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. 2020 Apr 24;11(29):7672-7675.
doi: 10.1039/d0sc01909g.

Programmable synthesis of multiply arylated cubanes through C-H metalation and arylation

Ryo Okude  1 , Genki Mori  2 , Akiko Yagi  1 , Kenichiro Itami  1   3
Affiliations

Programmable synthesis of multiply arylated cubanes through C-H metalation and arylation

Ryo Okude et al. Chem Sci. .

Abstract

Cubane (C8H8), a cubic alkane, has long attracted attention owing to its unique 3D structure. In order to utilize the cubane scaffold widely in science and technology, a powerful method for synthesizing diverse cubane derivatives is required. Herein, we report the synthesis of mono-, di-, tri-, and tetra-arylated cubanes. Directed ortho-metalation with lithium base/alkyl zinc and subsequent palladium-catalyzed arylation enabled C-H metalation and arylation of cubane. This reaction allows the late-stage and regioselective installation of a wide range of aryl groups, realizing the first programmable synthesis of diverse multiply arylated cubanes.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. Schematic illustration of this work.
Scheme 1
Scheme 1. Substrate scope of iodoarenes in palladium-catalyzed arylation of cubane. a Isolated yield. b 0.05 M, Pd2(dba)3·CHCl3/P(OPh)3 = 1/4, THF solution (10 mol%), 25 °C, 24 h. c1a: 0.10 mmol. d1a: 0.10 mmol, ortho-metalation: 1 h. e Pd2(dba)3·CHCl3 (20 mol%), P(OPh)3 (160 mol%).
Scheme 2
Scheme 2. Attempts at (a) arylation of 2b and (b) deuteration of 2b through directed ortho-metalation. (c) Synthesis of diarylcubanes and scope for iodoarenes. a 1H NMR yield.
Scheme 3
Scheme 3. Synthesis of triarylcubanes and programmable synthesis of triarylcubane regioisomers. (a) Synthesis of triarylcubanes 4a, 4b, and 4c. (b and c) Regioselective synthesis of triarylcubane isomers. (b) Arylation, hydrolysis, and decarboxylation.
Scheme 4
Scheme 4. The synthesis of tetraarylcubane 5a.
Fig. 2
Fig. 2. X-ray crystal structure of 5a at 50% thermal stability.
See this image and copyright information in PMC

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