Gold(I)-catalyzed formation of 5-methylene-1,3-oxazolidin-2-ones

Article abstract of DOI:10.1055/s-2006-950253

A study concerning the gold(I)-catalyzed rearrangement of propargylic tert-butylcarbamates into 5-methylene-1,3-oxazolidin-2-ones is described. The mild reaction conditions employed allow the efficient synthesis of a variety of these structures, which wou

Full text of DOI:10.1055/s-2006-950253

LETTER
2727
Gold(I)-Catalyzed Formation of 5-Methylene-1,3-oxazolidin-2-ones
G
A
old(I)-Catalyzed
n
Formation
o
d
f
5-Methylen
r
e
-1,3-ox
e
azolidin-2-
a
ones Buzas, Fabien Gagosz*
Laboratoire de Synthèse Organique, UMR CNRS 7652, Ecole Polytechnique, DCSO, 91128 Palaiseau, France
Fax +33(1)69333851; E-mail: gagosz@dcso.polytechnique.fr
Received 9 July 2006
O
O
O
Abstract: A study concerning the gold(I)-catalyzed rearrangement
O
of propargylic tert-butylcarbamates into 5-methylene-1,3-oxazoli-
din-2-ones is described. The mild reaction conditions employed al-
low the efficient synthesis of a variety of these structures, which
would be less conveniently obtained using other reported methods.
PPh3AuNTf2
O
O
(ref. 6)
R1
R1
R2
R2
2
1
Key words: gold catalysis, ring closure, oxazolidinones
R3
O
O
R3
PPh3AuNTf2
?
N
N
O
Oxazolidinones and their derivatives are structural motifs
of high importance in organic synthesis. Even if these are
mainly used as chiral auxiliaries in a variety of asymmet-
O
R1
R2
R1
R2
1
4
3
ric reactions, they also represent a useful source of pro-
2
tected 1,2-amino alcohols. Moreover, the oxazolidinone
Scheme 1
moiety is frequently found in the structure of a variety of
biologically active or naturally occurring compounds.3
Despite the diversity of methodologies to access such
structures, the development of practical and efficient
routes to synthesize functionalized oxazolidinones under
mild conditions remains of high interest.
,4
when the reaction mixture was refluxed (40%) or when
the loading of the catalyst was increased to 3 mol%
5
(
44%). These results strongly contrast with the one ob-
tained in the rearrangement of tert-butyl carbonates 7. In-
deed, the corresponding carbonate 8 was obtained in 83%
yield after only ten minutes of reaction. Such a decrease
in efficiency might be attributed to an equilibrium be-
tween the two possible rotamers of substrate 5a thus dis-
favoring the formation of the intermediate cyclizing
conformer (Figure 1).10
Following our recent results in using the air stable crystal-
line PPh AuNtf catalyst for the synthesis of 4-alkylidene-
3
2
1
1
,3-dioxolones 2 from propargylic tert-butyl carbonates
, we surmised that analogous tert-butyl carbamates 3
6
might react similarly to furnish the corresponding 5-meth-
7
ylene-1,3-oxazolidin-2-ones 4 (Scheme 1). In this case,
This problem was, however, overcome by simply substi-
tuting the nitrogen atom of the substrate by a benzyl
group. In this case, the corresponding oxazolidinone 6b
was obtained in 98% yield when substrate 5b was treated
with 1% of the catalyst (Table 1, entry 1). Alternatively,
substitution of the propargylic position by two methyl
the catalytic process would allow an easy and efficient ac-
cess to a variety of oxazolidinones bearing an interesting
exo-methylene bond that could be used for the elaboration
of more functionalized structures. During the preparation
of this manuscript, Carretero and coworkers reported that
such a transformation could be achieved by the combined
8
use of 5 mol% of Ph AuCl and 5 mol% of AgSbF . We
3
6
herein report our own results in that field which led to the
efficient synthesis of a variety of 5-methylene-1,3-oxazo-
lidin-2-ones substituted either on the nitrogen atom or at
O
O
O
NH
PPh3AuNTf2 (n mol%)
HN
O
(1)
9
0
.5 M in CH2Cl2
the propargylic position.
5
a
Simple carbamate 5a was first chosen as a model substrate
to validate our approach (Scheme 2, equation 1). We were
pleased to observe that the rearrangement of 5a catalyzed
by 1 mol% of PPh AuNtf in dichloromethane afforded
6a
n = 1
n = 1
n = 1
n = 3
1 h, r.t.
24 h, r.t.
37%
44%
40%
44%
3
2
2 h, reflux
72 h, r.t.
after one hour the desired oxazolidinone 6a, however, in
only 37% yield.
O
O
O
A longer reaction time (24 h) did not significantly im-
prove the yield (44%). Similar yields were also obtained
O
3
PPh AuNTf2 (1 mol%)
O
O
(2)
0
.5 M in CH2Cl2, r.t.
10 min, 83%
7
8
SYNLETT 2006, No. 17, pp 2727–2730
1
7
.1
0
.2
0
0
6
Advanced online publication: 09.10.2006
DOI: 10.1055/s-2006-950253; Art ID: D19806ST
Scheme 2
©
Georg Thieme Verlag Stuttgart · New York

