Remote Functionalization of Stereodefined Substituted Cyclopropanes towards Synthetically Useful Acyclic Fragments
05/06/2023
Hall 1
11:30
Mr. Anthony Cohen Marek Group
Remote Functionalization of Stereodefined Substituted Cyclopropanes towards
Synthetically Useful Acyclic Fragments
Despite the ever-expanding plethora of methods allowing chemists to meet synthetic challenges, the
rapid, efficient, and complete stereochemical control of remote stereocenters in acyclic systems is
still an ongoing challenge. The flexibility of linear hydrocarbon chains associated with the multiple
conformers that the molecular backbone can adopt represent one of the major difficulties for the
control of stereochemistry of distant stereocenters. As the ability to use an existing stereocenter as
directing or discriminating handles to generate the remote new stereocenter in acyclic system is
becoming less prominent, alternative strategies must be developed.
Recent developments in the stereoselective synthesis of polysubstituted cyclopropanes allowed
chemists to easily access these strained rings with high stereoselectivity. Further development of
efficient and reliable protocols for the selective carbon−carbon bond cleavage of these strained rings
has enabled a new strategy for the synthesis of challenging stereodefined acyclic molecules.
In my Ph.D. work, we have opted to merge this approach with the concept of remote
functionalization in order to achieve complex stereodefined acyclic scaffolds. Remote
functionalization consists of indirect activation of a site distant from the initial functional group. We
envisaged that a transition metal “chain walking” initiated at a remote site would lead to sequence
of chemical transformations, resulting in the cleavage of the cyclopropane ring and a concomitant
termination reaction at a remote event.
The implantation of the Heck reaction for this purpose revealed particularly beneficial, leading to the
establishment of new routes for the synthesis of terpenoids such as α -tocopherol and densely
substituted lactones. Subsequent mechanistic investigations shed light onto the remarkable
observed selectivity of the transformation.