Palladium‐Catalyzed Domino Cyclization/Phosphorylation of gem‐Dibromoolefins with P(O)H Compounds: Synthesis of Phosphorylated Heteroaromatics

Abstract

We presented a palladium-catalyzed domino cyclization/phosphorylation of gem-dibromoolefins, which utilize H-phosphinates and secondary phosphine oxides as the phosphine sources, respectively. A variety of phosphorylated heteroaromatics were obtained in moderate to good yields with wide functional group compatibility. This one-pot reaction enables multiple bond-forming events including CÀ X (X = O, N, S) and CÀ P bonds using easily available starting materials. Moreover, this protocol can be easily applied to largescale preparation and late-stage functionalization.

One-Pot Phosphonylation of Heteroaromatic Lithium Reagents: The Scope and Limitations of Its Use for the Synthesis of Heteroaromatic Phosphonates

“…66–67 °C (lit. [ 46 ] m.p. 81–82 °C); 31 P-NMR (243.12 MHz, CDCl 3 ,): δ = 10.54 ppm; 1 H-NMR (600.58 MHz, CDCl 3 ): δ = 1.36 (t, 6H, J = 7.1 Hz, POCH 2 C H 3 ), 4.12–4.25 (m, 4H, POC H 2 CH 3 ), 7.09 (s, 1H, C H = CP), 7.19 (t, 1H, J = 7.4 Hz, Ar H ), 7.33 (t, 1H, J = 8.3 Hz, Ar H ), 7.51 (d, 1H, J = 7.9 Hz, Ar H ), 9.67 (s, 1H, N H ) ppm; 13 C-NMR (151.02 MHz, CDCl 3 ): δ = 16.14 (d, J = 7.55 Hz, POCH 2 C H 3 ), 62.98 (d, J = 4.53 Hz, PO C H 2 ), 112.15 (d, J = 9.06 Hz, P-C= C ), 112.26 (d, J = 9.06 Hz), 120.48, 121.75, 123.01 (d, J = 220.49 Hz, P- C =C), 124.60, 127.23 (d, J = 15.10 Hz, P-C=C- C ), 138.43 (d, J = 12.08 Hz, P-C=C-N- C ) ppm; HRMS (ESI + TOF) m / z : [M + H] + .…”

Synthetic Methods for Azaheterocyclic Phosphonates and Their Biological Activity: An Update 2004–2024

“…209 The synthesis of 2-phosphonylated indoles 418 can be achieved by using palladium-catalyzed domino cyclization/ phosphonylation of gem-dibromoolefins 416, as reported by Zhu et al (Scheme 82). 210 This methodology utilizes diethyl phosphite 417 in the presence of the ligand 1,1′-bis-(diphenylphosphino)ferrocene (DPPF) and K 2 CO 3 as a base in toluene at 90 °C to afford the corresponding products 418 in moderate to good yields. This reaction has also been applied for the synthesis of other phosphonylated heteroaromatic compounds such as benzofuranes and benzothiophenes and allows the generation of the phosphonylated polycyclic compound 420 after some modifications in the reaction conditions.…”

Biocatalytic Friedel‐Crafts Reactions

“…[45] This broad enzyme family is often divided into three categories: Mg 2 + -dependent membrane-bound UbiA-type enzymes, dimethylallyltryptophan synthase (DMATS)-type enzymes, and ABBAtype enzymes. [46] The first type are found in bacteria, plants and fungi and contain an aspartate-rich motif for metal-ion binding, whilst the latter two types are not found in plants, and contain no metal-binding motif.…”

“…[67] The discussion on this diverse enzyme family provided here is far from exhaustive, and for further information we direct the reader to recent reviews on the topic. [46,68] The broad range of aromatic substrates identified with various aPTases, as well as their frequent acceptance of alternative and non-natural prenyl-donors, makes them appealing biocatalysts for the preparation of many alkyl-aryl linkages.…”