通过镍催化的碳环化反应区域选择性合成茚醇。

Regioselective synthesis of indenols via nickel-catalyzed carbocyclization reaction.

作者信息

Rayabarapu Dinesh Kumar, Yang Chun-Hui, Cheng Chien-Hong

机构信息

Department of Chemistry, Tsing Hua University, Hsinchu, Taiwan 300, ROC.

出版信息

J Org Chem. 2003 Aug 22;68(17):6726-31. doi: 10.1021/jo0346508.

DOI:10.1021/jo0346508

PMID:12919040

Abstract

2-Halophenyl ketones 1a-e (1a, o-IC(6)H(4)COCH(3)) undergo carbocyclization with alkyl propiolates (2a, CH(3)(CH(2))(4)C[triple bond]CCO(2)CH(3); 2b, TMSC[triple bond]CCO(2)Et 2c, CH(3)C[triple bond]CCO(2)CH(3); 2d, CH(3)OCH(2)C[triple bond]CCO(2)CH(3); 2e, CH(3)(CH(2))(3)C[triple bond]CCO(2)CH(3); 2f, PhC[triple bond]CCO(2)CH(3); and 2g, (CH(3))(3)C[triple bond]CCO(2)CH(3)) in the presence of Ni(dppe)Br(2) and zinc powder in acetonitrile at 80 degrees C to afford the corresponding indenol derivatives 3a-m with remarkable regioselectivity in good to excellent yields. The nickel-catalyzed carbocyclization reaction was successfully extended to other simple disubstituted alkynes. Thus, the reaction of 2-halophenyl ketones 1a-e with disubstituted alkynes (2h, PhC[triple bond]CPh; 2i, CH(3)C(6)H(4)C[triple bond]CC(6)H(4)CH(3); 2j, CH(3)CH(2)C[triple bond]CCH(2)CH(3); 2k, PhC[triple bond]CCH(3); 2l, TMSC[triple bond]CCH(3); and 2m, PhC[triple bond]C(CH(2))(3)CH(3)) proceeded smoothly to afford the corresponding indenols 4a-t in good to excellent yields. For unsymmetrical alkynes 2k-m, the carbocyclization gave two regioisomers with regioselectivities ranging from 1:2 to 1:12 depending on the substituents on the alkyne and on the aromatic ring of halophenyl ketone. A possible mechanism for this nickel-catalyzed carbocyclization reaction is also proposed.

摘要

2-卤代苯乙酮1a - e（1a，邻碘苯基苯乙酮）在80℃的乙腈中，于Ni(dppe)Br₂和锌粉存在下，与炔丙酸酯（2a，己基丙炔酸甲酯；2b，三甲基硅基丙炔酸乙酯；2c，甲基丙炔酸甲酯；2d，甲氧基乙基丙炔酸甲酯；2e，戊基丙炔酸甲酯；2f，苯基丙炔酸甲酯；2g，叔丁基丙炔酸甲酯）发生碳环化反应，以良好至优异的产率得到相应的茚醇衍生物3a - m，具有显著的区域选择性。镍催化的碳环化反应成功扩展到其他简单的二取代炔烃。因此，2-卤代苯乙酮1a - e与二取代炔烃（2h，二苯乙炔；2i，对二甲基苯乙炔；2j，己炔；2k，苯乙炔；2l，三甲基硅基乙炔；2m，苯丁炔）的反应顺利进行，以良好至优异的产率得到相应的茚醇4a - t。对于不对称炔烃2k - m，碳环化反应根据炔烃和卤代苯乙酮芳环上的取代基，生成两种区域异构体，区域选择性范围为1:2至1:12。还提出了这种镍催化碳环化反应的可能机理。