Reactions of monoaryl-substituted methylenecyclobutanes and methylenecyclopropanes with 1-hydroxybenzotriazole (HOBt), 1-hydroxy-7- azabenzotriazole (HOAt), and 1-hydroxysuccinimide (HOSu)

Article abstract of DOI:10.1021/jo9000299

Monoaryl-substituted methylenecyclobutanes (MCBs) and methylenecyclopropanes (MCPs) react with 1-hydroxybenzotriazole (HOBt), 1-hydroxy-7-azabenzotriazole (HOAt), and 1-hydroxysuccinimide (HOSu) smoothly to produce the corresponding cyclobutylmethanone an

Full text of DOI:10.1021/jo9000299

Reactions of Monoaryl-Substituted Methylenecyclobutanes and
Methylenecyclopropanes with 1-Hydroxybenzotriazole (HOBt),
1-Hydroxy-7-azabenzotriazole (HOAt), and 1-Hydroxysuccinimide
(HOSu)
Min Jiang and Min Shi*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, 354 Fenglin Lu, Shanghai 200032 China
mshi@mail.sioc.ac.cn
ReceiVed January 7, 2009
Monoaryl-substituted methylenecyclobutanes (MCBs) and methylenecyclopropanes (MCPs) react with
1-hydroxybenzotriazole (HOBt), 1-hydroxy-7-azabenzotriazole (HOAt), and 1-hydroxysuccinimide (HOSu)
smoothly to produce the corresponding cyclobutylmethanone and cyclopropylmethanone derivatives 2,
4, and 5 via a cascade epoxidation and nucleophilic addition process or the corresponding epoxides 6 in
moderate to good yields under mild conditions. A plausible mechanism has been proposed on the basis
of the control experiments and the isolation of the reaction intermediates.
Introduction
preparation of the antibiotic malonomicin.3 It should be noted
that, in the above cases, HOBt, HOAt, and HOSu acted as
nucleophiles for the transformation. On the other hand, besides
being the efficient coupling reagents in the peptide synthesis,
acylated HOBt compound can also undergo an intramolecular
rearrangement to produce the corresponding N-acylated ben-
zotriazole oxide. For example, in 1985, Rinehart reported the
rearrangement of the unsaturated acyl benzotriazole A to B in
good yield in the presence of potassium carbonate in acetone
(Scheme 1).4,5 It is conceivable that species B could act as an
oxidation reagent just like 4-methylmorpholine N-oxide (NMO)
as co-oxidant in Sharpless asymmetric dihydroxylation for a
The N-hydroxy-containing compounds, such as 1-hydroxy-
benzotriazole (HOBt·H2O), 1-hydroxy-7-azabenzotriazole (HOAt),
and 1-hydroxysuccinimide (HOSu), are widely used as activating
reagents in combination with N,N′-dicyclohexylcarbodiimide
(DCC) or N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide (EDC,
WSC) for the construction of an amide bond during the synthesis
of peptide1 and ꢀ-lactam antibiotics.2 Moreover, activated esters
by these N-hydroxy-containing compounds have also been
employed in the formation of a C(O)-C bond during the
(1) (a) Konig, W.; Geiger, R. Chem. Ber. 1970, 103, 788–798. (b) Castro,
B.; Domoy, J. R.; Evin, G.; Selve, C. Tetrahedron Lett. 1975, 1219–1222. (c)
Meldal, M. Acta Chem. Scand., Ser. B 1986, B40, 242–249.
(2) (a) Singh, J.; Przybyla, C.; Kissick, T. P.; Denzel, T.; Mueller, R. H.;
Moniot, J. L.; Cimarusti, C. M. Abstracts of Papers, 192nd National Meeting of
the American Chemical Society, Anaheim, CA; American Chemical Society:
Washington, DC, ORGN 243. (b) Blumbach, J.; Duerckheimer, W.; Reden, J.;
Seliger, H. German Patent 2758000, 1977. (c) Wheeler, W. J.; Finley, D. R.;
Ott, J. L. J. Antibiot. 1986, 39, 1611–1614.
