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Synlett 2014; 25(16): 2306-2310
DOI: 10.1055/s-0034-1378566
cluster
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Lactones and Lactams from Vinylcyclopropane by Palladium- Catalyzed Nucleophilic Allylation

Goki Hirata
Graduate School of Engineering, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan   Fax: +81(95)8192677   Email: masanari@nagasaki-u.ac.jp
,
Gen Onodera
Graduate School of Engineering, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan   Fax: +81(95)8192677   Email: masanari@nagasaki-u.ac.jp
,
Masanari Kimura*
Graduate School of Engineering, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan   Fax: +81(95)8192677   Email: masanari@nagasaki-u.ac.jp
› Author Affiliations
Further Information

Publication History

Received: 18 May 2014

Accepted after revision: 15 July 2014

Publication Date:
11 August 2014 (online)

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Abstract

A palladium-catalyzed nucleophilic allylation of aldehydes with vinylcyclopropane in the presence of diethylzinc proceeded to provide homoallyl alcohols with anti stereoselectivity. Aldimines prepared from aldehyde and primary amines in situ underwent a similar nucleophilic allylation to give homoallylamines with syn stereoselectivity. The resulting homoallyl alcohols and homoallylamines could be converted by treatment with a tetranuclear zinc cluster into γ-vinyl-δ-valerolactones and γ-vinyl-δ-valerolactams, respectively.

Key words

palladium - vinylcyclopropane - nucleophilic allylation - aldehyde - aldimine

Supporting Information

    for this article is available online at http://www.thieme-connect.com/products/ejournals/journal/ 10.1055/s-00000083.
  • Supporting Information
 

