Synthesis of a Mechanically Planar Chiral Rotaxane Ligand for Enantioselective Catalysis

Abstract

We report an enantioselective catalyst based on a ''mechanically chiral'' rotaxane. Catalysis with chiral molecules is extremely important in modern chemistry because it is one of the most efficient ways to make chiral molecules for applications in many areas. Our results demonstrate, for the first time, that mechanically chiral molecules are a promising and underexplored platform for generating such catalysts. We achieve enantioselectivities for the Au I -catalyzed Ohe-Uemura cyclopropanation of benzoate esters comparable to previously reported covalent catalysts.

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

“…The N,N-dibenzylfumaramide [2]rotaxanes 1d-i were prepared following a well-established methodology [53][54][55] starting from N,Ndibenzyl-N 0 ,N 0 -dibutylfumaramide T1a as the effective template already utilized in the synthesis of 1a. 46 Accordingly, [2]rotaxanes 1d-i bearing different polyamide rings were assembled through a ve-component reaction starting from T1a, p-xylylenediamine and the appropriate diacyl chloride in the presence of Et 3 N ( Table 1). The interlocked fumaramides 1d-h were obtained in yields ranging 29-47%.…”

“…As the reaction takes place, signals due to trans-2a emerged (highlighted in green, for lettering see Table 2), whereas the signals of the interlocked fumaramide 1a (marked in red and blue) diminished. Next, similar experiments with [2] rotaxanes 1b,c bearing Cl and MeO substituents at para position of both N-benzyl groups, were carried out. Aer integrating the specic resonances attributable to both reactant and reaction product and tting the data to a rst order equation, we calculated the respective rate constants (k) ( Fig.…”

“…In this particular case, the functionality of the thread is dramatically altered by being prepared within the macrocycle. 45 In 2016 we reported the CsOH-promoted intramolecular cyclization of archetype N-benzylfumaramides 1a-c embedded in the isophthalamide-based ring of a [2]rotaxane (Scheme 1, part (a)). 46 In these processes, the corresponding interlocked blactams trans-2a-c were isolated in almost quantitative yields as single diastereoisomers.…”

“…52 Despite the CsOH-promoted cyclization of interlocked fumaramides has turned out an interesting tool for the diastereoselective synthesis of b-lactams, the little knowledge about the mechanism hinders further applications. With the aim of inspiring further research, new insights of the cyclization mode of [2]rotaxanes 1 are necessary to lead to a ne tuneable design of our interlocked molecules without compromising their structural integrity and expand the synthesis to more complex b-lactams.…”

“…Herein, we disclose the unravelling of the mechanism of the base-promoted cyclization of interlocked fumaramides 1 through an exhaustive inspection tackled from three different but complementary perspectives. First, a range of novel fumaramide [2]rotaxanes 1d-i (Table 1) differing in the structure and electronic features of the macrocyclic counterpart were synthesised to conduct a detailed structure-reactivity relationship analysis (Scheme 1, part (b)). This piece of research has revealed that diadamantyl-derived rotaxanes sparks the cyclization process, being possible to further enhance the scope of this transformation.…”