Biaryl synthesis with control of axial chirality

Abstract

Biaryls have been a persistent focus of interest for chemists since it was recognised, more than 80 years ago, that they can manifest the axial chirality that is inherent in structures consisting of intersecting dissymmetric planes. In recent decades their importance has risen steeply as this structural motif proved spectacularly successful in catalytic synthetic roles and was found to be significant in the context of biological activity. As a consequence, synthetic methods which allowed the construction of biaryls with axial stereocontrol have become highly desirable, and this article traces the development of non-resolution approaches to biaryls with a chosen axial configuration.

Enantioselective Synthesis of Axially Chiral Biaryls by the Pd-Catalyzed Suzuki−Miyaura Reaction: Substrate Scope and Quantum Mechanical Investigations

“…TS3 is destabilized by 1.8 kcal/mol in comparison with TS1, even though similar H-bonding interactions are present in both transition structures; the phosphonate substituent presumably interacts more favorably with the hydrogen atom on an sp2-hybridized carbon atom in TS1 than with the hydrogen atom on an sp3-hybridized carbon atom on the tolyl addend in TS3. One expects hydrogen atoms on sp2-hybridized atoms to be stronger donors than hydrogen atoms on sp3-hybridized atoms, which could account for the greater stability of TS1. In addition, the aromatic proton in TS1 is sterically less demanding than the methyl group in TS3.…”

“…These reductively eliminate to give S and R biaryl products, respectively. Although both transition states form interactions with hydrogen atoms on both sp2 and sp3-hybridized carbon atoms, TS1 is 0.9 more stable than TS5. This is presumably due to the fact that the phosphonate group in TS1 is better aligned for interaction with a hydrogen atom on an sp2-hybridized carbon (∠P-O•••H = 158°), but this alignment is poor in TS5 (∠P-O•••H = 90°).…”

Towards the Design of Optically Active Thiophene S‐Oxides using Quantum Chemistry

“…[42][43][44] Diels-Alderc ycloadditionsb etween an aryl-substituted Soxide thiophene 2 anda na lkyne could result in axially chiral biarylc ompounds 3 (Scheme 1). The importance of axially chiralb iaryl compounds is demonstrated in asymmetrics ynthesis [45][46][47] and the configuration of the biaryl axis is knownt o be of high importance for the pharmacological properties of bioactive compounds. [48] The availability of chemical methods to generate enantiopure thiophene monoxides as starting materialsc ould enableanovel atroposelective synthesis of biaryl compounds through ac enter-to-axis chirality transfer.H ence, the chiral centero ft he thiophene monoxide 2 needs to be stablee nought oa void pyramidal inversion during the Diels-Alderc ycloaddition.…”

Transition Metal Catalyzed CarbonCarbon Bond Formation: The Key of Homogeneous Catalysis

“…Transition metal complex promoted formation of carbonacarbon bonds is a field of much current interest since it can lead to the design of new highly selective and efficient synthetic procedures for organic chemistry [1][2][3]. In this chapter we focus on the theoretical studies of CaC bond formation reactions through the reductive elimination pathway.…”