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Development of an Allenyne‐Alkyne [4+2] Cycloaddition and its Application to Total Synthesis of Selaginpulvilin A
Author(s) -
Le Anh,
Gupta Saswata,
Xu Man,
Xia Yuanzhi,
Lee Daesung
Publication year - 2022
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202202015
Subject(s) - nucleophile , alkyne , cycloaddition , chemistry , moiety , diradical , reactivity (psychology) , amine gas treating , medicinal chemistry , combinatorial chemistry , photochemistry , stereochemistry , organic chemistry , catalysis , medicine , alternative medicine , pathology , physics , nuclear physics , singlet state , excited state
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.