F. Kelleher, K. o´ Proinsias / Tetrahedron Letters 48 (2007) 4879–4882
4881
H
H
H
Ts
CO2Allyl
CO2H
CO2Allyl
c
a, b
N
HO
HO
Boc NHTrt
NH2
NHTrt
13
12
L-serine
g
d
e, f
H
H
H
PMB
CO2Allyl
Ts
CO2Allyl
Ts
CO2Allyl
N
N
H
N
e
Ns NHTrt
NH
Boc NH
Alloc
Alloc
16
15
14
e, f
H
PMB
CO2Allyl
N
Ns NH
Alloc
17
Scheme 2. Reagents and conditions: (a) trityl chloride, trichloromethylsilane, Et3N, DCM, rt, 48%; (b) (i) Cs2CO3, MeOH; (ii) allyl bromide, DMF,
rt, 90%; (c) 3, DEAD, PPh3, THF, rt, 72%; (d) (i) 5% TFA in CHCl3, (ii) allyl chloroformate, NaHCO3, H2O, 1,4-dioxane, rt, 19% from 13; (e) 50%
TFA in CHCl3, rt; (f) allyl chloroformate, NaHCO3, H2O, rt; (g) 11, DEAD, PPh3, THF, rt, 51%.
other reactions only the starting materials were re-
isolated. As before, 16 was efficiently converted to the
N-alloc protected compound 17 (Scheme 2).
(m, 2H, vinyl CH2), 4.24 (dd, 1H, J = 8.4 and 8.6 Hz,
allyl CH2), 4.11 (m, 1H, allyl CH2), 3.92 (dd, 1H,
J = 5.3 and 6.0 Hz, a-CH), 3.80 (m, 2H, b-CH2), 2.86
(d, 1H, J = 11.1 Hz, NH), 2.37 (s, 3H, tosyl CH3),
1.25 (s, 9H, t-butyl). 13C NMR (CDCl3, 75.45 MHz) d
ppm, 172.6 (ester C@O), 150.8 (Boc C@O), 145.7 (ipso
trityl), 144.1 (para tosyl), 137.4 (ipso tosyl), 131.8 (vinyl
CH), 129.2 (meta trityl), 128.8 (meta tosyl), 128.1 (ortho
trityl), 127.8 (ortho tosyl), 126.4 (para trityl), 118.3 (vinyl
CH2), 84.4 (Cq t-butyl), 70.9 (allyl CH2), 65.9 (C(Ph)3),
56.0 (a-CH), 50.4 (b-CH2), 27.8 (CH3 t-butyl), 21.6
(CH3 tosyl). Mass Spec: expected [M+1] 641.2685,
observed [M+1] 641.2690.
In conclusion, we have prepared orthogonally protected
a,b-diaminopropionic acids in good yields from pro-
tected L-serines using the Mitsunobu reaction of sulfon-
amide-derived nitrogen nucleophiles. Currently we are
studying the chemistry of these compounds, for exam-
ple, the clean removal of the individual protecting
groups, and their incorporation into peptide structures
using solid-phase peptide synthesis. We are also examin-
ing further functionalisation reactions of N–H sulfon-
amide compounds 6 and 15. The results of these
studies will be reported in due course.
Acknowledgement
We are grateful to Cycle III of the Higher Education
Authority’s Program for Research in Third Level Insti-
tutions (PRTLI) under the Irish Government’s National
2. Typical procedure for Mitsunobu reaction, exemplified
by the synthesis of 13
´
Development Plan (2000–2006) for funding for K.oP.
To a solution of N-(tert-butoxycarbonyl)-p-toluenesul-
fonamide 3 (0.16 g, 0.68 mmol) in dry THF (3 ml) was
added PPh3 (0.34 g, 1.4 mmol), followed by the addition
of 12 (0.16 g, 0.46 mmol) and DEAD (0.19 g, 1.2 mmol).
The resulting mixture was allowed to stir at room tem-
perature, under a nitrogen atmosphere, for 10 h. The
solvent was removed in vacuo giving an orange oil,
which was purified by flash column chromatography
on silica gel, in petroleum ether/ethyl acetate (10:1), to
give a white solid (0.30 g, 72%). Mp: 143–145 °C. Rf:
0.80, petroleum ether–ethyl acetate (2:1). IR (KBr)
cmÀ1: 3433, 3066, 2924, 1734, 1595, 1234, 1139. 1H
NMR (CDCl3, 300.4 MHz) d ppm, 7.77 (d, 2H,
J = 12.3 Hz, ortho tosyl), 7.54 (d, 6H, J = 12.9 Hz, ortho
trityl), 7.27–7.23 (d, 2H, J = 12.3 Hz, meta tosyl and m,
9H, para and meta trityl), 5.56 (m, 1H, vinyl CH), 5.11
References and notes
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