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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 wide range of functional groups can be aminated in high yields. The regioselectivity of amination for unsymmetrical internal alkynes is strongly influenced by substitution pattern (tertiary > secondary > primary) and by relatively remote heteroatomic substituents. We demonstrate that amination of alkynes bearing α-stereocenters occurs with retention of configuration at the newly-formed C–N bond. Competition experiments between alkynes, kinetic isotope effects, and DFT calculations are performed to confirm the mechanistic hypothesis that initial ene reaction of a selenium bis(imide) species is the rate- and product-determining step. This ene reaction has a transition state that results in substantial partial positive charge development at the carbon atom closer to the amination position. Inductive and/or hyperconjugative stabilization or destabilization of this positive charge explains the observed regioselectivities.
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Directing-Group-Free Arene C(sp 2 )–H Amination Using Bulky Aminium Radicals and DFT Analysis of Regioselectivity
A hydroxylamine-derived electrophilic aminating reagent produces a transient and bulky aminium radical intermediate upon in situ activation by either TMSOTf or TFA and a subsequent electron transfer from an iron(II) catalyst. Density functional theory calculations were used to examine the regioselectivity of arene C−H amination reactions on diversely substituted arenes. The calculations suggest a simple charge-controlled regioselectivity model that enables prediction of the major C(sp²)−H amination product.
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- Award ID(s):
- 2102462
- PAR ID:
- 10537030
- Publisher / Repository:
- American Chemical Society
- Date Published:
- Journal Name:
- The Journal of Organic Chemistry
- Volume:
- 88
- Issue:
- 16
- ISSN:
- 0022-3263
- Page Range / eLocation ID:
- 11847 to 11854
- Subject(s) / Keyword(s):
- arylamines aminium radical, C-H amination
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1021/acs.joc.3c01127