2
728
A. Buzas, F. Gagosz
LETTER
O
R
H+
O
O
H
O
O
N
O
O
H
N
Au
H+
O
NH
R
R'
HN
R'
11
1
2
Au+
Au+
Au+
favored rotamer
for cyclization
unfavored rotamer
for cyclization
O
H
Figure 1
O
H
R
O
N
N
Au
O
R
groups induced a Thorpe–Ingold effect which led to the
rapid and nearly quantitative formation of the correspond-
ing oxazolidinone 6c (Table 1, entry 2). The combination
R'
R'
9
10
of nitrogen atom substitution and propargylic position Scheme 3 Proposed mechanism for the formation of 5-methylene-
substitution led to an even more rapid reaction, which af- 1,3-oxazolidin-2-ones
forded oxazolidinone 6d in 99% yield (Table 1, entry 3).
The reaction proved to be quite general and various sub- As previously shown for the rearrangement of propargylic
6
stituted propargylic tert-butylcarbamates 5b–q were con- tert-butyl carbonates, we also attempted to trap the inter-
verted in the presence of 1 mol% of PPh AuNTf into the mediate vinylgold species 11 by a source of electrophilic
3
2
corresponding 5-methylene-1,3-oxazolidin-2-ones 6b–q iodine prior to protodemetallation. To this end, propargyl-
1
1
(
Table 1). Yields were generally high, ranging from ic carbamate 5d was reacted with as light excess of N-io-
0% to 99%. Various alkyl or aryl substituents were toler- dosuccinimide in the presence of 1 mol% of the gold(I)
7
ated on the nitrogen atom of the substrates (Table 1, en- catalyst. The transformation was rapid and stereoselec-
tries 1, 3–7). Secondary propargylic carbamates 5i–n tively furnished after 10 minutes at room temperature the
reacted equally, however, with a longer reaction time valuable Z-vinyliodide 13, which was isolated in 97%
1
2
(
Table 1, entries 8–13). The propargylic position could yield (Scheme 4).
be substituted by alkyl groups such as in the case of the
cyclohexyl, perillyl or pinenyl derivatives 5i–k (Table 1,
entries 8–10). Aryl groups possessing electron-withdraw-
ing group or electron-donating groups were also tolerated
Ph
N
O
O
O
PPh3AuNTf2 (1 mol%)
N
O
I
Ph
(
Table 1, entries 11–13). The reaction conditions em-
0
.5 M in acetone, NIS (1.2 equiv)
ployed were mild enough to prevent epimerization or deg-
radation of the substrates. Indeed, the 1:4.8
diastereoisomeric mixture of the acid sensitive pinenyl
1
0 min, 97%
5
d
13
derivative 5k was smoothly converted into the corre- Scheme 4
sponding oxazolidinone 6k with the same diastereoiso-
meric ratio (Table 1, entry 10). It was also possible to
In summary, we have developed an efficient gold(I)-cata-
lyzed cyclization–fragmentation process for the synthesis
of functionalized 5-methylene-1,3-oxazolidin-2-ones
from readily available propargylic tert-butyl carbamates.
synthesize the valuable bicyclic oxazolidinones 6o–q de-
rived from pyrrolidine, piperidine or azepine rings with
yields ranging from 65% to 99% (Table 1, entries 14–16).
To account for these results, a mechanism for the forma- Further studies related to the use of this process for the
tion of the 5-methylene-1,3-oxazolidin-2-ones is pro- synthesis of other valuable synthons are underway and
posed in Scheme 3. This mechanism is similar to that will be reported in due course.
previously described for the formation of 4-alkylidene-
1
,3-dioxolones from propargylic tert-butyl carbonates.
Acknowledgment
Gold(I) activation of the triple bond in propargylic tert-
butyl carbamate 9 promotes the formation of the stabilized The author wishes to thank Prof. S. Z. Zard, Dr. B. Quiclet-Sire, Dr.
cationic species 10. Subsequent fragmentation of the C–O
bond of the tert-butyloxy group in 10 can lead to the for-
I. Hanna for helpful discussions and Rhodia Chimie Fine for a do-
nation of HNTf2.
mation of the neutral vinyl-gold species 11. This latter is
then protiodemetallated to finally furnish 5-methylene- References and Notes
1
,3-oxazolidin-2-one 12 with the concomitant regenera-
(
1) For the use of oxazolidinoe as asymmetric auxiliaries, see:
a) Ager, D. J.; Prakash, I.; Schaad, D. R. Chem. Rev. 1996,
6, 835. (b) Evans, D. A. Aldrichimica Acta 1982, 15, 23.
tion of the gold(I) catalyst.
(
9
Synlett 2006, No. 17, 2727–2730 © Thieme Stuttgart · New York

