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. 2023 Oct 6;88(19):13995-14003.
doi: 10.1021/acs.joc.3c01536. Epub 2023 Sep 25.

Copper(II)-Catalyzed Three-Component Arylation/Hydroamination Cascade from Allyl Alcohol: Access to 1-Aryl-2-sulfonylamino-propanes

Camilla Loro  1 , Marta Papis  1 , Francesca Foschi  1 , Gianluigi Broggini  1 , Giovanni Poli  2 , Julie Oble  2
Affiliations

Copper(II)-Catalyzed Three-Component Arylation/Hydroamination Cascade from Allyl Alcohol: Access to 1-Aryl-2-sulfonylamino-propanes

Camilla Loro et al. J Org Chem. .

Abstract

A new straightforward approach to 1-aryl-2-aminopropanes using easily accessible substrates has been developed. Simple allyl alcohol is shown to be an ideal synthetic equivalent of the C3 propane-1,2-diylium bis-cation synthon in three-component cascade reactions with arenes and sulfonamide nucleophiles to regioselectively afford 1-aryl-2-aminopropanes. The reaction is catalyzed by Cu(OTf)2 and is expected to involve a Friedel-Crafts-type allylation of the arene, followed by hydroamination.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Selected Procedures for the Synthesis of 1-Aryl-2-aminopropanes
Scheme 2
Scheme 2. Allylic Alcohols as Variously Substituted C3 Synthons in Friedel–Crafts Reactions
Scheme 3
Scheme 3. Synthesis of 1-Mesityl-2-sulfonylamino-propanes 1b–h,
Reaction conditions: allyl alcohol (1.0 equiv), sulfonamide (2.0 equiv), mesitylene (5.0 equiv), Cu(OTf)2 (10 mol %), xantphos (20 mol %), and chlorobenzene as the solvent (0.25 M), 75 °C in an oil bath for 24 h. Isolated yields.
Scheme 4
Scheme 4. Arylation/Hydroamination with Different Hydrocarbons,
Reaction conditions: allyl alcohol (1.0 equiv), sulfonamide (2.0 equiv), hydrocarbons (5.0 equiv), Cu(OTf)2 (10 mol %), xantphos (20 mol %), and chlorobenzene as the solvent (0.25 M), 75 °C in an oil bath for 24 h. Isolated yields.
Scheme 5
Scheme 5. Arylation/Hydroamination with Different Arenes,
13a only observed by NMR and not isolated pure. 13b isolated with 39% yield. Reaction conditions: allyl alcohol (1.0 equiv), tosylamide (2.0 equiv), arene (5.0 equiv), Cu(OTf)2 (10 mol %), xantphos (20 mol %), and chlorobenzene as the solvent (0.25 M), 75 °C in an oil bath for 24 h. Isolated yields.
Scheme 6
Scheme 6. Proposed Mechanism for Arylation/Hydroamination of Allyl Alcohol
Scheme 7
Scheme 7. Variation on the Nature of the Alcohol,
Reaction conditions: allyl alcohol (1.0 equiv), sulfonamide (2.0 equiv), mesitylene (5.0 equiv), Cu(OTf)2 (10 mol %), xantphos (20 mol %), and chlorobenzene as the solvent (0.25 M), 75 °C in an oil bath for 24 h. Isolated yields.
Scheme 8
Scheme 8. Key Intermediates for Arylation/Hydroamination of Butenol Substrates
See this image and copyright information in PMC

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