Oxidative rearrangement of 2-furylcarbamates with dimethyldioxirane: A high-yielding preparation of 5-hydroxypyrrol-2(5H)-ones

Article abstract of DOI:10.1016/j.tetlet.2011.07.084

A mild, general and efficient method for the oxidative rearrangement of 2-furylcarbamates to N-Boc-5-hydroxypyrrol-2(5H)-ones is reported. The feasibility of removing the Boc group from the products was demonstrated by the synthesis of two hitherto unknown 5-aryl-5-hydroxypyrrol-2(5H)-ones.

Full text of DOI:10.1016/j.tetlet.2011.07.084

Tetrahedron Letters 52 (2011) 5047–5050
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Oxidative rearrangement of 2-furylcarbamates with dimethyldioxirane:
a high-yielding preparation of 5-hydroxypyrrol-2(5H)-ones
⇑
John Boukouvalas , Richard P. Loach, Etienne Ouellet
Département de Chimie, Pavillon Alexandre-Vachon, Université Laval, 1045 Avenue de la Médecine, Quebec City, Quebec, Canada G1V 0A6
a r t i c l e i n f o
a b s t r a c t
Article history:
A mild, general and efficient method for the oxidative rearrangement of 2-furylcarbamates to N-Boc-5-
hydroxypyrrol-2(5H)-ones is reported. The feasibility of removing the Boc group from the products
was demonstrated by the synthesis of two hitherto unknown 5-aryl-5-hydroxypyrrol-2(5H)-ones.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 5 June 2011
Revised 13 July 2011
Accepted 20 July 2011
Available online 27 July 2011
Keywords:
Curtius rearrangement
Lactam
Magnesium perchlorate
Oxidation
Shioiri–Yamada reagent
6,7
Previous Work
:
Practical methods for the synthesis of 5-hydroxypyrrol-2(5H)-
ones are in high demand due to the important biological properties
of several natural and unnatural products containing this
moiety.1,2 Furthermore, the functionality packed within the
5-hydroxypyrrol-2(5H)-one system can be readily exploited for
the synthesis of a host of other classes of nitrogen-containing
compounds.1,3
O
O
3
2
3
2
2
R
R
R
R
R
1
ð1Þ
ð2Þ
R
1
R
R
O
OSi
then
H O
O
O
N
HO
+
3
3
2
3
R
R
R
as
above
Despite a flurry of recent activity in this area,3–5 few of the
methods reported so far provide convenient access to a range of
substituted 5-hydroxypyrrolones from readily available starting
materials.1–5 Previous work from our laboratory has shown that
2-silyloxyfurans and 2-silyloxypyrroles undergo vinylogous oxy-
functionalization on sequential treatment with dimethyldioxirane
1
R
1
O
OSi
N
HO
COOR
COOR
Si = Si-protecting group
This Work:
3
2
3
2
(DMDO)/acid to furnish c-hydroxybutenolides and 5-hydroxypyr-
O
O
R
R
R
R
rolones, respectively, (Eqs. 1, 2).6,7 The versatility of this chemistry
has unequivocally been demonstrated by numerous applications in
natural product synthesis.8 We now report that 2-furylcarbamates
undergo DMDO-mediated oxidative rearrangement under strictly
neutral conditions to furnish 5-hydroxypyrrolones with high
efficiency (Eq. 3).
1
R
1
R
O
NHCOOR
O
N
HO
ð3Þ
COOR
3
2
R
R
1
R
NHCOOR
O
O
Though the photooxygenation and autoxidation of 2-furylcar-
bamates have long been known to give 5-hydroxypyrrol-2(5H)-
ones,9,10 these processes suffer from several drawbacks including
low to moderate yields, long reaction times and limited scope.
Nonetheless, 2-furylcarbamates are especially attractive starting
materials (more so than 2-silyloxypyrroles) since many of them
⇑
Corresponding author. Tel.: 418 656 5473; fax: 418 656 7916.
