Synlett 2017; 28(20): 2851-2854
DOI: 10.1055/s-0036-1588540
letter
© Georg Thieme Verlag Stuttgart · New York

Catalytic Deuteration of Aldehydes with D2O

Eric S. Isbrandt
Centre for Catalysis Research and Innovation, Department of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie Curie, Ottawa, Ontario, K1N 6N5, Canada   Email: stephen.newman@uottawa.ca
,
Jaya Kishore Vandavasi
Centre for Catalysis Research and Innovation, Department of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie Curie, Ottawa, Ontario, K1N 6N5, Canada   Email: stephen.newman@uottawa.ca
,
Wanying Zhang
Centre for Catalysis Research and Innovation, Department of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie Curie, Ottawa, Ontario, K1N 6N5, Canada   Email: stephen.newman@uottawa.ca
,
Mohammad P. Jamshidi
Centre for Catalysis Research and Innovation, Department of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie Curie, Ottawa, Ontario, K1N 6N5, Canada   Email: stephen.newman@uottawa.ca
,
Stephen G. Newman*
Centre for Catalysis Research and Innovation, Department of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie Curie, Ottawa, Ontario, K1N 6N5, Canada   Email: stephen.newman@uottawa.ca
› Author Affiliations
Financial support for this work was provided by the University of Ottawa, the National Science and Engineering Research Council of Canada (NSERC), and the Canada Research Chair program. The Canadian Foundation for Innovation (CFI) and the Ontario Ministry of Economic Development and Innovation are thanked for essential infrastructure. E.I. thanks NSERC and the Government of Ontario for USRA and OGS scholarships, respectively.
Further Information

Publication History

Received: 19 June 2017

Accepted after revision: 17 July 2017

Publication Date:
21 August 2017 (online)


Dedicated to Professor Victor Snieckus on the occasion of his 80th birthday

Abstract

A procedure is presented that enables the direct deuteration of the formyl C–H bond of aldehydes using D2O as the deuterium source and commercially available RuHCl(CO)(PPh3)3 as the catalyst. Up to 84% deuterium incorporation can be achieved in a single experiment. Multiple iterations can be carried out to further increase the deuteration.

Supporting Information

 
  • References and Notes

    • 1a Isin EM. Elmore CS. Nilsson GN. Thompson RA. Weidolf L. Chem. Res. Toxicol. 2012; 25: 532
    • 1b Marathe PH. Shyu WC. Humphreys WG. Curr. Pharm. Des. 2004; 10: 2991
    • 1c Elmore CS. Annu. Rep. Med. Chem. 2009; 44: 515
    • 1d Meanwell NA. J. Med. Chem. 2011; 54: 2529
    • 1e Katsnelson A. Nat. Med. 2013; 19: 656

      For select examples of the deuteride reduction, alcohol oxidation sequence, see:
    • 2a Sakamoto S. Mori K. Akiyama T. Org. Lett. 2012; 14: 3312
    • 2b Kihara M. Andoh J.-i. Yoshida C. Heterocycles 2000; 53: 359
    • 2c Schwab JM. Klassen JB. J. Am. Chem. Soc. 1984; 106: 7217
    • 2d Olsen EP. K. Singh T. Harris P. Andersson PG. Madsen R. J. Am. Chem. Soc. 2015; 137: 834
    • 2e Davies PW. Martin N. Spencer N. Beilstein J. Org. Chem. 2011; 7: 839
    • 2f Adcock HV. Chatzopoulou E. Davies PW. Angew. Chem. Int. Ed. 2015; 54: 15525
    • 2g Wu J. Wang D. Wan Y. Ma C. Chem. Commun. 2016; 52: 1661
    • 3a Spletstoser JT. White JM. Georg GI. Tetrahedron Lett. 2004; 45: 2787
    • 3b Spletstoser JT. White JM. Tunoori AR. Georg GI. J. Am. Chem. Soc. 2007; 129: 3408
  • 4 Thompson AF. Cromwell NH. J. Am. Chem. Soc. 1939; 61: 1374
  • 5 Seebach D. Erickson BW. Singh G. J. Org. Chem. 1966; 31: 4303
  • 6 For example, at the time of publication, both benzaldehyde and its formyl-deuterated analogue (98% D) are commercially available from Sigma-Aldrich, with the latter being over 1000 times more costly.
  • 7 Defoin A. Defoin-Straathann R. Kuhn HJ. Tetrahedron 1984; 14: 2651
  • 8 During the completion of this manuscript, an Ir-catalyzed method to deuterate aldehydes using D2 gas was published. See: Kerr WJ. Reid M. Tuttle T. Angew. Chem. Int. Ed. 2017; 129: 7916
  • 9 Tse SK. S. Xue P. Lin Z. Jia G. Adv. Synth. Catal. 2010; 352: 1512
    • 10a Chatterjee B. Gunanthan C. Org. Lett. 2015; 17: 4794
    • 10b Bai W. Lee K.-H. Tse SK. S. Chan KW. Lin Z. Jia G. Organometallics 2015; 34: 3686
    • 10c Bossi G. Putignano E. Rigo P. Baratta W. Dalton Trans. 2011; 40: 8986
    • 10d Khaskin E. Milstein D. ACS Catal. 2013; 3: 448
  • 11 Tse SK. S. Xue P. Lau CW. S. Sung HH. Y. Williams ID. Jia G. Chem. Eur. J. 2011; 17: 13918
    • 12a Levison JJ. Robinson SD. J. Chem Soc. A. 1970; 2947
    • 12b Jasimuddin S. Thakurata DG. Transition Met. Chem. 2009; 34: 937
  • 13 Skaddan MB. Yung CM. Bergman RG. Org. Lett. 2004; 6: 11
  • 14 Representative Procedure for Aldehyde Deuteration 2-Naphthaldehyde (1a, 46.9 mg, 0.3 mmol) and RuHCl(CO)(PPh3)3 (14.3 mg, 0.015 mmol, 5 mol%) were dissolved in PhMe (1.5 mL, 0.2 M) in an oven-dried screw-cap vial. D2O (27 μL, 1.5 mmol) was then added. The vial was sparged with argon and capped. The resulting solution was heated to 100 °C and stirred for 30 min. At the end of the reaction, the solvent was removed in vacuo and the crude material was purified by column chromatography using a 2 → 8% EtOAc in hexane gradient to afford 41.9 mg 2a as a white solid (89% yield, 72% D). 1H NMR (400 MHz, CDCl3): δ = 8.35 (s, 1 H), 8.02–7.90 (m, 4 H), 7.67–7.57 (m, 2 H). Residual formyl proton: δ = 10.1.
    • 15a Chakraborty S. Guan H. Dalton Trans. 2010; 39: 7427
    • 15b Wang D. Astruc D. Chem. Rev. 2015; 115: 6621