Organocatalytic Enantioselective 1,3‐Dipolar [6+4] Cycloadditions of Tropone

Abstract

A highly stereoselective 1,3‐dipolar [6+4] cycloaddition towards bridged azabicyclo[4.3.1]decane scaffolds has been developed, reacting aldehydes, 2‐aminomalonates and tropone under mild conditions in the presence of a chiral phosphoric acid catalyst. The scope is demonstrated for a series of aldehydes and 2‐aminomalonates, and the reaction proceeds in high yields, >95:5 d.r. and up to 99 % ee. A series of transformations, as well as a mechanistic proposal, are presented.

Synthesis of Substituted Tropones and Advancement for the Construction of Structurally Significant Skeletons

“…In 2020, Karl Anker Jørgensen and co-researcher constructed a bridged azobicyclo[4.3.1]decane system using the 1,3-dipolar [6 + 4] cycloaddition reaction of aldehyde 127, tropone 34, and 2-aminomalonate 126 (Scheme 22) (Table 3). [89] This organo- Under optimized conditions, unsubstituted benzaldehyde furnished excellent yield (92 %) of the corresponding product with excellent enantioselectivity (96 % ee). Benzaldehyde having Me at meta-position or the benzaldehyde with para-position having electron-withdrawing or electron-donating group afforded moderate to good yields of the expected product (55-92 %, 93-98 % ee).…”

“…In 2020, Karl Anker Jørgensen and co‐researcher constructed a bridged azobicyclo[4.3.1]decane system using the 1,3‐dipolar [6+4] cycloaddition reaction of aldehyde 127 , tropone 34 , and 2‐aminomalonate 126 (Scheme 22) (Table 3). [89] This organocatalytic enantioselective reaction was catalyzed by chiral phosphoric acid (CPA) under mild conditions. 4‐bromobenzaldehyde 127 a , diethyl 2‐aminomalonate 126 a , and tropone 34 were selected as model substrates and the conditions for this reaction were optimized.…”

Three-Component, Diastereoselective [6 + 3] Annulation of Tropone, Imino Esters, and Arynes

“…As a consequence of the careful optimization studies, herein we report the three-component and diastereoselective [6 + 3] annulation of tropone, imino esters, and arynes leading to the transition-metal-free access to azabicyclo[4.3.1]­decadienes. It may be noted in this context that Cu-catalyzed [6 + 3] annulation of tropone with azomethine ylides for the synthesis of related bridged azabicyclic compounds are reported independently by Guo and Wang groups. , Notably, related bridged bicyclic molecules are core structures present in medicinally important compounds and natural products …”

Stereodivergent Syntheses of N-heterocycles by Catalyst-Controlled Reaction of Imidazolidines with Allenes

“…Among them, the azabicyclo[4.3.1]­decane core is ubiquitous in natural products and synthetic molecules with a wide spectrum of biological activities (Figure ). Consequently, besides approaches for the total synthesis of related natural products, several elegant synthetic strategies toward different types of azabicyclo[4.3.1]­decanes have been established, including ring-closing metathesis, cyclizations, rearrangements, and cycloadditions . However, so far no reactions are available for the direct and efficient construction of 1,4-diazabicyclo[4.3.1]­decanes.…”