Enantioselective Synthesis of Axially Chiral Biaryls by Diels–Alder/Retro-Diels–Alder Reaction of 2-Pyrones with Alkynes

Abstract

The enantioselective synthesis of axially chiral biaryls by a copper-catalyzed Diels−Alder/retro-Diels−Alder reaction of 2-pyrones with alkynes is reported herein. Using electron-deficient 2-pyrones and electron-rich 1-naphthyl acetylenes as the reaction partners, a broad range of axially chiral biaryl esters are obtained in excellent yields (up to 97% yield) and enantioselectivities (up to >99% ee). DFT calculations reveal the reaction mechanism and provide insights into the origins of the stereoselectivities. The practicality and robustness of this reaction are showcased by gram-scale synthesis. The synthetic utilizations are demonstrated by the amenable transformations of the products.

Synthesis of pyrano[3,2-c]quinolones and furo[3,2-c]quinolonesviaacid-catalyzed tandem reaction of 4-hydroxy-1-methylquinolin-2(1H)-one and propargylic alcohols

“…Furthermore, novel tetracyclic compounds 6a–6e were forged from 3a and propargylic alcohols 2 in 41–60% yields, which proceeded via sequential Diels–Alder reaction of 2 H -pyran with alkynes followed by retro-Diels–Alder extrusion of benzophenone under thermal reaction conditions and Friedel–Crafts-type reaction at last. 26 Furo[3,2- c ]quinolones 4 could be isomerized to 7 under the catalysis p TsOH·H 2 O with excellent yields (Scheme 7b). The structure of the product 6a was additionally confirmed by X-ray crystallographic analysis (see ESI† for details).…”

tert-Butyl(2-oxo-2H-pyran-5-yl)carbamate as the First Chameleon Diene Bearing an Electron-Donating Substituent

“…Ring substituents play a critical role in the cycloadditions of 2( H )pyran-2-ones. Generally speaking, the unsubstituted ring 2( H )pyran-2-one, 18 ( Figure 2 ), undergoes cycloadditions only under harsh conditions and with alkynes to afford benzenes following the tandem loss of CO 2 [ 1 , 2 , 3 , 4 , 5 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. Examples of cycloadditions of 2( H )pyran-2-one, 18, with alkenes to afford bridged bicyclic lactones do exist, but are rare [ 65 , 66 , 67 , 68 , 69 , 70 ].…”

“…In particular, cycloadditions of 2( H )pyran-2-one dienes to alkene dienophiles affords bridged bicyclic lactones, e.g., 2 which can then be transformed in few steps to highly substituted, six-membered rings, e.g., 3 ( Scheme 1 ) [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. Under more forcing conditions, typically at higher temperatures, cycloadditions to alkyne dienophiles and subsequent aromatization via loss of bridging CO 2 leads to substituted benzenes, e.g., 4 [ 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ].…”

Recent advances in the catalytic asymmetric construction of atropisomers by central-to-axial chirality transfer

“…2). [26][27][28][29][30][31] Among these, central-to-axial chirality transfer represents a promising class of chemical processes where the stereogenic center of the precursor is destroyed while a new stereogenic axis is induced simultaneously. This method has been used to synthesize a series of atropisomers, which otherwise would be very difficult to access.…”