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C. R. Theberge, C. K. Zercher / Tetrahedron 59 (2003) 1521–1527
7.36–7.30 (m, 5H), 5.46 (bs, 1H), 5.12 (s, 2H), 4.16 (m,
2H), 3.68 (s, 3H), 2.75–2.68 (m, 4H); 13C NMR (90 MHz,
CDCl3) d 203.7, 172.8, 156.1, 136.2, 128.5, 128.1, 128.0,
67.0, 51.9, 50.6, 40.2, 34.3, 27.5. HRMS (MþHþ) calcd for
C14H18NO5 280.1185, found 280.1180.
CDCl3) d 7.72 (m, 2H), 7.51–7.20 (m, 8H), 6.77 (d, 1H,
J¼6.8 Hz), 5.07 (dt, 1H, J¼6.6, 6.6 Hz), 3.68 (s, 3H), 3.23
(ABX, 2H, J¼6.7, 14.1 Hz), 2.83 (m, 2H), 2.62 (m, 2H); 13C
NMR (90 MHz, CDCl3) d 206.8, 173.2, 166.8, 136.0, 133.9,
131.8, 129.3, 128.7, 128.6, 127.1, 126.9, 59.3, 51.9, 37.2,
35.2, 27.6. HRMS (MþNaþ) calcd for C20H21NO4Na
362.1363, found 362.1364.
4.2.22. (6)-Methyl 5-(carboxybenzyl)-amino-4-oxo-hex-
anoate (10f). 60%. Colorless oil. 1H NMR (360 MHz,
CDCl3) d 7.41–7.30 (m, 5H), 5.51 (bs, 1H), 5.11 (s, 2H),
4.43 (dq, 1H, J¼7.1 Hz), 3.68 (s, 3H), 2.94–2.59 (m, 4H),
1.41 (d, 3H, J¼7.1 Hz); 13C NMR (90 MHz, CDCl3) d
207.6, 172.9, 155.7, 136.1, 128.5, 128.1, 128.0, 66.9, 55.5,
51.8, 33.7, 28.7, 27.5, 17.6. HRMS (MþHþ) calcd for
C15H20NO5 294.1341, found 294.134147.
4.2.29. Methyl 5-(carboxy-9-fluorenylmethyl)-amino-4-
oxo-pentanoate (10m). 55%. White solid; mp 65–688C. 1H
NMR (360 MHz, CDCl3) d 7.75 (m, 2H), 7.60 (m, 2H),
7.42–7.29 (m, 4H), 5.56 (bs, 1H), 4.40 (m, 2H), 4.27 (m,
1H), 4.15 (m, 2H), 3.68 (s, 3H), 2.73–2.66 (m, 4H); 13C
NMR (90 MHz, CDCl3) d 204.0, 172.8, 156.2, 143.9, 141.3,
127.7, 127.0, 125.1, 119.9, 67.1, 52.2, 50.6, 47.1, 34.3, 27.5.
HRMS (MþHþ) calcd for C21H22NO5 368.1498, found
368.1497.
4.2.23. (6)-Methyl 5-(carboxybenzyl)-amino-4-oxo-5-
phenylpentanoate (10g). 48%. Colorless oil. 1H NMR
(360 MHz, CDCl3) d 7.40–7.33 (m, 10H), 6.16 (bs, 1H),
5.39 (d, 1H, J¼6.1 Hz), 5.05 (AB, 2H, J¼12.2 Hz), 3.67 (s,
3H), 2.73–2.51 (m, 4H); 13C NMR (90 MHz, CDCl3) d
204.0, 172.5, 155.5, 136.5, 136.2, 133.1, 129.2, 128.7,
128.5, 128.1, 127.9, 66.9, 64.5, 51.8, 34.3, 27.6. HRMS
(MþHþ) calcd for C20H21NO5 356.1492, found 356.1491.
4.2.30. (6)-Methyl 5-(carboxy-9-fluorenylmethyl)-
amino-4-oxo-hexanoate (10n). 57%. White solid; mp
1
95–978C. H NMR (360 MHz, CDCl3) d 7.77 (m, 2H),
7.60 (m, 2H), 7.42–7.30 (m, 4H), 5.56 (bs, 1H), 4.45–4.35
(m, 3H), 4.22 (m, 1H), 3.68 (s, 3H), 2.92–2.59 (m, 4H), 1.42
(d, 3H, J¼7.1 Hz); 13C NMR (90 MHz, CDCl3) d 207.7,
173.0, 155.8, 144.0, 141.3, 127.7, 127.0, 125.0, 120.0, 66.8,
55.5, 51.9, 47.1, 33.7, 27.5, 17.8. HRMS (MþHþ) calcd for
C22H24NO5 382.1654, found 382.1661.
4.2.24. (6)-Methyl 5-(carboxybenzyl)-amino-4-oxo-6-
phenylhexanoate (10h). 68%. Colorless oil. 1H NMR
(360 MHz, CDCl3) d 7.38–7.14 (m, 10H), 5.38 (d, 1H,
J¼7.3 Hz), 5.08 (s, 2H), 4.64 (q, 1H, J¼6.6 Hz), 3.67 (s,
3H), 3.16 (dd (A of AB), 1H, J¼6.4, 14.1 Hz), 2.99 (dd (B
of AB), 1H, J¼6.9, 14.1 Hz), 2.81–2.74 (m, 2H), 2.60–2.57
(m, 2H); 13C NMR (90 MHz, CDCl3) d 207.0, 173.0, 156.0,
136.2, 135.9, 129.2, 128.7, 128.5, 128.2, 128.1, 127.1, 66.9,
60.5, 51.8, 37.4, 35.1, 27.5. HRMS (MþNaþ) calcd for
C21H23NO5Na 392.1468, found 392.1472.