E-mail address: john.boukouvalas@chm.ulaval.ca (J. Boukouvalas).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.07.084

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J. Boukouvalas et al. / Tetrahedron Letters 52 (2011) 5047–5050
Table 1
Synthesis of N-Boc-5-hydroxypyrrol-2(5H)-ones from 2-furoic acids
O
O
3
2
3
2
3
2
R
R
R
R
R
R
1
DPPA, Et N
3
R
1
1
R
R
O
CO H
NHBoc
2
acetone
O
t-BuOH, Δ
O
N
HO
1
2
3
-78 °C to rt
Boc
Entry
1
Furoic acid
Furylcarbamatea (yield %)
Hydroxypyrrolonea (yield %)
HO
O
NHBoc
O
2a (83%)b
N
b
—
Boc
3a (92%)
HO
O
CO H
NHBoc
O
2
N
O
2
3
Boc
1b
2b (90%)
3b (94%)
O
N
CO H
2
NHBoc
O
O
HO
HO
Boc
3c (68%)c
1c
1d
2c
O
N
CO H
2
NHBoc
O
O
4
5
Boc
2d (79%)
3d (99%)
O
CO H
NHBoc
O
2
O
N
HO
Boc
2e (87%)
1e
3e (88%)
n-Bu
CO H
NHBoc
2
O
O
n-Bu
n-Bu
O
N
6
7
HO
1f
2f (85%)
Boc
3f (59%)
CO H
NHBoc
2
O
O
O
N
HO
1g
2g (78%)
Boc
3g (99%)
O N
2
CO H
NHBoc
2
O
O
O N
2
O N
2
O
8
9
N
HO
1h
2h (84%)
Boc
3h (91%)
Cl
Cl
Cl
Cl
CO H
NHBoc
2
O
O
O
N
Cl
Cl
HO
Boc
1i
2i (87%)
3i (96%)
Cl
Cl
Cl
CO H
NHBoc
2
O
O
F C
3
O
N
HO
10
Boc
F C
3
F C
3
1j
2j (80%)
3j (94%)
a
b
c
Yields refer to isolated products after flash chromatography.
Carbamate 2a was prepared from 2-furoyl chloride and NaN3 as previously reported.11c
Yield over two steps (without purification of carbamate 2c).
can be prepared in a single step from commercial chemicals.11
Hence, the development of viable methods for their transformation
to 5-hydroxypyrrolones is clearly worthwile.5
In consideration of the prospects of removing the N-protecting
group from the products, we opted for using Boc carbamates as
substrates (cf. 2a–j, Table 1). With the exception of the parent

J. Boukouvalas et al. / Tetrahedron Letters 52 (2011) 5047–5050
5049
compound 2a,11c all furylcarbamates were prepared from furoic
acids by using Padwa’s procedure.10a Thus, heating furoic acids
1b–j with the Shioiri–Yamada reagent (diphenylphosphoryl azide,
DPPA)12 and triethylamine in tert-butanol accomplished acyl azide
formation, Curtius rearrangement and isocyanate alcoholysis to af-
ford the corresponding carbamates 2b–j in high yields.13,14
The superior electron-donating ability of silyloxy groups over
that of carbamates, as reflected by the Hammett substituent con-
method, such as 4g, represent new chemical entities testifies to
its practical value.
Acknowledgments
We are indebted to the Natural Sciences and Engineering Re-
search Council of Canada (NSERC), the Department of Education
of Québec (FQRNT program), and the FQRNT Centre in Green
Chemistry and Catalysis (CGCC) for financial support. We also
thank NSERC for a postgraduate scholarship to R.P.L.
stants for OTMS and NHCOOEt (
r
para = ꢀ0.27 and ꢀ0.15, respec-
tively),15 suggested that furylcarbamates 2 should be somewhat
less reactive toward DMDO than their 2-silyloxyfuran counter-
parts.6,16 Even so, their oxidative rearrangement to 3 was complete
within 1–2 h at temperatures below ꢀ20 °C using only 1.1 equiv of
DMDO (ca. 0.06 M in acetone).17 For the sake of convenience, most
reactions were left to warm to room temperature before evapora-
tion of excess DMDO/acetone. Using this procedure, a variety of
mono and disubstituted 2-furylcarbamates 2b–j were transformed
to 5-hydroxypyrrolones 3b–j in high to excellent yields (Table 1).18
An exception was the acetylenic furylcarbamate 2f (entry 6),
whose conversion to 3f was accompanied by the formation of some
minor, as yet uncharacterized side products. Importantly, oxida-
tion of the furan nucleus is achievable in the presence of a remote
olefin group with high chemoselectivity, as demonstrated by the
clean transformation of 2e to 3e (entry 5).
References and notes
1. Recent review: Nay, B.; Riache, N.; Evanno, L. Nat. Prod. Rep. 2009, 26, 1044–
1062.
2. Dittami, J. P.; Xu, F.; Qi, H.; Martin, M. W.; Bordner, J.; Decosta, D. L.; Kiplinger,
J.; Reiche, P.; Ware, R. Tetrahedron Lett. 1995, 36, 4201–4204. and references
therein.
3. Recent synthetic applications: (a) Coleman, R. S.; Liu, P.-H. Org. Lett. 2004, 6,
577–580; (b) Coleman, R. S.; Walczak, M. C.; Campbell, E. L. J. Am. Chem. Soc.
