三组分反应高效合成螺[环戊烷-1,3'-吲哚啉]衍生物

doi:10.6023/cjoc202103034

摘要/Abstract

烷基异氰酸酯、丁炔二酸二酯(丙炔酸酯)和3-苯甲酰亚甲基-2-吲哚酮在甲苯中回流反应, 高产率地生成螺[环戊烷-1,3'-吲哚啉]衍生物. 然而, 含有游离氨基的3-苯甲酰亚甲基-2-吲哚酮参加反应时, 未取代的氨基可与另一分子丁炔二酸二酯及烷基异氰酸酯继续反应形成含有氨基取代的氮杂-1,3-二烯支链的螺[环戊烷-1,3'-吲哚啉]衍生物. 另一方面, 3-芳亚甲基吲哚-2-酮参与三组分反应时, 仅有游离氨基参与反应, 生成2-(2-氧吲哚-1-基)-3-[(烷基亚氨基)亚甲基]丁酸酯. 发现两种游离氨基参与多组分反应时, 分别形成了含有C2-取代的1-氮杂-1,3-丁二烯(C=C—C=NR)和C4-取代的1-氮杂-1,2-丁二烯(C—C=C=NR)结构单元的吲哚酮衍生物.

关键词: 异氰酸酯, 丁炔二酸二酯, 3-苯甲酰亚甲基吲哚酮, 螺[环戊烷-1,3'-吲哚啉], 多组分反应

The three-component reaction of alkylisocyanide, dialkyl acetylenedicarboxylate (alkyl propiolate) and 3-phenacylideneoxindole in refluxing toluene afforded the functionalized spiro[cyclopentane-1,3'-indolines] in satisfactory yields. However, the similar reaction of 3-phenacylideneoxindoles with unsubstituted NH group resulted in spiro[cyclopentane-1,3'-indolines] with additional aza-buta-1,3-diene scaffold. On the other hand, the three-component reactions with 3-arylideneoxindolin- 2-ones only gave 2-(2-oxoindolin-1-yl)-3-((alkylimino)methylene)succinates. It was also interesting to find that the reaction of free amino group in two kinds of functionalized 3-methyleneoxindoles with alkylisocyanide and dialkyl acetylenedicarboxylate selectively gave C2-substituted 1-aza-buta-1,3-diene (C=C—C=NR) or C4-substituted 1-aza-buta-1,2-diene (C—C=C=NR) scaffold in the molecules.

Key words: isocyanide, dialkyl acetylenedicarboxylate, 3-phenacylideneoxindole, spiro[cyclopentane-1,3'-indoline], multicomponent reaction

引用此文

马蔚青, 韩莹, 孙晶, 颜朝国. 三组分反应高效合成螺[环戊烷-1,3'-吲哚啉]衍生物[J]. 有机化学, 2021, 41(8): 3180-3191.

Weiqing Ma, Ying Han, Jin Sun, Chaoguo Yan. Three-Component Reaction for Efficient Synthesis of Functionalized Spiro[cyclopentane-1,3'-indolines][J]. Chinese Journal of Organic Chemistry, 2021, 41(8): 3180-3191.

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参考文献 18

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Entry	Solvent	Temp./	Time/h	Yield^b/%
1	CH₂Cl₂	r.t.	12	34
2	MeCN	r.t.	12	36
3	PhMe	r.t.	12	42
4	THF	r.t.	12	—
5	EtOH	r.t.	12	—
6	MeOH	r.t.	12	—
7	THF	60	12	—
8	MeCN	60	6	45
9	PhMe	60	2	70
10	PhMe	110	0.5	86
11	PhMe	110	2	83

Entry	Solvent	Temp./	Time/h	Yield^b/%
1	CH₂Cl₂	r.t.	12	34
2	MeCN	r.t.	12	36
3	PhMe	r.t.	12	42
4	THF	r.t.	12	—
5	EtOH	r.t.	12	—
6	MeOH	r.t.	12	—
7	THF	60	12	—
8	MeCN	60	6	45
9	PhMe	60	2	70
10	PhMe	110	0.5	86
11	PhMe	110	2	83

Compd.	R¹	R²	R³	E	Yield^b/%
1a	Cyclohexyl	H	Bn	p-CH₃C₆H₅	82
1b	Cyclohexyl	Cl	Bn	p-CH₃OC₆H₅	86
1c	Cyclohexyl	Cl	Bn	p-CH₃C₆H₅	82
1d	Cyclohexyl	F	Bn	p-CH₃OC₆H₅	78
1e	Cyclohexyl	F	Bn	p-CH₃C₆H₅	75
1f	Cyclohexyl	F	n-Bu	C₆H₅	62
1g	t-Bu	Cl	Bn	p-CH₃OC₆H₅	85
1h	t-Bu	Cl	Bn	p-CH₃C₆H₅	80
1i	t-Bu	F	Bn	p-CH₃C₆H₅	72
1j	t-Bu	Cl	Bn	OCH₂CH₃	75
1k	t-Bu	CH₃	Bn	OCH₂CH₃	71
1l	t-Bu	H	Bn	OCH₃	69
1m	t-Bu	Cl	Bn	OCH₃	78

Compd.	R¹	R²	R³	E	Yield^b/%
1a	Cyclohexyl	H	Bn	p-CH₃C₆H₅	82
1b	Cyclohexyl	Cl	Bn	p-CH₃OC₆H₅	86
1c	Cyclohexyl	Cl	Bn	p-CH₃C₆H₅	82
1d	Cyclohexyl	F	Bn	p-CH₃OC₆H₅	78
1e	Cyclohexyl	F	Bn	p-CH₃C₆H₅	75
1f	Cyclohexyl	F	n-Bu	C₆H₅	62
1g	t-Bu	Cl	Bn	p-CH₃OC₆H₅	85
1h	t-Bu	Cl	Bn	p-CH₃C₆H₅	80
1i	t-Bu	F	Bn	p-CH₃C₆H₅	72
1j	t-Bu	Cl	Bn	OCH₂CH₃	75
1k	t-Bu	CH₃	Bn	OCH₂CH₃	71
1l	t-Bu	H	Bn	OCH₃	69
1m	t-Bu	Cl	Bn	OCH₃	78

Compd.	R¹	R²	Ar	Yield^b/% (Z∶E)
2a	Cyclohexyl	CH₃	p-CH₃OC₆H₅	63 (1∶9)
2b	Cyclohexyl	H	p-CH₃C₆H₄	59 (1∶9)
2c	t-Bu	Cl	p-CH₃C₆H₄	70 (1∶9)
2d	t-Bu	CH₃	p-ClC₆H₄	64 (1∶9)
2e	t-Bu	F	p-CH₃OC₆H₅	67 (1∶9)