LETTER
Gold(I)-Catalyzed Formation of 5-Methylene-1,3-oxazolidin-2-ones
2729
Table 1 Synthesis of 5-Methylene-1,3-oxazolidin-2-ones
Entry
Precursor
R1
Time
Yield (%)a
R2
H
R3
H
Compd
5b
1
2
3
4
5
Bn
H
30 min
30 min
5 min
5 min
1 h
98 (6b)
99 (6c)
99 (6d)
95 (6e)
97 (6f)
Me
Me
H
Me
Me
H
5c
Bn
Ph
5d
5e
H
H
5f
6
7
8
H
H
H
H
H
5g
5h
1.5 h
10 min
20 h
99 (6g)
100 (6h)
H
H
5i
82 (6i) b
b
b
dr = 1:1
dr = 1:1
9
H
5j
dr = 1:1
16 h
91 (6j) b
dr = 1:1
1
1
0
1
H
H
H
H
5k
dr = 1:4.8
6 h
2 h
96 (6k)
dr = 1:4.8
b
b
5l
83 (6l)
Cl
1
1
2
3
H
H
H
H
5m
5n
4 h
70 (6m)
OMe
OMe
20 h
86 (6n)
OAllyl
1
4
5
5o
5p
3.5 h
1 h
74 (6o)
65 (6p)
Boc
N
1
Boc
N
16
5q
5 min
99 (6q)
Boc
N
a
All yields refer to chromatographically purified products.
Ratios determined by H NMR.
b
1
Synlett 2006, No. 17, 2727–2730 © Thieme Stuttgart · New York