2005, 127, 16038–16039; (c) Zhang, W.; Huang, L.; Wang, J. Synthesis 2006,
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Chem. Soc. 2007, 129, 13404–13405; (e) Pin, F.; Comesse, S.; Garrigues, B.;
Marchalín, Š.; Daïch, A. J. Org. Chem. 2007, 72, 1181–1191; (f) Kang, S. W.; Kim,
Y. H.; Kim, S. H. Bull. Korean Chem. Soc. 2008, 29, 755–757; (g) Yamada, S.;
Yamashita, K. Tetrahedron Lett. 2008, 49, 32–35; (h) Yamashita, S.; Mase, N.;
Takabe, K. Tetrahedron: Asymmetry 2008, 19, 2115–2118; (i) Kiren, S.; Hong, X.;
Leverett, C. A.; Padwa, A. Org. Lett. 2009, 11, 1233–1235.
4. For some recent syntheses, see: (a) Kanno, K.; Ren, S.; Li, Y.; Nakajima, K.;
Takahashi, T. Tetrahedron Lett. 2007, 48, 9199–9202; (b) Adib, M.; Mahdavi, M.;
Noghani, M. A.; Bijanzadeh, H. R. Tetrahedron Lett. 2007, 48, 8056–8059; (c) Fan,
M.-J.; Qian, B.; Zhao, L.-B.; Liang, Y.-M. Tetrahedron 2007, 63, 8987–8992; (d)
Haldar, P.; Ray, J. K. Tetrahedron Lett. 2008, 49, 3659–3662; (e) Yavari, I.;
Mokhtarporyani–Sanandaj, A.; Maradi, L.; Mirzaei, A. Tetrahedron 2008, 64,
5221–5225; (f) Yavari, I.; Souri, S. Synlett 2008, 1208–1210; (g) Basso, A.; Banfi,
L.; Galatini, A.; Guanti, G.; Rastrelli, F.; Riva, R. Org. Lett. 2009, 11, 4068–4071;
(h) Song, L.; Li, X.; Xing, C.; Li, D.; Zhu, S.; Deng, H.; Shao, M. Synlett 2010, 830–
834; (i) Dias-Jurberg, I.; Gagosz, F.; Zard, S. Z. Org. Lett. 2010, 12, 416–419; (j)
Yang, L.; Lei, C.-H.; Wang, D.-X.; Huang, Z.-T.; Wang, M.-X. Org. Lett. 2010, 12,
3918–3921; (k) Wu, M.-Y.; Li, K.; Wang, N.; He, T.; Yu, X.-Q. Synthesis 2011,
1831–1839.
Intrigued by the absence in the chemical literature of N-unsub-
stituted 5-aryl-5-hydroxypyrrolones, the feasibility of preparing
such compounds through cleavage of the N-Boc group was briefly
explored (cf. 3g?4g, Scheme 1). Initial attempts at deprotecting 3g
under standard conditions (neat TFA, 0 °C, 1 h),10a did not provide
the desired hydroxypyrrolone 4g but the known (E)-c-ketoamide
5g instead (Scheme 1).19,20 The formation of 5g can be explained
by acid-catalyzed Z–E isomerization21 of the open-lactam tautomer
of 3g and ensuing deprotection. Subsequent trials with chelating
Lewis acids, such as ytterbium(III) triflate22 and magnesium per-
chlorate,23 revealed that the latter was particularly effective in
cleaving the Boc group without side-reactions, presumably via che-
late A, to deliver 4g in excellent yield (Scheme 1).24 Similarly,
deprotection of 3i proceeded without incident affording 4i in 86%
yield.24
5. Recently, Padwa reported the conversion of unsubstituted 2-furylcarbamates
and amides to 5-hydroxypyrrol-2(5H)-ones using an excess of I2/aq NaHCO3:
Kiren, S.; Hong, X.; Leverett, C. A.; Padwa, A. Tetrahedron 2009, 65, 6720–6729.
6. Boukouvalas, J.; Lachance, N. Synlett 1998, 31–32.
7. Boukouvalas, J.; Xiao, Y.; Cheng, Y.-X.; Loach, R. P. Synlett 2007, 3198–3200.
8. (a) Boukouvalas, J.; Cheng, Y.-X.; Robichaud, J. J. Org. Chem. 1998, 63, 228–229;
(b) Boukouvalas, J.; Cheng, Y.-X. Tetrahedron Lett. 1998, 39, 7025–7026; (c)
Marcos, I. S.; Pedrero, A. B.; Sexmero, M. J.; Diez, D.; Basabe, P.; Hernández, F.
A.; Urones, J. G. Tetrahedron Lett. 2003, 44, 369–372; (d) Marcos, I. S.; Pedrero,
A. B.; Sexmero, M. J.; Diez, D.; García, N.; Escola, M. A.; Basabe, P.; Conde, A.;
Moro, R. F.; Urones, J. G. Synthesis 2005, 3301–3310; (e) Boukouvalas, J.; Wang,
J.-X.; Marion, O.; Ndzi, B. J. Org. Chem. 2006, 71, 6670–6673; (f) Boukouvalas, J.;
Robichaud, J.; Maltais, F. Synlett 2006, 2480–2482; (g) Boukouvalas, J.; Loach, R.
