3439, 2962, 1754, 1677, 1514, 1412, 1309, 1219, 1130, 819, 707 cm^-1; HRMS (ESI) calcd for C₂₂H₂₅NO₂Na [M+Na]⁺ 358.1783, found 358.1781.

(Z)-4-芳亚甲基-5-环丙基-5-甲基-3-(对甲苯基)噁唑啉-2-酮(5e):白色固体, 产率80%. m.p. 133~135 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 6.92~6.82 (m, 7H), 6.69~6.66 (m, 2H), 5.63 (s, 1H), 2.18 (s, 3H), 1.59 (s, 3H), 1.39~1.32 (m, 1H), 0.66~0.56 (m, 4H); ¹³C NMR (CDCl₃, 100 MHz) δ: 155.6, 141.4, 136.8, 133.3, 132.3, 128.7, 128.4, 126.9, 125.5, 125.5, 100.4, 84.0, 25.7, 20.8, 20.6, 1.4, 0.7; IR (KBr) ν: 3449, 3019, 1767, 1671, 1508, 1399, 1255, 1123, 816, 707 cm^-1; HRMS (ESI) calcd for C₂₁H₂₂NO₂ [M+H]⁺ 320.1651, found 320.1647.

(Z)-4-(4-甲基芳亚甲基)-3-(对甲苯基)-1-氧杂-3-氮杂螺[4.4]壬-2-酮(5f):白色固体, 产率78%. m.p. 112~114 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 6.89~6.83 (m, 4H), 6.67~6.64 (m, 2H), 6.54~6.51 (m, 2H), 5.58 (s, 1H), 2.35~2.30 (m, 2H), 2.20 (s, 3H), 2.15 (s, 3H), 2.08~1.91 (m, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ: 155.7, 140.5, 136.7, 135.2, 132.4, 130.4, 128.6, 128.2, 127.6, 125.8, 99.3, 93.1, 41.4, 24.4, 20.9, 20.8; IR (KBr) ν: 3413, 2965, 1764, 1665, 1514, 1344, 1255, 1101, 982, 835 cm^-1; HRMS (ESI) calcd for C₂₂H₂₃NO₂Na [M+Na]⁺ 356.1626, found 356.1627.

(Z)-4-芳亚甲基-3-(4-氟苯基)-5-异丁基-5-甲基噁唑啉-2-酮(5g):白色固体, 产率87%. m.p. 59~61 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 6.97~6.87 (m, 5H), 6.75~6.69 (m, 2H), 6.67~6.64 (m, 2H), 5.58 (s, 1H), 2.05~1.91 (m, 2H), 1.86~1.79 (m, 1H), 1.69 (s, 3H), 1.06 (d, J＝6.4 Hz, 3H), 1.04 (d, J＝6.4 Hz, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ: 162.3, 159.9, 155.4, 141.8, 133.2, 131.7, 130.9, 130.9, 128.3, 128.0, 127.7, 127.6, 127.2, 125.9, 115.1, 114.9, 99.8, 85.6, 49.2, 28.1, 24.4, 24.1; IR (KBr) ν: 3429, 2955, 1777, 1668, 1501, 1309, 1232, 1130, 829, 707 cm^-1; HRMS (ESI) calcd for C₂₁H₂₂FNO₂Na [M+Na]⁺ 362.1532, found 362.1533.

(Z)-4-芳亚甲基-5-环丙基-3-(4-氟苯基)-5-甲基噁唑啉-2-酮(5h):白色固体, 产率86%. m.p. 80~82 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 6.98~6.88 (m, 5H), 6.75~6.67 (m, 4H), 5.68 (s, 1H), 1.71 (s, 3H), 1.40~1.32 (m, 1H), 0.66~0.60 (m, 4H); ¹³C NMR (CDCl₃, 100 MHz) δ: 162.3, 169.9, 155.3, 141.5, 133.2, 131.0, 128.4, 127.6, 127.5, 127.2, 126.0, 115.1, 114.9, 100.6, 84.2, 25.7, 20.7, 1.4, 0.8; IR (KBr) ν: 3442, 3019, 1770, 1668, 1511, 1399, 1258, 1130, 1034, 835, 701 cm^-1; HRMS (ESI) calcd for C₂₀H₁₈FNO₂Na [M+Na]⁺ 346.1219, found 346.1220.

