4-二甲氨基吡啶促进的一锅法合成高选择性螺环丙烷吡唑啉酮衍生物

doi:10.6023/cjoc201904028

摘要/Abstract

发展了一种4-二甲氨基吡啶（DMAP）促进的高立体选择性合成多取代螺环丙烷吡唑啉酮的方法.该反应以吡唑啉酮、芳醛和溴乙酸酯为原料，DMAP作为碱，经三组分一锅反应，合成一系列收率高且非对映选择性好的目标化合物.该反应具有操作简单、产率高以及非对映选择性好等优点.该合成方法对于螺环丙烷的研究具有重要的价值.

关键词: 一锅法合成, 多组分反应, 螺环丙烷, 吡唑酮, 4-二甲氨基吡啶(DMAP)

A 4-dimethylaminopyridine (DMAP)-promoted high stereoselectivity method for the synthesis of polysubstituted spiropropane pyrazolone was developed. A series of target compounds were synthesized from using pyrazolone, aromatic aldehyde and bromoacetate as raw materials, and DMAP as a base with high yield via three-component one-pot reaction. This reaction has the advantages of simple operation, high yield and good diastereotopic selectivity. In addition, this synthetic method is of great value for the study of spiropropane.

Key words: one-pot synthesis, multicomponent reactions, spirocyclopropane, pyrazolones, 4-dimethylaminopyridine (DMAP)

引用此文

梁杰, 马会芳, 阿布拉江·克依木. 4-二甲氨基吡啶促进的一锅法合成高选择性螺环丙烷吡唑啉酮衍生物[J]. 有机化学, 2019, 39(11): 3169-3175.

Liang Jie, Ma Huifang, Ablajan Keyume. High-Selective One-Pot Synthesis of Spirocyclopropane Pyrazolones Promoted by 4-Dimethylaminopyridine[J]. Chinese Journal of Organic Chemistry, 2019, 39(11): 3169-3175.

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Entry	Base	Solvent	Temp./℃	Yield^b/%	trans^c/cis
1	No base	CH₃CN	81	NR	NR
2	NaOH	CH₃CN	81	41	45:55
3	Cs₂CO₃	CH₃CN	81	48	48:52
4	Pyridine	CH₃CN	81	82^c	72:28
5	TEBA	CH₃CN	81	56	80:20
6	CTAB	CH₃CN	81	60	85:15
7	DABCO	CH₃CN	81	70	72:28
8	DMAP	CH₃CN	81	86	94:6
9	DMAP	CH₂Cl₂	81	65	40:60
10	DMAP	H₂O	100	Trace	NR
11	DMAP	CH₃CO₂Et	81	78	88:12
12	DMAP	CH₃CN	81	86^d	94:6
13	DMAP	CH₃CN	25	36	46:54
14	DMAP	CH₃CN	60	68	79:21
15	DMAP	CH₃CN	81	50^e	90:10


Entry	Base	Solvent	Temp./℃	Yield^b/%	trans^c/cis
1	No base	CH₃CN	81	NR	NR
2	NaOH	CH₃CN	81	41	45:55
3	Cs₂CO₃	CH₃CN	81	48	48:52
4	Pyridine	CH₃CN	81	82^c	72:28
5	TEBA	CH₃CN	81	56	80:20
6	CTAB	CH₃CN	81	60	85:15
7	DABCO	CH₃CN	81	70	72:28
8	DMAP	CH₃CN	81	86	94:6
9	DMAP	CH₂Cl₂	81	65	40:60
10	DMAP	H₂O	100	Trace	NR
11	DMAP	CH₃CO₂Et	81	78	88:12
12	DMAP	CH₃CN	81	86^d	94:6
13	DMAP	CH₃CN	25	36	46:54
14	DMAP	CH₃CN	60	68	79:21
15	DMAP	CH₃CN	81	50^e	90:10


