10
Tetrahedron
4.4.10. Benzyl N-(4-oxopentan-2-yl)carbamate (5j). This
Method A or 89% yield (60.0 mg) by Method B. Compound 5o,
ACCEPTED MANUSCRIPT
product was obtained in 80% yield (37.7 mg) by Method A.
White solid; mp 43.5-45.0 °C (toluene); Rf 0.13
in each method, was obtained as a mixture of diastereomers (dr =
1
=
65:35). White solid; Rf = 0.19 (hexanes/AcOEt = 4:1). H NMR
1
(hexanes/AcOEt = 4:1). H NMR (600 MHz, CDCl3): δ 7.37-
7.29 (m, 5H), 5.17 (br s, 1H), 5.09 (d, J = 12.0 Hz, 1H), 5.08 (d,
J = 13.2 Hz, 1H) 4.11-4.04 (m, 1H), 2.72 (dd, J1 = 16.8 Hz, J2 =
4.2 Hz, 1H), 2.60 (dd, J1 = 16.8 Hz, J2 = 6.0 Hz, 1H), 2.14 (s,
3H), 1.23 (d, J = 6.6 Hz, 3H). 13C NMR (150 MHz, CDCl3): δ
207.4, 155.5, 136.5, 128.5, 128.1, 128.0, 66.5, 49.1, 43.8, 30.6,
20.5. IR (ATR): 3324, 2989, 1712, 1679, 1529, 1256, 1070 cm-1.
HRMS (ESI) m/z: calcd for C13H17NO3Na [M+Na]+ 258.1106,
found 258.1107.
(600 MHz, CDCl3): δ 7.36-7.20 (m, 10H), 6.12 (br d, J = 7.8 Hz,
0.35H), 6.06 (br d, J = 7.8 Hz, 0.65H), 5.10-5.01 (m, 2H), 4.96
(dd, J1 = 8.4 Hz, J2 = 6.6 Hz, 0.65H), 4.90 (dd, J1 = 8.1 Hz, J2 =
3.3 Hz, 0.35H), 2.94-2.90 (m, 0.35H), 2.90-2.81 (m, 0.65H),
2.38-1.33 (m, 8H). 13C NMR (150 MHz, CDCl3): δ 212.5, 211.4,
156.2, 155.7, 141.2, 140.1, 140.0, 136.4, 128.4, 128.3, 128.3,
128.0, 128.0, 127.9, 127.3, 127.1, 126.6, 66.7, 55.9, 55.7, 54.9,
42.5, 42.3, 32.6, 30.5, 28.1, 26.8, 24.5, 24.4. IR (ATR): 3317,
2951, 2862, 1701, 1678, 1530, 1243, 1143, 1143, 1047 cm-1.
4.4.11. Benzyl N-(4-oxo-1-phenylpentan-2-yl)carbamate (5k).
This product was obtained in 71% yield (44.4 mg) by Method A.
White solid; mp 52.0-54.0 °C (toluene/n-pentane); Rf = 0.11
(hexanes/AcOEt = 4:1). 1H NMR (400 MHz, CDCl3): δ 7.37-7.12
(m, 10H), 5.31 (br d, J = 6.8 Hz, 1H), 5.05 (s, 2H), 4.23-4.14 (m,
1H), 2.95 (dd, J1 = 13.2 Hz, J2 = 6.4 Hz, 1H), 2.84 (dd, J1 = 13.4
Hz, J2 = 7.8 Hz, 1H), 2.67-2.56 (m, 2H), 2.09 (s, 3H). 13C NMR
(100 MHz, CDCl3): δ 207.6, 155.7, 137.8, 136.5, 129.2, 128.6,
128.5, 128.0, 127.9, 126.6, 66.5, 49.1, 45.8, 40.0, 30.5. IR
(ATR): 3367, 3034, 1710, 1686, 1537, 1258, 1060 cm-1. HRMS
(ESI) m/z: calcd for C19H21NO3Na [M+Na]+ 334.1419, found
334.1422.