(3) Van der Baan, J. L.; Barnick, J. W. F. K.; Bickelhaupt, F. Tetrahedron
1978, 34, 223–231.
(4) Nagarajan, S.; Wilson, S. R.; Rinehart, K. L. J. Org. Chem. 1985, 50,
2174–2178.
(5) For reviews on HOBt: (a) Chan, L. C.; Cox, B. G. J. Org. Chem. 2007,
72, 8863–8869. (b) Bright, R.; Dale, D. J.; Dunn, P. J.; Hussain, F.; Kang, Y.;
Mason, C.; Mitchell, J. C.; Snowden, M. J. Org. Process Res. DeV. 2004, 8,
1054–1058.
2516 J. Org. Chem. 2009, 74, 2516–2520
10.1021/jo9000299 CCC: $40.75 2009 American Chemical Society
Published on Web 02/17/2009

Monoaryl-Substituted MCBs and MCPs
TABLE 1. Optimization of the Reaction Conditions
SCHEME 1. Rearrangement of A to B
cascade transformation. Therefore, it is interesting to find a
substrate which can react with HOBt, HOAt, and HOSu
smoothly to give the corresponding cascade nucleophilic addi-
tion and oxidation product in good yield.
Methylenecyclobutanes (MCBs) and methylenecyclopropanes
(MCPs) are both highly strained but readily accessible molecules
that have served as useful building blocks in organic synthesis.6
MCBs and MCPs undergo a variety of ring-opening reactions
in the presence of transition metal or Lewis acid because the
relief of ring strain provides a potent thermodynamic driving
force.7,8 For example, recently, we have found that the ring-
opening reactions of MCPs 1 with alcohols and other nucleo-
philes catalyzed by Lewis acids [Ln(OTf)3] took place smoothly
to give the corresponding homoallylic ring-opened products in
good yields under mild conditions.7j,k These results stimulated
us to investigate the reaction outcomes of MCBs and MCPs
with HOBt, HOAt, and HOSu under similar conditions. In this
paper, we wish to report the reaction of monoaryl-substituted
methylenecyclobutanes (MCBs) and methylenecyclopropanes
(MCPs) with N-hydroxy-containing compounds such as HOBt,
HOAt, and HOSu to form the corresponding cyclobutylmetha-
none and cyclopropylmethanone derivatives via a cascade
epoxidation and nucleophilic addition process as well as the
corresponding epoxides in moderate to good yields at 60 °C in
acetonitrile.
a Reaction conditions: 1a (0.2 mmol), HOBt (x mmol), solvent (2 0.0
mL), and the reactions were carried out at various temperatures.
b Isolated yields.
TABLE 2. Scope and Limitations of the Reaction of MCBs 1 with
HOBt
entrya
MCBs (R1)
yield (%)b of 2
1
2
3
4
1b (p-BrC6H4)
1c (m-BrC6H4)
1d (m-ClC6H4)
1e (p-FC6H4)
1f (C6H5)
2b, 81
2c, 79
2d, 76
2e, 78
5
2f, 7
9
Results and Discussion
6
7
8
9
10
11
1g (p-MeC6 H4)
1h (m-MeC6 H4)
1i (p-EtC6H4)
1j (o-ClC6H4)
1k (o,m-Cl2C6H3)
1l (C4H9)
2g, 76
2h, 73
2i, 7
2j, 62
2k, 60
2l, -
Initial examinations using p-chlorophenylmethylenecyclobu-
tane 1a as the substrate to react with HOBt in a variety of
solvents were aimed at determining the resulting products as
well as the optimal reaction conditions, and the results of these
experiments are summarized in Table 1. It was found that using
1a (1.0 equiv) with HOBt (1.0 equiv) in 1,2-dichloroethane
(DCE) at 60 °C afforded cyclobutylmethanone derivative 2a in
34% yield along with a trace of 4-chlorobenzaldehyde after 40 h
under ambient atmosphere (Table 1, entry 1). When the ratio
8
a Reaction conditions: 1a (0.2 mmol), HOBt (0.4 mmol), CH3 CN (2
0.0 mL), and the reactions were carried out at 60 °C for 40 h. b Isolated
yields.
