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Synlett 2020; 31(20): 2027-2034
DOI: 10.1055/s-0040-1707261
letter

Pd-Catalyzed Functionalization of Aryl Amines on a Soluble Polymer Support

A. Sofia Santos
,
M. Manuel B. Marques  ∗
LAQV@REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal   Email: msbm@fct.unl.pt
› Author AffiliationsThis work was supported by the Associate Laboratory for Green Chemistry – LAQV which is financed by national funds from Fundação para a Ciência e a Tecnologia (FCT, UID/QUI/50006/2019) and the Ministry of Science, Technology and Higher Education (MCTES) and co-financed by the European Regional Development Fund (ERDF) under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007265). The National NMR Facility is supported by the Fundação para a Ciência e a Tecnologia (FCT, ROTEIRO/0031/2013 and PINFRA/22161/2016), co-financed by FEDER through COMPETE 2020, POCI, and PORL and FCT through PIDDAC). We thank to the Fundação para a Ciência e a Tecnologia (FCT) for fellowship (PD/BD/142876/2018).
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Abstract

Herein we report the use of a soluble polymer support PEG-2000 on Pd-catalyzed reactions to improve the functionalization of aromatic amines and the synthesis of N-heterocycles. Compatibility of metal-catalyzed reactions for assembling privileged structures such as functionalized anilines were studied. PEG-supported anilines were found to be suitable substrates for Pd-catalyzed N-arylation, Sonogashira and Heck reactions. PEGylated substrates were prepared in yields up to 94%. This work consists on a proof of concept on the use of PEGylated anilines on Pd-catalyzed cross-coupling reactions. Indole core was attained in 82% and 62% yields, via two different routes.

Key words

aryl amine - metal-catalyzed - PEG - functionalization - anilines

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1707261.
  • Supporting Information


Publication History

Received: 21 May 2020

Accepted after revision: 28 July 2020

Article published online:
03 September 2020

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  • 29 General Procedure for Sonogashira Reaction DMF was previously degassed 7 times by applying vacuum when the mixture is completely frozen and then flushed with nitrogen. Three solutions were prepared with the degassed DMF, and the solids were dried under vacuum before DMF addition. Solution A A round-bottom flask was charged with product of C–N cross-coupling reaction (1 equiv), DIPEA (3.2 equiv), and DMF (c 0.47 M) and the final solution degassed thrice. Solution B A round-bottom flask was charged with CuI (5 mol%), PdCl2(PPh3)2 (3 mol%), and DMF (c 0.0137 M) and the final solution degassed thrice. Solution C A round-bottom flask was charged with ethynylbenzene (2.1 equiv) and DMF (c 0.5M) and the final solution degassed thrice. Solution A was added via syringe to solution B, then was degassed twice; and finally, solution C was added. The mixture was degassed one more time, then allowed to warm-up to 110 °C and stirred for 24 h. After reaction completion, DMF was evaporated; DCM was added to the residue and washed with sat. NH4Cl and water. The combined organic layers were dried over Na2SO4, the desiccant filtered, the solvent concentrated, and the product was vacuum dried. PEG–Bis[4-amino-3-(phenylethynyl)benzoate] (3e) Isolated as a brown solid (73%). IR (KBr): νmax = 3466, 3350, 3217, 2916, 1962, 1705, 1622, 1454, 1118 cm–1. 1H NMR (400 MHz, (CD3)2CO): δ = 8.01 (s, ArH-2, 1 H), 7.79 (dd, ArH-6, J = 8.6, 1.7 Hz, 1 H), 7.67–7.60 (m, ArH, 2 H), 7.43 (d, ArH, J = 5.9 Hz, 3 H), 6.88 (d, ArH-5, J = 8.6 Hz, 1 H), 4.39 (t, CH2 PEG J = 6 Hz, 2 H), 3.81 (t, CH2 PEG, J = 4 Hz, 2 H), 3.72–3.51 (m, CH2 PEG, 102 H) ppm. 13C NMR (101 MHz, (CD3)2CO): δ = 166.27 (C=O), 154.25 (C-4), 135.00 (C-2), 132.39 (C-6), 132.29 (CAr), 129.44 (CAr), 129.34 (CAr), 124.11 (C-1), 114.18 (C-5), 106.80 (C-3), 95.35 (C-8), 86.08 (C-7), 71.29 (CH2 PEG), 69.91 (CH2 PEG), 64.40 (CH2 PEG).
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