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

Abstract

Unlike related biphenyl compounds, 2-arylpyridines and 1-arylisoquinolines can be induced to adopt preferentially one of two axial conformations by the presence of a sulfinyl substituent adjacent to the Ar-Ar bond. In the case of more substituted biaryls, the compounds are atropisomeric, and thermodynamic selectivities of about 4:1 may be attained on heating. In the case of less hindered compounds, conformer ratios of up to 20:1 may be achieved. Preferred conformations are deduced by comparison of experimental CD spectra with those derived from theory. The conformational preferences induced by the sulfoxides may be exploited in the asymmetric synthesis of atropisomers, including the ligand QUINAP, by dynamic resolution under thermodynamic control.

Tautomerism and Atropisomerism in Free‐Base (meso)‐Strapped Porphyrins: Static and Dynamic Aspects

“…The results of the two experiments and definitions of the kinetic and thermodynamic terms referred to in this study are summarised in Figure 14 [Eqs. (1) and (2)]. Assuming reversible and first-order reactions [74] for the interconversion of two atropisomers of different stability, [78][79][80][81][82] the integrated rate law of the atropisomerisation process led to Equation (3) (see Figure 15), adapted from the equations previously reported by Carlier and co-workers for the epimerisation of diastereoisomers with different configurational stability. [76] As seen in Figure 16, the plots of c t (%) versus time for the two experiments are perfectly fitted by first-order exponential curves (decaying or growing) with a non-zero end-point (see the fitting model equation in Figure 15) with the correlation coefficients r = 0.99962 and 0.99968 for experiments 1 and 2, respectively, matching perfectly the integrated rate law.…”

Biocatalytic Dynamic Kinetic Resolution for the Synthesis of Atropisomeric Biaryl N‐Oxide Lewis Base Catalysts

“…BINOLderived phosphoric acids have been utilized as Brønsted acid catalysts, [2] and atropisomeric quinoline N-oxides such as QUINOX [3] are excellent Lewis base catalysts for various asymmetric transformations including asymmetric allylation of substituted benzaldehydes, [4,5] asymmetric desymmetrizations of meso epoxides, [6] and asymmetric aldol reactions. [12] Thep otential for subtle control of racemization rates in atropisomeric and near-atropisomeric structures allows the efficient use of dynamic kinetic [13] or thermodynamic [14] resolution. [12] Thep otential for subtle control of racemization rates in atropisomeric and near-atropisomeric structures allows the efficient use of dynamic kinetic [13] or thermodynamic [14] resolution.…”

Dynamic Kinetic Resolution of Biaryl Atropisomers via Peptide-Catalyzed Asymmetric Bromination

“…Steps have been taken in the control of atropisomer-selective biaryl bond forming reactions (7,8,9,10,11). Yet, only a few reports deal with the selective reaction of a single enantiomer of a dynamic mixture of atropisomeric biaryl compounds, as freely rotating, rapidly racemizing species, including pioneering work by Bringmann (12) and Clayden (13). Catalytic reactions of this nature are presently rare, and only modest atropisomer selectivity has been observed (14).…”