2
730
A. Buzas, F. Gagosz
LETTER
R.; Nolan, S. P. Angew. Chem. Int. Ed. 2006, 45, 1.
(
2) For the use of oxazolidinone as a source of protected 1,2-
amino alcohols, see: (a) Bhaket, P.; Morris, K.; Stauffer, C.
S.; Datta, A. Org. Lett. 2005, 7, 5875. (b) Ayad, T.;
Faugeroux, V.; Genisson, Y.; Andre, C.; Baltas, M.;
Gorrichon, L. J. Org. Chem. 2004, 69, 8775.
(h) Zhang, L.; Wang, S. J. Am. Chem. Soc. 2006, 128, 1442.
(i) Genin, E.; Toullec, P.; Antoniotti, S.; Brancour, C.;
Genêt, J. P.; Michelet, V. J. Am. Chem. Soc. 2006, 128,
3112. (j) Shi, X.; Gorin, D. J.; Toste, F. D. J. Am. Chem. Soc.
2005, 127, 5802. (k) Zhang, L.; Kozmin, S. A. J. Am. Chem.
Soc. 2005, 127, 6962. (l) Nieto-Oberhuber, C.; Lopez, S.;
Echavarren, A. M. J. Am. Chem. Soc. 2005, 127, 6178.
(m) Nieto-Oberhuber, C.; Lopez, S.; Munoz, M. P.;
Cardenas, D. J.; Bunel, E.; Nevado, C.; Echavarren, A. M.
Angew. Chem. Int. Ed. 2005, 44, 6146. (n) Markham, J. P.;
Staben, S. P.; Toste, F. D. J. Am. Chem. Soc. 2005, 127,
9708. (o) Antoniotti, S.; Genin, E.; Michelet, V.; Genêt, J. P.
J. Am. Chem. Soc. 2005, 127, 9976.
(
3) For biologically active molecules possessing an oxazolidine
fragment, see: (a) Puder, C.; Loya, S.; Hizi, A.; Zeeck, A. J.
Nat. Prod. 2001, 64, 42. (b) Thirkettle, J.; Alvarez, E.;
Boyd, H.; Brown, M.; Diez, E.; Hueso, J.; Elson, S.; Fuslton,
M.; Gershater, C.; Morata, M. L.; Perez, P. J. Antibiot. 2000,
5
3, 664.
(4) For natural compounds possessing an oxazolidine fragment,
see: (a) Pluotno, A.; Carmeli, S. Tetrahedron 2005, 61, 575.
b) Hsieh, T.-J.; Chang, F.-R.; Chia, Y.-C.; Chen, C.-Y.; Lin,
(
H.-C.; Chiu, H.-F.; Wu, Y.-C. J. Nat. Prod. 2001, 64, 1157.
5) Selected examples of oxazolidinones synthesis: (a) From
amino alcohols, see for instance: Tarnowski, A.; Retz, O.;
Baer, T.; Schmidt, R. Eur. J. Org. Chem. 2005, 1129.
(8) Robles-Machin, R.; Adrio, J.; Carretero, J. C. J. Org. Chem.
2006, 71, 5023.
(9) The work recently reported by Carretero and coworkers (see
ref. 8) was only dealing with the synthesis of oxazolidinones
substituted at the nitrogen and alkyne terminus.
(
(
b) From aziridines, see for instance: Miller, A. W.; Nguten,
S. T. Org. Lett. 2004, 6, 2301. (c) From epoxides, see for
instance: Mertin, R.; Murruzzu, C.; Pericas, M. A.; Riera, A.
J. Org. Chem. 2005, 70, 2325. (d) From carbamates, see for
instance: Tiecco, M.; Testaferri, L.; Temperini, A.; Terlizzi,
R.; Bagnoli, L.; Marini, F.; Santi, C. Synthesis 2005, 579.
(10) Ozaxolidinone 6a could, however, be synthesized in 94%
yield (3 h, CH Cl , r.t.) when the more electrophilic (p-
2
2
CF Ph) PAuNTf catalyst (1 mol%) was used instead of
3
3
2
PPh AuNTf
3
2.
(11) Representative Experimental Procedure – Synthesis of 3-
Benzyl-4,4-dimethyl-1,3-oxazolidin-2-one (6d).
(e) From isocyanates, see for instance: Fuentes, A.;
Martinez-Palou, R.; Jimenez-Vasquez, H. A.; Delgado, F.;
Reyes, A.; Tamariz, J. Monatsh. Chem. 2005, 136, 177.
6) (a) Buzas, A.; Gagosz, F. Org. Lett. 2006, 8, 515. (b) For a
related transformation using homopropargylic alcohol
derivatives, see: Kang, J.-E.; Shin, S. Synlett 2006, 717.
For other examples of transformations using the crystalline
and air-stable PR AuNTf catalysts, see: (c) Mezailles, N.;
To a solution of benzyl (1,1-dimethylprop-2-ynyl)carbamic
acid tert-butyl ester (5d, 136 mg, 0.5 mmol) in 1 mL of
CH Cl was added PPh AuNTf (3.7 mg, 0.005 mmol). The
reaction mixture was stirred for 5 min, then filtered through
a small pad of silica and the solvent was removed under
reduced pressure. The residue was then purified by flash
column chromatography (PE–EtOAc, 60:40) to give
(
2
2
3
2
3
2
Ricard, L.; Gagosz, F. Org. Lett. 2005, 7, 4133. (d) Buzas,
A.; Istrate, F.; Gagosz, F. Org. Lett. 2006, 8, 1957.
7) For recent reviews on gold catalysis, see: (a) Hashmi, A. S.
K. Angew. Chem. Int. Ed. 2005, 44, 6990. (b) Hoffman-
Röder, A.; Krause, N. Org. Biomol. Chem. 2005, 3, 387.
oxazolidinone 6d (108 mg, 99%, pale yellow solid); mp 69–
1
70 °C. H NMR (400 MHz, CDCl ): d = 7.39–7.27 (m, 5 H),
3
(
4.68 (d, J = 3.3 Hz, 1 H), 4.48 (s, 2 H), 4.25 (d, J = 3.3 Hz,
1
3
1 H), 1.33 (s, 6 H). C NMR (50 MHz, CDCl ): d = 160.7,
3
154.8, 137.6, 128.6, 127.8, 127.7, 84.1, 61.5, 44.0, 27.6. IR
(CCl ): 2979, 1786, 1692, 1663, 1393, 1054 cm . MS (CI +
NH ): m/z = 235 [MNH ], 218 [MH ]. HRMS (EI): m/z
3 4
–
1
(
c) Echavarren, A. M.; Nevado, C. Chem. Soc. Rev. 2004,
4
+
+
33, 431. (d) Arcadi, A.; Di Giuseppe, S. Curr. Org. Chem.
2
004, 8, 795. (e) Hashmi, A. S. K. Gold Bull. 2003, 36, 3.
calcd for C H O N: 217.1103; found: 217.1103.
13 15 2
For some recent examples of alkyne activation by Au(I)
complexes, see: (f) Sherry, B. D.; Maus, L.; Laforteza, B.
N.; Toste, F. D. J. Am. Chem. Soc. 2006, 128, 8132.
(12) These substrates substituted at the propargylic position (5i–
n) were synthesized according to the method developed by
Petrini and coworkers. See, for instance: Mecozzi, T.;
Petrini, M. J. Org. Chem. 1999, 64, 8970.
(g) Marion, N.; Diez-Gonzales, S.; de Frémont, P.; Noble, A.
Synlett 2006, No. 17, 2727–2730 © Thieme Stuttgart · New York