The Heck rxn was discovered in 1970 In 1977 Mori and Ban reported the first INTRAmolecuar Heck Shibasaka and Overman discovered the Asymmetric Heck Cyclization in 1989- still being studied to this day Makes tertiary and quaternary stereocenters Needs precatalyst, a chiral ligand, a base, a polar aprotic solvent, heat
The authors were initially concerned about the facial selectively of epoxidation. Using mCPBA the epoxide adds to the back face with 10:1 stereoselectivity.
Favored Conformation of Cyclohexene Ring Computational studies showed that the cyclohexene ring prefers to exist in a half chair conformation. Therefore mCPBA will approach anti to the indole bridge.
However, the acid conditions used to remove Boc promoted fragmentation of the molecule.
Because the fragmentation only occurred under acid conditions, other methods were attempted to remove the Boc protecting group. Heating in DMSO Heating in a microwave reactor None of these methods worked!
However, the Boc protecting group can be removed immediately following epoxidation. Why here and not later? The same protonation and initial ring opening will occur in the presence of acid, but the epoxide ensures that further fragmentation will not.
So following epoxidation, the Boc protecting group is removed with TFA.
Then the amine is REPROTECTED with alloc (allyloxy carbonyl)! Alloc can be removed using catalytic reduction conditions later in the scheme which will not cause a ring opening like acid did.
These conditions do not contain a phosphine ligand!!! But Pd(II) cannot do a Heck and Pd(0) cannot exist without any ligands… We think that water might act as a ligand in this reaction. Note that the salt Bu 4 NCl is believed to speed up the reaction.