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Synlett 2014; 25(4): 564-568
DOI: 10.1055/s-0033-1340312
letter
© Georg Thieme Verlag Stuttgart · New York

Exploring the Use of the Suzuki Coupling Reaction in the Synthesis of 4′-Alkyl-2′-hydroxyacetophenones

Christelle Pouget*
a   EA 1069-GDR CNRS 3049, Laboratoire de Chimie des Substances Naturelles, Faculté de Pharmacie, 2 rue du Docteur Marcland, 87025 Limoges, France   Fax: +33(5)55435801   eMail: christelle.pouget@unilim.fr
,
Patrick Trouillas
a   EA 1069-GDR CNRS 3049, Laboratoire de Chimie des Substances Naturelles, Faculté de Pharmacie, 2 rue du Docteur Marcland, 87025 Limoges, France   Fax: +33(5)55435801   eMail: christelle.pouget@unilim.fr
,
Rokhaya Gueye
a   EA 1069-GDR CNRS 3049, Laboratoire de Chimie des Substances Naturelles, Faculté de Pharmacie, 2 rue du Docteur Marcland, 87025 Limoges, France   Fax: +33(5)55435801   eMail: christelle.pouget@unilim.fr
,
Yves Champavier
b   Service Commun de Recherche et d’Analyses de Biomolécules de Limoges (SCRABL), Université de Limoges, 2 rue du Docteur Marcland, 87025 Limoges, France
,
Aurélie Laurent
a   EA 1069-GDR CNRS 3049, Laboratoire de Chimie des Substances Naturelles, Faculté de Pharmacie, 2 rue du Docteur Marcland, 87025 Limoges, France   Fax: +33(5)55435801   eMail: christelle.pouget@unilim.fr
,
Jean-Luc Duroux
a   EA 1069-GDR CNRS 3049, Laboratoire de Chimie des Substances Naturelles, Faculté de Pharmacie, 2 rue du Docteur Marcland, 87025 Limoges, France   Fax: +33(5)55435801   eMail: christelle.pouget@unilim.fr
,
Vincent Sol
a   EA 1069-GDR CNRS 3049, Laboratoire de Chimie des Substances Naturelles, Faculté de Pharmacie, 2 rue du Docteur Marcland, 87025 Limoges, France   Fax: +33(5)55435801   eMail: christelle.pouget@unilim.fr
,
Catherine Fagnere
a   EA 1069-GDR CNRS 3049, Laboratoire de Chimie des Substances Naturelles, Faculté de Pharmacie, 2 rue du Docteur Marcland, 87025 Limoges, France   Fax: +33(5)55435801   eMail: christelle.pouget@unilim.fr
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Publikationsverlauf

Received: 29. Oktober 2013

Accepted after revision: 01. November 2013

Publikationsdatum:
06. Dezember 2013 (online)

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Abstract

A series of 4′-alkyl-2′-hydroxyacetophenones were prepared by Suzuki cross-coupling reactions of 4′-bromo-2′-hydroxyacetophenone. In these reactions, alkyl(trifluoro)borates were found to be better reactants than alkylboronic acids. 4′-Alkyl-2′-hydroxyacetophenones are key intermediates for the further synthesis of ­lipoflavonoids that are more readily incorporated into lipid bilayer membranes than flavonoids and should, therefore, have superior ­biological effects through increased bioavailability.