  • References and Notes

  • 7 See the Supporting Information.
  • 8 In the absence of Zn cluster catalyst, no lactonization and lactamization proceeded at all. These cyclizations required Zn cluster catalyst as a promoter to provide lactones and lactams from homoallyl alcohols and homoallylamines, respectively. Simple lactonization or lactamization conditions using acid catalysts and dehydration–condensation agents were ineffective.
  • 11 General Procedure for the Nucleophilic Allylation of Aldehyde with Vinylcyclopropane (Entry 1, Table 1): To a solution of Pd(acac)2 (15.2 mg, 0.05 mmol), and Ph3P (26.2 mg, 0.1 mmol) in anhyd THF (2 mL) were successively added vinylcyclopropane (221.0 mg, 1.2 mmol), benzaldehyde (106.1 mg, 1 mmol), and diethylzinc (2.4 mmol, 1.0 M hexane solution) via syringe under a nitrogen atmosphere. The mixture was stirred at r.t. for 48 h. The mixture was diluted with EtOAc (30 mL) and washed with 2 M HCl, and then brine. The extract was dried (MgSO4) and concentrated in vacuo and the residual oil was subjected to column chromatography over silica gel (hexane–EtOAc, 2:1) to give 1a (210.5 mg, 72%; Rf 0.63; hexane–EtOAc, 2:1) and 2a (54.8 mg, 21%; Rf 0.5; hexane–EtOAc, 2:1). Dimethyl 2-[2-(Hydroxyphenylmethyl)but-3-en-1-yl]malonate (1a): IR (neat): 3524 (br), 3064 (m), 3030 (m), 1750 (s), 1732 (s), 1640 (m), 921 (m), 765 (m) cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.80 (ddd, J = 14.3, 11.8, 5.0 Hz, 1 H), 1.94 (ddd, J = 14.3, 10.0, 3.7 Hz, 1 H), 2.11 (d, J = 2.5 Hz, 1 H), 2.38 (dddd, J = 11.8, 9.3, 7.1, 3.7 Hz, 1 H), 3.38 (dd, J = 10.0, 5.0 Hz, 1 H), 3.67 (s, 6 H), 4.50 (d, J = 7.1 Hz, 1 H), 5.13 (dd, J = 17.5, 1.7 Hz, 1 H), 5.26 (dd, J = 10.2, 1.7 Hz, 1 H), 5.63 (ddd, J = 17.5, 10.2, 9.3 Hz, 1 H), 7.27–7.34 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ = 29.7, 30.9, 49.6, 50.3, 52.4, 52.5, 120.0, 126.8, 127.9, 128.4, 137.2, 141.7, 169.4, 169.9. HRMS: m/z [M] calcd for C16H20O5: 292.1311; found: 292.1311. Methyl Tetrahydro-2-oxo-6-phenyl-5-vinyl-2H-pyran-3-carboxylate (2a): obtained as a mixture of diastereomers in a 2:1 ratio. IR (neat): 3035 (w), 2954 (m), 1732 (s), 1643 (m), 1263 (m), 1070 (m), 1002 (m), 925 (m), 702 (s) cm–1. 1H NMR (400 MHz, CDCl3: δ (major isomer) = 2.15 (ddd, J = 13.9, 9.8, 7.3 Hz, 1 H), 2.44 (ddd, J = 13.9, 11.3, 5.9 Hz, 1 H), 2.80–2.89 (m, 1 H), 3.80 (dd, J = 7.3, 5.9 Hz, 1 H), 3.83 (s, 3 H), 4.99 (d, J = 17.2 Hz, 1 H), 5.08 (d, J = 10.5 Hz, 1 H), 5.09 (d, J = 3.7 Hz, 1 H), 5.56 (ddd, J = 17.2, 10.5, 7.0 Hz, 1 H) 7.26–7.36 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ (2:1 mixture of diastereomers) = 28.2, 29.4, 41.7, 43.6, 45.8, 47.8, 52.9, 85.9, 86.5, 118.2, 118.3, 127.1, 127.3, 128.5, 128.8, 128.9, 134.9, 135.1, 137.3, 137.6, 166.2, 166.7, 169.4, 169.5. HRMS: m/z [M] calcd for C15H16O4: 260.1049; found: 260.1047. Nucleophilic Allylation of Aldimine with Vinylcyclopropane (Entry 1, Table 2): A solution of benzaldehyde (106.1 mg, 1 mmol) and p-anisidine (129.3 mg, 1.05 mmol) in anhyd THF (1 mL) was refluxed for 30 min under nitrogen. The solvent was removed by distillation under atmospheric pressure of nitrogen (azeotropic removal of H2O). The azeotropic distillation of THF (1 mL)/H2O was repeated twice. A mixture of Pd(acac)2 (15.2 mg, 0.05 mmol) and triphenylphoshine (26.2 mg, 0.1 mmol) in anhyd THF (2 mL) and vinylcyclopropane (221.0 mg, 1.2 mmol) dissolved in THF (1 mL) and diethylzinc (2.4 mmol, 1.0 M hexane solution) were successively added to the aldimine residue. The mixture was stirred at r.t. for 48 h. The reaction mixture was diluted with EtOAc (30 mL) and washed with sat. NaHCO3, and brine. The organic phase was dried (MgSO4) and concentrated in vacuo to give a brown oil, which was subjected to column chromatography over silica gel (hexane–EtOAc, 70:30) to give 3a (167 mg, 42%; Rf 0.5; hexane–EtOAc, 2:1) and 4a (172 mg, 47%; Rf 0.27; hexane–EtOAc, 2:1). Dimethyl 2-[(p-Methoxyphenylamino)phenylmethylbut-3-en-1-yl]malonate (3a): obtained as a mixture of diastereomers in a 4:1 ratio. IR (neat): 3404 (m), 3001 (m), 2953 (m), 2833 (m), 1750 (s), 1732 (s), 1508 (s), 1435 (s), 1159 (br), 1038 (s), 925 (m), 704 (s) cm–1. 1H NMR (400 MHz, CDCl3): δ (major isomer) = 1.69 (ddd, J = 13.7, 11.3, 4.4 Hz, 1 H), 2.32 (ddd, J = 13.7, 10.5, 2.9 Hz, 1 H), 2.42–2.49 (m, 1 H), 3.37 (dd, J = 10.5, 4.4 Hz, 1 H), 3.67 (s, 6 H), 3.72 (s, 3 H), 4.30 (d, J = 5.1 Hz, 1 H), 5.09 (dd, J = 17.1, 1.5 Hz, 1 H), 5.17 (dd, J = 10.2, 1.5 Hz, 1 H), 5.46 (ddd, J = 17.1, 10.2, 9.8 Hz, 1 H), 6.45 (d, J = 8.9 Hz, 2 H), 6.65 (d, J = 8.9 Hz, 2 H), 7.18–7.31 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ (4:1 mixture of diastereomers) = 29.6, 30.4, 48.4, 49.1, 49.4, 49.5, 52.4, 52.5, 52.53, 55.56, 55.59, 51.0, 51.4, 114.6, 114.7, 114.74, 119.6, 127.8, 128.4, 128.6, 128.7, 128.8, 129.0, 132.8, 136.3, 137.2, 139.2, 140.5, 140.7, 141.1, 152.1, 152.3, 169.4, 169.6, 169.7, 169.8. HRMS: m/z [M] calcd for C23H27NO5: 397.1889; found: 397.1899. Methyl 1-(p-Methoxyphenyl)-2-oxo-6-phenyl-5-vinylpiperidine-3-carboxylate (4a): obtained as a mixture of diastereomers in a 2:1 ratio. IR (neat): 2955 (m), 2839 (m), 1738 (s), 1693 (s), 1514 (s), 1250 (s), 1033 (m), 833 (m) cm–1. 1H NMR (400 MHz, CDCl3): δ (major isomer) = 2.09 (dt, J = 13.9, 7.0 Hz, 1 H), 2.40–2.47 (m, 1 H), 2.74–2.84 (m, 1 H), 3.70 (s, 3 H), 3.76–3.81 (m, 1 H), 3.84 (s, 3 H), 4.69 (d, J = 5.6 Hz, 1 H), 5.18 (dt, J = 17.3, 1.2 Hz, 1 H), 5.21 (dd, J = 10.5, 1.2 Hz, 1 H), 5.92 (ddd, J = 17.3, 10.5, 6.6 Hz, 1 H), 6.72 (d, J = 9.0 Hz, 2 H), 6.97 (d, J = 9.0 Hz, 2 H), 7.16–7.35 (m, 5 H). 13C NMR (100 MHz, CDCl3; 2:1 mixture of diastereomers): δ = 26.7, 29.1, 42.7, 45.3, 47.2, 49.5, 52.3, 52.5, 55.11, 55.14, 70.0, 70.5, 113.9, 114.1, 117.1, 117.2, 127.6, 127.7, 127.8, 127.9, 128.3, 128.35, 128.43, 128.7, 133.4, 134.3, 137.1, 137.3, 139.5, 140.1, 158.0, 158.1, 166.3, 167.1, 170.7, 171.8. HRMS: m/z [M] calcd for C22H23NO4: 365.1627; found: 366.1663.