Iron-Catalyzed Reductive Vinylation of Tertiary Alkyl Oxalates with Activated Vinyl Halides

Abstract

We present herein a rare and efficient method for the creation of vinylated all carbon quaternary centers via Fe-catalyzed cross-electrophile coupling of vinyl halides with tertiary alkyl methyl oxalates. The reaction displays excellent functional group tolerance and broad substrate scope, which allows cascade radical cyclization and vinylation to afford complex bicyclic and spiral structural motifs. The reaction proceeds via tertiary alkyl radicals, and the putative vinyl–Br/Fe complexation appears to be crucial for activating the alkene and enabling a possibly concerted radical addition/C–Fe forming process.

Reductive Cross-Coupling of Vinyl Electrophiles

“…29 In 2020, they also achieved an ironcatalyzed reductive vinylation of tertiary alkyl methyl oxalates, providing an access for the construction of vinylated all carbon quaternary centers (Scheme 8c). 30 Scheme 8 Reductive coupling of vinyl halides with C-O electrophiles…”

Iron-catalysed reductive cross-coupling of glycosyl radicals for the stereoselective synthesis of C-glycosides

“…Other Fe(II) and Fe(II) salts were inferior, and the addition of ligands was detrimental to the efficiency (Supplementary Table 2). Given that simple iron salts are typically incapable of inducing oxidative cleavage of C(sp 2 )− Cl bonds 63 , and that fluoroalkenes also serve as effective reagents under the reaction conditions (see Table 1 for details), we surmised that the Fe-catalysed alkenylation probably proceeds through an addition-elimination pathway 19 . Control experiments further revealed that the C-alkenyl glycoside product was generated as a single E isomer regardless of the stereochemistry of the haloalkene used (see Supplementary Fig.…”

“…2a). After cage escape, the glycosyl radical could directly react with a sp 2 -or sp-hybridized organohalide or pseudohalide 5 through an iron-mediated stereocontrolled radical addition/β-halide elimination 19,44 to furnish 6 in high diastereoselectivity via ii. Alternatively, the incorporation of a suitable nickel-based co-catalyst 45 that first activates 5 to generate an organonickel intermediate iii, followed by stereocontrolled association with the glycosyl radical (to give iv) and reductive elimination would also afford 6.…”

Iron‐Catalyzed Regioselective Alkenylboration of Olefins

“…The observations that alkenyl fluorides served as competent substrates for alkenylboration (cf. Scheme 2) point in favor of an addition-elimination pathway, [9,15] since C(sp 2 )ÀF bonds are typically resistant to oxidative cleavage by an organoiron species. Hypothetically, a syn-diastereoselective carbometallation across the alkenyl halide p-bond followed by established base-promoted anti-selective bhalide-elimination, [16] would lead to stereoretention of the starting haloalkene geometry in each case (pathway 1, III!…”

“…IV). Conversely, if a long-lived radical species V is indeed generated (by adventitious homolytic fission of CÀFe bond in III), [12] radical addition likely proceeds anti to an ironcoordinated E-haloalkene [15] (i.e. to minimize steric repulsions), which would give VI that subsequently undergoes bhalide-elimination to furnish an adduct that bears a Z olefin motif (stereoinversion) as the major isomer (pathway 2, III!…”