P. J. Org. Chem. 2008, 73, 8109–8112; (h) Boukouvalas, J.; McCann, L. C.
Tetrahedron Lett. 2011, 52, 1202–1204; (i) Yamashita, M.; Yamashita, T.; Aoyagi,
S. Org. Lett. 2011, 13, 2204–2207; (j) Yamashita, T.; Yamashita, M.; Aoyagi, S.
Tetrahedron Lett. 2011, 52, 4266–4268.
In conclusion, we have shown that the DMDO-mediated oxida-
tive rearrangement of 2-furylcarbamates provides an exceptionally
mild, general and efficient method for the synthesis of 5-hydroxy-
pyrrol-2(5H)-ones. This protocol offers several advantages includ-
ing high regio and chemoselectivity, operational simplicity and
commercial availability of a wide range of starting materials. The
fact that even some ostensibly simple products obtained by this
9. (a) Ito, K.; Yakushijin, K. Heterocycles 1978, 9, 1603–1606; (b) Yakushijin, K.;
Kazuka, M.; Ito, Y.; Suzuki, R.; Furukawa, H. Heterocycles 1980, 14, 1073–1076;
(c) Yakushijin, K.; Kazuka, M.; Morishita, T.; Furukawa, H. Chem. Pharm. Bull.
1981, 29, 2420–2430; (d) Maeba, I.; Hara, O.; Suzuki, M.; Furukawa, H. J. Org.
Chem. 1987, 52, 2368–2373.
R
R
R
R
Mg(ClO )
4 2
10. (a) Yakushijin, K.; Suzuki, R.; Hattori, R.; Furukawa, H. Heterocycles 1981, 16,
1157–1160; (b) Yakushijin, K.; Suzuki, R.; Kawaguchi, N.; Tsuboi, Y.; Furukawa,
H. Chem. Pharm. Bull. 1986, 34, 2049–2055.
O
O
N
MeCN, 55 °C
N
HO
HO
H
Boc
11. (a) Padwa, A.; Dimitroff, M.; Waterson, A. G.; Wu, T. J. Org. Chem. 1997, 62,
4088–4096; (b) Padwa, A.; Brodney, M. A.; Liu, B.; Satake, K.; Wu, T. J. Org.
Chem. 1999, 64, 3595–3607; (c) Padwa, A.; Brodney, M. A.; Lynch, S. M. Org.
Synth. 2002, 78, 202–211.
3g R = H
3i R = Cl
4g R = H (92%)
4i R = Cl (86%)
12. Shioiri, T.; Ninomiya, K.; Yamada, S. J. Am. Chem. Soc. 1972, 94, 6203–6205.
13. Compounds 1c and 1e were prepared from 3-methyl and 5-bromo 2-furoic
acid, respectively, using the following literature procedures: (a) Knight, D. W.;
CF CO H
3
2
(R = H)
O
0 °C
Nott, A. P. J. Chem. Soc., Perkin Trans.
1 1981, 1125–1131; (b) Kopp, F.;
Ar
HO
Wunderlich, S.; Knochel, P. Chem. Commun. 2007, 2075–2077. All other 2-furoic
acids were obtained from commercial sources.
O
N
2+
Mg
14. Data for N-Boc-2-furylcarbamates: 2b mp: 47–48 °C; IR (NaCl, film) 3320, 2979,
1773, 1718, 1368, 1156 cmꢀ1;1H NMR: (400 MHz; CDCl3) d 1.46 (s, 9H), 1.93 (s,
3H), 6.03 (br s, 1H), 6.21 (d, J = 2.8 Hz, 1H), 7.15 (d, J = 2.8 Hz, 1H); 13C NMR:
(100 MHz; CDCl3) d 9.5, 28.1, 80.4, 81.0, 113.2, 138.5, 139.8, 153.7; HRMS (ESI),
NH
2
O
O
O
A
5g (62%)
C
10H15NO3: 197.1052, found 197.1024. Compound 2d 1H NMR: (400 MHz;
Scheme 1. Removal of the Boc group from compounds 3g and 3i.
