Enantioselective Synthesis of cis‐Decalin Derivatives by the Inverse‐Electron‐Demand Diels–Alder Reaction of 2‐Pyrones

Abstract

A novel strategy for the synthesis of cis-decalins by an ytterbium-catalyzed asymmetric inverse-electron-demand Diels-Alder reaction of 2-pyrones and silyl cyclohexadienol ethers is reported here. A broad range of synthetically important cis-decalin derivatives with multiple contiguous stereogenic centers and functionalities are obtained in good yields and stereoselectivities. A full set of diastereomeric substituted cis-decalin motifs are readily accessible by tuning the absolute configurations of substituted silyl cyclohexadienol ethers (R or S) as well as the ligands (R or S). The synthetic potential is showcased by the enantioselective total synthesis of 4-amorphen-11-ol, and further demonstrated by the first total synthesis of cis-crotonin. Scheme 1. Enantioselective synthesis of cis-decalin motifs by inverseelectron-demand Diels-Alder reaction of 2-pyrones.

Enantioselective synthesis of unsymmetrical α,α-diarylacetates via organocatalyzed formal C–H insertion reactions of sulfoxonium ylides with indoles and pyrroles

“…In recent times, the utilization of London dispersion (LD) interactions has emerged as a fundamental approach in catalyst design. [41][42][43][44][45][46] Drawing from this concept, we designed and synthesized two new chiral phosphoric acids (HA-7 and HA-8) to enhance LD interactions, with the goal of improving enantioselectivity. However, the achieved enantioselectivity was slightly lower compared to the utilization of HA-6 in the reaction (entries 11-13).…”

“…This involves employing an unconventional and attractive strategy that enhances London dispersion (LD) interactions within the principles of organocatalyst design. [41][42][43][44][45][46] Additionally, we have achieved the unprecedented organocatalytic asymmetric formal C-H insertion reaction of N-H free pyrrole with excellent stereoselectivity and yield (Fig. 1D).…”

Chiral Bis‐Oxalamide‐Rare Earth Complex Catalyzed Inverse‐ Electron‐Demand Asymmetric oxa‐Hetero‐Diels‐Alder Reaction for Optically Active Dihydropyran Core Structures

“…Among them, rare‐earth metal complex‐catalyzed Diels‐Alder reactions were directed and effective synthetic method for the construction of six‐membered ring adducts [13–15] . Kobayashi and co‐workers successfully established the chiral scandium complex catalyzed enantioselective Diels‐Alder reaction of acyl‐1,3‐oxazolidin‐2‐ones with dienes, and the corresponding Diels‐Alder adducts were obtained in high yields with high diastereo‐ and enantioselectivities (Scheme 1a) [13e] . Whereafter, Desimoni's group reported the pybox/Sc(OTf) 3 catalyzed asymmetric Diels‐Alder reaction of methyl ( E )‐2‐oxo‐4‐aryl‐3‐butenoates and cyclopentadiene, which furnished both DA and HDA adducts with optically pure form (Scheme 1b) [16] .…”

A nickel(ii)-catalyzed enantioselective all-carbon-based inverse-electron-demand Diels–Alder reaction of 2-pyrones with indenes

“…Moreover, benefiting from the introduction of an electron-deficient group (for instance, an ester group), 2-pyrone has been confirmed to be an attractive diene component in asymmetric IEDDA reactions catalyzed by chiral Lewis acid complexes. [13][14][15][16][17][18][19][20][21] A range of electron-rich dienophiles, such as 2,2-dimethyl-1,3-dioxole, 18 silyl cyclohexadienol 19 and 1-naphthyl acetylenes, 20 underwent the enantioselective IEDDA reactions of electron-withdrawing 2-pyrones to provide the corresponding [4 + 2] cycloaddition products with good to excellent outcomes. However, owing to their low reactivity and poor stereoinduction, the use of simple indenes as dienophiles has been rarely described in asymmetric IEDDA reactions, which remains a challenging task.…”