The aporhoeadane alkaloids

Abstract

The aporhoeadane alkaloids, exemplified by the natural products chilenine and lennoxamine, have received significant attention from the synthetic community over the course of nearly 50 years. This review details the approaches to these heterocycles, as well as their major reactions.

Zn-ProPhenol Catalyzed Enantio- and Diastereoselective Direct Vinylogous Mannich Reactions between α,β- and β,γ-Butenolides and Aldimines

“…A Mannich product with an appropriately tethered cinnamate ester was treated with Cs 2 CO 3 to afford isoindoline 8g via an intramolecular aza-Michael addition reaction (Scheme ). Given their biological importance and recent interest in the synthesis of isoindoline derivatives, this transformation is particularly notable. Additionally, our products can be further elaborated using cross-coupling chemistry, as demonstrated by the Sonogashira reaction performed on 3ae .…”

Intramolecular Arylation of Tertiary Enamides through Pd(OAc)2-Catalyzed Dehydrogenative Cross-Coupling Reaction: Construction of Fused N-Heterocyclic Scaffolds and Synthesis of Isoindolobenzazepine Alkaloids

“…HRMS (ESI) m/z: [M + Na] + calcd for C 21 H 23 NO 5 Na, 392.1468;found, 392.1467. 3,4,10,11-Tetramethoxy-7,8-dihydro-5H-benzo [4,5] azepino [2,1-a] isoindol-5-one (11). Under oxygen protection, Pd(OAc) 2 (9.0 mg, 0.02 mmol), Cu(OAc) 2 (80 mg, 0.40 mmol), and PivOH (68.8 μL, 0.60 mmol) were added to a mixture of tertiary enamides 10 (74 mg, 0.20 mmol) in DMSO (2 mL).…”

“…Interesting fused heterocyclic structures with sometimes dense functional groups have prompted a myriad of different synthetic approaches. As summarized by Leonard in a review among all synthetic methods reported, late-stage formation of five-membered isoindoline or isoindolinone ring and seven-membered azepine ring and concurrent construction of the fused five/seven ring system are the most popular strategies by means of various C–C and C–N bond forming protocols. Very recently, intramolecular Suzuki-Miyaura cross-coupling reaction and nucleophilic substitution reaction were applied respectively by Yudin and Yao to assemble the azepine ring, accomplishing the synthesis of 7,8,13,13a-tetrahydro- and 7,8-dihydro-5H-benzo­[4,5]­azepino­[2,1- a ]­isoindol-5-ones.…”

Enantio- and Diastereoselective Betti/aza-Michael Sequence: Single Operated Preparation of Chiral 1,3-Disubstituted Isoindolines

“…Isoindolines are common structural motifs in a variety of natural products and pharmaceuticals, such as pagoclone, nuevamine, and their functionalized derivatives (see Figure ), and as such, these compounds exhibit a range of biological activities, including anxiolytic, antileukemic, antitumoral, and potent endothelin A receptor antagonist activities. , Due to the potential application of isoindolines, development of novel new and efficient synthetic protocols for this heterocyclic system has received particular attention. , However, to date, only a few reports have described the catalytic synthesis of 1,3-disubstituted isoindolines in racemic or optically active forms …”