高鏡像選擇性銠(I)/掌性雙烯配體催化芳香基硼酸對馬來醯亞胺進行不對稱1,4加成反應及其合成應用α2腎上腺素受體拮抗劑全合成及合成掌性HSD-1的抑制劑前驅物

Abstract

本論文敘述以一價銠金屬與掌性雙烯配體形成之催化劑催化不對稱芳香基硼酸加成至馬來醯亞胺 (maleimides) 加成來合成出一系列具有不對稱中心的3-芳香基取代的琥珀醯亞胺 (3-Aryl Succinimide) 化合物。

以一價銠金屬及掌性雙烯配體77b所形成之錯合物催化馬來醯亞胺 (maleimides) 化合物與各種芳香基硼酸試劑進行不對稱共軛加成反應，都可以得到不錯產率及高立體選擇性的加成產物，其鏡像超越值最高可達98% ee。

此合成方法也利用在合成掌性3 - (2 -甲氧基) 苯基吡咯啶 ( α2 -腎上腺素受體拮抗劑) 127和化合物134為HSD-1的抑制劑前驅物。

Chiral α-substituted succimides with various N-protecting groups were prepared from the asymmetric addition of a range of arylboronic acids to maleimides in the presence of Rh(I) and chiral diene ligand 77b. This process offers the chiral α-substituted succimides in good yields and excellent enantioselectivities (ee values up to 98%) for various arylboronic acids and maleimides. This methodology was demonstrated by its utilization in the enantioselective total synthesis of 3 - (2-methoxyphenyl) pyrrolidine (an α2-adrenoceptor antagonist) 127 and HSD-1 inhibitor precursor 134.