CDCl3) d 1.50 (s, 9H), 1.89 (s, 3H), 2.03 (s, 3H), 5.82 (br s, 1H), 6.38 (br s, 1H);

5050
J. Boukouvalas et al. / Tetrahedron Letters 52 (2011) 5047–5050
13C NMR: (100 MHz; CDCl3) d 10.0, 10.9, 28.0, 82.9, 99.6, 115.2, 117.3, 141.2,
HRMS (ESI), C11H17NO4: calcd 227.1158, found 227.1155. Compound 3d mp:
71–72 °C; IR (NaCl, film) 3423 (br), 2981, 2933, 1770, 1723, 1323, 1160,
152.3; HRMS (ESI), C11H17NO3: calcd 211.1208, found 211.1209. Compound 2e
IR (NaCl, film) 3300, 2979, 2931, 1707, 1519, 1368, 1156 cmꢀ1;1H NMR:
(400 MHz; CDCl3) d 1.50 (s, 9H), 3.29 (d, J = 6.6 Hz, 2H), 5.05–5.16 (m, 2H),
5.82–5.91 (m, 2H), 5.93 (br s, 1H), 5.94 (s, 1H), 6.65 (br s, 1H); 13C NMR:
(100 MHz; CDCl3) d 28.1, 32.3, 81.0, 96.7, 106.9, 116.8, 133.9, 143.8, 147.5,
152.1; HRMS (ESI), C12H17NO3: calcd 223.1208, found 223.1179. Compound 2f
mp: 88 °C; IR (NaCl, film) 3266, 2925, 1703, 1532, 1152 cmꢀ1;1H NMR:
(400 MHz; CDCl3) d 0.92 (t, J = 7.6 Hz, 3H), 1.33–1.42 (m, 2H), 1.45–1.51 (m,
2H), 1.47 (s, 9H), 2.41 (t, J = 6.8 Hz, 2H), 6.00 (br s, 1H), 6.42 (d, J = 2.8 Hz, 1H),
6.63 (br s, 1H), 7.09 (m, 1H); 13C NMR: (100 MHz; CDCl3) d 13.6, 19.2, 22.0,
28.2, 30.5, 70.7, 81.6, 94.4, 94.6, 115.8, 130.6, 145.2, 151.1; HRMS (ESI),
1093 cmꢀ1 1H NMR: (400 MHz; CDCl3) d 1.58 (s, 9H), 1.72 (s, 3H), 2.06 (d,
;
J = 1.6 Hz, 3H), 4.38 (br s, 1H), 5.75 (q, J = 1.6 Hz, 1H); 13C NMR: (100 MHz;
CDCl3) d 12.2, 24.1, 28.2, 83.8, 90.7, 121.3, 150.5, 163.4, 166.5; HRMS (ESI):
C
11H17NO4: calcd 227.1158, found 227.1139; Anal. Calcd for C11H17NO4: C,
58.14; H, 7.54; N, 6.16. Found: C, 58.40; H, 7.69; N, 5.95. Compound 3e IR
(NaCl, film) 3429 (br), 3081, 2980, 2932, 1771, 1751, 1727, 1326, 1160 cmꢀ1
;
1H NMR: (400 MHz; CDCl3) d 1.57 (s, 9H), 2.84–2.95 (m, 2H), 4.38 (br s, 1H),
5.06–5.14 (m, 2H), 5.51–5.62 (m, 1H), 6.09 (d, J = 6.0 Hz, 1H), 6.99 (d, J = 6.0 Hz,
1H); 13C NMR: (100 MHz; CDCl3) d 28.1, 42.2, 84.0, 91.9, 120.1, 127.1, 130.6,
150.0, 150.4, 166.5; HRMS, C12H17NO4: calcd 239.1158, found 239.1156. Anal.
Calcd for C12H17NO4: C, 60.24; H, 7.16; N, 5.85. Found: C, 59.91; H, 6.90; N,
5.63. Compound 3f mp: 66–67 °C; IR (NaCl, film) 3418 (br), 3299 (br), 2959,
C
15H21NO3: calcd 263.1521, found 263.1518. Compound 2g mp: 91 °C; IR
(NaCl, film) 3298 (br), 3058, 2977, 2922, 2851, 1707, 1561, 1157 cmꢀ1;1H
NMR: (400 MHz; CDCl3) d 1.53 (s, 9H), 6.14 (br s, 1H), 6.61 (d, J = 3.6 Hz, 1H),
6.76 (br s, 1H), 7.17–7.23 (m, 1H), 7.33–7.37 (m, 2H), 7.54–7.57 (m, 2H); 13C
NMR: (100 MHz; CDCl3) d 28.5, 81.7, 96.6, 107.0, 123.2 (2C), 126.9, 128.9 (2C),
130.8, 145.4, 147.3, 151.7; HRMS (ESI), C15H17NO3: calcd 259.1208, found
260.1220. Compound 2i mp: 123 °C; IR (NaCl, film) 3321, 2980, 1702, 1558,
2213, 1781, 1753, 1655, 1324 cmꢀ1 1H NMR: (400 MHz; CDCl3) d 0.90 (t,
;
J = 7.6 Hz, 3H), 1.35–1.42 (m, 2H), 1.42–1.51 (m, 2H), 1.59 (s, 9H), 2.23 (t,
J = 7.2 Hz, 2H), 4.62 (br s, 1H), 6.10 (d, J = 6.4 Hz, 1H), 7.01 (d, J = 6.4 Hz, 1H);
13C NMR: (100 MHz; CDCl3) d 13.5, 18.2, 21.8, 28.1, 30.1, 75.2, 82.9, 84.3, 87.1,