(Z)-5-乙基-3-(4-氟苯基)-5-苯基-4-((三甲基甲硅烷基)亚甲基)噁唑啉-2-酮(5i):无色油状, 产率86%. ¹H NMR (CDCl₃, 400 MHz) δ: 7.54~7.51 (m, 2H), 7.42~7.40 (m, 3H), 7.16~7.14 (m, 2H), 7.13~7.11 (m, 2H), 4.35 (s, 1H), 2.36~2.31 (m, 1H), 2.23~2.17 (m, 1H), 1.06 (t, J＝8.0 Hz, 3H), -0.30 (s, 9H); ¹³C NMR (CDCl₃, 100 MHz) δ: 163.5, 161.1, 155.8, 153.0, 140.8, 130.0, 128.7, 128.3, 124.9, 116.7, 116.5, 96.4, 89.3, 33.1, 7.8, 0.3; IR (KBr) ν: 3442, 2968, 1777, 1636, 1514, 1514, 1226, 1136, 835, 752, 697 cm^-1; HRMS (ESI) calcd for C₂₁H₂₅FNO₂Si [M+H]⁺ 370.1639, found 370.1781.

(Z)-5-乙基-3-(4-氟苯基)-4-亚甲基-5-苯基噁唑啉-2-酮(5j):无色油状, 产率91%. ¹H NMR (CDCl₃, 400 MHz) δ: 7.57~7.54 (m, 2H), 7.44~7.37 (m, 3H), 7.31~7.27 (m, 2H), 7.18~7.13 (m, 2H), 4.25 (d, J＝3.0 Hz, 1H), 4.23 (d, J＝3.0 Hz, 1H), 2.38~2.29 (m, 1H), 2.25~2.16 (m, 1H), 1.07 (t, J＝7.3 Hz, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ: 163.3, 160.9, 154.7, 149.2, 140.6, 129.8, 129.2, 129.1, 128.7, 128.4, 124.7, 116.7, 116.5, 87.8, 84.0, 33.6, 7.7; IR (KBr) ν: 3436, 2978, 1681, 1463, 1383, 1277, 1136, 1079, 1027, 749, 701 cm^-1; HRMS (ESI) calcd for C₁₈H₁₇FNO₂ [M+H]⁺ 298.1243, found 298.1241.

(Z)-4-芳亚甲基-5, 5-二乙基-3-(萘-1-基)噁唑啉-2-酮(5k):白色固体, 产率85%. m.p. 123~125 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 7.80 (d, J＝8.4 Hz, 1H), 7.72 (d, J＝8.1 Hz, 1H), 7.58~7.51 (m, 2H), 7.47~7.43 (m, 1H), 7.08~7.01 (m, 2H), 6.64 (t, J＝7.4 Hz, 1H), 6.47 (t, J＝7.7 Hz, 2H), 6.39 (d, J＝7.4 Hz, 2H), 5.52 (s, 1H), 2.19~2.10 (m, 2H), 1.98~1.89 (m, 2H), 1.29 (t, J＝7.3 Hz, 3H), 1.22 (t, J＝7.3 Hz, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ: 156.1, 134.0, 133.0, 128.8, 128.1, 127.9, 126.9, 126.4, 126.1, 125.7, 125.5, 124.7, 122.4, 99.4, 88.8, 33.4, 33.3, 7.7, 7.3; IR (KBr) ν: 3420, 2959, 1761, 1684, 1565, 1405, 1239, 1143, 777, 954 cm^-1; HRMS (ESI) calcd for C₂₄H₂₃NO₂Na [M+Na]⁺ 380.1626, found 380.1631.

