O. Onomura et al. / Tetrahedron Letters 48 (2007) 9080–9084
9083
OH R3
N
OTs R3
N
OH R3
N
p
-TsCl (0.5 equiv)
Cu(OTf)2 (0.1 equiv),
R1
Ph
R1
Ph
R1
Ph
+
ð6Þ
(R,R)-Ph-BOX (0.1 equiv)
O
O
O
K2CO3 (1.0 equiv)
MeCN, rt, 12 h
DL-1an-az
(
S
)-3an-az
(R)-1an-az
11, 1679–1682; (c) Lin, W.-Q.; He, Z.; Jing, Y.; Cui, X.;
Liu, H.; Mi, A.-Q. Tetrahedron: Asymmetry 2001, 12,
1583–1587.
Tosyloxyl group is a good leaving group, thus (S)-3a
undergoes SN2 reaction with primary amine to form
N-alkylated a-amino acid (R)-6 with a slight degree of
racemization in high yield,15 while N,N-dialkylated
derivative (R)-7 was obtained using secondary amine
without any loss of optical purity (Eq. 7).
3. Recent literatures for kinetic resolution of 2-hydroxy-
alkanoic acid derivatives by enzymatic methods: (a)
Campbell, R. F.; Fitzpatrick, K.; Inghardt, T.; Karlsson,
O.; Nilsson, K.; Reilly, J. E.; Yet, L. Tetrahedron Lett.
2003, 44, 5477–5481; (b) Ito, T.; Matsushita, Y.; Abe, Y.;
Han, S.; Wada, S.; Hayase, S.; Kawatsura, M.; Takai, S.;
Morimoto, M.; Hirose, Y. Chem. Eur. J. 2006, 12, 9228–
9237.
4. Kinetic resolution of ethyl DL-mandelate by benzoylation
catalyzed with Cu(II)-aza(bisoxazoline) catalyst: Gissibl,
A.; Finn, M. G.; Reiser, O. Org. Lett. 2005, 7, 2325–2328.
5. A recent review of chiral bis(oxazoline) ligands: Desimoni,
G.; Faita, G.; Jørgensen, K. A. Chem. Rev. 2006, 106,
3561–3651.
Bn
Bn-NH2 (1.0 equiv)
OTs
NH
H
N
H
N
Et3N (1.2 equiv)
Ph
Ph
Ph
Ph
THF
60 ºC, 24 h
O
O
(
S
)-3a
(
R
)-6
80% ee
95% yield, 76% ee
Bn
Ph
Me
6. Cu(II)–Ph-BOX catalyzed mono-benzoylation of 1,2-
diols: (a) Matsumura, Y.; Maki, T.; Murakami, S.;
Onomura, O. J. Am. Chem. Soc. 2003, 125, 2052–2053;
Cu(II) catalyzed mono-benzoylation of 1,2-diols reported
by other groups: (b) Mazet, C.; Ko¨hler, V.; Pfaltz, A.
Angew. Chem., Int. Ed. 2005, 44, 4888–4891; (c) Nakam-
ura, D.; Kakiuchi, K.; Koga, K.; Shirai, R. Org. Lett.
2006, 8, 6139–6142; (d) Arai, T.; Mizukami, T.; Yanagis-
awa, A. Org. Lett. 2007, 9, 1145–1147; Cu(II)–Ph-BOX
catalyzed carbamoylation of 1,2-diols: (e) Matsumoto, K.;
Mitsuda, M.; Ushijima, N.; Demizu, Y.; Onomura, O.;
Matsumura, Y. Tetrahedron Lett. 2006, 47, 8453–8456;
Cu(II)–Ph-BOX catalyzed mono-oxidation of 1,2-diols: (f)
Onomura, O.; Arimoto, H.; Matsumura, Y.; Demizu, Y.
