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Synlett 2006(4): 0533-0538  
DOI: 10.1055/s-2006-926252
LETTER
© Georg Thieme Verlag Stuttgart · New York

Design and Synthesis of a New Generation of ‘NH’-Ni(II) Complexes of Glycine Schiff Bases and their Unprecedented C-H vs. N-H Chemoselectivity in Alkyl Halide Alkylations and Michael Addition Reactions

Trevor K. Ellis, Vadim A. Soloshonok*
Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019, USA
Fax: +1(405)3256111; e-Mail: vadim@ou.edu;
Further Information

Publication History

Received 26 October 2005
Publication Date:
20 February 2006 (online)

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Abstract

Within this manuscript the synthesis of a new generation of Ni(II) complexes that contain a secondary rather than a tertiary amino group, as well as the unusual chemoselectivity, was demonstrated in alkyl halide alkylations and Michael addition reactions. The complete C-H chemoselectivity observed in these reactions suggests that coordination of nitrogen to a metal has a significant synthetic potential as protecting a group without the need of introducing a transient N-C substituent. These new complexes have also proven highly synthetically useful nucleophilic glycine equivalents for the simple and highly diastereoselective synthesis of β-sub­stituted pyroglutamic acids via their reactions with chiral Michael acceptors.

Key words

amino acids - chemoselectivity - nickel - Schiff base - chiral auxiliary

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11

Synthesis of the Ni(II) Complexes of Glycine Schiff Bases with N -(2-Benzoylphenyl)-2-(alkylamino)acetamides 9a-c; General Procedure. A solution of KOH (10 equiv) in MeOH (7 mL/1 g of KOH) was added to a suspension of N-(2-benzoylphenyl)-2-(alkylamino)acetamides 8a-c (1 equiv), glycine (5 equiv), nickel nitrate hexahydrate (2 equiv) in MeOH (10 mL/1 g of 8a-c) at 60-70 °C. Upon complete consumption of the N-(2-benzoylphenyl)-2-(alkylamino)acetamides 8a-c, monitored by TLC, the reaction mixture was poured over slurry of ice and 5% AcOH. After the complete precipitation, product 9a-c was filtered and dried in a low temperature oven (50 °C) overnight. The product was obtained in high chemical yield (99%) and high chemical purity without further purification.
Compound 9a: mp >300 °C (decomp.). 1H NMR (299.95 MHz, CDCl3): δ = 1.95 (1 H, br s), 3.45 (2 H, s), 3.86 (2 H, s), 7.01 (1 H, td, J = 7.65, 0.72 Hz), 7.13-7.29 (3 H, m), 7.30-7.60 (7 H, m), 7.62-7.78 (2 H, m), 8.64 (1 H, dd, J = 8.4, 0.3 Hz), 11.66 (1 H, br s). 13C NMR (75.42 MHz, CDCl3): δ = 52.90, 54.10, 121.68, 122.32, 124.82, 125.55, 125.71, 127.30, 127.40, 128.32, 128.45, 128.48, 130.17, 132.62, 132.82, 133.66, 138.47, 139.12, 139.26, 171.19, 198.32. HRMS: m/z calcd for C22H20N2NaO2: 367.1417; found: 367.1103.
