Diastereo- and Atroposelective Synthesis of Bridged Biaryls Bearing an Eight-Membered Lactone through an Organocatalytic Cascade

Abstract

We present herein an unprecedented stereo­selective synthesis of bridged biaryls with defined axial and central chirality from readily available starting materials. This N-heterocyclic carbene-catalyzed method proceeds through propargylic substitution of azolium enolates followed by two-directional cyclization, as supported by DFT calculation. A range of benzo­furan/indole-derived bridged biaryls bearing an eight-membered lactone are accessed with uniformly high stereo­selectivity (>98:2 dr, mostly >98% ee).

Simultaneous construction of axial and planar chirality by gold/TY-Phos-catalyzed asymmetric hydroarylation

“…However, to the best of our knowledge, simultaneous construction of multiple chiralities by asymmetric gold catalysis has not been reported so far, this hypothesis faced considerable challenges: (1) the universal and efficient asymmetric intramolecular desymmetric cyclization for the construction of planar ferrocene derivatives was not well developed (In the work of refs. 11 , 12 , 10–20 mol% catalytic loading was used), (2) on the other hand, simultaneous construction of axial and planar chiral molecules via asymmetric catalysis has rarely been reported 52 , 53 and innate reluctance to undergo a related asymmetric desymmetric aromatization, and (3) the inherent difficulties to asymmetric gold catalysis, which stem from its linear coordination geometry and the outer-sphere nature of Au(I)-catalysis 44 – 50 . To test our hypothesis, our investigation began with the cyclization of ortho-alkynylaryl ferrocene derivative 1aa .…”

Catalytic Asymmetric Construction of Axially Chiral Indole‐Based Frameworks: An Emerging Area

“…Very recently,Z hao, Wong and co-workers discovereda nu nexpected cascade reaction between propargylic alcohols 41 and enals 42 in the presence of chiral N-heterocyclic carbene (NHC*) C11,w hich resulted in the atroposelective synthesis of bridgeda rylindoles and arylbenzofurans 43 bearing an eightmembered lactoner ing in good yields with excellent diastereo-and enantioselectivities (Scheme 11 a). [31] This approachi nvolvest he strategy of constructing an indole ring and serves as ag ood example for simultaneously controlling the axial and central chirality.B ased on theoretical calculations, the researchers suggested ap ossible reaction pathway as illustrated in Scheme 11 b. Very interestingly,b ecause arylindole frameworks 43 were bridgedb yalactone ring, the axial chirality of the frameworks was more similar to helical chirality,w hich will enlighten future investigations on the atroposelective construction of indole-based frameworks bearingh elical chirality.…”

Recent Advances in Catalytic Atroposelective Construction of Pentatomic Heterobiaryl Scaffolds

“…In 2019, Zhao and co‐workers disclosed an NHC‐catalyzed atroposelective construction of the bridged biaryls 72/73 in moderate to high yields with superb enantioselectivities (Scheme 17). [28] The in‐situ generated azolium enolate underwent an enantioselective propargylic substitution to afford a chiral Int‐14 , which proceeded a facile intramolecular dehydration to give the chiral allene species Int‐15 . Subsequently, a chemoselective intramolecular acylation occurred on the electron‐richer OH group (if employing unsymmetrical substrates 70 ), giving a chiral eight‐membered lactone Int‐17 , thus followed an NHC promoted nucleophilic addition of phenoxide on the remained allene moiety to give the target axially chiral bridged biaryls.…”