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. 2022 Oct 7;28(56):e202202015.
doi: 10.1002/chem.202202015. Epub 2022 Aug 3.

Development of an Allenyne-Alkyne [4+2] Cycloaddition and its Application to Total Synthesis of Selaginpulvilin A

Anh Le  1 , Saswata Gupta  1 , Man Xu  2 , Yuanzhi Xia  2 , Daesung Lee  1
Affiliations

Development of an Allenyne-Alkyne [4+2] Cycloaddition and its Application to Total Synthesis of Selaginpulvilin A

Anh Le et al. Chemistry. .

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.

Keywords: allenyne; cycloaddition; cycloaromatization; selaginpuvilin A; α,3-dehydrotoluene.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
The relationship between the Myers–Saito cyclization and the allenyne‐alkyne [4+2] cycloaddition.
Scheme 2
Scheme 2
Reversal of the zwitterionic polarity of α,3‐dehydrotoluene in trapping with oxygen and nitrogen nucleophiles and the diradical reactivity toward a hydrogen donor.
Scheme 3
Scheme 3
Total synthesis of selaginpuvilin A.
See this image and copyright information in PMC

References

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    1. Nakata R., Yamada H., Okazaki E., Saito I., Tetrahedron Lett. 1989, 30, 4995–4998;
    1. Myers A. G., Aryedson S. P., Lee R. W., J. Am. Chem. Soc. 1996, 118, 4725–4726;

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