The Mechanism Study Of Cobalt-catalyzed Oxidative Esterification Of Allylic C(sp~3)-H Bonds And The Development Of ?-damascenone Synthesis

?-Damascenone was firstly isolated from the essential oil of Rosa damascene,which is a precious perfume with strong flower flavor and fruit flavor.It was not only used as a component of cosmetics fragrance and edible flavor,but also used to improve the flavor of tobacco.The application scope of ?-Damascenone is extending with the rapid development of the spice industry,and the demand is also increased.Consequently,various synthetic routes to(3-Damascenone were available academically in the past decades.However,only Switzerland Firmenich Company presently has the corresponding industrial technology of man-made synthesis of p-Damascenone in the world.We were focused on the route leading to ?-Damascenone started from ?-ionone in the laboratory.In this study,the condition of the last step in terms of one pot oxidative dehydrogenation of ?-damascone,was further optimized and the production could therefore be scaled up to 300g.A high yield of 80%is reached even when the amount of solvent is 50 v%decreased as compared with conditions for laboratory scale.In addition,it is possible to rapidly isolate ?-Damascenone in a yield of 95%at a scale of hundreds grams with 94%purity through optimize the vacuum distillation unit.Despite the previous optimization,the yield of the last step of oxidative dehydrogenation of ?-damascone is still low and comparatively harsh conditions were required for the production.In order to address this special issue,the methodology of cobalt-catalyzed oxidative esterification of allylic C(sp3)-H bonds was studied.A protocol of cross-esterification of various allyls and carboxylic acids catalyzed by cobalt oxidative in present of DTBP was developed.Mechanistic studies revealed that C(sp3)-H bond activation in the hydrocarbon was the turnover-limiting step and the in-situ formed[Co(?)]Ot-Bu did not engage in hydrogen atom abstraction(HAA)of a C-H bond.In addition,we also found it is possible that cobalt-catalyzed oxidative esterification of benzyl C(sp3)-H bonds.This protocol can be applied to oxidative esterification of the cyclic allylic C(sp3)-H bond of ?-damascone to corresponding ester with 61%yield.Then,the obtained ester underwent Br?nsted acid-catalyzed decarboxylation smoothly to form?-damascenone with a good yield,there by avoided the use of NBS in the traditional route.