Compound 9b: mp 292.3 °C (decomp.). 1H NMR (299.95 MHz, CDCl3): δ = 1.56 (3 H, d, J = 6.3 Hz), 1.66 (3 H, d, J = 6.3 Hz), 2.76 (1 H, br s), 3.12 (1 H, dq, J = 13.2, 6.3 Hz), 3.29 (1 H, d, J = 17.7 Hz), 3.75 (2 H, s), 3.99 (1 H, dd, J = 17.7, 7.5 Hz), 6.83 (1 H, m), 6.93 (1 H, m), 7.01 (1 H, m), 7.19 (1 H, m), 7.35 (1 H, m), 7.53-7.59 (3 H, m), 8.55 (1 H, d, J = 7.8 Hz). 13C NMR (75.42 MHz, CDCl3): δ = 20.57, 21.74, 51.70, 53.33, 60.60, 121.28, 128.34, 125.69, 125.82, 136.24, 129.45, 129.75, 129.88, 132.66, 133.60, 134.66, 142.62, 173.23, 177.88, 177.91, 178.18. HRMS: m/z calcd for C20H21N3NaNiO3: 432.0828; found: 432.0837.
Compound 9c: mp >300 °C (decomp.). 1H NMR (299.95 MHz, CDCl3): δ = 1.54 (9 H, s), 2.60 (1 H, d, J = 7.8 Hz), 3.41 (1 H, d, J = 17.1 Hz), 3.73 (2 H, d, J = 3.9 Hz), 4.17 (1 H, dd, J = 17.1, 7.5 Hz), 6.84 (1 H, m), 6.93 (1 H, dd, J = 8.1, 1.8 Hz), 6.99 (1 H, m), 7.23 (1 H, m), 7.38 (1 H, m), 7.53-7.60 (3 H, m), 8.37 (1 H, d, J = 7.5 Hz). 13C NMR (75.42 MHz, CDCl3): δ = 28.02, 50.98, 58.25, 60.42, 121.33, 124.24, 125.71, 126.27, 129.41, 129.79, 129.90, 132.72, 133.50, 134.54, 142.38, 171.74, 177.36, 177.72. HRMS: m/z calcd for C21H23N3NaNiO3: 446.0985; found: 446.1015.
The Michael Addition of the Oxazolidinone Derived Amides of Cinnamic Acid and Nucleophilic Glycine Equivalents 9a-c; General Procedure. To a flask containing 9a, 9b, or 9c (0.10 g), 3-[(E)-3-alkyl-acryloyl]oxazolidin-2-one 20a,b (1.05 equiv) and 3 mL of DMF, DBU (15 mol%) was added to the reaction mixture, which was stirred at r.t. and monitored by TLC. After disappearance of starting glycine equivalent by TLC, the reaction mixture was poured into a beaker containing 100 mL ice water. After the ice had melted the corresponding product 21a,b, 22, 23, was filtered from the aqueous solution and dried in an oven to afford the corresponding product in high chemical yields.
Compound 23: mp 146.3 °C. 1H NMR (299.95 MHz, CDCl3): δ = 2.66-2.89 (4 H, m), 3.25-3.42 (3 H, m), 3.85 (1 H, dd, J = 16.2, 6.0 Hz), 4.18 (1 H, dd, J = 8.7, 3.9 Hz), 4.43 (1 H, d, J = 4.2 Hz), 4.60 (1 H, t, J = 8.7 Hz), 5.18 (1 H, dd, J = 8.7, 3.9 Hz), 6.71-6.84 (3 H, m), 6.97-7.01 (2 H, m), 7.05 (1 H, d, J = 6.9 Hz), 7.11-7.14 (2 H, m), 7.23-7.47 (10 H, m), 7.56-7.59 (2 H, m), 7.67-7.73 (3 H, m), 8.38 (1 H, d, J = 8.7 Hz). 13C NMR (75.42 MHz, CDCl3): δ = 36.44, 45.18, 53.08, 54.69, 57.47, 69.75, 73.38, 121.04, 123.85, 125.72, 125.86, 126.88, 126.96, 127.24, 127.97, 128.28, 128.37, 128.74, 128.89, 129.14, 129.62, 129.79, 130.72, 132.57, 133.53, 133.61, 133.98, 138.72, 132.84, 139.24, 142.93, 169.89, 171.02, 175.94, 176.60, 177.47. HRMS: m/z calcd for C42H36N4NaNiO6: 773.1880; found: 773.1813.
