Cyclization of interlocked fumaramides into β-lactams: experimental and computational mechanistic assessment of the key intercomponent proton transfer and the stereocontrolling active pocket

Abstract

A mechanistic study of the diastereoselective cyclization of interlocked fumaramides to give β-lactams unveils the key factors for successfully taming the process.

Modulating the catalytic activity by the mechanical bond: organocatalysis with polyamide [2]rotaxanes bearing a secondary amino function at the thread

“…All these results clearly show that the variation of the macrocyclic counterpart highly influences the catalytic outcomes. 22 Indeed, the Hammett plot of log( k 4 / k 4a ) against the σ m constants of the substituents at the aromatic rings of the macrocyclic moiety demonstrates a linearity between the catalytic activity and the electronics ( ρ = −1.97, R 2 = 0.987) (Fig. 5, rotaxane 4e was excluded in this analysis).…”

Ring‐to‐Thread Chirality Transfer in [2]Rotaxanes for the Synthesis of Enantioenriched Lactams

“…The excess of base employed in the experiments and the low temperature preserved the mechanical bond in the kinetically stabilized pseudorotaxane 9 a , precluding the dethreading process (the presence of the free thread was not observed in the screening experiments). [ 38 , 40 ] Moreover, decreasing the reaction temperature to 0 °C gave an improved 84 : 16 er of the trans ‐β‐lactam 6 a . With the optimized reaction conditions settled, we next performed the cyclization for each separated diastereoisomer of 9 a .…”

The Role of Dethreading Process in Pseudorotaxanes and Rotaxanes towards Advanced Applications: Recent Examples

“…Berna and colleagues have reported the stereocontrolled synthesis of β-lactams within [2]rotaxanes. [58][59][60] This reaction proceeds through the basepromoted cyclization of interlocked N-(arylmethyl)fumaramide threads by the assistance of the polyamide macrocycle. The tetralactam cyclic component plays a dual role, both as activating element and as the stereodifferenciating factor which led to diastereoselection over trans-β-lactams.…”

“…In these systems, the cyclic counterpart assists a chemical transformation of the directly surrounding functionality of the thread. Berna and colleagues have reported the stereocontrolled synthesis of β‐lactams within [2]rotaxanes [58–60] . This reaction proceeds through the base‐promoted cyclization of interlocked N ‐(arylmethyl)fumaramide threads by the assistance of the polyamide macrocycle.…”