Diastereoselective synthesis of a cyclic diamide‐bridged biphenyl as chiral atropos ligand

Abstract

Chiral compounds with a 1,2‐diamine structure motif and their derivatives are of great interest in organic chemistry and are broadly used in asymmetric transformations, as chiral auxiliaries, (co)ligands, and ligand core structure. Here, we present a straightforward, diastereoselective synthesis for a diamide‐bridged biaryl ligand. The ring closing reaction of the racemic atropos biphenyl 6,6′‐dimethoxy‐[1,1′‐biphenyl]‐2,2′‐dicarboxylic acid with (R,R)‐diaminocyclohexane yields the diasteromerically and enantiomerically pure cyclic (Sax,R,R)‐BIPOL, which can be used as a versatile chiral ligand. By NMR spectroscopy, we observed the formation of intermolecular aggregates of the diamide‐bridged BIPOL with anhydrous DMSO‐d6. DFT calculations at the B3LYP/6‐31G* level of theory corroborate the high interconversion barrier for the biaryl axis of ΔGǂ = 148.7 kJ mol−1 and the favoured formation of (Sax,R,R)‐BIPOL as single stereoisomer.

Synthesis and stereodynamics of intramolecular hemiacetals in biaryl aldehyde‐alcohols

“…These structures are interesting from two perspectives: Such systems can form tropos biaryls with high stereodynamic flexibility or can be atropisomers, if the free rotation around the central σ-bond is hindered by substituents, [25][26][27][28][29][30] naphthyl moieties or bridging cyclic structures. 31 Furthermore, the combination of the carbaldehyde and alcohol moiety enable an equilibrium F I G U R E 1 Identified catalytically active transient Znhemiacetalate-complex explaining the autocatalytic behavior of the Soai's asymmetric autocatalysis. 23 F I G U R E 2 (A) Reaction progress of the autocatalytic conversion of (2-(tert-butylacetylene-1-yl)pyrimidine-5-carbaldehyde (black) and (R)-2-(tert-butylacetylene-1-yl) pyrimidine-5-(iso-butan-1-ol) (red) in Soai's reaction.…”

“…These structures are interesting from two perspectives: Such systems can form tropos biaryls with high stereodynamic flexibility or can be atropisomers, if the free rotation around the central σ‐bond is hindered by substituents, 25–30 naphthyl moieties or bridging cyclic structures 31 . Furthermore, the combination of the carbaldehyde and alcohol moiety enable an equilibrium between the open form and a six‐membered ring.…”