(Z)-4-芳亚甲基-5, 5-二乙基-3-异丙基噁唑啉-2-酮(5l):白色固体, 产率87%. m.p. 69~71 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 7.35~7.30 (m, 2H), 7.27~7.18 (m, 3H), 5.32 (s, 1H), 3.74~3.68 (m, 1H), 1.92~1.87 (m, 2H), 1.70~1.62 (m, 2H), 1.25 (d, J＝6.8 Hz, 6H), 0.98 (t, J＝7.2 Hz, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ: 156.1, 140.7, 135.4, 128.8, 128.1, 126.7, 97.0, 87.3, 47.1, 33.1, 18.8, 7.1. IR (KBr) ν: 3436, 2968, 1758, 1671, 1456, 1408, 1328, 1280, 1030, 758 cm^-1; HRMS (ESI) calcd for C₁₇H₂₃NO₂Na [M+Na]⁺ 296.1626, found 296.1625.

(Z)-4-芳亚甲基-5-异丁基-3-异丙基-5-甲基噁唑啉-2-酮(5m):无色油状, 产率87%. ¹H NMR (CDCl₃, 400 MHz) δ: 7.45~7.42 (m, 2H), 7.29~7.28 (m, 3H), 4.45 (s, 1H), 3.81 (d, J＝6.1 Hz, 1H), 2.05~2.00 (m, 2H), 1.80 (s, 3H), 1.67 (s, 1H), 1.15 (d, J＝6.5 Hz, 6H, ), 1.04 (d, J＝6.3 Hz, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ: 153.98, 131.75, 128.14, 128.10, 122.93, 90.58, 84.53, 77.20, 75.54, 49.67, 42.72, 27.87, 24.99, 24.16, 23.89, 23.03; IR (KBr) ν: 3327, 2962, 1687, 1527, 1463, 1248, 1139, 1066, 765 cm^-1; HRMS (ESI) calcd for C₁₈H₂₅NO₂Na [M+Na]⁺ 310.1783, found 310.1777.

(Z)-4-芳亚甲基-5-环丙基-3-异丙基-5-甲基噁唑啉-2-酮(5n):白色固体, 产率87%. m.p. 95~97 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 7.35~7.30 (m, 2H), 7.26~7.19 (m, 3H), 5.47 (s, 1H), 3.69~3.61 (m, 1H), 1.54 (s, 3H), 1.27~1.15 (m, 7H, CH), 0.56~0.40 (m, 4H); ¹³C NMR (CDCl₃, 100 MHz) δ: 155.7, 143.5, 135.3, 128.8, 128.1, 126.7, 98.2, 82.8, 47.2, 25.8, 20.6, 18.8, 18.6, 1.2, 0.5; IR (KBr) ν: 3442, 2975, 1745, 1668, 1450, 1376, 1293, 1024, 694 cm^-1; HRMS (ESI) calcd for C₁₇H₂₁NO₂Na [M+Na]⁺ 294.1470, found 294.1464.

(Z)-4-芳亚甲基-3-异丙基-1-氧杂-3-氮杂螺[4.4]壬-2-酮(5o):白色固体, 产率88%. m.p. 119~121 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 7.34~7.30 (m, 2H), 7.26~7.18 (m, 3H), 5.44 (s, 1H), 3.74~3.67 (m, 1H), 2.18~2.17 (m, 2H), 1.92~1.84 (m, 6H), 1.27 (d, J＝6.8 Hz, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ: 155.7, 143.0, 135.2, 128.8, 128.1, 126.7, 97.3, 92.2, 47.3, 41.4, 24.4, 18.8. IR (KBr) ν: 3423, 2971, 1751, 1674, 1408, 1290, 1107, 1030, 701, 646 cm^-1; HRMS (ESI) calcd for C₁₇H₂₁NO₂Na [M+Na]⁺ 294.1470, found 294.1472.

