Lewis acid enhancement by hydrogen-bond donors for asymmetric catalysis

Abstract

Small molecule dual hydrogen-bond (H-bond) donors such as ureas, thioureas, squaramides, and guanidinium ions enjoy widespread use as effective catalysts for promoting a variety of enantioselective reactions. However, these catalysts are only weakly acidic, and therefore require highly reactive electrophilic substrates in order to be effective. We introduce here a mode of catalytic activity with chiral H-bond donors that enables enantioselective reactions of relatively unreactive electrophiles. Squaramides are shown to interact with silyl triflates by binding the triflate counterion to form a stable yet highly Lewis acidic complex. The silyl triflate-chiral squaramide combination promotes the generation of oxocarbenium intermediates from acetal substrates at low temperatures. Enantioselectivity in nucleophile additions to the cationic intermediates is then controlled through a network of non-covalent interactions between the squaramide catalyst and the oxocarbenium triflate.

Quaternary stereocentres via an enantioconvergent catalytic SN1 reaction

“…20 This dual-catalyst system was shown to promote the formation of oxocarbenium ions from dialkyl acetals – substrates that are unreactive under previously developed HBD-promoted reaction manifolds – while still engaging in attractive non-covalent interactions to achieve enantioinduction. We envisioned that the strong ionizing ability of this dual catalyst system could provide access to carbocationic intermediates lacking heteroatom stabilization, thus allowing us to examine whether small molecule H-bond donors can be used to promote productive, enantioselective reaction pathways from such high energy intermediates.…”

Enantioselective Catalyst Systems from Copper(II) Triflate and BINOL–Silanediol

“…Indeed, compound 4 a was isolated in 90 % yield with 27 % ee ; this possibly provides evidence for the reaction pathway depicted in Scheme . More specifically, the catalytic cyclic may begin with the silanediol interacting with Cu(OTf) 2 to generate enhanced Lewis acid species I . The complexation of I with alkylidene malonate 2 may give rise to II .…”

Chemiresistors for the Real‐Time Wireless Detection of Anions

“…The acidities of squaramides have recently been investigated as a fundamental physical organic parameter and point to their more acidic nature, relative to ureas, as important to their anion recognition properties . Building upon this understanding, a number of squaramide derivatives have been designed and investigated for colorimetric anion sensing, transmembrane anion transporters, optical imaging in cells, and organocatalysts …”

“…[9,10] Building upon this understanding, a number of squaramide derivatives have been designed and investigated for colorimetric anion sensing, [11] transmembrane anion transporters, [12] optical imaging in cells, [13,14] and organocatalysts. [15,16] Complementary electrostatic interactions can enhance anion binding affinity even in aqueous media. Recent examples include the use of cationic guanidinium, [17] imidazolium, [18][19][20] and pyridinium groups.…”