1,8-二氮杂双环[5.4.0]十一碳-7-烯(DBU)驱动的双分子硝基烷烃对重氮化合物的亲核加成反应: 多官能化腙和四氢哒嗪化合物的合成

doi:10.6023/cjoc202204033

摘要/Abstract

以重氮化合物作为有效的端氮亲电试剂, 成功实现了1,8-二氮杂双环[5.4.0]十一碳-7-烯(DBU)驱动的两分子硝基烷烃对重氮化合物分子间的亲核加成反应. 该反应从易得的起始原料出发, 提供了两种在温和反应条件下一步构建含有硝基烷烃基本结构单元的官能化腙和四氢哒嗪类化合物的新方法. 该反应涉及连续的分子间亲核加成/消除/分子间Aza-Henry反应/分子内环化反应过程, 一步产生两个或三个相邻的立体中心.

关键词: 重氮化合物, 端氮亲电试剂, 硝基烷烃, 腙, 四氢哒嗪

A 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)-promoted intermolecular addition reaction two molecules of nitroalkanes to diazo compounds has been developed, in which diazo compounds sereve as the efficient N-terminal electrophiles. The reaction provides two new and highly efficient methods for the construction of functionalized hydrazones and tetrahydropyridazines bearing the structure feature of nitroalkanes from readily available starting materials. The reaction involves a sequential intermolecular nucleophilic addition/elimination/intermolecular Aza-Henry reaction/intramolecular cyclization procedure where two or three adjacent stereocenters are created simultaneously in one-pot manner.

Key words: diazo compound, N-terminal electrophile, nitroalkane, hydrazone, tetrahydropyridazine

引用此文

张骁勇, 于丽丽, 高俊芳, 宫岳, 赵玉龙. 1,8-二氮杂双环[5.4.0]十一碳-7-烯(DBU)驱动的双分子硝基烷烃对重氮化合物的亲核加成反应: 多官能化腙和四氢哒嗪化合物的合成[J]. 有机化学, 2022, 42(11): 3704-3713.

Xiaoyong Zhang, Lili Yu, Junfang Gao, Yue Gong, Yulong Zhao. 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU)-Promoted Nucleophilic Addition of Two Molecules of Nitroalkanes to Diazo Compounds: Synthesis of Highly Functionalized Hydrazones and Tetrahydropyridazines[J]. Chinese Journal of Organic Chemistry, 2022, 42(11): 3704-3713.

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Entry	Base (equiv.)	1a∶2a	Solvent	t/min	Yield^b/%	dr
1	DBU (0.5)	2∶1	DMF	20	60	1/1
2	DBU (0.8)	2∶1	DMF	20	75	1/1
3	DBU (1.2)	2∶1	DMF	10	80	1/1
4	DBU (1.2)	3∶1	DMF	8	86	1/1
5	DBU (1.2)	4∶1	DMF	5	92	1/1
6	DBU (1.2)	4∶1	DMF	20	75	1/1.1^c
7	DBN (1.2)	4∶1	DMF	10	88	1/1
8	Et₃N (1.2)	4∶1	DMF	40	—	—
9	TMEDA (1.2)	4∶1	DMF	40	—	—
10	K₂CO₃ (1.2)	4∶1	DMF	40	—	—
11	DBU (1.2)	4∶1	DMSO	5	80	1/1
12	DBU (1.2)	4∶1	MeCN	60	71	1/1
13 14	DBU (1.2) DBU (1.2)	4∶1 4∶1	THF DCE	60 60	65 50	1/1.1 1/1.1

Entry	Base (equiv.)	1a∶2a	Solvent	t/min	Yield^b/%	dr
1	DBU (0.5)	2∶1	DMF	20	60	1/1
2	DBU (0.8)	2∶1	DMF	20	75	1/1
3	DBU (1.2)	2∶1	DMF	10	80	1/1
4	DBU (1.2)	3∶1	DMF	8	86	1/1
5	DBU (1.2)	4∶1	DMF	5	92	1/1
6	DBU (1.2)	4∶1	DMF	20	75	1/1.1^c
7	DBN (1.2)	4∶1	DMF	10	88	1/1
8	Et₃N (1.2)	4∶1	DMF	40	—	—
9	TMEDA (1.2)	4∶1	DMF	40	—	—
10	K₂CO₃ (1.2)	4∶1	DMF	40	—	—
11	DBU (1.2)	4∶1	DMSO	5	80	1/1
12	DBU (1.2)	4∶1	MeCN	60	71	1/1
13 14	DBU (1.2) DBU (1.2)	4∶1 4∶1	THF DCE	60 60	65 50	1/1.1 1/1.1