Recent Advances on the Application of Electrocyclic Reactions in Complex Natural Product Synthesis

Abstract

The electrocyclic reaction is one of the most powerful tools for the construction of complex polycyclic scaffolds in a highly stereocontrolled fashion. In this review, recent advances in its application in the total synthesis of representative natural products are discussed, with the aim of providing a complement to existing reviews.1 Introduction2 4π Electrocyclization2.1 Neutral 4π Electrocyclization2.2 Cationic 4π Electrocyclization3 6π Electrocyclization3.1 All-Carbon 6π Electrocyclization3.2 Oxa-6π Electrocyclization3.3 Aza-6π Electrocyclization3.4 Retro-6π Electrocyclization4 8π Electrocyclization5 Conclusion and Outlook

Insight into 6π Electrocyclic Reactions of 1,8‐Dioxatetraene

“…In principle, two types of reversible cyclizations, namely, oxa‐6π atom1,2,3,4,5,6 (Scheme a, left‐hand side) and oxa‐6π atom3,4,5,6,7,8 (Scheme a, right‐hand side) electrocyclic reactions, should exist simultaneously for this compound . To the best of our knowledge, the dual 6π electrocyclic reactions of the cis , cis ‐1,8‐dioxatetraene have not been studied so far, most likely because of the following challenges: 1) cis , cis ‐1,8‐dioxatetraene is a labile species and can rapidly isomerize into the thermodynamically more stable trans , trans ‐isomer (Scheme a, top), hampering it from meeting the geometric requirement for 6π electrocyclic reactions; 2) oxa‐6π electrocyclizations are thermoneutral and reversible reactions ,. Hence, the interconversions between the 1,8‐dioxatetraene and its two ring‐closed isomers 2 H ‐pyran A and B may be reversible, decreasing the synthetic value of these transformations; 3) cis , cis ‐1,8‐dioxatetraene and 2 H ‐pyran are reactive species, having a tendency to undergo [4+2] cycloaddition, give rise to dimer side products, and disturb rearrangement processes.…”

Borane‐Catalyzed Synthesis of Quinolines Bearing Tetrasubstituted Stereocenters by Hydride Abstraction‐Induced Electrocyclization

“…We anticipated to use this intriguing amine‐activation to obtain unconstrained access cyclic iminium ions as precursors for an electrocyclization leading to tetrahydroquinoline scaffolds bearing tetrasubstituted stereocenters. This reaction would not only extend the field of so far underrepresented borane‐catalyzed C−C bond forming reactions, but would also break new grounds in the synthesis of unprecedented, pharmacologically important polycyclic tetrahydroquinoline derivatives.…”

The expanding world of biosynthetic pericyclases: cooperation of experiment and theory for discovery

“…While enzyme catalyzed Diels-Alder reactions have been an attractive target for chemists due to the prominent usefulness in organic synthesis fields 25,26,31,51,52,74,75, other pericyclic reactions such as inverse electron demand Diels-Alder reaction (IEDDA), 76,77 Alder-ene reaction, 78,79 [3,3]-sigmatropic rearrangement 81,82 and electrocyclic reactions 9,83 are also widely utilized in synthetic chemistry. Given this and our recent discoveries of enzymatic ambimodal pericyclic reactions and retro-Claisen rearrangement, 66 we expect that more pericyclic biosynthetic enzymatic transformations remain to be discovered in naturally occurring enzymes.…”