Enantioselective Hydroazidation of Trisubstituted Non‐Activated Alkenes

Abstract

A one-pot procedure for the enantioselective hydroazidation of non-activated trisubstituted alkenes is described. Hydroboration with monoisopinocampheylborane (IpcBH ) provides dialkylboranes that are in situ selectively converted into monoalkyl-substituted catecholboranes; these undergo radical azidation upon treatment with benzenesulfonyl azide and a radical initiator. Enantiomerically enriched azides were thus obtained in yields of 59-81 % and enantioselectivities of up to 94:6 e.r. (98:2 e.r. if the intermediate dialkylborane is purified by crystallization). A rapid access to enantiomerically pure (+)-rodocaine is also described. The use of other arenesulfonyl radical traps enables enantioselective hydroallylation, hydrosulfanylation, and hydrobromination reactions with yields of 71-86 %.

Anti‐Markovnikov Hydroazidation of Alkenes by Visible‐Light Photoredox Catalysis

“…[12] However,c omparedw ith olefin difunctionalization azidation reactions, [13,14] hydroazidation of alkenes, av ariant of hydroamination, has been much less been explored.T here have only been several studies addressingt his issue during the last two decades. [15][16][17][18][19] In 2005, Waser and Car-reira developed aM arkovnikov olefin hydroazidations trategy featuring ac obalt-catalyzed radicalh ydrogen addition and azidylt ransfer process. [16] Latero n, Boger and co-workersa chieved similart ransformationsb yu sing iron as catalyst.…”

“…The alkenew as first hydroborated to give an organoborane, which was then azidated with benzenesulfonyl azide by ar adicalmediated azidyl transfer. [18] Recently,C hiba and Gagosz developed anotherr adical proceduref or the anti-Markovnikovh ydroazidation of functionalized alkenes. [19] This methodi nvolves the addition of azidylr adicalo nto the alkenem oiety followed by intramolecular hydrogen atom transfer from an internal benzyl protecting group.…”

Cyclopropanation of Terminal Alkenes through Sequential Atom‐Transfer Radical Addition/1,3‐Elimination

“…[7][8][9][10][11] They are prepared either through hydroboration, [12,13] reactions of organometallic species with borate esters and related reagents, [14] C À Ha ctivation, [15] and more recently radical borylation reactions. [17][18][19] Our long-standing interest in developing mild methods for the functionalization of alkenes through radical pathways [20][21][22][23][24][25][26][27][28][29][30][31][32] inspired us to investigate iodoalkylation involving 1-borylated alkyl radicals to give g-iodoalkylboronates.B ased on EPR studies and calculations,W alton, Carboni, and co-workers reported that 1-borylated radicals are stabilized when the boron is sp 2 -hybridized, however the extent of stabilization is smaller for radicals with aboronic ester substituent relative to the corresponding borinic ester or borane ( Figure 1A). [17][18][19] Our long-standing interest in developing mild methods for the functionalization of alkenes through radical pathways [20][21][22][23][24][25][26][27][28][29][30][31][32] inspired us to investigate iodoalkylation involving 1-borylated alkyl rad...…”

A Short Synthesis of (+)-Brefeldin C via Enantioselective Radical Hydroalkynylation

“…[35] Recently,o ur group reported am ethodf or enantioselective hydroazidationo ft risubstitutedn onactivated alkenes. [56] This reactionw as extended to other enantioselective hydrofunctionalization processes such as hydrobromination, [56] hydrofluorination, [57] hydrosulfurization, [56] and hydroallylation. [56] Brown et al have pioneered the enantioselective hydralkynylation of alkenes.…”

“…[56] This reactionw as extended to other enantioselective hydrofunctionalization processes such as hydrobromination, [56] hydrofluorination, [57] hydrosulfurization, [56] and hydroallylation. [56] Brown et al have pioneered the enantioselective hydralkynylation of alkenes. [58] However,t heir multistep approach was lengthy and required severe reactionc onditions to convert alkylboronates to thexyl(alkyl)boranes before treatment with lithium acetylide and iodine under Zweifel-type conditions.…”