Compound 22: mp 183.1 °C. 1H NMR (299.95 MHz, CDCl3): δ = 1.29 (3 H, d, J = 6.6 Hz), 1.37 (3 H, d, J = 6.6 Hz), 2.67 (1 H, s), 2.74 (1 H, h, J = 6.6 Hz), 2.86 (1 H, d, J = 16.5 Hz), 3.18-3.30 (2 H, m), 3.56 (1 H, dd, J = 18.6, 8.7 Hz), 3.72 (1 H, dd, J = 18.6, 8.7 Hz), 4.20 (1 H, dd, J = 8.7, 3.9 Hz), 4.49 (1 H, d, J = 4.5 Hz), 4.63 (1 H, t, J = 9.0 Hz), 5.18 (1 H, dd, J = 8.7, 3.9Hz), 6.74 (1 H, d, J = 2.7 Hz), 6.99-7.05 (3 H, m), 7.24 (1 h, d, J = 2.7 Hz), 7.27 (1 H, d, J = 2.7 Hz), 7.28-7.33 (5 H, m), 7.37 (1 H, t, J = 7.2 Hz), 7.47-7.52 (3 H, m), 7.56-7.62 (3 H, m), 8.40 (1 H, d, J = 9.3 Hz). 13C NMR (75.42 MHz, CDCl3): δ = 20.22, 21.44, 29.30, 44.95, 52.75, 53.78, 57.47, 69.77, 73.29, 124.67, 125.66, 125.91, 127.27, 127.95, 128.31, 128.42, 128.49, 128.75, 128.88, 129.33, 129.42, 130.32, 130.80, 132.57, 132.70, 132.86, 138.82, 139.21, 141.57, 153.35, 169.80, 169.98, 176.94, 177.08. HRMS: m/z calcd for C38H36N4NaNiO6: 759.1501; found: 759.1584.
Compound 21b: mp 183.1 °C. 1H NMR (299.95 MHz, CDCl3): δ = 1.28 (9 H, s), 2.67 (1 H, s), 2.97 (1 H, d, J = 16.8 Hz), 3.20-3.37 (2 H, m), 3.51 (1 H, dd, J = 17.7, 8.4 Hz), 3.74 (1 H, dd, J = 17.7, 8.4 Hz), 4.17 (1 H, dd, J = 9, 3.9 Hz), 4.46 (1 H, d, J = 4.5 Hz), 4.61 (1 H, t, J = 8.7 Hz), 5.18 (1 H, dd, J = 8.7, 3.6 Hz), 6.79 (1 H, m), 6.98-7.03 (3 H, m), 7.26-7.38 (7 H, m), 7.43-7.49 (3 H, m), 7.54-7.63 (4 H, m), 8.23 (1 H, d, J = 8.4 Hz). 13C NMR (75.42 MHz, CDCl3): δ = 27.78, 36.55, 44.93, 50.81, 57.45, 59.70, 69.72, 72.53, 120.89, 123.10, 125.81, 127.34, 127.63, 128.24, 128.32, 128.82, 128.87, 129.03, 129.18, 129.97, 130.62, 132.88, 133.62, 133.94, 138.83, 139.11, 142.79, 153.29, 169.99, 170.83, 176.36, 177.20. HRMS: m/z calcd for C39H39N4NiO6: 739.2037; found: 739.2078.
Compound 21a: mp 153.7 °C. 1H NMR (299.95 MHz, CDCl3): δ = 1.43 (9 H, s), 1.91 (3 H, s), 3.04 (1 H, dd, J = 18.3, 7.2 Hz), 3.24 (1 H, dd, J = 18.3, 7.2 Hz), 3.39 (1 H, d, J = 17.1 Hz), 4.16 (1 H, d, J = 4.5 Hz), 4.22 (1 H, dd, J = 9.0, 3.6 Hz), 4.39 (1 H, q, J = 17.1, 7.2 Hz), 4.61 (1 H, t, J = 8.7 Hz), 5.28 (1 H, dd, J = 8.7, 3.3 Hz), 6.78 (2 H, d, J = 4.8 Hz), 6.94 (1 H, d, J = 7.8 Hz), 7.25 (2 H, m), 7.30-7.47 (7 H, m), 7.53 (1 H, t, J = 7.8 Hz), 8.37 (1 H, d, J = 8.4 Hz). 13C NMR (75.42 MHz, CDCl3): δ = 16.85, 27.97, 33.75, 38.94, 51.51, 57.50, 57.89, 69.93, 72.32, 120.98, 123.04, 126.09, 127.33, 127.81, 128.59, 128.83, 129.03, 129.09, 129.85, 132.88, 133.68, 134.00, 139.23, 142.73, 153.55, 170.46, 171.24, 177.12, 177.78. HRMS: m/z calcd for C34H36N4NiO6: 677.1880; found: 677.1918.