Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml
Download PDF
Synlett 2013; 24(7): 823-826
DOI: 10.1055/s-0032-1318345
DOI: 10.1055/s-0032-1318345
letter
Synthesis of N-Cbz-Substituted β3-Amino Ketones Utilizing 4-Substituted 1,3-Oxazinan-6-ones
Further Information
Publication History
Received: 07 February 2013
Accepted after revision: 12 February 2013
Publication Date:
14 March 2013 (online)
Abstract
Stereoselective synthesis of N-Cbz-substituted β-amino ketones exploiting the versatile 1,3-oxazin-6-one scaffold is reported. The 4-substituted 1,3-oxazinan-6-ones were enolized and acylated diastereoselectively by addition of various acyl halides. Acidic decarboxylation was then employed to smoothly transform the 5-acylated products to chiral β-amino ketones. This methodology further highlights the utility of the 1,3-oxazinan-6-one as a scaffold to access valuable synthons that are used in the peptidomimetic field.
Supporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
- Supporting Information
-
References and Notes
- 1a Barluenga J, Olano B, Fustero S. J. Org. Chem. 1985; 50: 4052
- 1b Bosch J, Rubiralta M, Domingo A, Sistaré J. J. Heterocycl. Chem. 1981; 18: 47
- 1c Brough P, Pécaut J, Rassat A, Rey P. Chem. Eur. J. 2006; 12: 5134
- 1d Fisyuk AS, Poendaev NV. Chem. Heterocycl. Compd. 2003; 39: 895
- 1e Fisyuk AS, Ryzhova EA, Unkovskii BV. Chem. Heterocycl. Compd. 2001; 37: 597
- 1f Hansen CP, Jensen AA, Balle T, Bitsch-Jensen K, Hassan MM, Liljefors T, Fralund B. Bioorg. Med. Chem. Lett. 2009; 19: 87
- 1g Holzgrabe U. Arch. Pharm. (Weinheim) 1988; 321: 767
- 1h Keck GE, Truong AP. Org. Lett. 2002; 4: 3131
- 1i King FD. Tetrahedron Lett. 1983; 24: 3281
- 1j Lanter JC, Chen H, Zhang X, Sui Z. Org. Lett. 2005; 7: 5905
- 1k Richards JJ, Ballard TE, Huigens RW, Melander C. ChemBioChem 2008; 9: 1267
- 1l Son P.-N, Lai JT. J. Org. Chem. 1981; 46: 323
- 1m Winter A, Risch N. Synthesis 2003; 2667
- 1n Yagi T, Aoyama T, Shioiri T. Synlett 1997; 1063
- 2 Webster SP, Binnie M, McConnell KM. M, Sooy K, Ward P, Greaney MF, Vinter A, Pallin TD, Dyke HJ, Gill MI. A, Warner I, Seckl JR, Walker BR. Bioorg. Med. Chem. Lett. 2010; 20: 3265
- 3a Du Y, Li Q, Xiong B, Hui X, Wang X, Feng Y, Meng T, Hu D, Zhang D, Wang M, Shen J. Bioorg. Med. Chem. 2010; 18: 4255
- 3b Makarova N, Boreko E, Moiseev I, Pavlova N, Zemtsova M, Nikolaeva S, Vladyko G. Pharm. Chem. J. 2001; 35: 480
- 3c Schönenberger H, Bastug T, Bindl L, Adelheid A, Adam D, Petter A, Zwez W. Pharm. Acta Helv. 1969; 44: 691
- 4a Davies SG, McCarthy TD. Synlett 1995; 7: 700
- 4b Davis FA, Yang B. Org. Lett. 2003; 5: 5011
- 4c Gomtsyan A. Org. Lett. 1999; 2: 11