Key words

alkylation - cross-coupling - catalysis - palladium - ketones
 

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  • 32 4′-Alkyl-2′-hydroxyacetophenones; General Procedure for Microwave-Assisted Synthesis with Potassium Alkyl(trifluoro)borates 4′-Bromo-2′-hydroxyacetophenone, K+ (RBF3)– (1.5 equiv), Pd(OAc)2 (0.1 equiv), RuPhos (0.2 equiv), 3 M aq NaOH (0.5 mL, 3 equiv), and toluene (5 mL) were placed in a 10 mL microwave vessel that was sealed with a pressure lock. The mixture was then subjected to microwave irradiation in an Anton Paar Monowave 300 microwave reactor at 120 °C (150 W) for 5 h.
  • 33 4′-Butyl-2′-hydroxyacetophenone 1H NMR (400 MHz, CDCl3): δ = 0.93 (t, J = 7.3 Hz, 3 H), 1.35 (m, 2 H), 1.60 (m, 2 H), 2.60 (t, J = 7.5 Hz, 2 H), 2.60 (s, 3 H, COCH3), 6.72 (dd, J = 1.6, 8.2 Hz, 1 H, H-5′), 6.79 (d, J = 1.2 Hz, 1 H, H-3′), 7.63 (d, J = 8.2 Hz, 1 H, H-6′), 12.28 (s, 1 H, OH). 13C NMR (100 MHz, CDCl3): δ = 13.9 (CH3), 22.3 (CH2), 26.5 (CH3–CO), 32.8 (CH2), 35.9 (CH2), 117.8 (Cq, C-1′), 117.8 (CH, C-3′), 119.6 (CH, C-5′), 130.6 (CH, C-6′), 153.0 (Cq, C-4′), 162.6 (Cq, C-2′), 203.9 (C=O). HRMS (ESI): m/z [M + H]+ calcd for C12H17O2: 193.1223; found: 193.1225.
  • 34 4′-Decyl-2′-hydroxyacetophenone 1H NMR (400 MHz, CDCl3): δ = 0.88 (t, J = 6.8 Hz, 3 H), 1.27 (m, 14 H), 1.61 (m, 2 H), 2.59 (t, J = 7.5 Hz, 2 H), 2.60 (s, 3 H, COCH3), 6.72 (dd, J = 1.3, 8.2 Hz, 1 H, H-5′), 6.79 (br s, 1 H, H-3′), 7.63 (d, J = 8.2 Hz, 1 H, H-6′), 12.28 (s, 1 H, OH). 13C NMR (100 MHz, CDCl3): δ = 14.1 (CH3), 22.7 (CH2), 26.5 (CH3–CO), 29.2 (CH2), 29.3 (CH2), 29.4 (CH2), 29.5 (CH2), 29.6 (CH2), 30.7 (CH2), 31.9 (CH2), 36.2 (CH2), 117.8 (Cq, C-1′), 117.8 (CH, C-3′), 119.6 (CH, C-5′), 130.6 (CH, C-6′), 153.1 (Cq, C-4′), 162.6 (Cq, C-2′), 203.9 (C=O). HRMS (ESI): m/z [M + H]+ calcd for C18H29O2: 277.2162; found: 277.2162.
  • 35 4′-Hexyl-2′-hydroxyacetophenone 1H NMR (400 MHz, CDCl3): δ = 0.88 (t, J = 6.8 Hz, 3 H), 1.30 (m, 6 H), 1.61 (m, 2 H), 2.59 (t, J = 7.4 Hz, 2 H), 2.60 (s, 3 H, COCH3), 6.72 (dd, J = 1.6, 8.2 Hz, 1 H, H-5′), 6.79 (d, J = 1.3 Hz, 1 H, H-3′), 7.63 (d, J = 8.2 Hz, 1 H, H-6′), 12.28 (s, 1 H, OH). 13C NMR (100 MHz, CDCl3): δ = 14.1 (CH3), 22.6 (CH2), 26.5 (CH3–CO), 28.9 (CH2), 30.6 (CH2), 31.7 (CH2), 36.2 (CH2), 117.8 (Cq, C-1′), 117.8 (CH, C-3′), 119.6 (CH, C-5′), 130.6 (CH, C-6′), 153.0 (Cq, C-4′), 162.6 (Cq, C-2′), 203.9 (C=O). HRMS (ESI): m/z [M + H]+ calcd for C14H21O2: 221.1536; found: 221.1538.
  • 36 2′-Hydroxy-4′-octylacetophenone 1H NMR (400 MHz, CDCl3): δ = 0.88 (t, J = 6.8 Hz, 3 H), 1.28 (m, 10 H), 1.61 (m, 2 H), 2.59 (t, J = 6.7 Hz, 2 H), 2.60 (s, 3 H, COCH3), 6.72 (dd, J = 1.1, 8.2 Hz, 1 H, H-5′), 6.79 (br s, 1 H, H-3′), 7.63 (d, J = 8.2 Hz, 1 H, H-6′), 12.28 (s, 1 H, OH). 13C NMR (100 MHz, CDCl3): δ = 14.1 (CH3), 22.7 (CH2), 26.5 (CH3–CO), 29.2 (2 × CH2), 29.4 (CH2), 30.7 (CH2), 31.9 (CH2), 36.2 (CH2), 117.8 (Cq, C-1′), 117.8 (CH, C-3′), 119.6 (CH, C-5′), 130.6 (CH, C-6′), 153.1 (Cq, C-4′), 162.6 (Cq, C-2′), 203.9 (C=O). HRMS (ESI): m/z [M + H]+ calcd for C16H25O2: 249.1849; found: 249.1850.