Cu‐Catalyzed Hydroxymethylation of Unactivated Alkyl Iodides with CO To Provide One‐Carbon‐Extended Alcohols

Abstract

We have developed ar eductive carbonylation method by which unactivated alkyli odides can be hydroxymethylated to provideo ne-carbon-extended alcohol products under Cu-catalyzed conditions.The method is tolerant of alkyl b-hydrogen atoms,i sr obust towards aw ide variety of functional groups,a nd was applied to primary,s econdary,a nd tertiary alkyli odide substrates.M echanistic experiments indicate that the transformation proceeds by atom-transfer carbonylation (ATC) of the alkyli odide followed in tandem by two CuH-mediated reductions in rapid succession. This radical mechanism renders the Cu-catalyzed system complementary to precious-metal-catalyzed reductive carbonylation reactions.

Photoredox/Nickel‐Catalyzed Single‐Electron Tsuji–Trost Reaction: Development and Mechanistic Insights

“…Motivated by the advantageous biological properties demon-strated by molecules containing alkyl-substituted carbohydrate substructures, 30 DHP monosaccharides were successfully allylated under the dual catalytic conditions with modest to high diastereoselectivities (Table 4). Pyranose and furanose backbones with benzyl-, methoxy-, and dioxolane protecting groups were conserved.…”

Copper‐Catalyzed Borocarbonylative Coupling of Internal Alkynes with Unactivated Alkyl Halides: Modular Synthesis of Tetrasubstituted β‐Borylenones

“…According to our design, instead of oxidative addition of the alkyl halide to A to give the carboboration product G via intermediate F (Scheme 2, path b), an alkyl radical RC is favorably generated from the reaction of A and the alkyl halide (path a). Ther adical species RC then undergoes carbonylation to give the acyl radical species C, [15] which collapses with the copper(II) complex B to form the copper-(III) intermediate D.Finally,reductive elimination affords the b-borylated tetrasubstituted enone E.W er easoned that the corresponding highly-substituted products E would be sufficiently inert to avoid further borylation [16] under the current reaction conditions.However,several conditions must be met to execute the proposed four-component coupling reaction successfully.F irst, reaction conditions must be identified under which the rate of the electron-transfer step (path a) between A and the alkyl halide exceeds the rate of oxidative addition (path b). In addition, A should also be active enough towards the alkyl halide partner to outcompete base-mediated elimination of the alkyl halide substrate to generate HX, ultimately leading to hydroboration side products.N onetheless,w ef elt that if suitable reaction conditions could be identified, the targeted strategy would constitute ap ractical and modular way to synthesize tetrasubstituted enones using readily available alkynes and alkyl halides as starting materials.T he unique features of the method we have successfully developed include:1 )the first general synthetic method for tetrasubstituted enones;2)demonstration of C À C and CÀXc oupling reactions with b-borylated enone derivatives;3 )a rare example of af our-component carbonylative coupling reaction [17] that simultaneously installs two CÀC bonds and one CÀBb ond.…”

“…Ther adical species RC then undergoes carbonylation to give the acyl radical species C, [15] which collapses with the copper(II) complex B to form the copper-(III) intermediate D.Finally,reductive elimination affords the b-borylated tetrasubstituted enone E.W er easoned that the corresponding highly-substituted products E would be sufficiently inert to avoid further borylation [16] under the current reaction conditions.However,several conditions must be met to execute the proposed four-component coupling reaction successfully.F irst, reaction conditions must be identified under which the rate of the electron-transfer step (path a) between A and the alkyl halide exceeds the rate of oxidative addition (path b). Ther adical species RC then undergoes carbonylation to give the acyl radical species C, [15] which collapses with the copper(II) complex B to form the copper-(III) intermediate D.Finally,reductive elimination affords the b-borylated tetrasubstituted enone E.W er easoned that the corresponding highly-substituted products E would be sufficiently inert to avoid further borylation [16] under the current reaction conditions.However,several conditions must be met to execute the proposed four-component coupling reaction successfully.F irst, reaction conditions must be identified under which the rate of the electron-transfer step (path a) between A and the alkyl halide exceeds the rate of oxidative addition (path b).…”