Synlett 2015; 26(08): 1077-1080
DOI: 10.1055/s-0034-1378689
letter
© Georg Thieme Verlag Stuttgart · New York

Ruthenium-Catalyzed Direct N-Formylation of Lactams with Paraformaldehyde

Hoseong Lee
a  Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea   Email: soonhong@snu.ac.kr
b  Department of Chemical R&D Center, SK Innovation, Daejeon 305-712, Korea
,
Byungjun Kang
a  Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea   Email: soonhong@snu.ac.kr
,
Sang-Ick Lee
b  Department of Chemical R&D Center, SK Innovation, Daejeon 305-712, Korea
,
Soon Hyeok Hong*
a  Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea   Email: soonhong@snu.ac.kr
› Author Affiliations
Further Information

Publication History

Received: 27 November 2014

Accepted after revision: 16 February 2014

Publication Date:
18 March 2015 (online)


Abstract

Catalytic N-formylation of lactams was conducted with paraformaldehyde using Shvo’s catalyst. Various lactams were smoothly converted into N-formylimides without the use of a stoichiometric activating reagent.

Supporting Information

 
  • References and Notes

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  • 14 General Procedure for N-Formylation of Amides with Paraformaldehyde Lactam (1.25 mmol), paraformaldehyde (6.25 mmol, 5.0 equiv), Shvo’s catalyst (6.78 mg, 0.5 mol%), and toluene (2.0 mL) were placed in an oven-dried sealed reactor inside a glovebox under a nitrogen atmosphere. The sealed reactor was taken out and heated to 150 °C in an oil bath. After 1 h, the reaction mixture was cooled to r.t. All volatiles were removed under vacuum. Unless the crude product was in solution, the desired product could be simply precipitated by washing using hexane and EtOAc. In the case that the crude was in solution, purification was performed with silica gel column chromatography using hexane and EtOAc (or CH2Cl2 and MeOH solvent mixture) as eluent to afford the desired product. All of the reported formylation products, N-formylazetidin-2-one (1c),10 N-formylpyrrolidin-2-one (2c),9b N-formylpiperidin-2-one (3c),9b N-formylazepan-2-one (4c),9b N-formylazocan-2-one (5c),9b and N-formyl-5-methylpyrrolidin-2-one (6c),13 were identified by spectral comparison with literature data or with analogous literature data. N-Formylisoindolin-1-one (7c) White solid, yield 69%, mp 146 °C. 1H NMR (400 MHz, CDCl3): δ = 9.31 (s, 1 H), 7.91 (d, J = 8.0 Hz, 1 H), 7.67 (d, J = 7.6 Hz, 1 H), 7.54 (t, J = 8.0 Hz, 2 H), 4.74 (s, 2 H). 13C NMR (101 MHz, CDCl3): δ = 168.7, 160.1, 142.1, 134.7, 130.1, 128.9, 125.3, 123.8, 45.5. ESI-HRMS: m/z [M + Na]+ calcd for C9H7NO2: 184.0374; found: 184.0365. N-Formyl-5-methylisoindolin-1-one (8c) White solid, yield 99%, mp 110 °C. 1H NMR (400 MHz, CDCl3): δ = 9.21 (s, 1 H), 7.75 (d, J = 7.6 Hz, 1 H), 7.26 (d, J = 8.4 Hz, 2 H), 4.61 (s, 2 H), 2.43 (s, 3 H). 13C NMR (101 MHz, CDCl3): δ = 168.6, 160.1, 146.1, 142.5, 130.0, 127.4, 125.0, 124.1, 45.3, 22.1. ESI-HRMS: m/z [M + Na]+ calcd for C10H9NO2: 198.0531; found: 198.0524. N-Formyl-5-hydroxyisoindolin-1-one (9c) Ivory solid, yield 81%, mp 298 °C. 1H NMR (500 MHz, DMSO): δ = 10.18 (s, 1 H), 7.54 (d, J = 5.5 Hz, 1 H), 6.91 (s, 1 H), 6.88 (d, 1 H), 5.21 (s, 1 H), 4.38 (s, 2 H). 13C NMR (101 MHz, DMSO): δ = 180.34, 173.2, 166.2, 148.7, 129.7, 127.5, 120.8, 114.0, 53.9. HRMS (CI): m/z [M + H]+ calcd for C9H7NO3: 178.0504; found: 178.0505. N-Formyl-5-fluoroisoindolin-1-one (10c) White solid, yield 97%, mp 143 °C. 1H NMR (400 MHz, CDCl3): δ = 9.27 (s, 1 H), 7.94 (d, J = 5.2 Hz, 1 H), 7.21 (d, J = 7.6 Hz, 2 H), 4.73 (s, 2 H). 13C NMR (101 MHz, CDCl3): δ = 166.89 (d, J = 257.8 Hz), 167.5, 159.9, 144.8 (d, J = 11.4 Hz), 127.8 (d, J = 15.2 Hz), 126.3, 177.3 (d, J = 30.4 Hz), 111.3, (d, J = 26.6 Hz), 45.4 (d, J = 2.8 Hz). 19F NMR (282 MHz, CDCl3): δ = –103.1 (q, J = 8.4 Hz). HRMS (CI): m/z [M + H]+ calcd for C9H6FNO2: 184.0461; found: 180.0461. N-Formyl-5-chloroisoindolin-1-one (11c) White solid, yield 68%, mp 168 °C. 1H NMR (500 MHz, CDCl3): δ = 9.31 (s, 1 H), 7.91 (d, J = 8.0 Hz, 1 H), 7.57 (s, 1 H), 7.54 (d, J = 8.0 Hz, 1 H), 4.76 (s, 2 H). 13C NMR (101 MHz, CDCl3): δ = 167.5, 160.0, 143.5, 141.3, 129.7, 128.6, 126.5, 124.3, 45.2. ESI-HRMS: m/z [M + Na]+ calcd for C9H6ClNO2: 217.9985; found: 217.9981. N-Formyl-5-bromoisoindolin-1-one (12c) Yellow solid, yield 44%, mp 173 °C. 1H NMR (400 MHz, CDCl3): δ = 9.30 (s, 1 H), 7.82 (d, J = 7.6 Hz, 1 H), 7.79 (s, 1 H), 7.68 (d, J = 8.0 Hz, 1 H), 4.73 (s, 2 H). 13C NMR (101 MHz, CDCl3): δ = 168.1, 160.6, 145.6, 132.4, 129.6, 128.9, 128.2, 126.7, 45.8. ESI-HRMS: m/z [M + Na]+ calcd for C9H6BrNO2: 261.9480; found: 261.9471. N-Formyl-3,4-dihydroisoquinolin-1(2H)-one (13c) Ivory solid, yield 51%, mp 76 °C. 1H NMR (500 MHz, CDCl3): δ = 9.63 (s, 1 H), 8.15 (d, J = 2.0 Hz, 1 H), 7.57 (t, J = 1.5 Hz, 1 H), 7.43 (t, J = 6.5 Hz, 1 H), 7.30 (d, J = 6.5 Hz, 1 H), 4.01 (t, J = 6.3 Hz, 2 H), 3.05 (t, J = 6.3 Hz, 2 H). 13C NMR (101 MHz, CDCl3): δ = 165.6, 162.4, 139.9, 134.1, 129.3, 127.8, 127.7, 127.6, 38.7, 27.4. ESI-HRMS: m/z [M + Na]+ calcd for C10H9NO2: 198.0531; found: 198.0523.