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. 2024 Aug 21:163:134135.
doi: 10.1016/j.tet.2024.134135. Epub 2024 Jul 4.

Palladium-catalyzed dearomative 1,4-hydroamination

Robert Gilbert  1 , Christopher W Davis  1 , Tanner W Bingham  1 , David Sarlah  1
Affiliations

Palladium-catalyzed dearomative 1,4-hydroamination

Robert Gilbert et al. Tetrahedron. .

Abstract

A dearomative 1,4-hydroamination of nonactivated arenes has been developed, using a key arene-arenophile photocycloaddition strategy to disrupt aromaticity. Palladium catalysis with K-Selectride® as a hydride source uniquely enables selective reactivity and provides access to a range of substituted 1,4-cyclohexadienes from aromatic starting materials. We demonstrate a few synthetic applications of this scalable procedure by preparing highly-functionalized small molecules in three to four steps from naphthalene.

Keywords: Arenophiles; Catalysis; Dearomatization; Hydroamination; Palladium.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1.
Fig. 1.
(a) Previous work in arenophile-mediated dearomative aminofunctionalization. (b) Precedented examples of dearomative 1,4-hydroamination. (c) Biologically active natural products that could be accessed via a dearomative 1,4-hydroamination. (d) This work.
Fig. 2.
Fig. 2.
Derivatization of naphthalene-derived product 7i. Reagents and conditions: (a) OsO4 (cat.), NMO, citric acid, 48 %, >20:1 dr. (b) NaOCl, 22 %. (c) 2,2-DMP, TsOH, 83 %. (d) tBuOCl, AcOH, 18 %. (e) Et2Zn, ICH2Cl, 36 %, >20:1 dr. (f) α-bromoacetophenone, K2CO3, 76 %. (g) KOH, 41 %.
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