Asymmetric Latent Carbocation Catalysis with Chiral Trityl Phosphate

Abstract

Stable carbocations such as tritylium ions have been widely explored as organic Lewis acid catalysts and reagents in organic synthesis. However, achieving asymmetric carbocation catalysis remains elusive ever since they were first identified over one century ago. The challenges mainly come from their limited compatibility, scarcity of chiral carbocations, as well as the extremely low barrier to racemization of chiral carbenium ions. We reported here a latent concept for asymmetric carbocation catalysis. In this strategy, chiral trityl phosphate is employed as the carbocation precursor, which undergoes facile ionic dissociation upon mild external stimulation (e.g., acid, H-bonding, polar substrates) to form a catalytically active chiral ion pair for substrate activation and chiral induction. The latent strategy provides a solution for the long sought-after asymmetric carbocation catalysis as illustrated in three different enantioselective transformations.

Regiodivergent Glycosylations of 6-Deoxy-erythronolide B and Oleandomycin-Derived Macrolactones Enabled by Chiral Acid Catalysis

“…2). It also should be noted that the proposed involvement of the covalently linked catalyst intermediates is consistent with the mechanistic proposals made by our group for the CPA-catalyzed reactions of acetals 27 and for the related transformation by Toste, 28 List, 29 Luo 30 and Ta-kasu 31 groups.…”

Tropylium-promoted carbonyl–olefin metathesis reactions

“…Heteroaromatic aldehyde 5h formed an adduct with the tropylium ion at the nitrogen-centre and hence deactivated the reaction system. Aliphatic aldehydes also led to complicated reaction mixtures with some aldol and carbonyl-ene 18 byproducts.…”

Chiral Modification of the Tetrakis(pentafluorophenyl)borate Anion with Myrtanyl Groups

“…With the modified trityl salt [ Me Tr] + [ 4 ] – in hand, we tested its catalytic activity in two representative Diels–Alder reactions and two Mukaiyama aldol additions . Franzén and co‐workers demonstrated that trityl cations are able to catalyze difficult Diels–Alder reactions involving cyclohexa‐1,3‐diene ( 14 ) as enophile in good yields .…”

“…Franzén had also tested an enantioselective counteranion‐directed Diels–Alder reaction of 14 with methacrolein ( 16 ) but could only observe cycloadduct 17 in trace amounts. [15b] Even though our catalyst enabled the desired reaction of 16 and 14 in moderate yield, there was no enantioinduction (Scheme , bottom). Diels–Alder reactions with anthracene as the enophile did not show any conversion.…”