Chiral Phosphoric-Acid-Catalyzed Cascade Prins Cyclization

Abstract

Asymmetric Prins cyclization of in situ generated quinone methides and o-aminobenzaldehyde has been developed with chiral phosphoric acid as an efficient catalyst. This unconventional method provides a facile access to diverse functionalized trans-fused pyrano-/furo-tetrahydroquinoline derivatives in excellent yield and with excellent diastereo- and enantioselectivities (up to 99% yield and 99% ee). Mechanistic studies suggested that the three adjacent tertiary stereocenters were constructed through the sequential formation of C–O, C–C, and C–N bonds.

Asymmetric Synthesis of Quinoline-Naphthalene Atropisomers by Central-to-Axial Chirality Conversion

“…The central-to-axial chirality conversion has remained one of the most efficient approaches for the construction of axially biaryls that are difficult to obtain by other strategies. , Recently, we have developed an efficient atropselective synthesis of 2,3-diarylbenzoindoles by using a chiral phosphoric acid-catalyzed [3+2] formal cycloaddition and a mild central-to-axial chirality conversion strategy, in which the conversion of two stereocenters to one or two chiral axes was achieved . Given our interest in developing chiral phosphoric acid-catalyzed reactions and further applications, we envisioned that an enantioselective [4+2] annulation of 1-styrylnaphthols with in situ-generated aryl imines, the Povarov cycloaddition, followed by an oxidative aromatization would generate quinoline-naphthalene atropisomers (Scheme c). The principal challenges of the construction of quinoline-naphthalene atropisomers with fully blocked ortho positions arise from the control of both the efficiency and the stereochemistry of the designed substrate with large sterically hindered substituents, which could be enabled by the conformationally controlled oxidative dehydration reaction.…”

Asymmetric Sequential Michael Addition and Cyclization Reactions of 2-(2-Nitrovinyl)phenols Catalyzed by Bifunctional Amino-Squaramides

“…3 Therefore, investigation of cascade or tandem reactions is an important direction of development in organocatalysis, which allows the rapid construction of structurally complex molecules from simple and readily available starting materials. [4][5][6][7][8] Asymmetric organocatalytic cascade or sequential reactions are most commonly catalyzed by chiral amines, but over the past decade a number of hydrogenbonding catalysts such as ureas/thioureas, [9][10][11][12][13] guani-dines, 14,15 cinchona alkaloids, 16,17 and chiral phosphoric acids 18,19 have applied to promote a wide array of useful asymmetric sequential reactions.…”

Lewis Acid Catalyzed Intramolecular [4+2] Cycloaddition of In Situ Generated Aza‐Quinone Methides for the Stereoselective Synthesis of Furo/pyrano[3,2‐c]tetrahydroquinolines

“…[ 8,9 ] During the preparation of our manuscript, Zhou and co‐workers reported an interesting approach for the synthesis of trans ‐fused pyrano[3,2‐ c ]tetrahydroquinolines using chiral phosphoric acid catalyzed asymmetric Prins cyclization reaction involving o ‐QMs. [ 10 ] In continuation of our interest in the synthesis of oxa and aza ‐cycles using Lewis/Brønsted acids, we disclose herein, the first examples of TMSOTf catalyzed intramolecular [4+2] cycloaddition of in situ generated aza‐o ‐QMs for the stereoselective synthesis of furo/pyrano[3,2‐ c ]THQs. [ 11 ]…”