Gold(I)-Initiated Cycloisomerization/Diels–Alder/Retro-Diels–Alder Cascade Strategy to Biaryls

Abstract

A unique approach to biaryls was developed on the basis of propargyl vinyl ethers and dienophiles substrates via a gold(I)-initiated cycloisomerization/Diels-Alder/retro-Diels-Alder cascade reaction. The scope and mechanism of the reaction were investigated on the basis of a series of synthetic substrates, control experiments, and DFT calculations.

Axially Chiral Cannabinoids: Design, Synthesis, and Cannabinoid Receptor Affinity

“…By design, this transposition results in significant topological changes to the cannabinoid architecture: the ground-state biaryl dihedral angle increases from 19° in CBN to 38° in ax CBN. CBNs are relatively planar (θ = 19°) with little barrier to inversion, whereas ax CBNs have increased three dimensionality ((θ = 38°) and barriers to atropisomersim ranging from 14 to 17 kcal/mol (class 1 atropisomerisim). − Retrosynthetically, we envisaged access to ax CBN via an intramolecular Diels-Alder approach to biaryls (DAB). − This revealed dimethylpropargyl chloride 1 , allylcyanide 2 , and the olivetol derivative 3 as potential starting materials. A successful route to ax CBN and other C10-substituted analogues was achieved through a key biaryllactone intermediate 7 (Figure B).…”

“…32 Retrosynthetically, we envisaged access to axCBN via an intramolecular Diels-Alder approach to biaryls (DAB). [33][34][35] This revealed dimethylpropargyl chloride 1, allylcyanide 2, and the olivetol derivative 3 as potential starting materials. A successful route to axCBN and other C10-substituted analogs was achieved through a key biaryllactone intermediate 7 (Figure 2B).…”

Recent Advances in Gold(I)-Catalyzed Approaches to Three-Type Small-Molecule Scaffolds via Arylalkyne Activation

“…The authors achieved the syntheses of xanthone and acridone derivatives by designing a series of alkyne-enolether substrates with 25 examples and up to 98% yield (Scheme 9) [30]. Initially, the triple bonds of the substrates (33) were chelated by the gold(I) species, which promoted an intramolecular Michael addition to obtain intermediates (34) after protodeauration. Then, gold(I)-activated enolether was attacked by newly generated enolethers or enamines to undergo a 6-endo-trig cyclization.…”

“…In 2017, a gold(I)-catalyzed tandem cycloisomerization, Diels-Alder, and retro-Diels-Alder reactions were reported by the Liu lab (Scheme 12) [33]. Activation of alkyne in substrates (46) initiated the first cycloisomerization to yield furopyran intermediates (47).…”