Hydroamination versus Allylic Amination in Iridium-Catalyzed Reactions of Allylic Acetates with Amines: 1,3-Aminoalcohols via Ester-Directed Regioselectivity

Kim, Seung Wook; Wurm, Thomas; Brito, Gilmar A.; Jung, Woo‐Ok; Zbieg, Jason R.; Stivala, Craig E.; Krische, Michael J.

doi:10.1021/jacs.8b05683

Cited by 26 publications

(13 citation statements)

References 70 publications

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“…While significant advances have been made in anti-Markovnikov hydroamination in the past few years, controlling the selectivity remains challenging, due to the intrinsic electronic and steric bias embedded in the reacting alkene and amine substrates . Notable strategies in directing the amination in the anti-Markovnikov fashion include substrate and catalyst control, use of electrophilic amines in conjunction with a hydride source, , and photocatalysis and related means to generate amine radicals . In addition, some indirect, formal anti-Markovnikov hydroamination strategies have been put forward, such as hydroboration/amination, hydrozirconation/amination, and Wacker oxidation/reductive amination .…”

Section: Introductionmentioning

confidence: 99%

Iron-Catalyzed Anti-Markovnikov Hydroamination and Hydroamidation of Allylic Alcohols

Zhang

Fan

et al. 2019

J. Am. Chem. Soc.

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Hydroamination allows for the direct access to synthetically important amines. Controlling the selectivity of the reaction with efficient, widely applicable, and economic catalysts remains challenging, however. This paper reports an iron-catalyzed formal anti-Markovnikov hydroamination and hydroamidation of allylic alcohols, which yields γ-amino and γ-amido alcohols, respectively. Homoallylic alcohol is also feasible. The catalytic system, consisting of a pincer Fe-PNP complex (1–4 mol %), a weak base, and a nonpolar solvent, features exclusive anti-Markovnikov selectivity, broad substrate scope (>70 examples), and good functional group tolerance. The reaction could be performed at gram scale and applied to the synthesis of drug molecules and heterocyclic compounds. When chiral substrates are used, the stereochemistry and enantiomeric excess are retained. Further application of the chemistry is seen in the functionalization of amino acids, natural products, and existing drugs. Mechanistic studies suggest that the reaction proceeds via two cooperating catalytic cycles, with the iron complex catalyzing a dehydrogenation/hydrogenation process while the amine substrate acts as an organocatalyst for the Michael addition step.

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Section: Introductionmentioning

confidence: 99%

Iron-Catalyzed Anti-Markovnikov Hydroamination and Hydroamidation of Allylic Alcohols

Zhang

Fan

et al. 2019

J. Am. Chem. Soc.

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“…Finally, using the enantiomeric iridium catalysts ( S )-Ir- II and ( R )-Ir- II , the ( S )-citronellol-derived allylic acetate 1g reacts with 3m to form 6g and iso - 6g , respectively, with good levels of catalyst-directed diastereoselectivity. Under these conditions, aryl-substituted allyl acetates gave low yields (<10%) of allylic amination product, and linear allylic acetates provided mixtures of allylic amination and hydroamination product in low isolated yield …”

Section: Methodsmentioning

confidence: 99%

“…Under these conditions, aryl-substituted allyl acetates gave low yields (<10%) of allylic amination product and linear allylic acetates provided mixtures of allylic amination and hydroamination product in low isolated yield. 19…”

Section: Methodsmentioning

confidence: 99%

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

Kim

Schwartz

Zbieg³

et al. 2018

J. Am. Chem. Soc.

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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 labelled acetate 1h corroborate C-N bond formation via outer-sphere addition.

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“…Allylic amination of linear acetates with primary amines by neutral dppf‐modified iridium catalyst was studied by Krische et al [55] . Usage of neutral iridium catalyst under basic conditions provided products of allylic amination with complete 1,3‐regio selectivity.…”

Section: Classificationmentioning

confidence: 99%

An Overview of Iridium‐Catalyzed Allylic Amination Reactions

Biya¹,

Neetha²,

Anilkumar

2021

ChemistrySelect

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Amination reactions plays a paramount role as it finds wide applications in pharmaceuticals, production of natural compounds and in drug synthesis. Considering the wide tool chest of procedures, it is one of the key approaches to C−N bond construction. In recent years, substantial headway has been observed in reactions of these type and have progressed into vital assistance for building molecules in modern synthetic chemistry. Concerning the catalytic activity of Iridium complexes which are suitable for many organic transformations including amination reactions, studies on amination of allylic systems by Iridium catalysts are significant. This review concisely compiles information on Iridium‐catalyzed allylic amination, casing literature up to 2020.

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Hydroamination versus Allylic Amination in Iridium-Catalyzed Reactions of Allylic Acetates with Amines: 1,3-Aminoalcohols via Ester-Directed Regioselectivity

Cited by 26 publications

References 70 publications

Iron-Catalyzed Anti-Markovnikov Hydroamination and Hydroamidation of Allylic Alcohols

Iron-Catalyzed Anti-Markovnikov Hydroamination and Hydroamidation of Allylic Alcohols

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

An Overview of Iridium‐Catalyzed Allylic Amination Reactions

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