(Z)-4-芳亚甲基-3, 5, 5-三乙基噁唑啉-2-酮(5p):白色固体, 产率86%. m.p. 76~78 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 7.34~7.31 (m, 2H), 7.27~7.23 (m, 1H), 7.21~7.19 (m, 2H), 5.42 (s, 1H), 3.39 (q, J＝7.1 Hz, 2H), 1.98~1.88 (m, 2H), 1.77~1.66 (m, 2H), 0.91 (t, J＝7.4 Hz, 6H), 0.74 (t, J＝7.0 Hz, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ: 157.2, 139.4, 134.9, 131.6, 129.5, 128.2, 128.1, 127.9, 126.8, 97.7, 87.6, 38.0, 33.0, 12.3, 7.1; IR (KBr) ν: 3481, 2975, 1748, 1674, 1456, 1360, 1264, 1197, 1050, 950, 713 cm^-1; HRMS (ESI) calcd for C₁₆H₂₂NO₂ [M+H]⁺ 260.1651, found 260.1649.

(Z)-4-芳亚甲基-5-环丙基-3-乙基-5-甲基噁唑啉-2-酮(5q):白色固体, 产率84%. m.p. 74~76 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 7.34~7.30 (m, 3H), 7.25~7.19 (m, 2H), 5.56 (s, 1H), 3.42~3.29 (m, 2H), 1.57 (s, 3H), 1.32~1.00 (m, 2H), 0.74 (t, J＝7.1 Hz, 3H), 0.63~0.48 (m, 4H); ¹³C NMR (CDCl₃, 100 MHz) δ: 156.71, 142.05, 134.89, 130.10, 129.47, 128.07, 127.95, 126.90, 99.65, 83.28, 38.03, 25.94, 20.61, 12.38, 1.37, 0.64; IR (KBr) ν: 3439, 2975, 1745, 1674, 1674, 1364, 1059, 720, 633 cm^-1; HRMS (ESI) calcd for C₁₆H₁₉NO₂Na [M+Na]⁺ 280.1313, found 280.1314.

(Z)-4-芳亚甲基-5, 5-二乙基-3-苯基噁唑啉-2-硫酮(5r):白色固体, 产率83%. m.p. 127~129 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 7.09~7.00 (m, 5H), 6.90~6.84 (m, 3H), 6.82~6.63 (m, 2H), 5.56 (s, 1H), 2.18~2.09 (m, 2H), 1.89~1.82 (m, 2H), 1.13 (t, J＝7.3 Hz, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ: 188.9, 140.2, 136.7, 132.6, 128.4, 128.3, 128.1, 127.1, 125.8, 101.1, 94.3, 33.5, 7.4; IR (KBr) ν: 3455, 2971, 2360, 1658, 1591, 1463, 1341, 1117, 970, 688 cm^-1; HRMS (ESI) calcd for C₂₀H₂₂NOS [M+H]⁺ 324.1422, found 324.1072.

(Z)-4-芳亚甲基-3, 5, 5-三乙基噁唑啉-2-硫酮(5s):白色固体, 产率87%. m.p. 109~111 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 7.37~7.27 (m, 3H), 7.23~7.20 (m, 2H), 5.53 (s, 1H), 3.77 (q, J＝7.0 Hz, 2H), 2.04~1.96 (m, 2H), 1.77~1.69 (m, 2H), 0.97 (t, J＝7.3 Hz, 6H), 0.80 (t, J＝7.0 Hz, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ: 188.4, 139.2, 134.1, 129.4, 128.0, 127.3, 100.3, 93.0, 77.6, 41.6, 33.4, 11.4, 7.2; IR (KBr) ν: 3445, 2971, 1674, 1456, 1389, 1277, 1136, 915, 701 cm^-1; HRMS (ESI) calcd for C₁₆H₂₂NOS [M+H]⁺ 276.1422, found 276.0996.