of 1a/HOBt changed to 1/2, 2a was obtained in 72% yield under
identical conditions (Table 1, entry 2). Increasing the employed
amounts of HOBt to 3 equiv or raising the reaction temperature
to 80 °C did not significantly change the reaction outcomes
(Table 1, entries 3 and 4). When the reaction was carried out at
40 °C, a trace of 2a was obtained and the compound 10 was
produced as the major product in 91% yield (Table 1, entry 5).
Further examination of the solvent effects revealed that aceto-
nitrile (CH3CN) is the best one for this transformation, affording
2a in 82% yield within 40 h (Table 1, entries 6-10). It should
be also noted that HOBt is completely soluble in acetonitrile.
Therefore, the best conditions are to carry out the reaction in
CH3CN at 60 °C for 40 h using 1.0 equiv of 1a and 2.0 equiv
of HOBt as the substrates.
(6) (a) Binger, P.; Wedemann, P.; Kozhushkov, S. I.; de Meijere, A. Eur. J.
Org. Chem. 1998, 113–119. (b) de Meijere, A.; Kozhushkov, S. I. Eur. J. Org.
Chem. 2000, 3809–3822. (c) Molchanov, A. P.; Diev, V. V.; Magull, J.; Vidovic,
D.; Kozhushkov, S. I.; de Meijere, A.; Kostikov, R. R. Eur. J. Org. Chem. 2005,
593–599. (d) de Meijere, A.; Becker, H.; Stolle, A.; Kozhushkov, S. I.; Bes,
M. T.; Salau¨n, J.; Noltemeyer, M. Chem.sEur. J. 2005, 11, 2471–2482.
(7) For recent reviews on MCPs, see: (a) Nakamura, I.; Yamamoto, Y. AdV.
Synth. Catal. 2002, 344, 111–129. (b) Brandi, A.; Cicchi, S.; Cordero, F. M.;
Goti, A. Chem. ReV. 2003, 103, 1213–1270. (c) Nakamura, E.; Yamago, S. Acc.
Chem. Res. 2002, 35, 867–877. (d) Shi, M.; Chen, Y.; Xu, B.; Tang, J.
Tetrahedron Lett. 2002, 43, 8019–8024. (e) Shi, M.; Chen, Y.; Xu, B.; Tang, J.
Green Chem. 2003, 5, 85–88. (f) Shi, M.; Chen, Y. J. Fluorine Chem. 2003,
122, 219–227. (g) Chen, Y.; Shi, M. J. Org. Chem. 2004, 69, 426–431. (h)
Nakamura, I.; Oh, B. H.; Saito, S.; Yamamoto, Y. Angew. Chem., Int. Ed. 2001,
40, 1298–1300. (i) Oh, B. H.; Nakamura, I.; Saito, S.; Yamamoto, Y. Tetrahedron
Lett. 2001, 42, 6203–6205. (j) Shi, M.; Xu, B. Org. Lett. 2002, 4, 2145–2148.
(k) Shi, M.; Chen, Y.; Xu, B.; Tang, J. Tetrahedron Lett. 2002, 43, 8019–8024.
(l) Shi, M.; Jiang, M.; Liu, L.-P. Org. Biomol. Chem. 2007, 5, 438–440.
(8) For references on MCBs, see: (a) Graham, S. H.; William, A. J. S.