125.9, 148.2, 149.2, 165.9; HRMS (ESI), C15H21NO4: calcd 279.1463, found
279.1471. Compound 3h mp: 153 °C (decomp.); IR (NaCl, film) 3262, 3069,
1279, 1154, 778 cmꢀ1 1H NMR: (400 MHz; CDCl3) d 1.53 (s, 9H), 6.17 (br s,
;
1H), 6.95 (br s, 1H), 7.09 (d, J = 3.6 Hz, 1H), 7.22 (dd, J = 8.8, 2.4 Hz, 1H), 7.40 (d,
J = 2.4 Hz, 1H), 7.60 (d, J = 8.8 Hz, 1H); 13C NMR: (100 MHz; CDCl3) d 28.2, 81.7,
95.9, 113.5, 127.1, 127.4, 129.7, 130.3, 132.0, 142.2, 145.8, 151.2; HRMS (ESI),
2924, 1700, 1686, 1559, 1283, 1159 cmꢀ1 1H NMR: (400 MHz; CDCl3) d 1.44 (s,
;
9H), 4.85 (br s, 1H), 6.17 (d, J = 6.4 Hz, 1H), 6.99 (d, J = 6.4 Hz, 1H), 7.63 (d, J =
8.8 Hz, 2H), 8.25 (d, J = 8.8 Hz, 2H); 13C NMR: (100 MHz; CDCl3) d 27.9, 85.2,
91.7, 124.2, 125.6, 126.1, 146.1, 148.2, 149.6, 150.6, 166.5; HRMS (ESI),
C
15H15Cl2NO3: calcd 327.0418, found 327.0429. Compound 2j mp: 155 °C; IR
(NaCl, film) 3259, 3147, 3059, 2990, 2932, 1704, 1600, 1376, 1121, 769 cmꢀ1
;
C
15H16N2O6: calcd 320.1008, found 320.1003. Compound 3i mp: 135 °C
(decomp.); IR (NaCl, film) 3393 (br), 3099, 2979, 2932, 1776, 1323, 1159,
818 cmꢀ1 1H NMR: (400 MHz; CDCl3) d 1.38 (s, 9H), 4.81 (br s, 1H), 6.19 (d,
1H NMR: (400 MHz; CDCl3) d 1.54 (s, 9H), 6.23 (br s, 1H), 6.96 (br s, 1H), 7.23 (d,
J = 3.7 Hz, 1H), 7.33–7.37 (dd, J = 8.8, 2.0 Hz, 1H), 7.50–7.53 (d, J = 8.8 Hz, 1H),
7.95–7.98 (d, J = 2.0 Hz, 1H); 13C NMR: (100 MHz; CDCl3) d 28.2, 81.9, 95.5,
114.7, 123.8 (q, J = 270.8 Hz), 123.2 (q, J = 3.2 Hz), 123.4 (q, J = 3.1 Hz), 129.3,
129.5 (q, J = 32.8 Hz), 131.3, 132.3, 141.5, 146.4, 151.1; HRMS (ESI),
;
J = 5.6 Hz, 1H), 6.87 (d, J = 5.6 Hz, 1H), 7.35 (dd, J = 8.4, 2.4 Hz, 1H), 7.39 (d,
J = 2.4 Hz, 1H), 7.82 (d, J = 8.4 Hz, 1H); 13C NMR: (100 MHz; CDCl3) d 27.9, 84.2,
90.7, 126.9, 127.6, 129.8, 131.2, 131.7, 133.7, 135.4, 147.6, 149.2, 167.3; HRMS
C
16H15ClF3NO3: calcd 361.0693, found 361.0665.
(ESI),
15H15Cl2NO4: C, 52.34; H, 4.39; N, 4.07. Found: C, 52.46; H, 4.42; N, 3.96.
Compound 3j mp: 146 °C (decomp.); IR (NaCl, film) 3398 (br), 3111, 2982,
2933, 2255, 1780, 1699, 1370, 1329, 1169, 822 cmꢀ1 1H NMR: (400 MHz;
C15H15Cl2NO4: calcd 343.0378, found 343.0381. Anal. Calcd for
15. Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165–195.
C
16. For the facile reaction of 2-silyloxyfurans with carbon electrophiles, see: (a)
Asaoka, M.; Sugimura, N.; Takei, H. Bull. Chem. Soc. Jpn. 1979, 52, 1953–1956;
(b) Jefford, C. W.; Sledeski, A. W.; Boukouvalas, J. Chem. Commun. 1988, 364–
365; (c) Boukouvalas, J.; Maltais, F.; Lachance, N. Tetrahedron Lett. 1994, 35,
7897–7900; (d) Ko, S. Y.; Lerpiniere, J. Tetrahedron Lett. 1995, 36, 2101–2104;
(e) Boukouvalas, J.; Maltais, F. Tetrahedron Lett. 1995, 36, 7175–7176; (f)
Martin, S. F. Acc. Chem. Res. 2002, 35, 895–904; (g) Hanessian, S.; Giroux, S.;
Buffat, M. Org. Lett. 2005, 7, 3989–3992; (h) Boukouvalas, J.; Pouliot, M. Synlett
2005, 343–345; (i) Boeckman, R. K., Jr.; Pero, J. E.; Boehmler, D. J. J. Am. Chem.
