Download PDF
Synlett 2020; 31(04): 369-372
DOI: 10.1055/s-0039-1690786
letter
© Georg Thieme Verlag Stuttgart · New York

An Efficient Palladium-Catalysed Aminocarbonylation of Benzyl Chlorides

Eloise Rilvin-Derrick
,
Niall Oram
,
Jeffery Richardson  ∗
Discovery Research and Technologies, Eli Lilly and Company, Erl Wood Manor, Sunninghill Road, Windlesham, Surrey, GU20 6PH, UK   Email: Richardson_jeffery@lilly.com
› Author Affiliations
Further Information

Publication History

Received: 09 November 2019

Accepted after revision: 11 December 2019

Publication Date:
10 January 2020 (online)

    Permissions and Reprints All articles of this category


Abstract

An improved procedure for the aminocarbonylation of benzyl chloride derivatives using carbon monoxide and either primary or secondary amines has been developed. Studying the competing background alkylation reaction allowed the solvent and base to be selected for a simple catalyst screen, which, in turn, enabled the discovery of a method for the preparation of 2-arylacetamides under mild conditions, with minimal side-products using an inexpensive phosphine ligand. This non-traditional optimisation strategy allowed us to overcome the background alkylation, which has been cited as justification for the development of more complex and less atom-economical approaches.

Key words

palladium catalysis - carbonylation - amides - reaction optimisation

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0039-1690786.
  • Supporting Information
 

  • References and Notes

  • 1 Frutos-Pedreño R, García-López JA. Adv. Synth. Catal. 2016; 358: 2692
    Crossref
  • 2 Kalyanasundaram M, Mathew N. J. Med. Entomol. 2006; 43: 518
    PubMed
  • 3 Hao J, Beck JP, Schaus JM, Krushinski JH, Chen Q, Beadle CD, Vidal P, Reinhard MR, Dressman BA, Massey SM, Boulet SL, Cohen MP, Watson BM, Tupper D, Gardinier KM, Myers J, Johansson AM, Richardson J, Richards DS, Hembre EJ, Remick DM, Coates DA, Bhardwaj RM, Diseroad BA, Bender D, Stephenson G, Wolfangel CD, Diaz N, Getman BG, Wang X, Heinz BA, Cramer JW, Zhou X, Maren DL, Falcone JF, Wright RA, Mitchell SN, Carter G, Yang CR, Bruns RF, Svensson KA. J. Med. Chem. 2019; 62: 8711
    CrossrefPubMed
  • 4 Zhu C, Wang L, Zhu Y, Guo ZZ, Liu P, Hu Z, Szewczyk JW, Kang L, Chicchi G, Ehrhardt A, Woods A, Seo T, Woods M, van Heek M, Dingley KH, Pang J, Salituro GM, Powell J, Terebetski JL, Hornak V, Campeau L.-C, Orr RK, Ujjainwalla F, Miller M, Stamford A, Wood HB, Kowalski T, Nargund RP, Edmondson SD. Bioorg. Med. Chem. Lett. 2017; 27: 1124
    CrossrefPubMed
  • 5 Zhang W, Ready JM. Angew. Chem. Int. Ed. 2014; 53: 8980
    CrossrefPubMed
  • 6 Schoenberg A, Heck RF. J. Org. Chem. 1974; 39: 3327
    Crossref
  • 7 Schoenberg A, Bartoletti I, Heck RF. J. Org. Chem. 1974; 39: 3318
    Crossref
  • 8 Ho S, Bondarenko G, Rosa D, Dragisic B, Orellana A. J. Org. Chem. 2012; 77: 2008
    CrossrefPubMed
  • 9 Fang W, Deng Q, Xu M, Tu T. Org. Lett. 2013; 15: 3678
    CrossrefPubMed
  • 10 Salvadori J, Balducci E, Zaza S, Petricci E, Taddei M. J. Org. Chem. 2010; 75: 1841
    CrossrefPubMed
  • 11 Martinelli JR, Clark TP, Watson DA, Munday RH, Buchwald SL. Angew. Chem. Int. Ed. 2007; 46: 8460
    CrossrefPubMed
  • 12 Brennfuehrer A, Neumann H, Beller M. Angew. Chem. Int. Ed. 2009; 48: 4114
    CrossrefPubMed
  • 13 Barnard CF. J. Organometallics 2008; 27: 5402
    Crossref
  • 14 Roy S, Roy S, Gribble GW. Tetrahedron 2012; 68: 9867
    Crossref
  • 15 Troisi L, Granito C, Rosato F, Videtta V. Tetrahedron Lett. 2010; 51: 371
    Crossref
  • 16 Yu H, Gao B, Hu B, Huang H. Org. Lett. 2017; 19: 3520
    CrossrefPubMed
  • 17 Xie P, Xia C, Huang H. Org. Lett. 2013; 15: 3370
    CrossrefPubMed
  • 18 Cunico RF, Pandey RK. J. Org. Chem. 2005; 70: 9048
    CrossrefPubMed
  • 19 Zhang W, Cao P, Guo Q, Chen J. Curr. Org. Synth. 2017; 14: 1067
  • 20 Wang L, Neumann H, Beller M. Angew. Chem. Int. Ed. 2019; 58: 5417
    CrossrefPubMed
  • 21 Wu X.-F, Schranck J, Neumann H, Beller M. ChemCatChem 2012; 4: 69
    Crossref
  • 22 Karimi F, Långström B. Org. Biomol. Chem. 2003; 541
    CrossrefPubMed
  • 23 Kihlberg T, Långström B. J. Org. Chem. 1999; 64: 9201
    Crossref
  • 24 Gockel SN, Hull KL. Org. Lett. 2015; 17: 3236
    CrossrefPubMed
  • 25 Ren W, Yamane M. J. Org. Chem. 2010; 75: 3017
    CrossrefPubMed
  • 26 Ren W, Yamane M. J. Org. Chem. 2010; 75: 8410
    CrossrefPubMed
  • 27 Iranpoor N, Firouzabadi H, Motevalli S, Talebi M. Tetrahedron 2013; 69: 418
    Crossref
  • 28 General Procedure: To a round-bottomed ACE glass pressure flask containing a magnetic stirrer was added toluene (20 mL), chloromethylbenzene (1.0 g, 7.9 mmol) and N,N-diisopropylethylamine (1.5 equiv). The mixture was degassed with subsurface nitrogen purge for 5 minutes. Palladium(II) acetate (2.5 mol%) and bis(2-diphenylphosphinophenyl)ether (5 mol%) were added, followed by the primary or secondary amine (1.2 equiv) to give a pale-yellow solution. The flask was purged with nitrogen, filled with carbon monoxide to 50 psig and heated at 70 °C with magnetic stirring overnight. The reaction mixture was cooled to ambient temperature and residual CO vented. The reaction mixture was partitioned between EtOAc (200 mL) and 10% aq. citric acid (2 × 30 mL). The organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was loaded to the top of a silica gel plug with CH2Cl2 and eluted with a gradient of EtOAc in isohexane to afford the amide products.