Stereo- and Regioselective Synthesis of Molecular Baskets

Abstract

We describe a stereoselective method for obtaining multigram quantities of molecular basket 1 syn in overall 11% yield, using inexpensive cyclopentadiene and diethyl fumarate as starting materials. First, an asymmetric synthesis of enantioenriched bromo­(trimethylstannyl)­alkene (−)-8 was accomplished by the stereoselective bromination of dibromonorbornene (+)-4 guided by anchimeric assistance and subsequent syn-exo-elimination of tetrabromonorbornane (−)-5a as the key steps. Subsequent Cu­(I)-catalyzed cyclotrimerization of (−)-8 was optimized to give 1 syn / anti in 85% yield and 1:1 ratio of diastereomers. Importantly, the results of our mechanistic experiments were in line with the cyclotrimerization occurring in a chain-type fashion with racemization of a Cu­(I) homochiral dimeric intermediate, reducing the stereoselectivity of the transformation. Enabled by more facile access to molecular baskets of type 1 syn , a range of recognition studies can now be completed for producing novel supramolecular catalysts, organophosphorus scavengers, and nanostructured materials.

Enantioselective Construction of Modular and Asymmetric Baskets

“…That is to say, l-(À)-menthol ($140 kg À1 ,Sigma-Aldrich) was used as chiral auxiliary for stereoselective synthesis of cycloadduct (À)-1 M ,f ollowed by its conversion into (À)-2 (98 % ee). [34] With the facile access to sufficient quantities of (À)-2,w ew ondered if this compound and its enantiomer (+ +)-2 (Scheme 1A)c ould be converted into functional and enantioenriched A, B,a nd C building blocks (Scheme 1B). Next, would stepwise A-to-B and AB-to-C couplings,f ollowed by electrocyclic (EC) ring closure and oxidation or elimination, [35] give an ABC basket as the sole product?T he Suzuki-Miyaura (SM) C À Cbond formation [36] was envisioned to provide sufficient fidelity for the consecutive head-to-tail couplings [37] of A, B,a nd C blocks so that the exclusive and stereoselective formation of an enantioenriched ABC basket would ensue.…”

“…Using (À)-1 iB ,weprepared (+ +)-2 by following the same optimized route for converting (À)-1 M into (À)-2. [33,34] With both enantiomers of 2 in hand, we went on to probe the sequential ABC couplings in the preparation of previously studied basket 8 (Scheme 2, strategy 1). [33] Chemoselective borylation of (À)-2 into fragment A ((À)-3, Scheme 2) was conducted with CuI and bis(pinacolato)diboron.…”

Rapid Access to Chiral and Tripodal Cavitands from β‐Pinene

“…However, these fascinating molecules were not used for chiral recognition about which we note that a lack of functional groups may limit their utility. Similarly, Stille type cyclotrimerization [28] of tin derivatives of (+)‐camphor [29] or (−)‐borneol [30] resulted in the formation of shallow benzocyclotrimers [31] functionalized at the rim. We wondered, would chiral scaffold of type 2 syn (Figure 1B) be accessible by Pd‐catalyzed cyclotrimerization of monomers derived from a vast pool of terpenes? [32] That is to say, will (+)‐bromoenone 1 , derived from monoterpene β‐pinene, undergo Pd‐catalyzed cyclotrimerization [33] to give tris ‐nopinone 2 syn (Figure 1B)?…”