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Palladium-Catalyzed Carbene Coupling Reactions of Cyclobutanone N-Sulfonylhydrazones

Xiaoqin Ning, Yongke Chen, Fangdong Hu* and Ying Xia*

*School of Chemistry and Chemical Engineering, Linyi University, Linyi 276000; Sichuan University, Chengdu 610041, China, Email: hufangdonglyu.edu.cn, xiayingscuscu.edu.cn

X. Ning, Y. Chen, F. Hu, Y. Xia, Org. Lett., 2021, 23, 8348-8352.

DOI: 10.1021/acs.orglett.1c03052


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Abstract

Palladium-catalyzed cross-coupling reactions of cyclobutanone-derived N-sulfonylhydrazones with aryl or benzyl halides provide structurally diversified products including cyclobutenes, methylenecyclobutanes, and conjugated dienes in very good yields. The reaction also offers a promising route for the synthesis of enantioenriched four-membered-ring molecules.


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synthesis of a methylenecyclobutane in a one-pot procedure



Synthesis of Cyclobutenes

A 4 mL vial equipped with a magnetic stir bar was charged with Cs2CO3 (162.9 mg, 0.5 mmol, 2.5 equiv), N-tosylhydrazone (0.24 mmol, 1.2 equiv). The vial was sealed with screwcap and transferred into a glove box. Then, the vial was added 1,4-dioxane (1.0 mL) and bromobenzene (0.2 mmol, 1.0 equiv). In the glove box, another 4 mL vial equipped with a stir bar was charged with Pd2(dba)3 (3.7 mg, 0.004 mmol, 0.02 equiv), PPh3 (4.2 mg, 0.016 mmol, 0.08 equiv) and 1,4-dioxane (1.0 mL). The mixture was stirred for about 5 min until an orange homogeneous solution was formed and then transferred the catalyst solution into the first 4 mL vail. Generally, several such type of reactions were carried out parallelly. Thus, the catalyst solution can be prepared in one vial together. The 4 mL vial was sealed again and removed from the glove box. The resulting mixture was heated in a pie-block at 90C for 24 h. After cooling to room temperature, the reaction mixture was filtered and concentrated in vacuo. The crude mixture was purified by column chromatography on silica gel to afford the desired product.

Synthesis of Methylenecyclobutanes

To an 8 mL vial equipped with a magnetic stir bar was charged with LiOtBu (40.0 mg, 0.5 mmol, 2.5 equiv), N-tfsylhydrazone (0.3 mmol, 1.5 equiv). The vial was sealed with screwcap and transferred into a glove box. Then, the vial was added 1,4-dioxane (1.0 mL) and benzyl chloride (0.2 mmol, 1.0 equiv). In the glove box, another 4 mL vial equipped with a stir bar was charged with Pd2(dba)3 (3.7 mg, 0.004 mmol, 0.02 equiv), PPh3 (4.2 mg, 0.016 mmol, 0.08 equiv) and 1,4-dioxane (1.0 mL). The mixture was stirred for about 5 min until an orange homogeneous solution was formed and then transferred the catalyst solution into the above 8 mL vial. Generally, several such type of reactions were carried out parallelly. Thus, the catalyst solution can be prepared in one vial together. The 8 mL vial was sealed again and removed from the glove box. The resulting mixture was heated in a pie-block at 90C for 12 h. After cooling to room temperature, the reaction mixture was filtered and concentrated in vacuo. The crude mixture was purified by column chromatography on silica gel to afford the desired product.


Key Words

cyclobutenes, cyclobutanes


ID: J54-Y2021