Enantioselective Carbon-Carbon Bond Cleavage for Biaryl Atropisomers Synthesis

Abstract

Development of new synthetic strategies for enantioselective carbon-carbon and carbon-heteroatom bond formation is one of the pillars of modern organic chemistry. Whereas significant advances have been achieved in center chirality construction, catalytically asymmetric construction of axial chirality is still under development. Moreover, axially chiral molecules constructed through carboncarbon and carbon-heteroatom bond cleavage are extremely limited. Here, we report an asymmetric synthesis of biaryl atropisomers via palladium-catalyzed chemoselective carbon-carbon cleavage of 9-aryl-9H-fluoren-9-ols. The reaction demonstrated broad substrate scope and produced the atropisomers in high yields and enantioselectivity. The ring-opening reactivity was considerably accelerated by the torsional strain created by the steric repulsion between two ortho-substituents of the biaryl skeleton in the substrates. The high enantiocontrol hinges on the evolvement of a new TADDOL-based phosphoramidite as ligand. These findings set up a new platform for the development of novel synthetic methods via asymmetric carbon-carbon cleavage.

Palladium‐Catalyzed Enantioselective Cacchi Reaction: Asymmetric Synthesis of Axially Chiral 2,3‐Disubstituted Indoles

“…Indeed, axially chiral bisindoles have been found in nature [2] and have been elaborated as efficient chiral ligands for asymmetric synthesis (Scheme 1a). [3] In sharp contrast to the longstanding interest in asymmetric synthesis of axially chiral six-membered arylaryl and aryl-heteroaryl compounds, [4,5] catalytic enantioselective synthesis of atropisomers bearing af ive-membered heterocycle in general, and an indole unit in particular, attracted the attention of synthetic chemists only very recently. [6][7][8][9][10][11] Due to the reduced rotational energy barrier around the 5-6 and 5-5 biaryl axis,t he atropenantioselective synthesis of this two types of biaryls is known to be ac hallenging endeavor.…”

Organocatalytic asymmetric N-sulfonyl amide C-N bond activation to access axially chiral biaryl amino acids

“…This strategy presents some challenges, including (i) increasing the reactivity of unreactive amide bonds, (ii) choosing a proper organocatalyst to both activate unreactive amide groups and other reactants, and (iii) ensuring excellent enantioselectivity of the desired products. On the basis of Bringmann's pioneering work 41,42 , and the recent advance in constructing axially chiral backbones by ring opening of conformationally labile bridged biaryls [44][45][46][47][48] , we envisaged that the N-electron-withdrawing group configurationally labile biaryl lactams with an inherent torsional strain might act as suitable substrates for activation of amide C-N bonds, promoted by a bifunctional organocatalyst. According to our understanding of organocatalysis [49][50][51][52][53][54] , we herein present a strategy for direct organocatalytic asymmetric activation of N-sulfonyl amide C-N bonds promoted by a bifunctional organocatalyst under mild reaction conditions.…”

Hypervalent‐Iodine‐Mediated Carbon–Carbon Bond Cleavage and Dearomatization of 9H‐Fluoren‐9‐ols

“…Thus,these molecules showed higher reactivity than the nondistorted ones in ring-opening reactions. [13] Our investigation started with 4,5-dimethyl-9-phenyl-9H-fluoren-9-ol (1a), and we anticipated to obtain the ring-opening/bromination products (3a)i nt he presence of CuBr and bis(trifluoroacetoxy)iodobenzene (PIFA). [14] Surprisingly,t he reaction of 1a with PIFAa nd KBr catalyzed by CuBr afforded at race amount of bromination product 3a,w hich was detected by GC-MS (Table 1, entry 1).…”

“…At last, commonly used oxidants were investigated. PIDAa nd PIFAp roduced acceptable yields of 2a.H owever,H 2 O 2 and m-CPBAg ave unknown mixtures,w hile NaIO 4 was an ineffective oxidant (entries [9][10][11][12][13].…”