Soc. 2006, 128, 11032–11033; (j) Boukouvalas, J.; Beltrán, P. P.; Lachance, N.;
Côté, S.; Maltais, F.; Pouliot, M. Synlett 2007, 219–222; (k) Kong, K.; Romo, D.;
Lee, C. Angew. Chem., Int. Ed. 2009, 48, 7402–7405; (l) Chabaud, L.; Jousseaume,
T.; Retailleau, P.; Guillou, C. Eur. J. Org. Chem. 2010, 5471–5481; (m)
Boukouvalas, J.; McCann, L. C. Tetrahedron Lett. 2010, 51, 4636–4639; (n)
Frings, M.; Atodiresei, I.; Wang, Y.; Runsink, J.; Raabe, G.; Bolm, C. Chem. Eur. J.
2010, 16, 4577–4587.
;
CDCl3) d 1.39 (s, 9H), 4.72 (br s, 1H), 6.27 (d, J = 6.0 Hz, 1H), 6.93 (d, J = 6.0 Hz,
1H), 7.48–7.53 (m, 1H), 7.56–7.60 (m, 1H), 8.18 (s, 1H); 13C NMR: (100 MHz;
CDCl3) d 27.8, 84.5, 90.6, 123.5 (q, J = 270.8 Hz), 126.2 (q, J = 3.8 Hz), 126.7 (q,
J = 3.8 Hz), 127.3, 129.8 (q, J = 32.8 Hz), 132.2, 134.8, 136.4, 147.1, 148.9, 167.0;
19F NMR: (376 MHz; CDCl3)
377.0642, found 377.0640.
d 63.06; HRMS (ESI), C16H15ClF3NO4: calcd
19. Lawrence, D. S.; Zilfou, J. T.; Smith, C. D. J. Med. Chem. 1999, 42, 4932–4941.
20. Data for 5g: white crystals that turned gray on exposure to air, mp: 110–
112 °C; IR (NaCl, film) 3407, 3183, 3053, 2923, 1656, 1626 1410, 1013 cmꢀ1 1H
;
NMR: (400 MHz; CDCl3) d 6.08 (br s, 2H), 7.08 (d, J = 15.4 Hz, 1H), 7.48–7.54
(m, 2H), 7.59–7.65 (m, 1H), 7.98 (d, J = 15.4 Hz, 1H), 8.02–8.08 (m, 2H); 13C
NMR: (100 MHz; CDCl3) d 128.9 (2C), 133.9, 134.0, 134.5, 136.7, 165.7 189.5;
HRMS (ESI), C10H9NO2: calcd 175.0633, found 175.0636.
21. For related isomerizations see Ref. 9c and the following articles: (a) Shen, R.;
Lin, C. T.; Bowman, E. J.; Bowman, B. J.; Porco, J. A., Jr. J. Am. Chem. Soc. 2003,
125, 7889–7901; (b) Maras, A.; Altay, A.; Ballini, R. Synth. Commun. 2008, 38,
212–216.
22. Çalimsiz, S.; Lipton, M. A. J. Org. Chem. 2005, 70, 6218–6221.
23. Stafford, J. A.; Brackeen, M. F.; Karanewsky, D. S.; Valvano, N. L. Tetrahedron
Lett. 1993, 34, 7873–7876.
17. (a) Adam, W.; Bialas, J.; Hadjiarapoglou, L. Chem. Ber. 1991, 124, 2377; (b)
Murray, R. W.; Singh, M. Org. Synth. 1997, 74, 91–100.
18. Typical procedure: 305 mg of 2g (1.18 mmol, 1.00 equiv) was dissolved in dry
acetone (7 mL), cooled to ꢀ78 °C, and DMDO17 (23.5 mL, 0.055 M in acetone,
1.29 mmol, 1.10 equiv) was added. The temperature was allowed to rise to rt
over 1.5 h, and after TLC verification of the complete conversion of 2g, the
volatiles were evaporated under reduced pressure. Flash column
chromatography on silica gel of the resulting white solid (hexanes–ethyl
acetate, 3:1, v:v) furnished 3g as white crystals (319 mg, 99% yield); mp:
110 °C; IR (NaCl, film) 3419 (br), 3090, 3063, 2980, 2931, 2253, 1775, 1324,
24. Deprotection of 3g and 3i; Typical procedure: 177 mg of 3g (0.64 mmol,
1.00 equiv) was dissolved in 6 mL of dry acetonitrile under argon, and
28.7 mg of magnesium (II) perchlorate (0.13 mmol, 0.20 equiv) was added.
