S. R. Dandepally, A. L. Williams / Tetrahedron Letters 50 (2009) 1071–1074
1073
Table 2 (continued)
Entry
Substrate
K3PO4ÁH2O
Conditions
Time
Product
Yielda (%)
O2N
O2N
N
N
6
7
—
MeOH, MW
MeOH, MW
MeOH, reflux
20 min
2 min
15 min
99
97
93
N
N
H
Boc
20 mol %
20 mol %
6b
6a
CHO
CHO
—
MeOH, MW
MeOH, MW
MeOH, reflux
20 min
2 min
15 min
60b
100
100
N
N
20 mol %
20 mol %
H
Boc
7a
7b
N(Boc)2
NHBoc
8
—
MeOH, MW
MeOH, MW
MeOH, reflux
20 min
8 min
10 h
0
93
97
8b
8a
100 mol %
100 mol %
NHBoc
NHBoc
CO2Me
9
—
MeOH, MW
MeOH, MW
MeOH, reflux
20 min
5 min
8 h
5b
CO2Me
100 mol %
100 mol %
72
62
N
N
H
Boc
9a
9b
Boc
N
H
N
O
O
10
—
MeOH, MW
10 min
96
O
O
10a
10b
11b
11
—
MeOH, MW
20 min
87
N
O
N
H
O
Boc
11a
a
Isolated yield, all compounds were either identified with authentic commercially available samples, or new, fully characterized by 1H NMR, 13C NMR, and MS.
Conversion based on TLC and LCMS.
b
aliphatic secondary amines are also unreactive under the present
conditions.22 Most N-Boc-protected heterocyclic compounds
cleanly underwent the deprotection except 10a and 11a (Table 2,
entries 10 and 11). Use of 20 mol % of K3PO4ÁH2O in both micro-
wave and conventional heating conditions resulted in the cleavage
of oxazolone moiety 10a to give tert-butyl 2-hydroxyphenylcarba-
mate (10c).23 Fortunately, microwave irradiation of 10a in MeOH
without any base afforded the desired deprotection in excellent
yield. Similarly, tert-butyl 2-oxo-3,4-dihydroquinol-ine-1(2H)-car-
boxylate (11a)24 in MeOH under microwave irradiation conditions
gave 3,4-dihydroquinolin-2(1H)-one (11b) in good yield. Our
methodology greatly compliments previously reported strong ba-
sic N-Boc deprotection methods due to its ability to deprotect het-
eroaromatic secondary amines, amides, and heterocyclic
compounds.10
References and notes
1. (a) Greene, T. W.; Wuts, P. G. M. Protective groups in Organic Synthesis, 3rd ed.;
John Wiley & Sons, 1999. and references cited therein; (b) Philip, J. K. Protecting
Groups, 3rd ed.; Georg Thieme: Stuttgart, New York, 2005. and references cited
therein.
2. Li, B.; Bemish, R.; Buzon, R. A.; Chiu, C. K.-F.; Colgan, S. T.; Kissel, W.; Le, T.;
Leeman, K. R.; Newell, L.; Roth, J. Tetrahedron Lett. 2003, 44, 8113.
3. Bose, D. S.; Kumar, K. K.; Narsimha Reddy, A. V. Synth. Commun. 2003, 33, 445.
and references cited therein.
4. Shaikh, N. S.; Gajare, A. S.; Deshpande, V. H.; Bedekar, A. V. Tetrahedron Lett.
2000, 41, 385.
5. Appelquist, T.; Wenbo, D. Tetrahedron Lett. 1996, 37, 1471.
6. (a) Hwu, J. R.; Jain, M. L.; Tsay, S.-C.; Hakimelahi, G. H. Tetrahedron Lett. 1996,
37, 2035; (b) Kuttan, A.; Nowshudin, S.; Rao, M. N. A. Tetrahedron Lett. 2004, 45,
2663.
7. Marcantoni, G.; Massccesi, M.; Torregiani, E.; Bartoli, G.; Bosco, M.; Sambri, L. J.
Org. Chem. 2001, 66, 4430.
8. (a) Routier, S.; Saugé, L.; Ayerbe, N.; Coudert, G.; Mérour, J.-Y. Tetrahedron Lett.
2002, 43, 589; (b) Jacquemard, U.; Bénéteau, V.; Lefoix, M.; Routier, S.; Mérour,
J.-Y.; Coudert, G. Tetrahedron 2004, 60, 10039.
9. (a) Rawal, V. H.; Jones, R. J.; Cava, M. P. J. Org. Chem. 1987, 52, 19; (b)
Wasserman, H. H.; Berger, G. D.; Cho, K. R. Tetrahedron Lett. 1982, 23, 465.
10. (a) Hasan, I.; Marinelli, E. R.; Lin, L.-C. C.; Fowler, F. W.; Levy, A. B. J. Org. Chem.
1981, 46, 157; (b) Ravinder, K.; Reddy, V.; Mahesh, K. C.; Narasimhulu, M.;
Venkateswarlu, Y. Synth. Commun. 2007, 37, 281.
In summary, we have developed a mild, simple, and efficient
method for the deprotection of secondary Boc-protected amino
compounds under basic conditions assisted by microwave irradia-
tion. The scope for the chemoselective deprotection of different N-
Boc groups has been demonstrated.
11. Tom, J. N.; Simon, W. M.; Frost, H. N.; Ewing, M. Tetrahedron Lett. 2004, 45, 905.
12. Mohapatra, D. K.; Durugkar, K. A. Arkivoc 2005, 20.
13. Kazzouli, S. A.; Koubachi, J.; Berteina-Raboin, S.; Mouaddib, A.; Guillaumet, G.
Acknowledgments
Tetrahedron Lett. 2006, 47, 8575.
14. Gedye, R.; Smith, F.; Westaway, K.; Ali, H.; Baldisera, L. Tetrahedron Lett. 1986,
27, 279.
15. (a) Hayes, B. L. Microwave Synthesis Chemistry at the Speed of Light; CEM
Publishing: Matthews, NC, 2002; (b) Loupy, A. Microwaves in Organic Synthesis,
1st ed.; Wiley-VCH GmbH & KGaA: Weinheim, 2002; (c) Kappe, C. O.; Stadler,
A. In Microwaves in Organic and Medicinal Chemistry; Manhold, R., Kubinyi, H.,
Folkers, G., Eds., 1st ed.; Wiley-VCH GmbH & KGaA: Weinheim, 2005.
We gratefully acknowledge The Golden LEAF Foundation, Rocky
Mount, NC, for the financial support. We thank Dr. Li-An Yeh,
Director, BRITE, for the encouragement, and Dr. Sabapathy Sankar,
Lab Supervisor for NMR facility, Department of Chemistry, NC State
University, for NMR discussions. We also thank the Department of
Chemistry at NC Central University for using their NMR facility.