Entry	R¹	R²	R³	4	Yield^b/%	trans/cis^c
1	Ph	4-ClC₆H₄	Me	4a	62	6:1
2	Ph	4-BrC₆H₄	Me	4b	67	8:1
3	Ph	2-O₂NC₆H₄	Me	4c	84	11:1
4	Ph	2-ClC₆H₄	Me	4d	85	12:1
5	Ph	2, 4-Cl₂C₆H₄	Me	4e	79	10:1
6	4-CH₃C₆H₄	4-ClC₆H₄	Me	4f	62	15:1
7	4-CH₃C₆H₄	4-BrC₆H₄	Me	4g	65	11:1
8	4-CH₃C₆H₄	2-O₂NC₆H₄	Me	4h	86	18:1
9	4-CH₃C₆H₄	2-ClC₆H₄	Me	4i	86	17:1
10	4-CH₃C₆H₄	2, 4-Cl₂C₆H₄	Me	4j	80	15:1
11	4-CH₃C₆H₄	Ph	Me	4k	65	6:1
12	4-ClC₆H₄	4-ClC₆H₄	Me	4l	62	9:1
13	4-ClC₆H₄	4-BrC₆H₄	Me	4m	66	8:1
14	4-ClC₆H₄	2-O₂NC₆H₄	Me	4n	58	> 25:1
15	4-ClC₆H₄	2, 4-Cl₂C₆H₄	Me	4o	82	15:1
16	2-ClC₆H₄	4-ClC₆H₄	Me	4p	77	11:1
17	2-ClC₆H₄	4-BrC₆H₄	Me	4q	78	12:1
18	2-ClC₆H₄	2-O₂NC₆H₄	Me	4r	83	18:1
19	2-ClC₆H₄	2, 4-Cl₂C₆H₄	Me	4s	80	13:1
20	Ph	2, 4-Cl₂C₆H₄	C(Me)₃	4t	89	> 25:1
21	4-CH₃C₆H₄	2-O₂NC₆H₄	C(Me)₃	4u	87	> 25:1
22	2-ClC₆H₄	2-O₂NC₆H₄	C(Me)₃	4v	87	> 25:1
23	4-ClC₆H₄	2, 4-Cl₂C₆H₄	C(Me)₃	4w	85	> 25:1


Entry	R¹	R²	R³	4	Yield^b/%	trans/cis^c
1	Ph	4-ClC₆H₄	Me	4a	62	6:1
2	Ph	4-BrC₆H₄	Me	4b	67	8:1
3	Ph	2-O₂NC₆H₄	Me	4c	84	11:1
4	Ph	2-ClC₆H₄	Me	4d	85	12:1
5	Ph	2, 4-Cl₂C₆H₄	Me	4e	79	10:1
6	4-CH₃C₆H₄	4-ClC₆H₄	Me	4f	62	15:1
7	4-CH₃C₆H₄	4-BrC₆H₄	Me	4g	65	11:1
8	4-CH₃C₆H₄	2-O₂NC₆H₄	Me	4h	86	18:1
9	4-CH₃C₆H₄	2-ClC₆H₄	Me	4i	86	17:1
10	4-CH₃C₆H₄	2, 4-Cl₂C₆H₄	Me	4j	80	15:1
11	4-CH₃C₆H₄	Ph	Me	4k	65	6:1
12	4-ClC₆H₄	4-ClC₆H₄	Me	4l	62	9:1
13	4-ClC₆H₄	4-BrC₆H₄	Me	4m	66	8:1
14	4-ClC₆H₄	2-O₂NC₆H₄	Me	4n	58	> 25:1
15	4-ClC₆H₄	2, 4-Cl₂C₆H₄	Me	4o	82	15:1
16	2-ClC₆H₄	4-ClC₆H₄	Me	4p	77	11:1
17	2-ClC₆H₄	4-BrC₆H₄	Me	4q	78	12:1
18	2-ClC₆H₄	2-O₂NC₆H₄	Me	4r	83	18:1
19	2-ClC₆H₄	2, 4-Cl₂C₆H₄	Me	4s	80	13:1
20	Ph	2, 4-Cl₂C₆H₄	C(Me)₃	4t	89	> 25:1
21	4-CH₃C₆H₄	2-O₂NC₆H₄	C(Me)₃	4u	87	> 25:1
22	2-ClC₆H₄	2-O₂NC₆H₄	C(Me)₃	4v	87	> 25:1
23	4-ClC₆H₄	2, 4-Cl₂C₆H₄	C(Me)₃	4w	85	> 25:1