J. Chem. Soc. 1959, 4066–4072. (b) Farcasiu, D.; Schleyer, P. V. R.; Ledlie, D.
J. Org. Chem. 1973, 38, 3455–3459. (c) Shen, Y. M.; Wang, B.; Shi, Y. Angew.
Chem., Int. Ed. 2002, 45, 1429–1432. (d) Jiang, M.; Liu, L.-P.; Shi, M.
Tetrahedron 2007, 63, 9599–9604. (e) Jiang, M.; Shi, M. Org. Lett. 2008, 10,
2239–2242. (f) Jiang, M.; Shi, M. Tetrahedron 2009, 65, 798–801.
With these optimal conditions in hand, we next carried out
this reaction using a variety of MCBs 1 with HOBt, and the
reaction outcomes are outlined in Table 2. We found that the
corresponding products 2 were obtained in moderate to good
yields within 40 h for a variety of MCBs 1 with electron-
J. Org. Chem. Vol. 74, No. 6, 2009 2517

Jiang and Shi
TABLE 3. Scope and Limitations of the Reaction of MCPs 3 with
HOBt
entrya
MCBs (R2)
yield (%)b of 4
1
2
3
4
5
6
3a (p-ClC6H4)
3b (p-BrC6H4)
3c (o-ClC6H4)
3d (m-FC6H4)
3e (C6H5)
4a, 81
4b, 79
4c, 76
4d, 78
4e, 79
4f, 76
3f (p-EtC6H4)
a Reaction conditions: 3 (0.2 mmol), HOBt (0.4 mmol), CH3 CN (2.0
mL), and the reactions were carried out at 60 °C for 40 h. b Isolated
yields.
FIGURE 1. ORTEP drawing of 2b.
TABLE 4. Scope and Limitations of the Reaction of MCBs 1 with
HOAt and HOSu
donating, electron-neutral, and electron-withdrawing substituents
on the benzene ring under ambient atmosphere. The substituents
on the aromatic ring of MCBs 1 did not have significant
influence on the reaction outcomes. As can be seen from Table
2, in the presence of an electron-poor or electron-rich substituent
at the para or meta position of benzene ring, the corresponding
products 2b-2i were afforded in 73-81% yields (Table 2,
entries 1-8). However, as for MCBs 1j and 1k with the
substituents at the ortho position of benzene ring, the corre-
sponding products 2j and 2k were obtained in lower yields (62
and 60%), presumably due to the steric effect (Table 2, entries
9 and 10). Using aliphatic MCB 1l as the substrate, the reaction
became disordered to give the complex product mixtures,
suggesting that an aromatic group is required in this transforma-
tion (Table 2, entry 11).
N-hydroxy-
containing
compound
yield (%)b
yield (%)b
entrya
MCBs (R1)
of 5
of 6 + 7 (6:7)c
1
2
3
4
5
6
7
8
1a (p-ClC6H4)
1b (p-BrC6H4)
1c (m-BrC6H4)
1d (m-ClC6H4)
1f (C6H5)
1g (p-MeC6H4)
1i (p-EtC6H4)
1a (p-ClC6H4)
1b (p-BrC6H4)
1c (m-BrC6H4)
1d (m-ClC6H4)
HOAt
-
80 (1.00:1.20)
76 (1.00:1.21)
77 (1.00:1.24)
75 (1.00:1.12)
-
-
-
75 (1.00:1.18)
76 (1.00:1.25)
81 (1.00:1.16)
76 (1.00:1.21)
-
-
-
5a, 52
5b, 62
5c, 51
-
HOSu
9
10
11
-
Their structures were determined by 1H and 13C NMR
spectroscopic data, HRMS, and microanalyses (see the Sup-
porting Information). Furthermore, the X-ray crystal structure
of 2b was determined, and its CIF data are presented in the
Supporting Information (Figure 1).9
-
-
a Reaction conditions:
1 (0.2 mmol), N-hydroxy compound (0.4
mmol), CH3CN (2 0.0 mL), and the reactions were carried out at 60 °C.
