The chelation of lithium cation with the methoxy group is one of the most important features of the transition state for Enders hydrazone alkylation reaction. It is necessary to have this chelation effect to achieve high stereoselectivity. The development and modification of Enders hydrazone alkylation reaction mainly focus on the addition of more steric hindrance on the pyrrolidine rings of both SAMP and RAMP, while preserving the methoxy group for lithium chelation.
The most famous four variants of SAMP and RAMP are SADP, SAEP, SAPP and RAMBO, whose structures are shown below.
In 2011, several N-amino cyclic carbamates were synthesized and studied for asymmetric hydrazone alkylation reactions. Both the stereochemistry and regioselectivity of the reactions turned out to be very promising. These new compounds consist of a new class of chiral auxiliary based on the carbamate structure and, therefore, no longer belong to the family of SAMP and RAMP. But they do provide very powerful alternatives to the traditional pyrrolidine systems.