Download PDF
Synlett 2008(4): 539-542  
DOI: 10.1055/s-2008-1032079
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of β,β′-Diamino Acids from α-Amino Acid Derived β-Lactams

Alexander A. Taubingera, Dieter Fenskeb, Joachim Podlech*a
a Institut für Organische Chemie, Universität Karlsruhe (TH), Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
Fax: +49(721)6087652; e-Mail: joachim.podlech@ioc.uka.de;
b Institut für Anorganische Chemie, Universität Karlsruhe (TH), Engesserstraße 15, 76131 Karlsruhe, Germany
Further Information

Publication History

Received 3 December 2007
Publication Date:
12 February 2008 (online)

    Permissions and Reprints All articles of this category

Abstract

Ring opening of protected 3-aminoalkyl-substituted azetidin-2-ones with O-, N-, or S-nucleophiles led to β,β′-diaminocarboxylic esters, amides, and thioesters, respectively. The reaction outcome is improved by addition of catalytic amounts of sodium azide. Reduction of the β-lactam amide moiety led to diamino alcohols.

Key words

amino acids - chiral pool - diazo compounds - amino alcohols - lactams

14

Methyl (2 R ,3 S ,1′ S )-3-(Benzyloxycarbonylamino)-2-[( tert -butyloxycarbonylamino)phenylmethyl]butanoate (10)
Et3N (100 µL, 718 µmol) was added to β-lactam 1a (102 mg, 240 µmol) in anhyd MeOH (7 mL). After stirring for 21 h at r.t. (TLC) the volatile components were removed at reduced pressure and the remnant was purified by chromatography (SiO2, n-hexane-EtOAc, 3:1) yielding methyl ester 10 (109 mg, 239 µmol, 99%) as a colorless wax: [α]D 20 -23.0 (c 1.05, CHCl3). 1H NMR (500 MHz, DMSO-d 6): δ = 1.03 (d, 3 J = 6.7 Hz, 3 H, 4-H), 1.35 [s, 9 H, C(CH3)3], 2.89 (dd, 3 J = 8.3 Hz, 3 J = 6.7 Hz, 1 H, 2-H), 3.49 (s, 3 H, OCH3), 3.54 (ddq, 3 J = 9.1 Hz, 3 J = 7.0 Hz, 1 H, 3-H), 4.85 (dd, 3 J = 9.6, 8.4 Hz, 1 H, 1′-H), 4.96 (d, 2 J = 12.6 Hz, 1 H, OCH aHbPh), 5.05 (d, 2 J = 12.6 Hz, 1 H, OCHa H bPh), 6.87 (d, 3 J = 9.2 Hz, 1 H, NH), 7.13 (d, 3 J = 9.9 Hz, 1 H, 2′-H), 7.22-7.39 (m, 10 H, C6H5). 13C NMR (126 MHz, CDCl3): δ = 19.5 (q, C-4), 28.3 [q, C(CH3)3], 46.5 (d, C-3), 52.0 (q, OCH3), 53.3 (d, C-1′), 56.2 (d, C-2), 66.6 (t, OCH2Ph), 79.8 [s, C(CH3)3], 126.2, 127.7, 128.1, 128.1, 128.5, 128.7 (6 d, 2 C6H5), 136.6, 139.9 (2 s, C6H5 ipso), 155.0 (s, NHCO2 t-Bu), 155.4 (s, NHCO2Bn), 173.1 (s, C-1). IR (DRIFT): ν =3416, 3337 (NH), 3065, 3033, 2978 (CH), 1722 (C=O), 1604, 1587, 1500 (C=C) cm-1. MS (FAB pos.): m/z (%) = 479 (3) [M + Na]+, 457 (4) [M + H]+, 357 (89), 282 (10), 178 (26), 163 (15), 106 (17), 91 (100). HRMS (EI): m/z calcd for 12C25 1H33 14N2 16O6: 457.2339; found: 457.2344.

