Nickel-catalyzed site- and stereoselective reductive alkylalkynylation of alkynes

Abstract

Development of a catalytic multicomponent reaction by orthogonal activation of readily available substrates for the streamlined difunctionalization of alkynes is a compelling objective in organic chemistry. Alkyne carboalkynylation, in particular, offers a direct entry to valuable 1,3-enynes with different substitution patterns.Here, we show that the synthesis of stereodefined 1,3-enynes featuring a trisubstituted olefin is achieved by merging alkynes, alkynyl bromides and redox-active N-(acyloxy)phthalimides through nickel-catalyzed reductive alkylalkynylation. Products are generated in up to 89% yield as single regio-and E isomers.Transformations are tolerant of diverse functional groups and the resulting 1,3-enynes are amenable to further elaboration to synthetically useful building blocks. With olefin-tethered N-(acyloxy)phthalimides, a cascade radical addition/cyclization/alkynylation process can be implemented to obtain 1,5-enynes. The present study underscores the crucial role of redox-active esters as superior alkyl group donors compared to haloalkanes in reductive alkyne dicarbofunctionalizations. File list (2) download file view on ChemRxiv Koh, Zhao_text.pdf (2.30 MiB) download file view on ChemRxiv Koh, Zhao_SI.pdf (12.48 MiB)

Stereoconvergent Synthesis of Monofluoroalkenes via Photoinduced Dual Decarboxylative Cross-Coupling of α-Fluoroacrylic Acids with Redox-Active Esters

“…1 H NMR (400 MHz, chloroform- d ) δ 7.87 (d, J = 3.0 Hz, 2H), 7.79 (d, J = 2.8 Hz, 2H), 2.75 (t, J = 10.8 Hz, 1H), 2.10 (d, J = 11.7 Hz, 2H), 1.93–1.75 (m, 2H), 1.73–1.56 (m, 3H), 1.49–1.21 (m, 3H). Spectral data match the reported literature values …”

“…White solid ( S2 , 2.4 g, 88% yield) 1 H NMR (400 MHz, chloroform- d ) δ 7.83 (dd, J = 5.5, 3.1 Hz, 2H), 7.75 (dd, J = 5.6, 3.1 Hz, 2H), 5.88–5.58 (m, 2H), 2.98–2.90 (m, 1H), 2.42–2.33 (m, 2H), 2.26–2.06 (m, 3H), 1.98–1.76 (m, 1H). Spectral data match the reported literature values …”

“…White solid ( S5 , 3.0 g, 80% yield) 1 H NMR (400 MHz, chloroform- d ) δ 7.87 (dt, J = 7.4, 3.7 Hz, 2H), 7.83–7.72 (m, 2H), 4.02 (s, 2H), 2.99 (t, J = 11.2 Hz, 2H), 2.89 (m, 1H), 2.05 (dd, J = 13.2, 2.8 Hz, 2H), 1.83 (m, 2H), 1.45 (s, 9H). Spectral data match the reported literature values …”

Ni-Catalyzed Reductive Arylalkenylation of Alkynes for the Selective Synthesis of Polysubstituted Naphthalenes

“…Recently, a sharper focus has been placed on the difficulty of reactivity and regioselectivity with untethered electrophiles (Scheme C) . In this context, Koh, Shu, and Chu recently reported a nickel-catalyzed reductive difunctionalization of alkynes with two-carbon electrophiles. Despite the impressive progress in the work described above, the reductive difunctionalization of alkynes remains underexploited.…”

Access to Z-Selective 1,3-Enynes via Ni-Catalyzed Intermolecular Cross-Alkylalkynylation of Terminal Alkynes

“…However, few examples utilizing this strategy to construct 1,3-enynes have been developed, probably due to the competitive oligomerization of alkynes. Recently, Koh and Zhao reported a nickel-catalyzed three-component reductive alkylalkynylation of terminal alkynes with alkyl precursors and alkynyl bromides to deliver E -1,3-enynes (Scheme c). The Ikeda group reported a three-component reaction of nickel-catalyzed cross-coupling of alkynes, enones with organostannane, organozinc, or organoaluminum reagents, providing access to 1,3-enynes in Z -selectivity .…”