- 4d Wabnitz TC, Spencer JB. Tetrahedron Lett. 2002; 43: 3891
- 5a Cardova A, Notz W, Zhong G, Betancort JM, Barbas CF. III. J. Am. Chem. Soc. 2002; 124: 1842
- 5b Das B, Reddy KR, Ramu R, Thirupathi P, Ravikanth B. Synlett 2006; 1756
- 5c Das B, Srilatha M, Veeranjaneyulu B, Rama RaoB. Synthesis 2010; 803
- 5d Davis FA, Yang B, Deng J, Zhang J. ARKIVOC 2006; (viii): 120
- 5e Eftekhari-Sis B, Abdollahifar A, Hashemi MM, Zirak M. Eur. J. Org. Chem. 2006; 5152
- 5f Hartman AE, Brophy CL, Cupp JA, Hodge DK, Peelen TJ. J. Org. Chem. 2009; 74: 3952
- 5g Jia X.-D, Wang X.-E, Yang C.-X, Huo C.-D, Wang W.-J, Ren Y, Wang X.-C. Org. Lett. 2010; 12: 732
- 5h Josephsohn NS, Snapper ML, Hoveyda AH. J. Am. Chem. Soc. 2004; 126: 3734
- 5i List B. J. Am. Chem. Soc. 2000; 122: 9336
- 5j List B, Pojarliev P, Biller WT, Martin HJ. J. Am. Chem. Soc. 2002; 124: 827
- 5k Lou S, Dai P, Schaus SE. J. Org. Chem. 2007; 72: 9998
- 5l Lou S, Taoka BM, Ting A, Schaus SE. J. Am. Chem. Soc. 2005; 127: 11256
- 5m Mei H, Xiong Y, Han J, Pan Y. Org. Biomol.Chem. 2010; 9: 1402
- 5n Notz W, Sakthivel K, Bui T, Zhong G, Barbas CF. III. Tetrahedron Lett. 2001; 42: 199
- 5o Ollevier T, Nadeau E. J. Org. Chem. 2004; 69: 9292
- 5p Ranu BC, Samanta S, Guchhait SK. Tetrahedron 2002; 58: 983
- 5q Schunk S, Enders D. Org. Lett. 2001; 3: 3177
- 5r Sieber JD, Morken JP. J. Am. Chem. Soc. 2005; 128: 74
- 5s Syu S.-e, Lee Y.-T, Jang Y.-J, Lin W. J. Org. Chem. 2011; 76: 2888
- 5t Terada M, Machioka K, Sorimachi K. Angew. Chem. Int. Ed. 2006; 45: 2254
- 5u Yang JW, Chandler C, Stadler M, Kampen D, List B. Nature (London) 2008; 452: 453
- 5v Yang J.-W, Stadler M, List B. Angew. Chem. Int. Ed. 2007; 46: 609
- 6 Geng H, Huang K, Sun T, Li W, Zhang X, Zhou L, Wu W, Zhang X. J. Org. Chem. 2011; 76: 332
- 7 Nguyen NH, Sleebs BE, Hughes AB. Tetrahedron 2012; 68: 4745
- 8a Sleebs BE, Hughes AB. Helv. Chim. Acta 2006; 89: 2611
- 8b Sleebs BE, Hughes AB. Aust. J. Chem. 2006; 58: 778
- 9 Sleebs BE, Hughes AB. J. Org. Chem. 2007; 72: 3340
- 10 Sleebs BE, Nguyen NH, Hughes AB. Tetrahedron 2013; 69: in press
- 11 General Procedure 1 5-Acylation of 1,3-Oxazinan-6-ones A solution of the 1,3-oxazinan-6-one 1–4 (0.1 M in dry freshly distilled THF) was cooled to –78 °C under an argon atmosphere. Then LiHMDS (1.1 equiv of a 1.0 M solution in THF) was added dropwise, and the solution was left to stir at –78 °C for 40 min. The acylating agent (3.0 equiv) was then added dropwise and stirring was continued for 3 h at –78 °C. The solution was then allowed to warm to –50 °C, and the reaction was then quenched with sat. NH4Cl solution (5 mL). The solution was diluted with EtOAc (20 mL) and washed