(Z)-4-芳亚甲基-3-乙基-5-异丁基-5-甲基噁唑啉-2-硫酮(5t):无色油状, 80%.¹H NMR (CDCl₃, 400 MHz) δ: 7.37~7.28 (m, 3H), 7.21~7.18 (m, 2H), 5.55 (s, 1H, ), 3.76 (q, J＝7.0 Hz, 2H), 1.91~1.84 (m, 2H), 1.72~1.69 (m, 1H), 1.58 (s, 3H), 1.00 (t, J＝6.7 Hz, 6H), 0.81 (t, J＝7.0 Hz, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ: 187.6, 141.9, 134.0, 129.3, 128.0, 127.3, 100.4, 89.7, 49.3, 41.5, 28.3, 24.3, 24.2, 23.8, 11.3; IR (KBr) ν: 3442, 2955, 1677, 1463, 1389, 1277, 1223, 1136, 745, 701 cm^-1; HRMS (ESI) calcd for C₁₇H₂₄NOS [M+H]⁺ 290.1579, found 290.1571.

(Z)-5-乙基-4-(4-氟苯亚甲基)-5-甲基-3-(对甲苯基)噁唑啉-2-酮(5u):白色固体, 产率90%. m.p. 81~83 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 6.86~6.85 (m, 4H), 6.62~6.53 (m, 4H), 5.48 (s, 1H), 2.22 (s, 3H), 2.05~1.86 (m, 2H), 1.68 (s, 3H), 1.08 (t, J＝7.6 Hz, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ: 162.1, 159.7, 155.7, 141.5, 137.3, 132.2, 130.0, 129.9, 128.9, 125.9, 113.9, 113.7, 98.2, 85.5, 34.2, 27.0, 20.9, 7.6; IR (KBr) ν: 2960, 1756, 1676, 1513, 1406, 1326, 1232, 1139, 1066, 812, 626 cm^-1; HRMS (ESI) calcd for C₂₀H₂₁FNO₂ [M+H]⁺ 326.1556, found 326.1554.

(Z)-5-乙基-4-(4-甲氧基苯亚甲基)-5-甲基-3-(对甲苯基)噁唑啉-2-酮(5v):白色固体, 产率80%. m.p. 93~95 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 6.87~6.86 (m, 4H), 6.58~6.56 (m, 2H), 6.41~6.39 (m, 2H), 5.48 (s, 1H), 3.66 (s, 3H), 2.21 (s, 3H), 2.02~1.87 (m, 2H), 1.67 (s, 3H), 1.08 (t, J＝7.4 Hz, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ: 157.6, 155.9, 140.1, 136.8, 132.5, 129.5, 128.7, 125.9, 125.7, 112.5, 99.2, 85.5, 55.2, 34.3, 27.0, 20.9, 7.6; IR (KBr) ν: 2973, 1773, 1663, 1509, 1329, 1239, 1126, 1029, 812, 616 cm^-1; HRMS (ESI) calcd for C₂₁H₂₄NO₃ [M+H]⁺ 338.1756, found 338.1752.

(Z)-5-乙基-4-(4-氰基苯亚甲基)-5-甲基-3-(对甲苯基)噁唑啉-2-酮(5w):无色油状, 产率91%. ¹H NMR (CDCl₃, 400 MHz) δ: 7.58~7.56 (m, 2H), 7.35~7.32 (m, 2H), 7.23~7.20 (m, 4H), 5.66 (s, 1H), 2.41 (s, 3H), 1.88~1.83 (dq, J＝14.6, 7.3 Hz, 2H), 1.60~1.53 (m, 2H), 1.07 (t, J＝7.3 Hz, 6H); ¹³C NMR (CDCl₃, 100 MHz) δ: 155.1, 144.2, 140.2, 139.2, 131.9, 130.9, 130.6, 129.5, 127.7, 118.6, 110.6, 99.8, 89.2, 31.9, 21.2, 7.3; IR (KBr) ν: 2966, 2360, 1759, 1669, 1409, 1356, 1166, 1062, 826, 669 cm^-1; HRMS (ESI) calcd for C₂₂H₂₃N₂O₂ [M+H]⁺ 347.1760, found 347.1753.