b Isolated yields. c The mixtures of 6 and 7 cannot be separated by silica
gel column chromatography, and the ratios of 6 and 7 were determined
1
Using MCPs 3 instead of MCBs 1 as the substrates, we found
that these reactions also proceeded smoothly to give the
corresponding cyclopropylmethanone derivatives 4a-4f in
76-81% yields whether they have electron-poor or electron-
rich aromatic rings (Table 3, entries 1-6). Their structures were
also determined by 1H and 13C NMR spectroscopic data, HRMS,
and microanalyses (see the Supporting Information).
by H NMR spectroscopic data.
were isolated in 51-62% yields exclusively (Table 4, entries
5-7). However, in the reaction of MCBs 1f, 1g, and 1i with
HOSu, complicated product mixtures were produced under
identical conditions, and the results were not shown in
Table 4.
Furthermore, under these optimal conditions, we investigated
the reaction of a variety of MCBs 1 with the other N-hydroxy-
containing compounds such as HOAt and HOSu and found that,
as for MCBs 1 bearing electron-poor substituents on the benzene
ring, the epoxides 6 were obtained along with the corresponding
arylaldehydes 7 in overall 75-81% yields rather than the
expected cyclobutylmethanone products under the standard
conditions (Table 4, entries 1-4 and 8-11). The epoxides 6
and arylaldehydes 7 might be derived from the oxidation of 1
with HOAt or HOSu upon heating at 60 °C.10 As for the reaction
of MCBs 1f, 1g, and 1i bearing neutral or electron-rich aromatic
ring with HOAt, the expected cyclobutylmethanone products 5
The MCBs 1 having a hydrogen atom are essential in this
transformation because no reactions occurred if using MCBs
8a (R3 ) C6H5) and 8b (R3 ) Me) as the substrates to react
with HOBt, HOAt, and HOSu under the standard conditions
(Table 5, entries 1-3). Moreover, as for the reactions of MCPs
8c and 8d with HOBt, the ring-opening product 9a and the
alcohol 9b were obtained in 82 and 74% yield, respectively
(Table 5, entries 4 and 7), although no reactions occurred with
HOAt and HOSu under the standard conditions (Table 5, entries
5-6 and 8-9). Using aliphatic MCPs 8e and 8f as the substrates
to react with HOBt, complex product mixtures were formed,
indicating again that one aromatic group is required in this
transformation (Table 5, entries 10 and 11). Furthermore, the
reactions of monoaryl-substituted methylenecyclopentane 8g
with HOBt, HOAt, and HOSu produced the complex product
mixtures under the standard conditions (Table 5, entries 12-14).
Using 2,2-dimethyl-1-phenylethene 8h as the substrate to react
with HOBt produced the compound 9c in 24% yield. However,
(9) The crystal data of 2b have been deposited in CCDC with number 668263.
Empirical formula: C17H14BrN3O2; formula weight: 372.22; crystal color, habit:
colorless, prismatic; crystal dimensions: 0.256 × 0.113 × 0.079 mm; crystal
system: monoclinic; lattice type: primitive; lattice parameters: a ) 5.8939(10)
Å, b ) 10.3365(18) Å, c ) 26.251(5) Å, R ) 90°, ꢀ ) 90.417(4)°, γ ) 90°, V
) 1599.2(5) Å3; space group: P2(1)/c; Z ) 4; Dcalcd ) 1.546 g/cm3; F000 ) 752;
diffractometer: Rigaku AFC7R; residuals: R; Rw: 0.0527, 0.1172.
