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. 2019 Jan 9;141(1):671-676.
doi: 10.1021/jacs.8b12152. Epub 2018 Dec 20.

Regio- and Enantioselective Iridium-Catalyzed Amination of Racemic Branched Alkyl-Substituted Allylic Acetates with Primary and Secondary Aromatic and Heteroaromatic Amines

Seung Wook Kim  1 , Leyah A Schwartz  1 , Jason R Zbieg  2 , Craig E Stivala  2 , Michael J Krische  1
Affiliations

Regio- and Enantioselective Iridium-Catalyzed Amination of Racemic Branched Alkyl-Substituted Allylic Acetates with Primary and Secondary Aromatic and Heteroaromatic Amines

Seung Wook Kim et al. J Am Chem Soc. .

Abstract

The air- and water-stable π-allyliridium C,O-benzoate modified by ( S)-tol-BINAP, ( S)-Ir-II, catalyzes highly regio- and enantioselective Tsuji-Trost-type aminations of racemic branched alkyl-substituted allylic acetates using primary or secondary (hetero)aromatic amines. Specifically, in the presence of ( S)-Ir-II (5 mol%) in DME solvent at 60-70 °C, α-methyl allyl acetate 1a (100 mol%) reacts with primary (hetero)aromatic amines 2a-2l (200 mol%) or secondary (hetero)aromatic amines 3a-3l (200 mol%) to form the branched products of allylic amination 4a-4l and 5a-5l, respectively, as single regioisomers in good to excellent yield with uniformly high levels of enantioselectivity. As illustrated by the conversion of heteroaromatic amine 3m to adducts 6a-6g, excellent levels of regio- and enantioselectivity are retained across diverse branched allylic acetates bearing normal alkyl or secondary alkyl substituents. For reactants 3n-3p, which incorporate both primary and secondary aryl amine moieties, regio- and enantioselective amination occurs with complete site-selectivity to furnish adducts 7a-7c. Mechanistic studies involving amination of the enantiomerically enriched, deuterium-labeled acetate 1h corroborate C-N bond formation via outer-sphere addition.

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Figures

Figure 1.
Figure 1.
Cationic vs neutral chiral iridium complexes for regio- and enantioselective allylic amination.
Scheme 1.
Scheme 1.
Iridium-catalyzed amination of enantiomerically enriched deuterated allylic acetate 1h with the enantiomeric catalysts (S)-Ir-II and (R)-Ir-II.a a Yields of material isolated by silica gel chromatography. Enantioselectivities were determined by chiral stationary phase HPLC analysis. See Supporting Information for further experimental details.
Scheme 2.
Scheme 2.
General catalytic mechanism and stereochemical model for enantioselective iridium-catalyzed allylic amination.
See this image and copyright information in PMC

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