Achieving conformational control over C–C, C–N and C–O bonds in biaryls, N,N′-diarylureas and diaryl ethers: advantages of a relay axis

Abstract

The orientation of Ar-C, Ar-N and Ar-O bonds in biaryls, N,N'-diarylureas and diaryl ethers (whose conformers are distinguishable by NMR) may be controlled with a selectivity up to >95 : 5 by an adjacent stereogenic centre; the selectivity may be greater when a second stereogenic axis is inserted between the controlling centre and the slowly rotating bond.

Nonbiaryl and Heterobiaryl Atropisomers: Molecular Templates with Promise for Atropselective Chemical Transformations

“…103 The strategy involved the incorporation of a temporary chiral group (sulfoxide) that can influence the adjacent C−O chiral axis after which it was transformed into a bulky group preserving the axial chirality. 104 The authors term this process as dynamic-thermodynamic resolution. While conformational control in the initial sulfinylation was rather poor (157a, 157b), series of further alkylations biased the process toward the major conformer (157b) with dr up to 98:2.…”

Enantioselective Synthesis of an Atropisomeric Diaryl Ether

“…Previous studies15 suggested that alkylsulfinyl groups with tertiary alkyl substituents were essential for high levels of conformational control, but we were unable to make tert ‐alkylsulfoxides directly from 4 or 7 . We therefore treated 5 and 8 with a base to deprotonate α to the sulfur center, and quenched the resulting anions with methyl iodide.…”

“…The versatility of sulfoxide chemistry,12 along with the powerful dipole associated with the SO bond,13 prompted us to choose a sulfinyl group as a means of achieving conformational control. Sulfinyl groups have previously performed well in controlling functional group orientation in aromatic amides10, 13, 14 and ureas 15. We chose to make the required ethers by the route shown in Scheme .…”

Controlling Axial Conformation in 2-Arylpyridines and 1-Arylisoquinolines: Application to the Asymmetric Synthesis of QUINAP by Dynamic Thermodynamic Resolution

“…While an adjacent sulfoxide substituent provides only a weak influence over an aryl-aryl axis joining two benzenoid rings, 2 we have shown that its ability to orientate a similar axis in substituted or ring-fused 2-phenylpyridyls is much greater. Thermodynamic selectivities for one of the two diastereoisomeric conformers or atropisomers range from 4:1 to >20:1.…”