D
Synlett
K. Ikeuchi et al.
Letter
amine derivative 11 (Scheme 6c). Because 11 barely dis-
solved in EtOAc (12 mg/mL), EtOAc was used as the solvent.
Despite observing that the reaction mixture changed from a
suspension to a clear solution, the reaction did not go to
completion, instead giving a 3:2 mixture of -12 and 11.
The reason might be attributed to the low reactivity of 11
due to the decrease of the nucleophilicity of the hydroxy
group induced by the presence of electron-withdrawing
protecting groups and a hydrogen bond in the phthaloyl
group.
Funding Information
The Ministry of Education, Culture, Sports, Science and Technology
MEXT) in Japan supported the program for the Strategic Research
(
Foundation at Private Universities (Grant No. S1311046), and the Ja-
pan Society for the Promotion of Science (JSPS) (KAKENHI) (Grant No.
JP16H01163 in Middle Molecular Strategy, and Grant No.
JP16KT0061) partly supported this work.
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Supporting Information
Supporting information for this article is available online at
(
a)
https://doi.org/10.1055/s-0037-1611551.
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OAc
OAc
Cl3CCN
cat. DBU
NH
O
O
AcO
AcO
AcO
AcO
OH
hexane or t-BuOMe
References and Notes
O
CCl3
AcO
0 °C
AcO
5
6
(1) For Bn-TCAI, see: (a) Eckenberg, P.; Groth, U.; Huhn, T.; Richter,
in hexane: 5%
in t-BuOMe: 98% (α/β = 11:1)
N.; Schmeck, C. Tetrahedron 1993, 49, 1619. (b) Boa, A. N.;
Jenkins, P. R. In Encyclopedia of Reagents for Organic Synthesis,
(
b)
OBn
OBn
2nd ed., Vol. 2; Paquette, L. A.; Crich, D.; Fuchs, P. L.; Molander,
NH
O
O
G. A., Ed.; John Wiley & Sons: New York, 2009, 680.
BnO
BnO
BnO
BnO
OH
OH
O
CCl3
(2) For PMB-TCAI, see: (a) Nakajima, N.; Horita, K.; Abe, R.;
Yonemitsu, O. Tetrahedron Lett. 1988, 29, 4139. (b) Wuts, P. G.
M. In Encyclopedia of Reagents for Organic Synthesis, 2nd ed., Vol.
8; Paquette, L. A.; Crich, D.; Fuchs, P. L.; Molander, G. A., Ed.;
John Wiley & Sons: New York, 2009, 6598.
3) Comprehensive Organic Name Reactions and Reagents, Vol. 3;
Wang, Z., Ed.; John Wiley & Sons: New York, 2009, 3026.
4) Overman, L. E.; Carpenter, N. E. Org. React. 2005, 66, 1.
5) Fernandes, R. A.; Kattanguru, P.; Gholap, S. P.; Chaudhari, D. A.
Org. Biomol. Chem. 2017, 15, 2672.
BnO
BnO
Cl3CCN
cat. DBU
7
9: 98% (α/β = 2.2:1)
toluene
O
O
H
H
H
O
O
O
O
O
7 to 9: 0 °C to rt
CCl3
(
8
to 10: 0 °C aa
H
H
NH
O
O
O
O
(
(
8
10: 96% (α only)
OBz
OBz
(6) (a) Schmidt, R. R.; Michel, J. Angew. Chem. Int. Ed. 1980, 19, 731.
b) Zhu, X.; Schmidt, R. R. Angew. Chem. Int. Ed. 2009, 48, 1900.
(
c)
BzO
BzO
(
O
Cl3CCN
cat. DBU
O
O
BzO
BzO
(
7) For examples of the preparation of Bn-TCAI, see: (a) Lonca, G.
H.; Ong, D. Y.; Tran, M. T. H.; Tejo, C.; Chiba, S.; Gagosz, F. Angew.
Chem. Int. Ed. 2017, 56, 11440. (b) Li, C.; Li, W.; Wang, J. Tetrahe-
dron Lett. 2009, 50, 2533. (c) Trappeniers, M.; Goormans, S.; Van
Beneden, K.; Decruy, T.; Linclau, B.; Al-Shamkhani, A.; Elliott, T.;
Ottensmeier, C.; Werner, J. M.; Elewaut, D.; Van Calenbergh, S.
ChemMedChem 2008, 3, 1061. (d) Wessel, H.-P.; Iversen, T.;
Bundle, D. R. J. Chem. Soc., Perkin Trans. 1 1985, 2247.
CCl3
OH
O
O
N
O
N
O
EtOAc
NH
0
°C
1
1/β-12 = ca. 2:3
11
12 (β only)
Scheme 6 Application to four glycosyl TCAIs: (a) 2,3,4,6-tetra-O-ace-
tyl--D-glucopyranose (5), (b) 2,3,4,6-tetra-O-benzyl-D-glucopyranose
7) and 2,3:5,6-bis-O-isopropylidene-D-mannofuranose (8), (c) 3,4,6-
(8) For examples of the preparation of PMB-TCAI, see: (a) Green, R.
A.; Jolley, K. E.; Al-Hadedi, A. A. M.; Pletcher, D.; Harrowven, D.
C.; Frutos, O. D.; Mateos, C.; Klauber, D. J.; Rincoń, J. A.; Brown,
R. C. D. Org. Lett. 2017, 19, 2050. (b) Kumar, R.; Rej, R. K.; Halder,
J.; Mandal, H.; Nanda, S. Tetrahedron: Asymmetry 2016, 27, 498.
(
tri-O-benzoyl-2-deoxy-2-phthalimido-D-glucopyranose (11)
In summary, we have developed a method for obtaining
stainless TCAI compounds without purification by chroma-
tography or distillation. The crucial aspect was the selection
of a solvent that barely dissolved the reactant alcohol. The
method effectively provided Bn- and PMB-TCAIs (1 and 2),
commonly used for protecting alcohols. We also confirmed
that the method was applicable not only for the gram-scale
synthesis of 1 and 2, but also for the preparation of various
allylic and glycosyl TCAIs (4a–f, 6, 9 and 10). This method is
proposed here as a new standard procedure for the prepa-
ration of TCAIs.
(
c) Wadavrao, S. B.; Ghogare, R. S.; Narsaiah, A. V. Synthesis
2015, 47, 2129. (d) Chen, T.; Altmann, K.-H. Chem. Eur. J. 2015,
21, 8403.
(
9) For examples of the preparation of allylic TCAIs, see:
(a) Debbarma, S.; Bera, S. S.; Maji, M. S. J. Org. Chem. 2016, 81,
1
1716. (b) Das, D.; Halder, J.; Bhuniya, R.; Nanda, S. Eur. J. Org.
Chem. 2014, 5229. (c) Ghosh, A. K.; Cheng, X.; Bai, R.; Hamel, E.
Eur. J. Org. Chem. 2012, 4130. (d) Cui, Y.; Tu, W.; Floreancig, P. E.
Tetrahedron 2010, 66, 4867.
(10) In the case of preparing glycosyl TCAIs, the mainly used
base/solvent combination is NaH/CH Cl . For examples, see:
2
2
(a) Lee, A. M. M.; Painter, G. F.; Compton, B. J.; Larsen, D. S. J. Org.
Chem. 2014, 79, 10916. (b) Ganesh, N. V.; Fujikawa, K.; Tan, Y.
H.; Stine, K. J.; Demchenko, A. V. Org. Lett. 2012, 14, 3036.
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–E