J . Org. Chem. 2002, 67, 1719-1721
1719
Sch em e 1
Electr ogen er a ted Ba se-In d u ced
N-Acyla tion of Ch ir a l Oxa zolid in -2-on es. 21
Marta Feroci,*,† Achille Inesi,*,‡,§ Laura Palombi,§ and
Giovanni Sotgiu|
Dipartimento Ingegneria Chimica, Materiali, Materie Prime
e Metallurgia, Universita` “La Sapienza”, via Castro
Laurenziano, 7, I-00161 Roma, Italy, Dipartimento
Chimica, Ingegneria Chimica e Materiali, Universita` degli
Studi, I-67040, Monteluco di Roio, L'Aquila, Italy, and
Dipartimento di Ingegneria Elettronica, Universita' di
Roma Tre, via Vasca Navale, 84, I-00146 Roma, Italy
Ta ble 1. Electr olyses, u n d er Differ en t Con d ition s, of
Solu tion s of Oxa zolid in -2-on e 1 (MeCN-0.1 m ol d m -3
TEAP a s Solven t) F ollow ed by Ad d ition of Acetic
An h yd r id e 7a ,b (Sch em e 1)
1a , yield recovered 1
entry cathode anode I/mA cm-2
(%)c
(%)
Ptd
Ptd
Ptd
Ptd
Ptd
Mgf
Alf
25
25
25
16
16
16
16
16
16
63
77
81
96
54
32
-
28
3
11
-
28
61
96
79
2
marta.feroci@uniroma1.it
Received November 27, 2001
1
2
3
C
Pb
Cu
Pt
Pt
Pt
Pt
Pt
Pt
4
5e
6
Abstr a ct: An improved and efficient electrochemical N-
acylation of chiral oxazolidin-2-ones has been achieved. The
generation of the nitrogen anion is obtained under mild
conditions and without addition of base or probase, by direct
electrolysis of a solution of MeCN-TEAP containing the
oxazolidinone. Acylation agents (acid chlorides or anhy-
drides) were added at the end of the electrolysis. N-Acylated
products were isolated in high to excellent yields.
7
8g
9h
Ptd
Ptd
10
96
a
n ) 1.0 (number of Faradays per mol of 1 supplied to the
electrodes). F ) 1.0 (mole ratio 1/ acetic anhydride). c Isolated
b
yields. Divided cell. e DMF instead of MeCN as solvent. f Undi-
d
g
vided cell. LiClO4 instead of TEAP as supporting electrolyte.
Oxazolidinone 1 was added at the end of the electrolysis.
h
Since the initial papers of Evans,2 chiral oxazolidin-
2-ones have been often used as chiral auxiliaries in
asymmetric synthesis.3 Actually, N-acyloxazolidin-2-ones
are able to induce a considerable diastereoselectivity in
alkylation,4 acylation,2 aldol reaction,5 and enantioselec-
tive Diels-Alder reactions.6
Recently, a highly enantioselective and diastereose-
lective Mukaiyama-Michael reaction of enolsilanes and
acryloyloxazolidinones has been set up by Evans and co-
workers.7 Studying the addition reactions with chiral
Ni(II) complex of glycine, Soloshonok and co-workers8
have demonstrated that 3-(trans-enoyl)oxazolidin-2-ones
are synthetically superior Michael acceptors than the
corresponding alkyl enolates, allowing for a remarkable
improvement in reactivity and diastereoselectivity. Fi-
nally, asymmetric aldol additions, carried out using
chlorotitanium enolates of N-acyloxazolidinone, oxazo-
lidinethione, or thiazolidinethione has been described by
Crimmins and co-workers.9
The frequent utilization of chiral or nonchiral oxazo-
lidin-2-ones in asymmetric synthesis has spurred many
authors to investigate new methodologies of synthesis
and acylation of this class of molecules. Traditionally, the
methods for N-acylation of chiral oxazolidin-2-ones in-
volve the presence of an acylating agent (acid chlorides,
symmetrical or mixed anhydrides) and, in any case, of a
base (nBuLi or triethylamine and catalytic amounts of
4-(N,N-dimethylamino)pyridine) strong enough to depro-
tonate the substrate, yielding the corresponding N-
anion.10
On this subject, the electrochemical methodology is
able to suggest effective alternative solutions. In fact,
anionic intermediates can be obtained (selectively, in mild
conditions and avoiding the use of chemical deprotonat-
ing reagents) by cathodic reduction of suitable substrates.
