Stereoretentive and regioselective selenium-catalyzed intermolecular propargylic C–H amination of alkynes

Abstract

Herein we report an intermolecular propargylic C-H amination of alkynes. This reaction is operationally convenient and requires no transition metal catalysts or additives. Terminal, silyl, and internal alkynes bearing a...

Boryl-Dictated Site-Selective Intermolecular Allylic and Propargylic C–H Amination

“…During the preparation of this work, Michael reported a selenium-catalyzed propargylic C–H amination of alkynes and found that several electronegative substituents could discriminate propargylic C–H bonds to provide moderate to good regioselectivity. In only one case, the use of an electropositive silyl substituent at the α position resulted in a reversed site-selectivity of 1:9 …”

“…In only one case, the use of an electropositive silyl substituent at the α position resulted in a reversed site-selectivity of 1:9. 42 By slightly modifying the reaction conditions (with PhI-(OOCBn) 2 as oxidant), we discovered that the boryl-directed aminations gave a surprisingly high level of regioselectivity, with almost no other regioisomers detected (Table 3). It was only in the gram-scale synthesis of 53 that we were able to isolate 5 mg of the minor isomer, suggesting a site-selectivity of around 300:1.…”

Metal-Free Intermolecular Allylic C–H Amination of Alkenes Using Primary Carbamates

“…As such, a wide variety of catalytic methods for selective amination at the allylic position have been developed . Intermolecular delivery of nitrogen groups via allylic C–H amination reactions of alkenes has been well established using a variety of transition-metal and main-group catalysts, allowing controlled synthesis of allylic sulfonamides, − amides, − and more recently alkylamines − (Scheme A).…”

“…We and others have recently demonstrated allylic C−H amination reactions catalyzed by selenium complexes. [8][9][10][11]45 Our protocol enabled regioselective C−N bond formation on a wide variety of complex alkene substrates. Importantly, this metal-free reaction directly employed a wide range of primary sulfonamides and sulfamates as nitrogen sources without the need for separate synthesis of a nitrenoid precursor.…”

Diastereoconvergent synthesis of anti-1,2-amino alcohols with N-containing quaternary stereocenters via selenium-catalyzed intermolecular C–H amination

“…We previously reported a metal-free allylic amination catalyzed by phosphine selenides that proceeds via a mechanism distinct from most other C–H functionalizations. 7 Initial ene reaction between an imidoselenium species cleaves the C–H bond and transposes the alkene, and a subsequent [2,3]-sigmatropic rearrangement delivers the new C–N bond ( Scheme 1A ). This “flip-flop” mechanism has several distinct properties that enable new modes of diastereocontrol without requiring intramolecular delivery of the nitrogen group: (i) C–H bond cleavage and C–N bond formation occur in separate steps, (ii) both steps are concerted and proceed suprafacially, (iii) initial activation of the C C bond by Se takes place distal to the C–H bond being functionalized, and (iv) there is no allylic transposition of the intermediate, allowing either step to be stereodetermining depending on the substrate.…”