4.4.16. Benzyl N-[1-(1-oxo-1,2,3,4-tetrahydronaphthalen-2-
yl)ethyl]carbamate (5p).27 This product was obtained in 97%
yield (74.9 mg) by Method A. Compound 5p was obtained as a
mixture of diastereomers (dr = 55:45). White solid, Rf = 0.26
(hexanes/AcOEt = 4:1).1H NMR (600 MHz, CDCl3): δ 8.00 (d, J
= 7.8 Hz, 0.45H), 7.95 (d, J = 7.8 Hz, 0.55H), 7.50-7.12 (m,
13H), 6.93 (br d, J = 9.6 Hz, 0.45H), 5.90 (br s, 0.55H), 5.16-
5.01 (m, 3H), 3.15-2.87 (m, 3H), 2.29-1.73 (m, 2H). 13C NMR
(150 MHz, CDCl3): δ 198.9, 198.5, 156.0, 155.7, 143.7, 143.4,
141.0, 139.6, 136.5, 136.4, 133.7, 133.7, 132.7, 132.5, 132.1,
132.0, 128.7, 128.6, 128.5, 128.4, 128.3, 128.1, 128.0, 127.9,
127.5, 127.4, 127.3, 66.8, 66.7, 56.9, 55.4, 52.6, 52.1, 29.2, 27.9,
27.2, 27.0. 39.2, 29.7, 23.3. IR (ATR): 3338, 3029, 1682, 1496,
1454, 1495, 1226, 1156, 1046 cm-1.
4.4.12. Benzyl N-(2-methyl-6-oxoheptan-4-yl)carbamate (5l).
This product was obtained in 65% yield (34.4 mg) by Method A.
1
Colorless oil; Rf = 0.11(hexanes/AcOEt = 4:1). H NMR (400
References and notes
MHz, CDCl3): δ 7.39-7.27 (m, 5H), 5.13 (br d, J = 8.4 Hz, 1H),
5.07 (s, 2H), 4.07-3.97 (m, 1H), 2.69 (dd, J1 = 17.0 Hz, J2 = 5.0
Hz, 1H), 2.63 (dd, J1 = 16.8 Hz, J2 = 5.2 Hz, 1H), 2.13 (s, 3H),
1.64-1.46 (m, 2H), 1.30-1.23 (m, 1H), 0.92 (d, J = 8.4 Hz, 3H),
0.90 (d, J = 6.8 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 207.7
155.8, 136.6, 128.5, 128.0, 128.0, 66.5, 48.1, 46.2, 43.6, 30.6,
25.0, 23.0, 22.0.IR (ATR): 3331, 2956, 1697, 1526, 1228, 1045
cm-1. HRMS (ESI) m/z: calcd for C16H23NO3Na[M+Na]+
300.1576, found 300.1577.
1.
For the reviews on β-amino carbonyl compounds (Mannich
bases) synthesis and significance, see: (a) Tramontini, M.;
Angiolini, L. Tetrahedron 1990, 46, 1791-1837. (b) Tramontni,
M.; Angiolini, L. Mannich Bases: Chemistry and Uses; CRC
Press, Inc.: Boca Raton, FL, 1994. (c) Arend, M.; Westermann,
B.; Risch, N. Angew. Chem. Int. Ed. 1998, 37, 1044-1070. (d)
Allochio Filho, J. F.; Lemos, B. C.; de Souza, A. S.; Pinheiro, S.;
Greco, S. Tetrahedron 2017, 73, 6977-7004.
2. For the reviews on β-amino acids synthesis and significance, see:
(a) Liu, M.; Sibi, M. P. Tetrahedron 2002, 58, 7991-8035. (b)
Lelais, G.; Seebach, D. Biopolymers 2004, 76, 206-243. (c)
Enantioselective Synthesis of β-Amino Acids, 2nd ed.; Juaristi, E.,
Soloshonok, V., Eds.;Wiley: Hoboken, New Jersey, 2005. (d)
Kudo, F.; Miyanaga, A.; Eguchi, T. Nat. Prod. Rep. 2014, 31,
1056-1073. (e) Kiss, L.; Cherepanova, M.; Fülöp, F. Tetrahedron
2015, 71, 2049-2069.
4.4.13. Benzyl N-(3-oxo-1-phenylbutyl)carbamate (5m).25 This
product was obtained in 82% yield (46.5 mg) by Method A.
White solid; mp 65.5-67.0 °C (toluene); Rf
=
0.14
(hexanes/AcOEt = 4:1).1H NMR (600 MHz, CDCl3): δ 7.37-7.24
(m, 10H), 5.74 (br s, 1H), 5.19-5.13 (m, 1H), 5.11 (d, J = 12.0
Hz, 1H), 5.09 (d, J = 12.6 Hz, 1H), 3.08 (d, J = 13.8 Hz, 1H),
2.93 (dd, J1 = 16.5 Hz, J2 = 5.7 Hz, 1H), 2.08 (s, 3H). 13C NMR
(150 MHz, CDCl3): δ 206.7, 155.6, 141.1, 136.3, 128.7, 128.5,
128.1, 127.5, 126.2, 66.8, 51.4, 48.6, 30.6. IR (ATR): 3332,
1711, 1687, 1530, 1254, 1051 cm-1.
