A General Approach to Site‐Specific, Intramolecular C−H Functionalization Using Dithiocarbamates

Abstract

Intramolecular hydrogen atom transfer is an established approach for the site-specific functionalization of unactivated, aliphatic CÀHb onds.T ransformations using this strategy typically require unstable intermediates formed using strong oxidants and have mainly targeted CÀHh alogenations or intramolecular aminations.Herein, we report asite-specific C À Hfunctionalization that significantly increases the synthetic scope and convergency of reactions proceeding via intramolecular hydrogen atom transfer.S table,i solable N-dithiocarbamates are used as precursors to amidyl radicals formed via either light or radical initiation to efficiently deliver highly versatile alkyl dithiocarbamates across aw ide range of complex structures.

Enantioselective Copper-Catalyzed Cyanation of Remote C(sp3)-H Bonds Enabled by 1,5-Hydrogen Atom Transfer

“…Although inert C(sp 3 )-H bonds are almost impossible to distinguish from other aliphatic C-H bonds on the alkyl side chain, 1,n-hydrogen-atom transfer strategy offers us a reliable solution to selectively cleave the remote C(sp 3 )-H bonds in a high chemo- and regioselective path. Starting from the pioneering work of Hofmann (Hofmann, 1883), known as Hofmann–Lӧffler–Freytag (HLF) reaction with N-haloamines used as precursors to generate N-centered radical (Hofmann, 1883, Lӧffler and Freytag, 1909, Wolff, 1963, Neale, 1971, Mackiewicz and Furstoss, 1978), the selective cleavage of remote C(sp 3 )-H bonds via 1,5-HAT process is well documented (Robertson et al., 2001, Čeković, 2003, Chiba and Chen, 2014, Stateman et al., 2018, Chu and Rovis, 2016, Chu and Rovis, 2018, Martínez and Muñiz, 2015, Wappes et al., 2016, Choi et al., 2016, Xia et al., 2018, Na and Alexanian, 2018). Although the early examples utilize transition metal to facilitate electron transfer, to further expand the scope of this remote C(sp 3 )-H functionalization process, many domino processes involving a metal-catalyzed cross-coupling pathway have developed (Scheme 1A) (Zhou and Andrus, 2002, Zhang et al., 2016, Zhang et al., 2019a, Zhang et al., 2019b, Zhang et al., 2019c; Wang et al., 2018, Groendyke et al., 2016, Li et al., 2018, Liu et al., 2019, Bao et al., 2019).…”

Sulfamate Esters Guide C(3)-Selective Xanthylation of Alkanes

“…1b,d,15 Recently, Alexanian and co-workers have disclosed a directed C( 4)−H dithiocarbamate-transfer reaction (Scheme 2B). 16 Herein, we describe a reaction with complementary position selectivity: a sulfamate ester guided light-initiated reaction to xanthylate unactivated alkyl C(3)−H bonds (Scheme 2C). This approach enables generation of molecular diversity on the basis of guided functionalization of a single C(sp 3 )−H center, with expected practical value to medicinal chemists.…”

Photocarboxylation of remote C–H bonds through nitrogen-centred radical 1,5-hydrogen atom transfer

“…Prompted by the interest in the nitrogen-centered-radical based 1,5-HAT strategy, researchers recently have made remarkable contributions to remote C-H bond functionalization via nitrogen-centered-radical (NCR)-triggered radical translocation processes. These innovative approaches have enabled the formation of a diverse range of bonds, including the building of C-C, 13,20 C-O, 21,22 C-N, [23][24][25][26] C-S, 27 and C-X (X = halogen) bonds. 14,19,28 Owing to its abundance, minimal toxicity, and renewability, carbon dioxide (CO 2 ), the well-known greenhouse gas, emerges as an ideal one-carbon building block for the formation of C-C bonds in organic synthesis.…”

“…4,17–19 Prompted by the interest in the nitrogen-centered-radical based 1,5-HAT strategy, researchers recently have made remarkable contributions to remote C–H bond functionalization via nitrogen-centered-radical (NCR)-triggered radical translocation processes. These innovative approaches have enabled the formation of a diverse range of bonds, including the building of C–C, 13,20 C–O, 21,22 C–N, 23–26 C–S, 27 and C–X (X = halogen) bonds. 14,19,28…”