Synlett 2020; 31(10): 982-986
DOI: 10.1055/s-0040-1708011
letter
© Georg Thieme Verlag Stuttgart · New York

The Use of α-Diazo-γ-butyrolactams in the Büchner–Curtius–Schlotterbeck Reaction of Cyclic Ketones Opens New Entry to Spirocyclic Pyrrolidones

Maria Eremeyeva
,
Daniil Zhukovsky
,
Dmitry Dar’in
,
Saint Petersburg State University, Saint Petersburg, 199034, Russian Federation   Email: m.krasavin@spbu.ru
› Author Affiliations
This research was supported by the Russian Foundation for Basic Research (project grant 19-03-00775).
Further Information

Publication History

Received: 15 February 2020

Accepted after revision: 08 March 2020

Publication Date:
23 March 2020 (online)


ABSTRACT

The only cyclic α-diazocarbonyl compound employed in the Büchner–Curtius–Schlotterbeck ring expansion of cyclic ketones to date was α-diazo-γ-butyrolactone. Encouraged by the recent success using α-diazo acetamides in related Tiffeneau–Demjanov type ring expansions, we extended this approach to various α-diazo-γ-butyrolactams, which produced, under BF3·OEt2-promoted conditions, spirocyclic seven-membered ketones. These findings substantially enhance the possibilities offered by cyclic α-diazocarbonyl compounds in constructing privileged spirocyclic scaffolds for drug design.

Supporting Information

 
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  • 14 Characterization data for representative compounds: Compound 2a: Yield: 59 mg (70%); white amorphous solid. 1H NMR (400 MHz, CDCl3): δ = 7.63–7.58 (m, 2 H), 7.40–7.31 (m, 2 H), 7.18–7.11 (m, 1 H), 3.95 (dt, J = 9.3, 7.7 Hz, 1 H), 3.74 (td, J = 9.0, 3.7 Hz, 1 H), 3.09 (ddd, J = 12.4, 11.2, 2.7 Hz, 1 H), 2.86 (ddd, J = 12.6, 7.9, 3.7 Hz, 1 H), 2.55–2.39 (m, 2 H), 2.06–1.94 (m, 2 H), 1.94–1.78 (m, 3 H), 1.66–1.53 (m, 1 H), 1.52–1.39 (m, 1 H), 1.31–1.16 (m, 1 H). 13C NMR (101 MHz, CDCl3): δ = 210.9, 171.9, 139.2, 128.8, 124.8, 120.1, 63.7, 46.3, 41.7, 34.7, 30.4, 28.8, 26.7, 25.3. HRMS (ESI/Q-TOF): m/z [M + H]+ calcd for C16H19NO2: 258.1489; found: 258.1488. Compound 2e: Yield 52 mg (51%); white semi-solid. 1H NMR (400 MHz, CDCl3): δ = 7.56–7.39 (m, 2 H), 7.02–6.73 (m, 2 H), 3.92 (dt, J = 9.4, 7.8 Hz, 1 H), 3.79 (s, 3 H), 3.70 (td, J = 9.1, 3.1 Hz, 1 H), 3.54 (ddd, J = 11.9, 8.1, 5.4 Hz, 1 H), 3.12–3.00 (m, 1 H), 3.11–2.78 (m, 4 H), 2.79–2.69 (m, 1 H), 2.60–2.48 (m, 1 H), 2.19 (ddd, J = 15.3, 7.0, 2.8 Hz, 1 H), 1.83 (ddd, J = 12.8, 8.9, 7.8 Hz, 1 H). 13C NMR (101 MHz, CDCl3): δ = 207.0, 170.9, 156.9, 132.2, 121.9, 114.1, 63.0, 55.5, 46.6, 43.3, 36.4, 28.2, 27.8, 25.3. HRMS (ESI/Q-TOF): m/z [M + Na]+ calcd for C16H19NO3S: 328.0978; found: 328.0970. Compound 2l: Yield: 33 mg (55%); white solid; mp 110.3–111.5 °C. 1H NMR (400 MHz, CDCl3): δ = 6.79 (s, 1 H), 4.09 (ddd, J = 13.0, 6.3, 2.2 Hz, 1 H), 3.94 (ddd, J = 12.2, 6.0, 4.2 Hz, 1 H), 3.66 (ddd, J = 12.4, 9.2, 3.4 Hz, 1 H), 3.56 (ddd, J = 13.0, 9.4, 1.9 Hz, 1 H), 3.46 (dt, J = 9.6, 7.5 Hz, 1 H), 3.36–3.28 (m, 1 H), 3.24 (ddd, J = 13.3, 9.2, 4.3 Hz, 1 H), 2.75 (ddd, J = 12.9, 7.9, 3.7 Hz, 1 H), 2.69–2.53 (m, 2 H), 1.92–1.76 (m, 2 H). 13C NMR (101 MHz, CDCl3): δ = 208.2, 175.8, 68.2, 66.1, 59.7, 45.7, 39.5, 35.4, 32.0. HRMS (ESI/Q-TOF): m/z [M + H]+ calcd for C9H13NO3: 184.0968; found: 184.0972. Compound 2n: Yield: 49 mg (53%); yellow semi-solid. 1H NMR (400 MHz, CDCl3): δ = 6.65–6.46 (m, 1 H), 3.88–3.61 (m, 2 H), 3.61–3.44 (m, 2 H), 3.40 (dt, J = 9.6, 7.5 Hz, 1 H), 3.30 (tdd, J = 9.6, 3.6, 1.2 Hz, 1 H), 3.18 (s, 1 H), 2.76 (ddd, J = 12.9, 7.7, 3.6 Hz, 1 H), 2.70–2.59 (m, 1 H), 2.48–2.36 (m, 1 H), 1.90–1.72 (m, 2 H), 1.46 (s, 9 H). 13C NMR (101 MHz, CDCl3): δ = 207.5, 176.1, 154.7, 80.2, 60.3, 44.1, 43.1, 42.7, 42.4, 41.7, 39.4, 34.5, 34.2, 31.7, 31.4, 28.4. HRMS (ESI/Q-TOF): m/z [M + H]+ calcd for C14H22N2O4: 283.1652; found: 283.1641.
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