3.
(a) Bates, R. W.; Sa-Ei, K. Tetrahedron 2002, 58, 5957-5978. (b)
Neochoritis, C. G.; Stephanidou-Stephanatou, J.; Tsoleridis, C.A.
Eur. J. Org. Chem. 2011, 5336-5346. (c) Roman, G. Eur. J. Med.
Chem. 2015, 89, 743-816.
4. (a) Cheng, R. P.; Gellman, S. H.; DeGrado, W. F. Chem. Rev.
2001, 101, 3219-3232. (b) Steer, D. L.; Lew, R. A.; Perlmutter, P.;
Smith, A. I.; Aguilar, M-I. Curr. Med. Chem. 2002, 9, 811-822.
(c) Seebach, D.; Gardiner, J. Acc. Chem. Res. 2008, 41, 1366-
1374. (d) Cabrele, Ch.; Martinek, T. A.; Reiser, O.; Berlicki, Ł. J.
Med. Chem. 2014, 57, 9718-9739. (e) Del Borgo, M. P.; Ketav,
K.; Aguilar, M-I. Curr. Pharm. Des. 2017, 23, 3772-3785. (f)
Stefanucci, A.; Uysal, S.; Ceylan, R.; Zengin, G. Curr. Bioact.
Compd. 2018, 14, 3-8.
5. For Mannich-type reactions of imines with silyl enolates using
Lewis acids, see: (a) Kerwin, F. J.; Danishefsky, S. Tetrahedron
Lett. 1982, 23, 3739-3742. (b) Gennari, C.; Schimperna, G.;
Venturini, I. Tetrahedron 1988, 44, 4221-4232. (c) Kobayashi, S.;
Araki, M.; Ishitani, H.; Nagayama, S.; Hachiya, I. Synlett 1995, 3,
233-234. (d) Kobayashi, S.; Nagayama, S. J. Org. Chem. 1997,
62, 232-233. (e) Russowsky, D.; Petersen, R. Z.; Godoi, M. N.;
Pilli, R. A. Tetrahedron Lett. 2000, 41, 9939-9942. (f) Komoto, I.;
Kobayashi, S. Chem. Comm. 2001, 1842-1843. (g) Ranu, B. C.;
Samanta, S.; Guchhait, S. K. Tetrahedron 2002, 58, 983-988. (h)
Onodera, G.; Toeda, T.; Toda, N.; Shibagishi, D.; Takeuchi, R.
Tetrahedron 2010, 66, 9021-9031.
4.4.14. Benzyl N-[1-(2-oxocyclohexyl)ethyl]carbamate (5n).
This product was obtained in 81% yield (44.6 mg) by Method A
or 76% yield (41.9 mg) by Method B. Compound 5n, in each
method, was obtained as a mixture of diastereomers (dr = 50:50).
1
White solid; Rf = 0.17 (hexanes/AcOEt = 4:1). H NMR (600
MHz, CDCl3): δ 7.37-7.29 (m, 5H), 5.49 (d, J = 9.6 Hz, 0.5H ),
5.45 (d, J = 9.0 Hz, 0.5H), 5.12-5.03 (m, 2H), 3.91-3.85 (m,
0.5H), 3.85-3.79 (m, 0.5H), 2.57-2.21 (m, 3H), 2.08-1.87 (m,
3H), 1.70-1.51 (m, 3H), 1.24 (d, J = 7.2 Hz, 1.5H), 1.20 (d, J =
6.6 Hz, 1.5H). 13C NMR (150 MHz, CDCl3): δ 212.9, 212.3,
156.1, 155.7, 136.6, 136.6, 132.1, 132.0, 128.4, 128.0, 128.0,
66.5, 55.1, 54.6, 48.0, 47.6, 42.9, 42.5, 31.8, 31.0, 28.0, 27.2,
24.9, 24.7, 19.8, 16.8. IR (ATR): 3295, 2970, 1770, 1683, 1541,
1291, 1254, 1090, 1049 cm-1. HRMS (ESI) m/z: calcd for
C16H22NO3 [M+H]+ 276.1600, found 276.1596.
4.4.15. Benzyl N-[(2-oxocyclohexyl)(phenyl)methyl]carbamate
6. Akiyama, T.; Takaya, J.; Kagoshima, H. Adv. Synth. Catal. 2002,
344, 338-347.
(5o).26 This product was obtained in 88% yield (59.6 mg) by