Development of an Allenyne‐Alkyne [4+2] Cycloaddition and its Application to Total Synthesis of Selaginpulvilin A. Issue 56 (3rd August 2022)

• Record Type: Journal Article
• Authors: Le, Anh; Gupta, Saswata; Xu, Man; Xia, Yuanzhi; Lee, Daesung
• Is Part Of: Chemistry. Volume 28:Issue 56(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-08-03
• Subjects: allenyne -- α, 3-dehydrotoluene -- cycloaddition -- cycloaromatization -- selaginpuvilin A; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202202015
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: A new [4+2] cycloaddition of allenyne‐alkyne is developed. The reaction is believed to proceed with forming an α, 3‐dehydrotoluene intermediate. This species behaves as a σπ‐diradical to react with a hydrogen atom donor, whereas it displays a zwitterionic reactivity toward weak nucleophiles. The efficiency of trapping α, 3‐dehydrotoluene depends not only on its substituents but also the trapping agents. Notable features of the reaction are the activating role of the extra alkyne of the 1, 3‐diyne that reacts with the allenyne moiety and the opposite mode of trapping with oxygen and nitrogen nucleophiles. Oxygen nucleophiles result in the oxygen‐end incorporation at the benzylic position of the α, 3‐dehydrotoluene, whereas with amine nucleophiles the nitrogen‐end is incorporated into the aromatic core. Relying on the allenyne‐alkyne cycloaddition as an enabling strategy, a concise total synthesis of phosphodiesterase‐4 inhibitory selaginpulvilin A is realized. Abstract : Complex character of a strained molecule. the α, 3‐dehydrotoluene generated via the [4+2] cycloaddition of allenyne‐alkyne can be trapped with a hydrogen atom donor or nucleophiles with two opposite regioselectivity; oxygen nucleophiles are incorporated at the benzylic position whereas amine nucleophiles are incorporated onto the aromatic core. This unique reactivity and selectivity is exploited for selaginpuvilin synthesis.