with H2O (20 mL). The organic layer was dried (MgSO4) and concentrated in vacuo to give an oil. The oil was subjected to flash column chromatography, eluting with 5–30% EtOAc–hexane. Data for (4S,5R)-N-Benzyloxycarbonyl-4-isopropyl-5-propionyl-1,3-oxazinan-6-one (5) General Procedure 1 was followed for the acylation of oxazinanone 1 (63 mg, 0.23 mmol) with propionyl chloride (59.8 μL, 0.68 mmol), to afford the desired 5-substituted 1,3-oxazinan-6-one 5 as a clear oil (crystallized on standing; 60 mg, 80% yield); mp 82–84 °C; Rf = 0.23 (20% EtOAc–hexane); [α]D 25 +116 (c 2.17, MeOH). 1H NMR (300 MHz, CDCl3): δ = 7.33 (s, 5 H), 5.93 (d, 1 H, J = 9.9 Hz), 5.17 (s, 2 H), 4.93 (d, 1 H, J = 9.9 Hz), 4.59 (t, 1 H, J = 7.2 Hz), 3.73 (d, 1 H, J = 7.2 Hz), 2.84–2.73 (m, 1 H), 2.58–2.47 (m, 1 H), 1.88–1.77 (m, 1 H), 1.09 (t, 3 H, J = 7.2 Hz), 0.89 (d, 3 H, J = 7.2 Hz), 0.85 (d, 3 H, J = 7.2 Hz). 13C NMR (75 MHz, CDCl3): δ = 202.7 167.3, 154.5, 134.9, 128.3, 128.1, 127.8, 72.9, 68.2, 55.9, 55.1, 36.5, 31.0, 18.3, 18.1, 7.2. IR (film): νmax = 2967, 2940, 1748, 1717, 1458, 1412, 1258, 1123, 979 cm–1. HRMS (ESI–): m/z calcd for C18H23NO5 [M – H]–: 332.1503; found: 332.1496.
- 12
General Procedure 2
Formation of the β3-Amino Ketones The oxazinanone 15–24 was dissolved in a mixture of THF–2 M HCl (1:1, 0.013 M solution), and the reaction mixture was gently heated to 50 °C for 4–6 h. The THF was then removed under reduced pressure. The aqueous solution was taken up EtOAc and washed with H2O (3 × 10 mL) followed by brine (1 × 10 mL). The organic layer was dried (MgSO4) and evaporated in vacuo to give an oil. The oil was subjected to flash column chromatography, eluting with 5–20% EtOAc–hexane. - 13 Data for (5R)-(N-Benzyloxylcarbonyl-5-amino)-6-methyl-heptan-2-one (15) General Procedure 2 was followed for the hydrolysis of the 1,3-oxazinan-6-one 5 (31 mg, 0.09 mmol), and afforded the β-amino ketone 15 as a white solid (24 mg, 92% yield); mp 75–77 °C; Rf = 0.50 (30% EtOAc–hexane); [α]D 25 –3.6 (c 1.09, MeOH). 1H NMR (300 MHz, CDCl3): δ = 7.32–7.27 (m, 5 H), 5.14 (d, 1 H, J = 8.9 Hz), 5.06 (s, 2 H), 3.83–3.76 (m, 1 H), 2.61 (br d, 2 H, J = 5.7 Hz), 2.47–2.33 (m, 2 H), 1.89–1.80 (m, 1 H), 1.00 (t, 3 H, J = 7.2 Hz), 0.89 (d, 3 H, J = 4.2 Hz), 0.87 (d, 3 H, J = 4.5 Hz). 13C NMR (75 MHz, CDCl3): δ = 210.0, 155.7, 136.3, 128.1, 127.6, 127.5, 66.2, 53.2, 43.9, 35.8, 31.2, 19.1, 18.2, 7.3. IR (film): νmax = 3325, 2940, 2878, 1709, 1682, 2539, 1454, 1416, 1308. HRMS (ESI+): m/z calcd for C16H23NO3 [M + H]+: 278.1751; found: 278.1756. HPLC [Chiralpak AD-H, PE–2-PrOH (90:10), 25 °C, 254 nm]: t R (major) = 7.1 min; t R (minor) = 6.1 min, 97% ee.