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

Abstract

We report a diastereoconvergent synthesis of anti-1,2-amino alcohols bearing N-containing quaternary stereocenters using an intermolecular direct C-H amination of homoallylic alcohol derivatives catalyzed by a phosphine selenide. Destruction of the...

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

“…However, we found that the addition of lithium acetate greatly improved the desired reactivity, allowing us to obtain 68% of the allylic amide product. In our previous work, basic additives have been shown to improve the yield, presumably to scavenge acidic byproducts of the reaction . To test the generality of this protocol, we screened a few natural terpene scaffolds using trifluoroacetamide as the nitrogen source and obtained moderate to good yields of the desired amination products in every case (Scheme ).…”

“…In our previous work, basic additives have been shown to improve the yield, presumably to scavenge acidic byproducts of the reaction. 10 To test the generality of this protocol, we screened a few natural terpene scaffolds using trifluoroacetamide as the nitrogen source and obtained moderate to good yields of the desired amination products in every case (Scheme 3). Other amides were not suitable coupling partners under these conditions, presumably due to competing Hofmann rearrangement (see the Supporting Information (SI) for examples).…”

“…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.…”

Selective C–H activation of unprotected allylamines by control of catalyst speciation

“…6 Several methods have been developed to synthesize allylamines that involve forming the C-N bond by substitution on allylic systems, either through simple SN2 reactions 7 or through many recent and elegant approaches to allylic C-H amination. [8][9][10][11] However, these methods require the pre-synthesis of the allyl fragment, which means the majority of these methods give rise to disubstituted or 1,1-symmetrical trisubstituted alkene products due to the challenge of accessing more complex allyl substrates (Scheme 1a).Meanwhile, methods that make use of the amine as a structural feature to facilitate further elaboration have generally been limited to protected amine substrates. [12][13][14] We were particularly interested in how the use of C-H activation could enable rapid access to substitution of the alkene from simple precursors, rather than relying on low-yielding and multistep reaction sequences to prepare unsymmetrical 3,3-disubstituted allylamines.…”