Ln(III)/Chiral Brønsted Acid Catalyzed Asymmetric Cascade Ring Opening/Aza-Piancatelli Rearrangement of D–A Cyclopropanes

Abstract

The first Lewis acid and chiral Brønsted acid cooperatively catalyzed asymmetric cascade ring opening/aza-Piancatelli rearrangement reaction of furyl-substituted donor–acceptor cyclopropanes is achieved, enabling the construction of functionalized aminocyclopentenones bearing α-quaternary carbon stereocenters in high yields with excellent enantio- and diastereoselectivities under remarkably low catalyst loading of 0.2–1.2 mol %.

Retro-Aza-Piancatelli Rearrangement Triggered Cascade Reaction of Methyl Furylacrylates with Anilines to Access Cyclopenta[b]pyrrolidinones

“…Subsequent acid-promoted nucleophilic addition by the aniline via intermediate II to generate intermediate III and further upon furan ring opening/isomerization delivers the pentadienyl carbocation IV . Conrotatory 4π electrocyclization of IV furnishes the major cis -adduct and minor trans -adduct, which is consistent with the previous reports. , Although only minor trans -adduct can undergo lactamization, a retro -aza-Piancatelli rearrangement of major cis -adduct to minor trans -adduct proceeds smoothly, thus significantly increasing the yield of the desired lactam product.…”

“…Nevertheless, it is important to note that all these reactions have almost exclusively relied on furfuryl alcohols to generate the key furanoxonium ion intermediates via an acid-catalyzed dehydration process (Scheme a). The discovery of novel strategies and/or employing other furan derivatives for the generation of functionalized furanoxonium ion intermediates to trigger the Piancatelli reaction is highly desirable, but still less developed. , In this context, Read de Alaniz reported the ring opening-initiated aza-Piancatelli reaction using furyl-substituted donor–acceptor cyclopropanes (CPs) as novel precursors (Scheme b) . More recently, we developed the radical-mediated Piancatelli-type rearrangement of furyl-substituted terminal alkenes with diverse fluoroalkyl radical precursors and anilines .…”

Organocatalytic Reductive Amination of the Chiral Formylcyclopropanes: Scope and Applications

“…The initial investigation was carried out with chiral formylcyclopropane (-)- 2a having 98% ee /95% de and p -anisidine 1a using Hantzsch ester 3 as the reducing reagent in the presence of known diphenyl phosphate 4 (10 mol %) as a catalyst. − The reductive amination reaction was carried out in DCM at 25 °C for 240 min with 5 Å molecular sieves acting as a water scavenger and furnished the expected product (-)- 5aa in 93% yield with 96% ee and >98% de without any cyclopropane ring-opened adduct with p -anisidine or epimerized products (Table , entry 1) . Surprisingly, when we stirred the reductive amination reaction for just 30 and 10 min, it gave the product (-)- 5aa in 98 and 46% yields with sustained ee and de , respectively, and demonstrating the importance of time for C–N bond formation (Table , entries 2 and 3).…”

Recent Advances on Piancatelli Reactions and Related Cascade Processes

“…In 2020, Cai and Tang described a catalytic asymmetric version of this reaction by employing Lewis acid and chiral Brønsted acid cooperative catalysis. 56 Through the Ln(III)facilitated CP ring opening and chiral N-triflylphosphoramide anion-controlled enantioselective 4 electrocyclization process, this transformation affords diverse chiral aminocyclopentenones bearing an -quaternary carbon stereocenter in high yields with excellent enantio-and diastereoselectivities (Scheme 26).…”