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DOI: 10.1055/s-2008-1032079
Synthesis of β,β′-Diamino Acids from α-Amino Acid Derived β-Lactams
Publication History
Publication Date:
12 February 2008 (online)
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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
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References and Notes
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.
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.