944
M. E. F. Braibante
PAPER
equivalents of ethyl chloroformate in order to protect the step. This high reactivity of isocyanates was utilized in the
nitrogen atom and activate the carboxy group of C-4 thia- reaction with (R)-phenylethylamine in order to afford the
zolidine. The addition of sodium azide to mixed anhy- asymmetrical urea 8a (Scheme 2). The spectroscopic data
drides afforded acyl azide intermediates 5a,b (Scheme 2). of structures 2–4 and 6–8 are reported in the Table. IR and
Their conversion into desired derivatives depends on re- elemental analysis are reported in the experimental sec-
action conditions.
tion.
When the Curtius rearrangements of 5a,b were carried out Ureas and amine derivatives analogues to the compounds
in a benzene/water 9:1 emulsion, the symmetrical ureas 6, 7 were prepared in good yields using our methodology
7a,b were obtained in good yields. If the acyl azides were from the (4R)-3-(Boc)-4-carboxylic acids 3a,b. The spec-
treated in non aqueous conditions (anhydrous benzene) troscopic data relevant to products obtained are in agree-
and subsequently refluxed with anhydrous tert-butyl alco- ment with their structures.
hol the (4S)-4-[amine-(Boc)]thiazolidines derivatives
were obtained. The compounds 6b and 7b have the de-
fined configuration at C-2 (2R), due to the N-protection
The compounds obtained from the Curtius rearrangement
in this work were isolated without any evidence of racem-
Table Thiazolidines and Thiazolidines Derivatives Prepareda
Product
Yieldb
(%)
mp (oC)
1H NMR (CDCl3 )
d, J(Hz)
13C NMR(CDCl3 )
d
2bc,d
90
>166 (dec)
Isomer A: 3.08 (dd,1H, Jab=10.00, Jax=8.40), 3.38
(dd,1H, Jba=10.00, J=7.20), 3.90 (dd,1H, J=8.40,
J=7.20), 5.50 (s,1H), 7.30–7.51(m,5H, arom.)
Isomer B: 3.14 (dd,1H, J=10.40, J=4.80 ), 3.30 (dd,1H,
J=10,40, J=7.0) 4.24 (dd,1H, J=7.20, J=4.80 ) 5.68
(s,1H,) 7.30–7.51 (m, 5H, arom.)
38.0, (38.5), 64.9, (65.5), 71.1,
(71.8), 126.9, 127.3, 128.2, 128.5,
127.6, (128.3) ,138.9, (141.2), 172.3,
(173.0).
3ae
3be
86
85
131–132
(s,9H), 3.27 (m,2H), 4.44 (d,1H, J=8.80), 4.62 (d,1H,
J=8.80 ), 4.81 (sl,1H), 9.37 (sl,1H,OH)
28.1, 32.9(34.3), 48.2(48.9), 61.3,
81.7, 153.1(153.7), 175.1(176.0)
>179(dec)
1.23 (s,9H), 3.26 (m,2H, Jax + Jbx = 12.40), 4.69
(t,1H,Jax + Jbx = 12.40), 5.96 (s,1H), 7.20 (m, 3H, Ph)
7.55 (m,2H, Ph)
27.2, 32.4, 63.5, 65.6, 80.1, 125.7,
126.4, 127.2, 140.9, 152.4, 171.3
4b
6a
76
55
oil
1.11 (t,3H, J=7.00), 3.35 (d,2H, J=6.40), 4.11 (q, 2H,
J=7.00), 4.94 (t,1H, Jax + Jbx =12.80), 6.12 (s,1H),
7.58–7.23 (m,5H, Ph.), 9.34 (br, 1H, OH)
14.2, 32.7, 62.5, 64.3, 66.6, 126.5,
127.8, 128.3, 140.2, 154.9, 174.7
116–119
1.86 (t,3H,J=7.20), 1.46 (s,9H), 2.90 (d,1H,
Jba=11.60),3.17 (dd,1H, Jab=11.60, Jax=4.80), 4.17
(q,2H, J=7.20), 4.43 (s,2H), 5.31(sl,1H,NH), 5.97
(m,1H)
14.4, 28.2, 38.6, 47.5, 61.9, 65.9,
79.9, 153.5, 153.8
6be
51
oil
1.24 (t,3H, J=7.00), 1.48 (s,9H,), 2.92 (dd,1H,
Jba =11.80, Jbx = 1.80), 3.20 (dd,1H, Jab=11.80,
Jax=4.80), 4.10 (q,2H, J=7.00), 5.31(br, 1H,
NH ), 6.03 (s,1H), 6.26 (m,1H), 7.27–7.36 (m,5H,Ph.)
14.3, 28.3, 38.4, 62.1, 65.2, 68.6,
80.2, 126.0, 127.9, 128.5, 140.0,
153.9
7a
48
41
52
179–181
177–180
193–195
1.22 (t,3H,J=7.10), 2.88 (d,1H, Jba=11.50 ), 3.17
(dd,1H, Jab= 11.50, Jax= 4.40 ), 4.11 (q,2H, J=7.10),
4.33 (d,1H, J=8.80), 4.49 (d,1H, J=8.80), 6.04 (br,1H)
13.8, 36.9, 46.5, 61.5, 67.0, 153.5,
155.0
7b
8ac
1.01 (t,3H, J=7.20), 2.93 (d,1H,Jba=11.80), 3.29
(dd,1H, Jab =11.80, Jax=5.0), 3.86 (q,2H, J=7.20), 5.97
(s,1H,), 6.22 (br,1H,CH), 7.22–7.46 (m,5H,Ph)
14.1, 38.2, 62.1, 65.7, 69.2, 126.5,
127.9, 128.3, 139.9, 154.6, 156.0
1.18 (t,3H, J=7.00), 1.30 (d,3H, J=6.80 ), 2.78 (d,1H,
Jab=11.40) 3.12 (dd,1H, Jab=11.40 , Jax=4.80), 4.06
(q,2H, J=7.00 ), 4.29 (d,1H, J=8.80 ), 4.42 (d,1H,
J=8.80 ), 4.74 (m,1H,NH), 5.91(t,1H, Jax + Jbx =11.80),
6.43 (m,1H), 7.19–7.30 (m,5H,Ph.)
14.4, 23.3, 37.6, 46.9, 48.4, 61.2,
65.7, 125.5, 126.5, 128.2, 145.3,
153.1,155.6
a All compounds gave satisfactory elemental analyses: C ± 0.16, H ± 0.08, N ± 0.14.
b yield of pure isolated product.
c NMR spectrum in DMSO-d6.
d Obtained as a 45:55 A/B diastereoisomeric mixture.
e NMR 1H spectrum adquired at 50oC.
Synthesis 1999, No. 6, 943–946 ISSN 0039-7881 © Thieme Stuttgart · New York