2518 J. Org. Chem. Vol. 74, No. 6, 2009

Monoaryl-Substituted MCBs and MCPs
TABLE 5. Scope and Limitations of this Reaction
SCHEME 2. Reation Pathway
SCHEME 3. Control Experiments
SCHEME 4. Determination of the Other Product
SCHEME 5. Proposed Mechanism for the Reaction of
MCBs 1 and MCPs 3 with HOBt
a Reaction conditions: 8 (0.2 mmol), HOBt (0.4 mmol), solvent (2.0
mL), and the reactions were carried out at 60 °C for 40 h. b Isolated
yields.
using HOAt and HOSu instead of HOBt, the reactions became
disordered to produce the complex product mixtures (Table 5,
entries 15-17). These results suggest that monoaryl-substituted
MCBs and MCPs are the suitable substrates in this transforma-
tion to produce the corresponding cyclobutylmethanone and
cyclopropylmethanone derivatives in moderate to good yields.
To confirm the reaction pathway, we attempted to determine
the intermediates in this reaction. During the examination of
the optimal conditions, we found that when the reaction was
carried out at 40 °C the alcohol 10 was obtained in 91% yield
along with the trace of product 2a (Table 1, entry 5). Interest-
ingly, if alcohol 10 was heated to 60 °C in CH3CN without any
reagent, 2a was produced in 86% yield, suggesting that alcohol
10 is the reaction intermediate (Scheme 2).
To clarify the mechanism of this reaction, two control
experiments were carried out as shown in Scheme 3. First, using
0.5 equiv of HOBt to react with MCB 1a (1.0 equiv) and
quenching the reaction after 10 h, we found that the product 2a
was formed in 8% yield along with the epoxide 6a in 31% yield
and the trace of arylaldehyde (Scheme 3). Second, the isolated
epoxide 6a was further used to react with 1.0 equiv of HOBt at
60 °C in CH3CN. It was found that 2a was obtained in 62%
yield after 40 h, indicating that 2a is derived from the reaction
of epoxide 6a with HOBt (Scheme 3). It is noteworthy that
benzotriazole (11) was isolated from the reaction mixture in
92% yield along with 2a in 82% yield under the standard
conditions, and its 1H NMR spectroscopic data are identical with
the authentic sample (Scheme 4 and see the Supporting
Information).
On the basis of above control experiments and the isolation
of the reaction intermediates, a plausible mechanism for the
formation of products 2, 4, 5 and 6 is outlined in Schemes 5
and 6, respectively. In Scheme 5, HOBt generates intermediate
C as mentioned in the Introduction,4 which acts as an oxidant
like as N-methylmorpholine oxide (NMO)11 to oxidize substrate
1 or 3 to give the epoxide D along with the compound 11. The
arylaldehyde is derived from the decomposition of epoxide D
during the reaction. Then, the epoxide is activated by the
protonation of another molecule of HOBt12 to give intermediate
(10) (a) Sawaki, Y.; Ogata, Y. J. Am. Chem. Soc. 1981, 103, 2049–2053.
(b) Rigaudy, J.; Scribe, P.; Breliere, C. Tetrahedron 1981, 37, 2585–2593. (c)
Zieger, H. E.; Tsang, C. H.; Malik, M.; Todaro, L. J. Tetrahedron Lett. 2002,
43, 4845–4848. (d) Hayashi, Y.; Takeda, M.; Miyamoto, Y.; Shoji, M. Chem.
Lett. 2002, 414–415.
(11) (a) Katarina, B.; Joeri, J. N.; Backvall, J. E. J. Org. Chem. 1999, 64,
2545–2548. (b) Hou, Y. X.; Tulevski, G. S.; Valint, P. L. Macromolecules 2002,
35, 5953–5962.
J. Org. Chem. Vol. 74, No. 6, 2009 2519

Jiang and Shi
SCHEME 6. Proposed Mechanism for the Reaction of
MCBs 1 with HOAt
and nucleophilic addition process as well as the corresponding
epoxides 6 in moderate to good yields under mild conditions.
A plausible mechanism has been proposed on the basis of
control experiments and the isolation of the reaction intermedi-
ates. Clarification of the reaction mechanism and further
application of this transformation are in progress.