(Z)-5, 5-二乙基-4-戊基-3-(对甲苯基)噁唑啉-2-酮(5x):白色固体, 产率65%. m.p. 77~79 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 7.22 (d, J＝8.1 Hz, 2H), 7.16 (d, J＝8.2 Hz, 2H), 4.16 (t, J＝7.6 Hz, 1H), 2.38 (s, 3H), 1.90 (dd, J＝14.4, 7.2 Hz, 2H), 1.67 (dd, J＝14.4, 7.3 Hz, 2H), 1.43 (dd, J＝14.4, 7.2 Hz, 2H), 1.12~1.05 (m, 4H), 1.02 (t, J＝7.3 Hz, 6H), 0.71 (t, J＝7.0 Hz, 3H); ¹³C NMR (CDCl₃, 100 MHz) δ: 156.5, 138.4, 138.3, 133.9, 129.8, 127.6, 99.6, 88.0, 32.9, 32.3, 24.4, 21.9, 21.1, 13.6, 7.2, 0. IR (KBr) ν: 2973, 1706, 1606, 1546, 1466, 1406, 1323, 1246, 1052, 816 cm^-1; HRMS (ESI) calcd for C₁₉H₂₈NO₂ [M+H]⁺ 302.2120, found 302.2113.

(Z)-4-(环丙基)-5, 5-二乙基-3-(对甲苯基)噁唑啉-2-酮(5y):白色固体, 产率62%. m.p. 79~82 ℃; ¹H NMR (CDCl₃, 400 MHz) δ: 7.26~7.20 (m, 4H), 3.72 (d, J＝9.0 Hz, 1H), 2.37 (s, 3H), 1.89~1.85 (dq, J＝14.5, 7.3 Hz, 2H), 1.65~1.59 (m, 2H), 1.01 (t, J＝7.3 Hz, 6H), 0.61~0.57 (m, 1H), 0.41~0.40 (m, 2H), 0.12 (m, 2H); ¹³C NMR (CDCl₃, 100 MHz) δ: 156.3, 138.3, 138.1, 133.6, 129.5, 127.3, 103.4, 87.8, 32.9, 21.1, 7.8, 7.5, 7.2. IR (KBr) ν: 3293, 2980, 1706, 1596, 1539, 1316, 1239, 1052, 912, 816 cm^-1; HRMS (ESI) calcd for C₁₈H₂₃NO₂Na [M+Na]⁺ 308.1626, found 308.1620.

辅助材料(Supporting Information)所有化合物的 ¹H NMR和¹³C NMR谱图.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 噁唑啉-2-(硫)酮衍生物5的合成路线

