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T. P. Boyle et al. / Tetrahedron 61 (2005) 7271–7276
JZ6.0, 8.7 Hz, 2H, H1); 2.36–2.29 (m, 2H, H2); 1.51 (s,
18H, 6!CH3). 13C NMR: d 152.5, (CO); 135.0, (C3);
116.7, (C4); 82.0, (2!C(CH3)3); 45.6, (C1); 33.5, (C2);
28.0, (6!CH3). MS (ES, Cve) m/z 272 (40%) [MHC], 294
(30%) [MNaC], 310 (55%) [MKC]. HRMS (ES) calcd for
C14H26NO4 272.1862, found 272.1848.
4.1.5. Methyl (2S,4E/Z)-2-(benzyloxycarboxamido)-7-
(N,N0-di-tert-butoxycarbonyl-guanidino)-4-heptenoate
(8). To a solution of 7 (52 mg, 0.128 mmol) in CH2Cl2
(2 mL) was added TFA (2 mL) and the resulting solution
was allowed to stir at rt for 3 h before being evaporated to
dryness and resuspended in CH2Cl2 (2 mL) and triethyl-
amine (0.2 mL). To this solution was added N,N0-Bis(tert-
butoxycarbonyl)N00-triflylguanidine methyl propanamide
(75 mg, 0.192 mmol) and the resulting mixture was allowed
to stir overnight under a nitrogen atmosphere. The mixture
was concentrated and the crude product purified by flash
column chromatography (silica gel, 5% MeOH/CH2Cl2) to
yield the title compound 8 (64 mg, 0.12 mmol, 93%) as a
light brown/red oil. [a]2D3 C13.2 (c 0.05 in EtOH).
4.1.2. tert-Butyl N-3-butenylcarbamate (5). To a solution
of 4 (708 mg, 2.60 mmol) in CH2Cl2 (21 mL) was added
TFA (593 mg, 5.20 mmol) and the mixture was allowed to
stir at rt for 5 min before being quenched with 2 M NaOH
(25 mL) and extracted with CH2Cl2 (3!20 mL). The
combined organic fractions were dried (MgSO4) and
concentrated to yield the title compound 515 (429 mg,
2.50 mmol, 96%) as a light brown oil. nmax(neat) 2979 (s),
1799 (m), 1732 (s), 1697 (s), 1392 (m), 1367 (s), 1130
(s) cmK1. 1H NMR: d 5.83–5.69 (m, 1H, H3); 5.13–5.05 (m,
2H, H4); 4.59 (br s, 1H, NH); 3.20 (dd, JZ6.3, 12.6 Hz, 2H,
H1); 2.24 (dd, JZ6.9, 12.6 Hz, 2H, H2); 1.44 (s, 9H, 3!
CH3). 13C NMR: d 155.9, (CO); 135.3, (C3); 117.0, (C4);
82.0, (C(CH3)3); 39.6, (C1); 34.2, (C2); 28.4, (3!CH3). MS
(ES, Cve) m/z 116 (100%).
nmax(neat) 2925, 2851, 2352, 2336, 1866, 1644, 1403 cmK1
.
1H NMR: d 8.28 (br s, 1H, NH); 7.39–7.30 (m, 5H, ArH);
5.68–5.35 (m, 3H, H4, H5, NH); 5.09 (s, 2H, ArCH2); 4.49–
4.39 (m, 1H, H2); 3.74/3.72 (s, 3H, OCH3); 3.49–3.35 (m,
2H, H7); 2.58–2.46 (m, 2H, H3); 1.89–1.82 (m, 2H, H6);
1.48/1.47 (s, 9H, CH3). 13C NMR: d 171.59, (C1); 163.4,
(CN3); 156.0, (NCO0); 155.7, (NCO); 131.7, (C4); 130.1,
(C5); 128.5, (ArC10); 128.1, (ArC20 and ArC60); 126.6,
(ArC30 and ArC50); 126.0, (ArC40); 83.3, (C(CH3)3); 79.4,
(C0(CH3)3); 67.0/66.9, (ArCH2); 53.4, (OCH3); 52.4/52.3,
(C2); 40.3/40.1, (C7); 35.3/34.5, (C3); 31.8/30.1, (C6);
28.2/28.0, (C(CH3)3); 26.9/26.8, (C(C0H3)3). MS (ES, Cve)
m/z 549 (100%) [MHC]. HRMS (ES) calcd for C27H41N4O8
549.2924, found 549.2947.
4.1.3. Methyl (2S)-2-benzyloxycarboxamido-4-penteno-
ate (6).16 To a solution of methyl (2S)-2-amino-4-
pentenoate hydrochloride24 (422 mg, 2.56 mmol) and
NaHCO3 (645 mg, 7.68 mmol) in THF/water (3 mL/3 mL)
was added benzyl chloroformate (482 mg, 2.82 mmol) and
the mixture was allowed to stir at rt for 16 h. The reaction
was quenched with 3% HCl (20 mL) and extracted with
CH2Cl2 (3!20 mL), and the combined organic fractions
were dried (MgSO4) and concentrated to give the title
known compound 6 (676 mg, 2.56 mmol, 100%) as a
colourless oil. Spectral data matched closely with that in the
literature16 [a]D20 C9.1 (c 0.15 in CHCl3). 1H NMR: d 7.38–
7.22 (m, 5H, ArH); 5.75–5.58 (m, 1H, H4); 5.56 (d, JZ
7.8 Hz, 1H, NH); 5.18–5.08 (m, 4H, ArCH2 and C5); 4.47
(dd, JZ6.3, 13.2 Hz, 1H, H2); 3.72 (s, 3H, OCH3); 2.54
(ABq, JZ6.3, 13.8 Hz, 2H, H3).
