Programmed serial stereochemical relay and its application in the synthesis of morphinans

Abstract

A rationally designed, serial point-to-axial and axial-to-point stereoinduction and its integration into a multi-step and target-oriented organic synthesis was demonstrated in a novel chemical method to access morphinans and it is potentially applicable to other structurally related alkaloids.

Frontier molecular orbital effects control the hole-catalyzed racemization of atropisomeric biaryls

“…10 Similar SET conditions have been recently reported by Akai to promote biaryl racemization at 35–50 °C, which underpins the development of an enzymatic dynamic kinetic resolution of biaryls in the same laboratory 11. Chen has also found that oxidation with a hypervalent iodine reagent promotes BINOL racemization 12. The precise mechanistic origins to explain why biaryl oxidation should render more facile axial rotation, leading to easier racemization, remain unclear.…”

Dynamic Thermodynamic Resolution of Racemic 1,1′-Binaphthyl-2,2′-diol (BINOL)

“…Hypervalent iodine compounds have been found to facilitate the rotation of biaryl bonds. 22 In our experiments, phenyliodine(III) diacetate (PIDA, 5 mol %) catalyzed the racemization of (R)-1 in an HFIP/CH 2 Cl 2 solution [1:1 ratios (Figure 1B, pink circles)]. The electron paramagnetic resonance (EPR) spectrum of this solution (Figure 1C) reveals radical species that correspond to the simulated spectrum of the binaphthoxyl radical (1•).…”

Recent Advances in the Total Synthesis of the Tetrahydroisoquinoline Alkaloids (2002–2020)

“…Chen and co-workers' alternative synthetic approach to the morphinan family of natural products was developed from their method of oxidative dearomatization of atropisomerically pure biaryl phenols to achieve complex intramolecular Diels− Alder products such as 303. 100 To demonstrate the synthetic utility of these intermediates, 303 was elaborated into lactam 305 via Beckmann rearrangement of oxime 304 (Scheme 42). Reduction of the amide, followed by Hoffmann elimination, induced further cleavage of the bridgehead C−N bond to furnish amine 306.…”