An aromatic ion platform for enantioselective Brønsted acid catalysis

Abstract

Chiral acid catalysts are useful for the synthesis of enantioenriched small molecules, but the standard catalysts require laborious and expensive preparations. Here, we describe a chiral Brønsted acid prepared in one step from naturally occurring (-)-menthol and readily available 1,2,3,4,5-pentacarbomethoxycyclopentadiene. Aromatic stabilization serves as a key contributing factor to the potent acidity of the resulting compound, which is shown to catalyze both Mukaiyama-Mannich and oxocarbenium aldol reactions with high efficiency and enantioselectivity. Catalyst loadings as low as 0.01 mole percent and preparative scalability (25 grams) are demonstrated. Alternative amide catalysts are also shown to be promising platforms. In addition to proton catalysis, a chiral anion pathway is demonstrated to be viable with this catalyst system.

Synthetic Routes towards Multifunctional Cyclopentadienes

“…Another prominent class of anionic Cps are the pentacarboxycyclopentadienes (PCCPs). These were recently found to be very efficient Bronsted acid catalysts when derivatized with chiral substituents . In a subsequent report, Lambert and co‐workers described the preparation of a series of differently substituted PCCPs (Scheme B), expanding the scope of their original work significantly …”

“…These were recently found to be very efficient Bronsted acid catalysts when derivatized with chiral substituents. [42] In as ubsequentr eport, Lambert andc o-workersd escribed the preparation of as eries of differently substituted PCCPs (Scheme 11 B), expanding the scope of their originalwork significantly. [43] An interestingp rospectt hat the anionic Cps open up is their potentials olubility in water.B eing able to preparep olysubstituted and water-soluble Cps and metal complexes would be desirable from agreen-chemistry point of view.Additionally, for some groups it is also favorable for the preparation of 99m Tc complexes,w hichf requently feature Cp-ligands and all reactions need to be conducted in water because the product is directly used for radioimaging in patients.…”

Promotion of Organic Reactions by Non‐Benzenoid Carbocyclic Aromatic Ions

“…[33] It was estimated that compounds similar to 70 possess strong acidity (pK a % 8. [33] It was estimated that compounds similar to 70 possess strong acidity (pK a % 8.…”

Methods for the Synthesis of Functionalized Pentacarboxycyclopentadienes

“…10 The motivation for this work was a desire to identify a catalytic platform that would be trivial to synthesize and simple to diversify, and that might offer unique opportunities for transition state stabilization. In the course of this work, we found that while 1,2,3,4,5-pentacarbomethoxycyclopentadiene ( 2 ) was readily available on a preparative scale (Figure 1b), there was a dearth of synthetic procedures to access derivatives of this core material.…”