Asymmetric Organocatalytic Synthesis of Benzopyran‐ and Benzofuran‐Fused Polycyclic Acetals

Abstract

An efficient organocatalytic method for the asymmetric preparation of benzopyran‐ and benzofuran‐fused polycyclic acetals is described for the first time. This useful approach includes an interesting tunable Michael–acetalization of nitrostyrenes or α‐aromatization–acetalization of quinones. Under mild conditions, simple cyclic hemiacetals could be stereoselectively converted into four different types of polyheterocycles that serve as scaffolds for a number of bioactive natural products.magnified image

The chemistry of 2-hydroxy-β-nitrostyrenes: versatile intermediates in synthetic organic chemistry

“…The proposed mechanism shows that the enamine 145 is responsible for the stereochemistry outcome of the reaction. 54…”

Strategies and Methods for the Catalytic Asymmetric Synthesis of Benzofuran/Benzopyran Fused Acetals: A Review

“…In the same year, by employing hemiacetal 10 as the C2 synthon, Zhang's group successfully realized a proline-catalyzed formal [3 + 2] annulation with quinones 1 for the preparation of structurally benzofuranfused polycyclic acetals 3. [20] The optically enriched polycyclic acetal products could be afforded in moderate to excellent yields and enantioselectivities with (S)-α,α-diarylprolinol silyl ethers, also known as Jørgensen-Hayashi catalysts, used as the chiral catalyst in the presence of acidic additive (49-79% yields, 81-99% ee). A working mechanistic model was proposed for this transformation based on the experiment results.…”

Phosphine-catalyzed divergent domino processes between γ-substituted allenoates and carbonyl-activated alkenes

“… 17 The biological activities of these compounds are often dependent on the substitution pattern of the chiral acetal moiety, thus the asymmetric synthesis of these molecules is highly desirable. While there are a number of reports on the synthesis of benzofused acetals, 18 efficient catalytic asymmetric preparation of bicyclic furofurans was barely explored. 19 We recently introduced a C2-symmetric chiral phosphine catalyst NUSIOC-Phos, which effectively promoted the formation of tricyclic γ-lactams via an enantioselective domino process.…”