4.2.31. (6)-Methyl 5-(carboxy-9-fluorenylmethyl)-
amino-4-oxo-5-phenylpentanoate (10o). 63%. White
1
solid; mp 110–1158C. H NMR (360 MHz, CDCl3) d 7.76
(m, 2H), 7.56 (m, 2H), 7.41–7.21 (m, 9H), 6.21 (m, 1H),
5.41 (m, 1H), 4.40–4.29 (m, 2H), 4.21–4.17 (m, 1H), 3.64
(s, 3H), 2.81–2.48 (m, 4H); 13C NMR (90 MHz, CDCl3) d
204.0, 172.5, 155.8, 143.8, 141.2, 136.3, 129.3, 128.8,
127.9, 127.6, 127.0, 125.0, 119.9, 67.0, 64.5, 51.9, 47.1,
34.3, 27.2. HRMS (MþHþ) calcd for C27H26NO5 444.1811,
found 444.1815.
4.2.25. Methyl 5-(N-benzoyl)-amino-4-oxo-pentanoate
1
(10i). 58%. Colorless oil. H NMR (360 MHz, CDCl3) d
7.83–7.75 (m, 2H), 7.55–7.41 (m, 3H), 6.93 (bs, 1H), 4.42
(d, 2H, J¼4.5 Hz), 3.70 (s, 3H), 2.88–2.70 (m, 4H); 13C
NMR (90 MHz, CDCl3) d 203.9, 172.8, 167.2, 133.7, 131.7,
128.6, 127.0, 51.9, 49.6, 34.6, 27.6. HRMS (MþNaþ) calcd
for C13H15NO4Na 272.0899, found 272.0907.
4.2.32. (6)-Methyl 5-(carboxy-9-fluorenylmethyl)-
amino-4-oxo-6-phenylhexanoate (10p). 68%. White
1
solid; mp 108–1108C. H NMR (360 MHz, CDCl3) d 7.78
(m, 2H), 7.55 (m, 2H), 7.42 (m, 2H), 7.31–7.24 (m, 5H),
7.16 (m, 2H), 5.48 (d, 1H, J¼7.81 Hz), 4.67 (dt, 1H, J¼7.6,
7.8 Hz), 4.43–4.33 (m, 2H), 4.21–4.17 (m, 1H), 3.68 (s,
3H), 3.19 (A of AB, 1H, J¼6.0, 14.0 Hz), 3.00 (B of AB,
1H, J¼7.5, 14.0 Hz), 2.79–2.74 (m, 2H), 2.64–2.60 (M,
2H); 13C NMR (90 MHz, CDCl3) d 206.8, 173.0, 155.8,
143.7, 141.3, 136.0, 129.2, 128.7, 127.7, 127.1, 127.0,
125.0, 120.0, 66.9, 60.5, 51.9, 47.1, 37.3, 35.0, 27.5. HRMS
(MþHþ) calcd for C28H28NO5 458.1962, found 458.1938.
4.2.26. (6)-Methyl 5-(N-benzoyl)-amino-4-oxo-hexano-
ate (10j). 58%. Colorless oil. 1H NMR (360 MHz, CDCl3) d
7.82–7.79 (m, 2H), 7.53–7.42 (m, 3H), 7.02 (d, 1H,
J¼6.3 Hz), 4.85 (dq, 1H, J¼7.0, 7.0 Hz), 3.68 (s, 3H),
3.01–2.61 (m, 4H), 1.52 (d, 3H, J¼7.1 Hz); 13C NMR
(90 MHz, CDCl3) d 207.9, 173.0, 166.6, 134.0, 131.7,
128.5, 127.0, 54.4, 51.9, 33.8, 27.6, 17.6. HRMS (MþNaþ)
calcd for C14H17NO4Na 286.1055, found 286.1049.
4.2.27. (6)-Methyl 5-(N-benzoyl)-amino-4-oxo-5-phenyl-
pentanoate (10k). 43%. Colorless oil. 1H NMR (360 MHz,
CDCl3) d 7.81 (m, 1H), 7.55–7.33 (m, 9H), 5.79 (d, 1H,
J¼6.1 Hz), 3.65 (s, 3H), 2.90–2.50 (m, 4H); 13C NMR
(90 MHz, CDCl3) d 204.6, 172.8, 166.5, 136.5, 133.9,
131.7, 129.3, 128.7, 128.5, 128.1, 127.1, 63.3, 52.0, 34.5,
27.7. HRMS (MþNaþ) calcd for C19H19NO4Na 348.1206,
found 348.1199.
4.3. Scheme 3 experimentals
4.3.1. Phenylmethyl (4S)-4-(carboxy-t-butyl)-amino-3-
oxo-pentanoate (11). Boc-L-alanine 8b (176 mg,
0.93 mmol) was dissolved in 10 mL anhydrous THF in a
25 mL round-bottomed flask and 154 mg (0.95 mmol) CDI
added while stirring. After being allowed to stir for 15 min,
the acyl imidazole was transferred to a 100 mL flask
containing a solution of monobenzyl malonate (722 mg,
3.72 mmol) in 30 mL anhydrous THF to which 1.86 mL
(1.86 mmol) of a 1 M solution of dibutylmagnesium was
4.2.28. (6)-Methyl 5-(N-benzoyl)-amino-4-oxo-6-phenyl-
1
hexanoate (10l). 58%. Colorless oil. H NMR (360 MHz,