Scheme 1 Synthetic routes for the oxazolidin-2-(thi)one derivatives 5

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图 1 噁唑啉-2-硫酮5s的晶体结构

Figure 1 Crystal structure of the oxazolidin-2-thione 5s

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图式 2 反应选择性研究

Scheme 2 Planned synthesis for selectivity study

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图式 3 可能的反应机理

Scheme 3 Possible reaction mechanism

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表 1 模型反应的条件优化

Table 1. Optimization of reaction conditions for the model reaction

Entry	Catalyst^a	Solvent	Temp./ ℃	Time/ h	Yield^b/%
Entry	Catalyst^a	Solvent	Temp./ ℃	Time/ h	Carbamate ester	5a
1	AgNO₃	Toluene	30	24	0	0
2	PdCl₂	CH₃CN	30	24	0	0
3	CuI	CH₃CN	30	24	0	0
4	I₂	Toluene	30	24	0	0
5	DMAP	DMF	50	24	80	0
6	DBU	CH₂Cl₂	30	12	70	30
7	DBU	CH₂Cl₂	30	24	5	85
8	DBU	Toluene	30	24	0	0
9	DBU	CHCl₃	30	24	90	0
10	DBU	Et₂O	30	24	0	0
11	DBU	EtOAc	30	24	0	0
12	DBU	CH₃OH	30	24	0	0
13	DBU	CH₃CN	30	12	0	90
14	K₂CO₃	CH₃CN	30	24	0	40
15	Morpholine	CH₃CN	30	24	0	0
16	Et₃N	CH₃CN	30	24	0	30
17	NaOH	CH₃CN	30	24	0	0
18	DBU^c	CH₃CN	30	24	0	60
19	DBU^d	CH₃CN	30	12	0	90
20	DBU^e	CH₃CN	30	12	0	80
21	DBU	CH₃CN	40	8	0	90
22	DBU	CH₃CN	50	8	0	60
23	DBU	CH₃CN	20	24	40	60
^aGeneral conditions: catalyst (20 mol%) was added into the mixture of 3a (95 mg, 0.5 mmol) and 4a (67 mg, 0.5 mmol) in corresponding solvent (2.0 mL). ^b Isolated yield. ^c10 mol% of DBU was used. ^d30 mol% of DBU was used. ^e40 mol% of DBU was used.

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表 2 噁唑啉-2-(硫)酮衍生物5衍生物

Table 2. Oxazolidin-2-(thi)one derivatives 5

Entry	Product	Substitution					Isolated yield/%
Entry	Product	R¹	R²	R³	R⁴	X	Isolated yield/%
1	5a	C₆H₅	Me	Et	p-MeC₆H₄	O	91
2	5b	C₆H₅	Et	Et	p-MeC₆H₄	O	90
3	5c	C₆H₅	Me	i-Pr	p-MeC₆H₄	O	86
4	5d	C₆H₅	Me	i-Bu	p-MeC₆H₄	O	85
5	5e	C₆H₅	Me	Cyclopropyl	p-MeC₆H₄	O	80
6	5f	p-MeC₆H₄		Cyclopentyl	p-MeC₆H₄	O	78
7	5g	C₆H₅	Me	i-Bu	p-FC₆H₄	O	87
8	5h	C₆H₅	Me	Cyclopropyl	p-FC₆H₄	O	86
9	5i	TMS	Et	C₆H₅	p-FC₆H₄	O	75
10	5j	H	Et	C₆H₅	p-FC₆H₄	O	91
11	5k	C₆H₅	Et	Et	Naphthyl	O	85
12	5l	C₆H₅	Et	Et	i-Pr	O	87
13	5m	C₆H₅	Me	i-Bu	i-Pr	O	86
14	5n	C₆H₅	Me	Cyclopropyl	i-Pr	O	87
15	5o	C₆H₅		Cyclopentyl	i-Pr	O	88
16	5p	C₆H₅	Et	Et	Et	O	86
17	5q	C₆H₅	Me	Cyclopropyl	Et	O	84
18	5r	C₆H₅	Et	Et	C₆H₅	S	83
19	5s	C₆H₅	Et	Et	Et	S	87
20	5t	C₆H₅	Me	i-Bu	C₆H₅	S	80
21	5u	p-FC₆H₄	Me	Et	p-MeC₆H₄	O	90
22	5v	p-MeOC₆H₄	Me	Et	p-MeC₆H₄	O	80
23	5w	p-CNC₆H₄	Et	Et	p-MeC₆H₄	O	91
24	5x	n-Bu	Et	Et	p-MeC₆H₄	O	65
25	5y	Cyclopropyl	Et	Et	p-MeC₆H₄	O	62

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