Tetrahedron Lett. 2007, 48, 8668–8672; Cu(II)–Ph-BOX
catalyzed benzoylation of vic-aminoalcohols: (g) Mitsuda,
M.; Tanaka, T.; Tanaka, T.; Demizu, Y.; Onomura, O.;
Matsumura, Y. Tetrahedron Lett. 2006, 47, 8073–8077;
Review: (h) Matsumura, Y.; Onomura, O.; Demizu, Y.
Yuki Gosei Kagaku Kyokaishi 2007, 65, 216–225.
Bn-NH-Me (1.0 equiv)
Et3N (1.2 equiv)
N
H
N
(
S
)-3a
Ph
THF
60 ºC, 24 h
80% ee
O
(
R
)-7
94% yield, 80% ee
ð7Þ
In conclusion, we have demonstrated a new non-enzy-
matic method for kinetic resolution of 2-hydroxyalkan-
amides16 and converted the chiral tosylated products to
optically active a-amino acid derivatives. The mechanis-
tic study of this tosylation and its further synthetic
application are underway.
Acknowledgements
7. Asymmetric monosulfonylation of meso-1,2-diols cata-
lyzed with Cu(II)–Ph-BOX: Demizu, Y.; Matsumoto, K.;
Onomura, O.; Matsumura, Y. Tetrahedron Lett. 2007, 48,
7605–7609.
O.O. and Y.D. are very grateful for a Grant-in-Aid for
Scientific Research (C) (19550109) from Japan Society
for the Promotion of Science and a Grant-in-Aid for
Young Scientists (B) (19790017) from the Ministry of
Education, Science, Sports and Culture, Japan,
respectively.
8. A typical procedure for kinetic resolution: Under an
aerobic atmosphere, a solution of Cu(OTf)2 (18.1 mg, 0.05
mmol) and (R,R)-Ph-BOX (16.7 mg, 0.05 mmol) in MeCN
(2 mL) was stirred for 10 min. Into the solution were
added 1a (113.5 mg, 0.5 mmol), potassium carbonate
(69.1 mg, 0.5 mmol) and p-TsCl (47.7 mg, 0.25 mmol).
After stirring for 12 h at rt, the solution was poured in
water and extracted with AcOEt (20 mL · 3). The com-
bined organic layer was dried over MgSO4 and the solvent
was removed under reduced pressure. The residue was
purified by silica gel column chromatography (n-hexane/
AcOEt = 3:1) to afford (S)-3a (42% yield, 80% ee) as a
References and notes
1. (a) Bigi, F.; Bocelli, G.; Maggi, R.; Sartori, G. J. J. Org.
Chem. 1999, 64, 5004–5009; (b) Groger, H. Adv. Synth.
Catal. 2001, 343, 547–558; (c) Tao, J.; McGee, K. In
Asymmetric Catalysis on Industrial Scale: Challenges,
Approaches and Solutions; Blaser, H. U., Schmidt, E.,
Eds.; John Wiley and Sons Ltd: Weinheim, 2004; pp 323–
334; (d) Momiyama, N.; Yamamoto, H. J. Am. Chem.
Soc. 2005, 127, 1080–1081.
26
1
white solid. Mp 140–141 ꢁC. ½aꢀD +8.9 (c 1.0, CHCl3). H
NMR (300 MHz, CDCl3) d 8.06 (s, 1 H), 7.71 (d,
J = 8.1 Hz, 2H), 7.48 (d, J = 7.8 Hz, 2H), 7.35–7.22 (m,
9H), 7.17 (t, J = 7.5 Hz, 1H), 5.85 (s, 1H), 2.38 (s, 3H).
HR-FAB: [M+H]+ calcd for C21H20NO4S, 381.1113;
found, 382.1111. The optical purity of 3a was determined
by chiral HPLC: Daicel Chiralcel OD-H column (4.6 mm
2. (a) Szymanski, W.; Ostaszewski, R. Tetrahedron: Asym-
metry 2006, 17, 2667–2671; (b) Blaser, H.-U.; Burkhardt,
S.; Kirner, H. J.; Mo¨ssner, T.; Studer, M. Synthesis 2003,