节点文献
2,3-联烯酸酯合成反应研究
Studies on the Synthesis of 2,3-Allenoates
【作者】 张万里；
【导师】 麻生明；
【作者基本信息】 华东师范大学 ， 有机化学， 2018， 博士
【摘要】 联烯作为一类含有两个碳碳双键的最简单的累积烯烃,在许多天然产物和活性药物分子中都有着广泛的存在,而其独特的轴手性也使得含有联烯片段的手性化合物可以作为手性催化剂或配体应用于不对称催化反应中。同时,联烯由于其多样的反应活性也被运用于许多天然产物和药物分子的合成中。2,3-联烯酸酯作为一类重要的官能团化联烯,同样具有着优异的反应活性,是有机合成中非常重要的合成砌块,因而发展简单高效的方法来选择性地合成2,3-联烯酸酯,尤其是光学活性的2,3-联烯酸酯也就显得十分重要。本论文从炔丙醇出发,围绕着2,3-联烯酸酯的合成展开了研究,主要包括以下三个部分:第一部分:钯催化炔丙基碳酸酯出发2,3-联烯酸酯的不对称合成。我们从炔丙基碳酸酯出发,在之前工作的基础上,通过对富电子手性双膦配体的修饰与改造,发现当使用（R）-或（S）-3,4,5-（MeO）3-MeOBIPHEP作为手性配体时,可以在温和的条件下以90-98%的ee值制备一系列三取代2,3-联烯酸酯,与之前使用（R）-或（S）-ECNU-Phos的结果相比,反应的对映选择性有了明显的提升。在反应过程中酯基、氰基、甲氧基和卤素这样的官能团都可以被兼容。第二部分:钯催化炔丙醇出发的2,3-联烯酸酯合成。我们从炔丙醇出发,通过向反应体系中加入催化量的Br?nsted酸来帮助切断炔丙醇中的C-O键,进而在过渡金属催化剂的作用下与一氧化碳和醇反应以中等到优秀的产率合成了多取代的联烯酸酯产物。在对手性配体的筛选过程中我们发现,使用（R）-DTBM-Garphos作为配体可以经过动力学拆分以84%的对映选择性得到光学活性的四取代联烯酸酯,但其产率只有16%,同时还有82%的原料回收;而使用（R）-BTFM-Garphos作为配体时,联烯酸酯的产率可以提高至83%,但其ee值降至63%。第三部分:基于炔丙醇拆分的2,3-联烯酸酯合成。在（R）-或（S）-DTBM-Segphos作为配体时,可以通过Pd催化剂和Br?nsted酸的共同作用实现三级炔丙醇的动力学拆分,以90-99%的ee值制备一系列光学活性的三级炔丙醇化合物,为这一类手性三级炔丙醇的制备提供了新的方法与思路。同时,拆分得到的手性炔丙醇也可以在过渡金属与Br?nsted酸的催化下转化为光学活性的四取代联烯酸酯产物,反应过程中并没有观察到明显的手性丢失。
【Abstract】 Allene is the common name given to hydrocarbons characterized by a cumulative diene functionality with two mutually perpendicularπ-orbitals.This 1,2-diene structure has also been found in a variety of natural products and pharmaceutical molecules,and the unique axial chirality makes allene-containing chiral compounds applicable in asymmetric catalysis as catalyst or ligand.Besides,the unique chemical properties derived from this distinctive structure as well as the substituent-loading ability attributes to the broad application of allenes in the synthesis of natural products and pharmaceuticals.As an important class of functionalized allenes,2,3-allenoates are becoming significant building blocks in organic synthesis due to the versatile reactivity,which gives rise to ample interest in simple and efficient synthesis of2,3-allenoates,especially the optically active 2,3-allenoates.In this dissertation,we focused on the synthesis of 2,3-allenoates starting from propargylic alcohols,and the work can be divided into three parts:Part I:Palladium-catalyzed enatioselective synthesis of 2,3-allenoates from propargylic carbonates.Employing readily available differently substituted propargyliccarbonatesassubstrates,weidentified（R）-or（S）-3,4,5-（MeO）3-MeOBIPHEP as the chiral ligand for a general highly enantioselective synthesis of optically active trisubstitued 2,3-allenoates with 90-98%ee.Comparing with the results applying（R）-or（S）-ECNU-Phos,an impressive improvement in enatioselectivity was observed.Functional groups such as ester,cyano,methoxy,and halogen are compatible in this transformation.Part II:Palladium/H+-catalyzed synthesis of 2,3-allenoates directly from propargylic alcohols.Applying propargylic alcohols as starting materials,a catalytic amount of Br?nsted acid was added for helping to cleave the propargylic carbon-oxygen bond.Subsequent reaction with CO and alcohol afforded multi-substituted 2,3-allenoates with moderate to excellent yields.In the primary screening of chiral ligands,（R）-DTBM-Garphos was able to accelerate the kinetic resolution process to obtain chiral allenoates with 84%ee,albeit with only 16%yield and 82%recovery of substrates;applying（R）-BTFM-Garphos may promote the yield to 83%,while the enantiomeric excess value was 63%.Part III:Palladium/H+-catalyzed kinetic resolution of tertiary propargylic alcohols aiming at the synthesis of 2,3-allenoates.A kinetic resolution reaction catalyzed by palladium and Br?nsted acid was realized recovering optically active tertiary propargylic alcohols with 90-98%ee,providing a new approach for the synthesis of such chiral alcohols.The obtained optically active alcohols may also be transferred into optically active tetrasubstitued allenoates without loss of enantiomeric excess.