Selectivity in Olefin-Intervened Macrocyclic Ring-Closing Metathesis

The
ring-closing metathesis (RCM) of α,m,ω-triene
was employed for the syntheses of four slightly different EE, EZ, ZE, and ZZ isomers of macrocycles with two greatly separated type
I olefins. Kinetic control of the RCM reaction using G1 was achieved, in which secondary metathesis of the initially formed
RCM product that usually afforded the thermodynamically favored product
was inhibited, and a reliable model was built to differentiate the
kinetic or thermodynamic control in the RCM reaction. Kinetic studies
of olefin metathesis using the kinetically controlled Z-selective catalyst Cat-Z were conducted to determine
its thermodynamic capability to convert (Z)-olefin
to (E)-olefin. Finally, the ring size selectivity
of α,ω- vs α,m-/m,ω-products in the RCM reaction of α,m,ω-triene revealed that all types of isomeric α,ω-products
are favored for the 18-membered ring and above, and α,m-/m,ω-products are predominant for
the rings with 14-members and less. For the 15-, 16-, and 17-membered
rings, each of the E/Z-selective
RCM reactions of starting (mE)- and (mZ)-trienes has a different performance under the optimized conditions.
These studies provide insights into the applications of RCM on the
synthesis of macrocycles with two separate type I olefins.

本研究采用α,m,ω-三烯烃的闭环复分解（ring-closing metathesis，RCM）反应，合成了四种存在细微差异的大环异构体，分别为EE、EZ、ZE及ZZ构型，这些大环均带有两个间距较大的I型烯烃（type I olefins）。通过使用G1催化剂实现了RCM反应的动力学控制，该条件下通常会生成热力学优势产物的初始RCM产物的二级复分解反应被抑制，同时我们建立了可靠的模型以区分RCM反应中的动力学控制与热力学控制路径。使用动力学控制型Z选择性催化剂Cat-Z开展烯烃复分解反应的动力学研究，以测定其将(Z)-烯烃转化为(E)-烯烃的热力学能力。最后，针对α,m,ω-三烯烃的RCM反应，对比α,ω-产物与α,m-/m,ω-产物的环尺寸选择性发现：对于18元环及更大环尺寸的大环，所有构型的α,ω-产物均为优势产物；而对于14元环及更小环尺寸的大环，α,m-/m,ω-产物占主导地位。对于15、16及17元环，在优化条件下，起始原料(mE)-和(mZ)-三烯烃的各E/Z选择性RCM反应表现出不同的反应特性。本研究为闭环复分解反应在合成带有两个分离I型烯烃的大环化合物中的应用提供了重要见解。