4.1.6. Methyl (2S)-2-amino-7-(tert-butoxycarboxamido)-
heptanoate (9). To a solution of 7 (25 mg, 0.061 mmol) in
THF (4 mL) was added, palladium (10%) on activated
carbon (13 mg, 0.006 mmol). The reaction vessel was
evacuated, flushed with H2 and allowed to stir at rt for
16 h. The resulting crude product was filtered through Celite
and the solvent evaporated to yield the title compound 9
(15 mg, 0.055 mmol, 90%) as a colourless oil. [a]2D4 C9.6 (c
0.1, in EtOH). nmax(neat) 2923, 2310, 2290, 1664,
1
1526 cmK1. H NMR: d 4.55 (br s, 1H, NH); 3.72 (s, 3H,
OCH3); 3.44 (t, JZ6.0 Hz, 1H, H2); 3.10 (dd, JZ6.0,
12.6 Hz, 2H, H7); 1.80–1.68 (m, 4H, H3, H4); 1.44 (s, 9H,
CH3); 1.39–1.23 (m, 4H, H5, H6). 13C NMR: d 176.5, (C1);
155.9, (NCO); 79.9, (C(CH3)3); 54.2, (OCH3); 51.8, (C2);
40.3, (C7); 34.7, (C3); 29.9, (C6); 28.3, (CH3); 26.4, (C4);
25.3, (C5). MS (ES, Cve) m/z 219 (100%); 275 (90%)
[MHC]. HRMS (ES) Calcd for C13H27N2O4 275.1971,
found 275.1967.
4.1.4. Methyl (2S,4E/Z)-2-(benzyloxycarboxamido)-7-
(tert-butoxycarboxamido)-4-heptenoate (7). To a solution
of 5 (220 mg, 1.29 mmol) in CH2Cl2 (13 mL) was added, 6
(169 mg, 0.64 mmol) and RuCl2(PCy3)2(]CHPh) (53 mg,
0.064 mmol). The mixture was heated at reflux for 16 h
before the solvent was removed by rotary evaporation and
the crude product purified by flash column chromatography
(silica gel, 6:1, hexane/EtOAc) to yield the title compound 7
(180 mg, 0.44 mmol, 69%) as a brown oil. [a]2D4 K34.6 (c
0.3 in EtOH). nmax(neat) 2345, 2225, 1684, 1630 cmK1. 1H
NMR: d 7.36–7.28 (m, 5H, ArH); 5.52–5.34 (m, 3H, H4,
H5, NH); 5.11/5.10 (s, 2H, H40); 4.61 (br s, 1H, NH); 4.49–
3.90 (m, 1H, H2); 3.75/3.72 (s, 3H, OCH3); 3.18–3.04 (m,
2H, H7); 2.62–2.40 (m, 2H, H3); 2.26–2.12 (m, 2H, H6);
1.43 (s, 9H, CH3). 13C NMR: d 172.1/172.0, (C1); 155.8,
4.1.7. Methyl (2S)-2-amino-7-(N,N-di-tert-butoxycar-
bonyl-guanidino)-heptanoate (10). To a solution of 8
(50 mg, 0.091 mmol) in THF (10 mL) was added, palladium
(10%) on activated carbon (19 mg, 0.009 mmol). The
reaction vessel was evacuated, flushed with H2 and the
mixture allowed to stir at rt for 16 h. The resulting crude
mixture was filtered through Celite and the solvent was
evaporated to yield the title compound 10 (28 mg,
0.091 mmol, 100%) as a red oil. [a]2D8 K15.3 (c 0.25, in
EtOH). nmax(neat) 2934, 2360, 2338, 1746, 1722, 1633,
0
(NCO2 ); 155.6, (NCO2); 131.8, (C4); 130.4, (C5); 129.3,
(ArC100); 128.6/128.4, (ArC20 and ArC60); 128.0/126.8,
(ArC3 and ArC50); 126.0/125.3, (ArC40); 79.0, (C(CH3)3);
66.9, (ArCH2); 53.6/53.4, (OCH3); 52.3/52.2, (C2); 39.9/
39.7, (C7); 35.5/35.2, (C3); 33.0/32.9, (C6); 28.3/28.1,
(CH3). MS (ES, Cve) m/z 297 (100%), 407 (20%) [MHC],
429 (90%) [MNaC]. HRMS (ES) calcd for C21H31N2O6
407.2182, found 407.2171.
1
1371, 1155 cmK1. H NMR: d 8.34 (br s, 1H, NH); 3.79–
3.76 (m, 1H, H2); 3.74 (s, 3H, OCH3); 3.40 (t, JZ6.6 Hz,
2H, H7); 1.92–1.82 (m, 4H, H3 and H4); 1.50 (s, 18H, 6!
CH3); 1.42–1.35 (m, 4H, H5 and H6). 13C NMR: d 171.6,
(C1); 163.4, (CN3); 156.1/153.3, (NCO); 83.1/79.3,