不對稱有機連鎖[4＋2]環化加成反應

Abstract

本文使用環己烯酮及(E)-2-(3-苯亞丙二烯基)-氫茚-1,3-二酮，利用天然物奎寧衍生之一級胺催化劑經由2-胺基-1,3-雙烯的活化方式，進行[4+2]環加成反應，建構雙環[2.2.2]辛烷架構。透過一系列條件篩選以甲苯為最佳溶劑，於室溫下添加20 mol%的一級胺催化劑及20 mol%的苯甲酸，可得到帶有一個螺環四級碳及三個掌性中心之雙環[2.2.2]辛酮，其產率可高達91%、非鏡像選擇性>20:1及98%鏡像選擇性。此反應亦能進行一鍋化地利用肉桂醛、1,3-茚二酮及環己烯酮經由Knoevenagel/ [4+2]環加成連鎖反應，有效的合成預期雙環[2.2.2]辛-2-酮產物且仍保有優異的非鏡像選擇性>20:1及97%鏡像選擇性。A method to build the framework of bicyclo[2.2.2]octanes via 2-amino-1,3-dienes system with quinine-derived primary amine catalyst was disclosed. According to optimized conditions, cyclohexenones and 2-aryllidene-1,3-indanediones were dissolved in toluene at the room temperature, then 20 mol% of primary amine catalyst and 20 mol% of benzoic acid were added. The substituted bicyclo[2.2.2]octanones, bearing one spiro quaternary carbon and three chiral centers, were obtained in high yields (up to 91 %), excellent diastereoselective ( up to >20:1 dr) and enantioselective (98% ee). This reaction was also operated with cinnamaldehyde, 1,3-indandione and cyclohexenone, through Knoevenagel condensation/ [4+2] cycloaddition in one-pot manner to get desired product bicyclic with the high level of stereoselectivities (>20:1 dr, 97% ee).