酸促進矽保護的2-(3-芳香基丙炔基甲苯磺醯胺基甲基)環己-2-烯-1-醇化合物之分子內環化反應－異喹啉衍生物的合成

Abstract

本文分別使用路易士酸以及三氟甲磺酸輔佐第三丁基二甲基矽保護的2-(3-芳香基丙炔基甲苯磺醯胺基甲基)環己-2-烯-1-醇化合物進行分子內環化反應，合成異喹啉衍生物。 利用三氟化硼乙醚(BF3•OEt2)輔佐帶有矽保護的2-(3-芳香基丙炔基甲苯磺醯胺基甲基)環己-2-烯-1-醇化合物進行分子內環化和氟化反應，得到烯氟異喹啉衍生物。反應中BF3•OEt2同時作為路易士酸以及氟化試劑，反應在室溫下，且不需要金屬的條件下生成新的碳(sp2)-氟鍵和八氫異喹啉骨架，提供了簡便的方法得到氟化含氮雙環化合物。產物為單一的(Z)-構型。其中矽保護基與無水條件在這個反應中扮演重要的角色。 利用0.1當量的三氟甲磺酸催化帶有矽保護的2-(3-芳香基丙炔基甲苯磺醯胺基甲基)環己-2-烯-1-醇化合物進行分子內環化和經由烯醇-酮互變異構化，得到八氫異喹啉骨架的酮基衍生物。反應經由碳陽離子中間體，因此無法使用有拉電子基取代基的起始物。當使用乙腈作為溶劑時，可以得到醯胺化合物。

Lewis acid and TfOH-mediated intramolecular cyclization reaction of tert-butyldimethylsilyl-protected 2-(3-arylpropargyltosylaminomethyl) cyclohex-2-en-1-ols afforded isoquinoline derivatives. The use of BF3•OEt2 for the cyclization/fluorination of silyl-protected 2-(3-arylpropargyltosylaminomethyl)cyclohex-2-en-1-ols produced isoquinoline derivatives containing a C(sp2)-F bond. In this reaction, BF3•OEt2 reacted as both the Lewis acid and the fluoride source. The reaction generates a new C(sp2)-F bond and an octahydroisoquinoline skeleton at ambient temperature under metal-free reaction conditions, providing an easy access to fluorinated azabicycles. The reaction proceeds stereoselectivity to obtain (Z)-isomers. Silyl-protection and water-free reaction conditions played important roles in this transformation. The TfOH-catalyzed intramolecular cyclization followed by enol-keto tautomerization of silyl-protected 2-(3-arylpropargyltosylaminomethyl) cyclohex-2-en-1-ols in CH2Cl2 afforded octahydroisoquinoline skeleton containing a keto functionality. An electron-withdrawing group on the phenyl ring impeded the reaction. The corresponding amide derivatives were obtained when CH3CN was employed as the reaction media.