Experimental Section
General Procedure for the Reactions. Under an argon atmo-
sphere, methylenecyclobutanes (MCBs 1 or MCPs 3) (0.2 mmol)
and HOBt ·H2O (HOAt or HOSu) (0.4 mmol) were added into a
Schlenk tube. After 2.0 mL of dry CH3CN was added rapidly into
the tube via a syringe, the reaction mixture was stirred at 60 °C for
40 h. Then, the solvent was removed under reduced pressure, and
the residue was purified by a flash column chromatography (SiO2)
to give the corresponding product 2, 4, 5, or 6 in moderate yields.
Compound 2a: A colorless oil; IR (CH2Cl2) ν 2986, 2957, 1686,
1588, 1488, 1402, 1217, 1090, 966, 843, 781, 744 cm-1; 1H NMR
(300 MHz, CDCl3, TMS) δ 1.75-1.88 (1H, m, CH2), 1.98-2.10
(1H, m, CH2), 2.62-2.73 (2H, m, CH2), 2.76-2.85 (2H, m, CH2),
7.33-7.38 (2H, m, ArH), 7.45 (1H, d, J ) 8.1 Hz, ArH), 7.51
(2H, d, J ) 8.4 Hz, ArH), 7.98 (1H, d, J ) 8.1 Hz, ArH), 8.18
(2H, d, J ) 8.4 Hz, ArH); 13C NMR (75 MHz, CDCl3, TMS) δ
12.8, 29.7, 94.0, 108.6, 120.3, 124.7, 128.4, 128.6, 129.0, 131.5,
131.6, 140.0, 142.9, 193.3; MS (EI) m/z (%) 327 (7.93) [M+], 201
(13.96), 193 (27.47), 166 (7.43), 139 (100.00), 111 (30.54), 91 (6.7),
75 (9.08); HRMS (EI) calcd for C17H14N3O2Cl (M+) requires
327.0775, found 327.0775.
E,8d which undergoes counteranion (-OBt) attack at the position
b to provide the alcohol F (compound 10 in Scheme 2). The
alcohol can be transformed to the product 2 or 4 upon heating
at 60 °C.
Moreover, HOAt can also produce intermediate G,4 which
can oxidize MCB 1 to give the corresponding epoxide D along
with compound H similarly. Since the counteranion AtO- do
not have the strong nucleophilicity as that of BtO- due to the
electron-withdrawing 2-pyridyl group and the protonation can
also take place at the pyridine ring, the counteranion AtO- can
only attack at the epoxide I having an electron-rich or a neutral
aromatic ring to form the product 58d,12 through intermediate
J. However, as for the epoxide D having an electron-poor
aromatic ring, the protonated epoxide I is not stable enough to
undergo the nucleophilic attack by -OAt. Therefore, in this case,
epoxide D can be isolated as the product.
Acknowledgment. We thank the Shanghai Municipal Com-
mittee of Science and Technology (06XD14005, 08dj1400100-
2), National Basic Research Program of China (973)-
2009CB825300, and the National Natural Science Foundation
of China (20872162, 20672127, and 20732008).
In summary, we have developed a novel reaction of monoaryl-
substituted methylenecyclobutanes and methylenecyclopropanes
with N-hydroxy-containing compounds such as HOBt, HOAt,
and HOSu to produce cyclobutylmethanone and cyclopropyl-
methanone derivatives 2, 4, and 5 via a cascade epoxidation
Supporting Information Available: Spectroscopic data (1H,
13C spectroscopic data), HRMS of the compounds shown in
Tables 1-4, the X-ray crystal structure of compound 2b along
with the detailed description of experimental procedures. This
material is available free of charge via the Internet at
http://pubs.acs.org.
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Wuts, P. G. M.; Ashford, S. W.; Anderson, A. M.; Atkins, J. R. Org. Lett. 2003,
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2520 J. Org. Chem. Vol. 74, No. 6, 2009