Organocatalytic Asymmetric Atroposelective Construction of Axially Chiral 1,4-Distyrene 2,3-Naphthalene Diols

Abstract

An efficient organocatalytic construction of enantioenriched axially chiral 1,4-distyrene 2,3-naphthalene diols through the nucleophilic addition of α-amido sulfone to in situ generated vinylidene o-quinone methide is described. The reaction pathway was investigated by isolating reaction intermediates and performing a kinetic resolution process. Axially chiral 1,4-distyrene 2,3-naphthalene diol was used as the chiral ligand for the enantioselective addition of diethylzinc to naphthalene formaldehyde. The preliminary results revealed that these adducts could be potentially used as ligands in asymmetric synthesis.

Axially chiral alkenes: Atroposelective synthesis and applications

“…This reaction overcame the low atom economy associated with the use of α-amido sulfones in asymmetric Mannich reaction as precursors of imines to synthesize chiral amines where the sulfone groups are usually wasted in the form of sulfinates. Later, Yan also described the stereoselective construction of axially chiral 1,4-distyrene 2,3-naphthalene diols (59) bearing two rotation axes by using quinine-derived squaramide catalyst C3 (Scheme 6b) [45].…”

“…Among these, phosphonic acid ester 138c and sulfide 138d represented a potential organocatalyst and S/P ligand respectively. In their other work on construction of chiral 1,4-distyrene 2, 3-naphthalene diols (59) bearing two rotation axes [45], Yan used the chiral diol as ligand for the enantioselective addition of diethylzinc to naphthalene formaldehyde. Despite the poor enantioselectivity (27% ee for 140), this signified the first exploration of the stereoinduction capability of axially chiral alkenes.…”

Recent Progress on the Synthesis of Chiral Sulfones

“…Three months later, this group further developed the organocatalytic asymmetric atroposelective construction of axially chiral 1,4‐distyrene 2,3‐naphthalene diols (Scheme 80). [92] The asymmetric nucleophilic addition of α‐amido sulfones 184 to 1,4‐bis(arylethynyl)‐naphthalene 2,3‐diols 185 catalyzed by dimeric cinchona alkaloid derivative catalyst OC 24 , affording the axially chiral 1,4‐distyrene 2,3‐naphthalene diols 186 in moderate to good yields, excellent E/Z selectivity (>99 : 1 E/Z ) and excellent stereoselectivities (>20 : 1 dr, 97–>99 % ee). One of the products 186 could promote the addition of diethylzinc to aldehyde to give chiral sec‐alcohols, proving the potential of axially chiral 1,4‐distyrene 2,3‐naphthalene diols 186 as a catalyst for asymmetric synthesis.…”

Enantioselective Synthesis of Atropisomers with Multiple Stereogenic Axes

“…In this context, the group of Yan developed a series of elegant methods for the enantioselective synthesis of atropisomers . In 2018, this group disclosed a bidirectional enantioselective construction of 1,4‐diaxially chiral bis‐styryl diols 74 from 1,4‐dialkynylnaphthalene‐2,3‐diols 72 with organocatalyst X (Scheme ) . First, the chiral VQMs‐1 intermediate was generated through an enantioselective prototropic rearrangement in the presence of squaramide catalyst X .…”