16

CCDC 668750 (27), CCDC 668751 (15), and CCDC 668749 (17) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

18

(2 S ,3 S ,1′ R )-3-(Benzyloxycarbonylamino)- N -butyl-2-[( tert -butyloxycarbonylamino)-4-chlorphenylmethyl]-butanamide (24)
BuNH2 (23 µL, 233 µmol) and NaN3 (2 mg, 31 µmol) were added to a solution of β-lactam 2b (81 mg, 176 µmol) in anhyd DMF (1 mL) under argon. The mixture was stirred for 42 h at r.t. (TLC), poured into brine (6 mL), and extracted with Et2O (3 × 10 mL). The combined organic layers were dried (MgSO4), concentrated, and purified by chromatography (SiO2, n-hexane-EtOAc, 4:1 → 2:1) yielding 24 (74 mg, 139 µmol, 79%) as a colorless solid: mp 176-178 °C; [α]D 20 +3.9 (c 1.00, CHCl3). 1H NMR (500 MHz, DMSO-d 6): δ = 0.72 (t, 3 J = 7.2 Hz, 3 H, CH2CH 3), 0.86 (dtq, 2 J = 13.7 Hz, 3 J = 7.9, 7.0 Hz, 2 H, CH 2CH3), 0.98 (d, 3 J = 6.5 Hz, 3 H, 4-H), 1.05 (dtt, 2 J = 13.1 Hz, 3 J = 7.8, 6.5 Hz, 2 H, CH 2CH2CH3), 1.36 [s, 9 H, C(CH3)3], 2.57 (dd, 3 J = 10.9 Hz, 3 J = 3.6 Hz, 1 H, 2-H), 2.68 (ddt, 2 J = 13.3 Hz, 3 J = 6.7, 4.9 Hz, 1 H, NHCH aHb), 2.94 (ddt, 2 J = 13.2 Hz, 3 J = 6.6, 5.9 Hz, 1 H, NHCHa H b), 3.86 (ddq, 3 J = 10.8 Hz, 3 J = 8.8, 6.5 Hz, 1 H, 3-H), 4.94 (dd, 3 J = 8.4, 3.5 Hz, 1 H, 1′-H), 4.98 (d, 2 J = 12.4 Hz, 1 H, OCH aHbPh), 5.02 (d, 2 J = 12.5 Hz, 1 H, OCHa H bPh), 6.95 (d, 3 J = 8.4 Hz, 1 H, NHCO2 t-Bu), 7.21 (d, 3 J = 8.5 Hz, 2 H, C6H4Cl: 2′′-H, 6′′-H), 7.30-7.36 (m, 7 H, C6H4Cl: 3′′-H, 5′′-H, Ph), 7.49 (d, 3 J = 8.8 Hz, 1 H, NH), 7.92 (t, 3 J = 5.4 Hz, 1 H, NHCH2). 13C NMR (126 MHz, CDCl3): δ = 13.6 (q, CH2CH3), 18.4 (q, C-4), 19.7 (t, CH2CH3), 28.4 [q, C(CH3)3], 31.1 (t, CH2CH2CH3), 39.0 (t, NHCH2), 47.4 (d, C-3), 52.6 (d, C-1′), 56.2 (d, C-2), 66.6 (t, OCH2Ph), 79.5 [s, C(CH3)3], 127.3 (d, C6H4Cl: C-2′′, C-6′′), 128.0, 128.1, 128.5 (3 d, Ph), 128.5 (d, C6H4Cl: C-3′′, C-5′′), 132.8 (s, C6H4Cl: C-4′′), 136.5 (s, Ph), 140.1 (s, C6H4Cl: C-1′′), 155.5 (s, NHCO2 t-Bu), 155.6 (s, NHCO2Bn), 171.3 (s, C-1). IR (DRIFT): ν = 3344 (NH), 3067, 3035, 2966, 2934, 2874 (CH), 1688, 1645 (C=O, amide I), 1537 (NHCO, amide II) cm-1. MS (FAB pos.): m/z (%) = 554 (30) [M + Na]+, 532 (34) [M + H]+, 476 (24), 432 (100), 238 (77), 180 (12), 165 (15), 140 (12), 91 (79). Anal. Calcd for C28H38ClN3O5 (532.07): C, 63.21; H, 7.20; N, 7.90. Found: C, 63.24; H, 7.18; N, 8.15.