The mixture was stirred for approximately 4 h at 55 °C by which time TLC
analysis showed complete disappearance of 3g. The resulting purple solution
was then concentrated in vacuo and flash column chromatography on silica gel
(hexanes–ethyl acetate, 2:1?1:1?1:2, v:v) furnished 5-hydroxy-5-phenyl-
pyrrol-2(5H)-one 4g as white crystals (104 mg, 92% yield); mp: 125 °C
(decomp.); IR (NaCl, film) 3290 (br), 3090, 2925, 2853, 1696, 1450,
1162 cmꢀ1 1H NMR: (400 MHz; CDCl3) d 1.38 (s, 9H), 4.60 (br s, 1H), 6.07 (d,
;
J = 5.8 Hz, 1H), 6.98 (d, J = 5.8 Hz, 1H), 7.33–7.45 (m, 5H); 13C NMR: (100 MHz;
CDCl3) d 27.9, 84.2, 92.4, 124.3, 124.8, 128.8, 128.9, 138.9, 149.2, 151.7, 167.7;
HRMS (ESI), C15H17NO4: calcd 275.1158, found 275.1169. Data for other N-Boc-
5-hydroxypyrrol-2(5H)-ones: 3a mp: 100–101 °C; IR (NaCl, film) 3428 (br),
2981, 2935, 1767, 1723, 1368, 1162, 1106 cmꢀ1
;
1H NMR: (400 MHz; CDCl3) d
1101 cmꢀ1 1H NMR: (400 MHz; CDCl3) d 3.81 (br s, 1H), 5.98 (d, J = 6.0 Hz,
;
1.58 (s, 9H), 4.13 (d, J = 4.4 Hz, 1H), 5.98 (br m, 1H), 6.16 (d, J = 6.5 Hz, 1H), 7.04
(dd, J = 6.5, 4.4 Hz, 1H); 13C NMR: (100 MHz; CDCl3) d 28.2, 82.3, 84.4, 129.1,
146.4, 150.2, 166.6; HRMS (ESI), C9H13NO4: calcd 199.0845, found 199.0839.
Compound 3b mp: 86 °C; IR (NaCl, film) 3437, 2981, 1765, 1717, 1367,
1H), 6.73 (br s, 1H), 6.98 (d, J = 6.0 Hz, 1H), 7.34–7.40 (m, 3H), 7.49–7.55 (m,
2H); 13C NMR: (100 MHz; CDCl3) d 89.8, 124.3, 125.4, 128.8, 128.9, 137.8,
152.9, 173.0; HRMS (ESI), C10H9NO2: calcd 175.0633, found 175.0633. Data for
4i mp: 140 °C (decomp.); IR (NaCl, film) 3285 (br), 2924, 2853, 1705, 1587,
1075 cmꢀ1
;
1H NMR: (400 MHz; CDCl3) d 1.58 (s, 9H), 1.90 (t, J = 1.9 Hz, 3H),
1377, 815, 791 cmꢀ1 1H NMR: (400 MHz; CDCl3) d 3.46 (br s, 1H), 6.14 (dd,
;
3.99 (d, J = 4.0 Hz, 1H), 5.87 (s, 1H), 6.69 (m, 1H); 13C NMR: (100 MHz; CDCl3) d
10.4, 28.1, 80.3, 83.9, 137.2, 139.0, 150.3, 167.2; HRMS (ESI), C10H15NO4: calcd
213.1001, found 213.1018. Compound 3c mp: 78–79 °C; IR (NaCl, film) 3441
J = 5.2, 1.6 Hz, 1H), 6.65 (br s, 1H), 7.24 (dd, J = 5.2, 1.6 Hz, 1H), 7.29 (dd, J = 8.4,
1.8 Hz, 1H), 7.44 (d, J = 1.8 Hz, 1H), 7.66 (d, J = 8.4 Hz, 1H); 13C NMR: (100 MHz;
CDCl3) d 88.6, 126.8, 127.4, 129.0, 131.3, 133.0, 133.6, 135.8, 149.6, 172.0;
HRMS (ESI), C10H7Cl2NO2: calcd 242.9854, found 242.9858. Anal. Calcd for
(br), 2980, 2930, 1771, 1740, 1456, 1325, 1160 cmꢀ1 1H NMR: (400 MHz;
;
CDCl3) d 1.58 (s, 9H), 1.75 (s, 3H), 1.86 (s, 3H), 4.34 (br s, 1H), 6.67 (s, 1H); 13
NMR: (100 MHz; CDCl3) d 10.5, 25.4, 28.2, 83.8, 88.4, 134.3, 144.8, 150.3, 167.5;
C
C
5.53.
10H7Cl2NO2ꢁ1/6H2O: C, 48.61; H, 2.99; N, 5.67. Found: C, 48.62; H, 2.84; N,