The electrochemical methods for generating organic
anions either by two-electron cleavage of a σ bond or by
direct cathodic deprotonation of relatively weak organic
acids have been reviewed by V. A. Petrosyan.11 Organic
syntheses founded on the electrochemical deprotonation
of N-H acids have been reported by several authors.11,12
Recently, nitrogen anions have been obtained via elec-
trochemical reduction of oxazolidin-2-ones.13 In a previous
paper1 we have described the N-acylation of chiral
* To whom correspondence should be addressed. Fax +39 06
49766749.
† Dip. of ICMMPM.
‡ inesi@ing.univaq.it.
§ University of L’Aquila.
| University of Roma Tre.
(1) Part 1: Feroci, M.; Inesi A.; Palombi L.; Rossi L.; Sotgiu G. J .
Org. Chem. 2001, 66, 6185-6188.
(2) Evans, D. A.; Bartroli, J .; Shih, T. L. J . Am. Chem. Soc. 1981,
103, 2127-2129. Evans, D. A. Aldrichim. Acta 1982, 15, 23-32.
(3) Ager, D. J .; Prakash, I.; Schaad, D. R. Chem. Rev. 1996, 96,
5-875. Ager, D. J .; Prakash, I.; Schaad, D. R. Aldrichim. Acta 1997,
30, 3-12.
(9) Crimmins, M. T.; King, B. W.; Tabet, E. A.; Chaudhary, K. J .
Org. Chem. 2001, 66, 894-902.
(10) Ager, D. J .; Allen, D. R.; Schaad, D. R. Synthesis 1996, 1283-
1285. Prashad, M.; Kim, H.-Y.; Har, D.; Repic, O.; Blacklock, T. J .
Tetrahedron Lett. 1998, 39, 9369-9372. Knol, J .; Feringa, B. L. Synth.
Commun. 1996, 26, 261-268. Ho, G.-J .; Mathre, D. J . J . Org. Chem.
1995, 60, 2271-2273.
(11) Petrosyan, V. A. Russ. Chem. Bull. 1995, 44, 1-12.
(12) Utley, J . H. P.; Folmer Nielsen, M. in Organic Electrochemistry;
Lund, H., Hammerich, O., Eds.; Marcel Dekker Inc., New York, 2001;
pp 1227-1257 and references therein.
(13) Feroci, M.; Inesi, A.; Rossi, L.; Sotgiu, G. Eur. J . Org. Chem.
2001, 2765-2769.
(4) Evans, D. A.; Ennis, M. D.; Mathre, D. J . J . Am. Chem. Soc.
1981, 104, 1737-1739.
(5) Evans, D. A.; Ennis, M. D.; Le, T. J . Am. Chem. Soc. 1984, 106,
1154-1156.
(6) Evans, D. A.; Chapman, K. T.; Bisaha, J . J . Am. Chem. Soc. 1988,
110, 1238-1256.
(7) Evans, D. A.; Scheidt, K. A.; J ohnston, J . N.; Willis, M. C. J .
Am. Chem. Soc. 2001, 123, 4480-4491.
(8) Cai, C.; Soloshonok, V. A.; Hruby, V. J . J . Org. Chem. 2001, 66,
1339-1350.
10.1021/jo016323a CCC: $22.00 © 2002 American Chemical Society
Published on Web 02/12/2002