Diastereoselective C-H Insertions

The prevalence of C-H bonds in organic structures, together with the dominance of petrochemical feedstocks, have led to great interest in the development of stereoselective C-H activating processes. Interest in this field is further piqued by the fact that C-H activation remains a fundamentally important, but difficult problem in chemical reactivity. 

H One Holy Grail of C- H activation research, therefore, is not simply to find new C-H activation reactions but to obtain an understanding of them that will allow the development of reagents capable of selective transformations of C-H boruis into more reactive Junctionalized molecules.  

A key observation by Wenkert proved vital in the subsequent popularity of rhodium as a highly effective catalyst for the generation of carbenes from diazoketones and their engagement in C-H insertion reactions (Equation 27) [15, 16, 88], In this experiment, treatment of diazoketone 153 with Rh2(OAc)4 led to a stereoselective C-H insertion reaction to generate ketone 154 in 59% yield [88], Importantly, no cyclization was observed in the presence of CuSO,. 

---

Asymmetric allylic C-H activation of more complex substrates reveals some intrinsic features of the Rh2(S-DOSP)4 donor/acceptor carbenoids [135, 136]. Cyclopropanation of trans-disubstituted or highly substituted alkenes is rarely observed, due to the steric demands of these carbenoids [16]. Therefore, the C-H activation pathway is inherently enhanced at substituted allylic sites and the bulky rhodium carbenoid discriminates between accessible secondary sites for diastereoselective C-H insertion. As a result, the asymmetric allylic C-H activation provides alternative methods for the preparation of chiral molecules traditionally derived from classic C-C bond-forming reactions such as the Michael reaction and the Claisen rearrangement [135, 136]. 

The demonstration of a diastereoselective C-H insertion to form the furofuranoid nucleus opens a way to total synthesis of lignans such as asarinin." ... 

---