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

doi:10.6023/cjoc202204033

Abstract

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

Cite this article

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

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