TY - JOUR

T1 - Cyclocondensation of 2-(α-Diazoacyl)-2H-azirines with Amidines in Diazo Synthesis of Functionalized Naphtho[1,2-d]imidazoles

AU - Zanakhov, Timur O.

AU - Galenko, Ekaterina E.

AU - Novikov, Mikhail S.

AU - Khlebnikov, Alexander F.

PY - 2024/6/21

Y1 - 2024/6/21

N2 - A diazo approach toward functionalized naphtho[1,2-d]imidazole derivatives has been developed. It involved a new reaction of arylamidines with 2-(α-diazoacyl)-2H-azirines giving 5-aryl-4-(α-diazoacyl)-1H-imidazoles under mild conditions in good yields. The mechanism of annulation of azirines with amidines is discussed based on DFT calculations. The reaction proceeds in an unusual manner by cleavage of the azirine C-C bond, allowing for the transfer of the aryl substituent from the arylamidine to the proper position of the key intermediate of naphtho[1,2-d]imidazole synthesis. Under thermolysis conditions, 5-aryl-4-(α-diazoacyl)-1H-imidazoles undergo Wolff rearrangement followed by the selective 6π-cyclization of transient ketene to form 3H-naphtho[1,2-d]imidazoles bearing various substituents in the positions 2,3,4,5,7,8,9. Additionally, variation of the substituents at position 5 of naphtho[1,2-d]imidazoles is possible through the formation of triflates and subsequent cross-coupling reactions. One more heterocyclic pharmacophoric skeleton, 3H-furo[3′,2’:3,4]naphtho[1,2-d]imidazole, was easily constructed from methyl 5-hydroxy-3H-naphtho[1,2-d]imidazole-4-carboxylates in a one-pot mode using O-alkylation with phenacyl bromides followed by base-induced intramolecular acyl substitution at room temperature with high yields.

AB - A diazo approach toward functionalized naphtho[1,2-d]imidazole derivatives has been developed. It involved a new reaction of arylamidines with 2-(α-diazoacyl)-2H-azirines giving 5-aryl-4-(α-diazoacyl)-1H-imidazoles under mild conditions in good yields. The mechanism of annulation of azirines with amidines is discussed based on DFT calculations. The reaction proceeds in an unusual manner by cleavage of the azirine C-C bond, allowing for the transfer of the aryl substituent from the arylamidine to the proper position of the key intermediate of naphtho[1,2-d]imidazole synthesis. Under thermolysis conditions, 5-aryl-4-(α-diazoacyl)-1H-imidazoles undergo Wolff rearrangement followed by the selective 6π-cyclization of transient ketene to form 3H-naphtho[1,2-d]imidazoles bearing various substituents in the positions 2,3,4,5,7,8,9. Additionally, variation of the substituents at position 5 of naphtho[1,2-d]imidazoles is possible through the formation of triflates and subsequent cross-coupling reactions. One more heterocyclic pharmacophoric skeleton, 3H-furo[3′,2’:3,4]naphtho[1,2-d]imidazole, was easily constructed from methyl 5-hydroxy-3H-naphtho[1,2-d]imidazole-4-carboxylates in a one-pot mode using O-alkylation with phenacyl bromides followed by base-induced intramolecular acyl substitution at room temperature with high yields.

UR - https://www.mendeley.com/catalogue/9e6f7e7e-f42f-3164-a79f-359503cdfb98/

U2 - 10.1021/acs.joc.4c00598

DO - 10.1021/acs.joc.4c00598

M3 - Article

VL - 89

SP - 8641

EP - 8655

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

SN - 0022-3263

IS - 12

ER -