Reaction of methylenecyclobutanes with NXS-H2O system

Article abstract of DOI:10.1080/00397911.2010.517614

Reactions of methylenecyclobutanes (MCBs) with NXS-H₂O system were investigated. The results were quite different from that of methylenecyclopropanes (MCPs), and an interesting aryl-transfer reaction happened to give substituted cyclobutyl keto

Full text of DOI:10.1080/00397911.2010.517614

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Reaction of Methylenecyclobutanes with
NXS-H2O System
Lei Yu a , Lingfeng Ren a , Bei Xu a & Rong Guo a
a School of Chemistry and Chemical Engineering, Yangzhou
University , Yangzhou , China
Published online: 27 Jul 2011.
To cite this article: Lei Yu , Lingfeng Ren , Bei Xu & Rong Guo (2011) Reaction of
Methylenecyclobutanes with NXS-H2O System, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 41:21, 3237-3245, DOI:
10.1080/00397911.2010.517614
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Synthetic Communications1, 41: 3237–3245, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.517614
REACTION OF METHYLENECYCLOBUTANES WITH
NXS-H2O SYSTEM
Lei Yu, Lingfeng Ren, Bei Xu, and Rong Guo
School of Chemistry and Chemical Engineering, Yangzhou University,
Yangzhou, China
GRAPHICAL ABSTRACT
Abstract Reactions of methylenecyclobutanes (MCBs) with NXS-H2O system were
investigated. The results were quite different from that of methylenecyclopropanes
(MCPs), and an interesting aryl-transfer reaction happened to give substituted cyclobutyl
ketones as products when disubstituted MCBs were employed. When monosubstituted
MCBs were employed, the direct halohydroxylation gave the cyclobutyl ring untouched
adducts. All of these analogs have potential application value in organic synthesis.
Supplemental materials are available for this article. Go to the publisher’s online edition
of Synthetic Communications1 to view the free supplemental file.
Keywords Aryl transfer; cyclobutyl ketones; electrophilic addition; halohydroxylation;
methylenecyclobutanes
INTRODUCTION
During the past decade, highly activated small organic molecules have
attracted the interest of chemists, and their novel reactions have been widely inves-
tigated. The highly activated small organic molecules include methycyclopropanes
Received February 5, 2010.
Address correspondence to Lei Yu, School of Chemistry and Chemical Engineering, Yangzhou
University, Yangzhou 225002, China. E-mail: yulei@yzu.edu.cn
3237

3238
L. YU ET AL.
(MCPs),[1] vinylidenecyclopropanes (VCPs),[2] allenes,[3] cyclopropyl allenes,[4] and
=
so on. Because of their high intramolecular ring strain or cumulated C C bonds,
these compounds have high reactivity and can undergo a series of interesting reac-
tions under mild conditions, providing convenient methods for the construction of
many useful organic structures. Therefore, they are all useful building blocks in
organic synthesis. Containing a four-membered carbon ring and an exocyclic double
bond, methylenecyclobutanes (MCBs) are very similar to MCPs. Hence, MCBs may
undergo a series of reactions like MCPs and have potential applications in organic
synthesis. Recently, the novel reactions of MCBs have been reported in several
studies.[5]
Being able to introduce two functional groups simultaneously, halohydroxyla-
=
[6]
tions of the C C double bonds are potent tools in organic synthesis. In the
investigation of highly activated small moleculars, Ma has reported the halohydrox-
ylation of allenes, providing a facile access to halogen substituted allyl alcohols.[7]
Huang and coworkers reported the halohydroxylation of cyclopropyl allenes using
a N-halogen succinimide (NXS)–H2O system, giving 5-halohexa-3,5-dien-1-ol deri-
vatives as products stereoselectively.[4c] The halohydroxylation of MCPs was also
reported by them recently.[8] Encouraged by these works, we became interested in
the halohydroxylation of activated olefins. Herein, we report the reaction of MCBs
with the NXS–H2O system. Compared with the reported MCP reactions,[8] the
experimental results are quite different.
We initially examined the reaction of MCB 1a with N-bromo succinimide
(NBS) in CH2CN–H2O (3:1). The reaction occurred smoothly, and the substrate
1a disappeared in less than 30 min. However, instead of the desired cyclobutyl
Table 1. Reaction of MCB 1a with NXS under different conditionsa
Entry
Solvent
Conditions
X
Timeb (h)
Yield of 2a (%)c
1
2
CH3CN-H2O (3:1)
CH3CN-H2O (4:1)
CH3CN-H2O (5:1)
CH3CN-H2O (4:1)
CH3CN-H2O (4:1)
C2H5OH (95%)
rt=N2
rt=N2
Br
Br
Br
Br
Br
Br
Br
Br
Cl
I
<0.5
<0.5
<0.5
<0.5
<0.5
4
70
86
77
78
74
18
20
71
0
3
rt=N2
4
50 ꢀC=N2
80 ꢀC=N2
rt=N2
5
6
7
Acetone-H2O (4:1)
CH3CN-H2O (4:1)
CH3CN-H2O (4:1)
CH3CN-H2O (4:1)
rt=N2
rt=air
24
8
<0.5
<0.5
<0.5
9
10
rt=N2
rt=N2
83
a0.3 mmol of 1a, 0.6 mmol of NXS, and 1 mL of solvent were employed.
bThe reaction was monitored by TLC (eluent: petroleum ether).
cIsolated yields based on 1a.

REACTION OF METHYLENECYCLOBUTANES AND NXS-H2O
3239
ring-intact adduct 3 or cyclobutyl ring-opened adduct 4, an interesting product, 2a,
was obtained (Table 1, entry 1). Four-membered carbon ring structures are widely
present in natural products.[9] Containing a cyclobutyl ketone structure unit, 2a
may have value in introducing a four-membered carbon ring and acting as useful
building blocks in organic synthesis.[5b,5e,10] Therefore, we tried to optimize this
novel reaction, and the experimental results are listed in Table 1. It is obviously that
the CH3CN-H2O (4:1) system was a better solvent, and heat was not needed in this
reaction (Table 1, entry 2). The reaction could even be carried out without nitrogen
protection, and the yield of 2a was less (Table 1, entry 8). We then examined the
reactions by employing other halogen cations and found that the yield of 2a would
not be decreased much when N-iodo succinimide was employed (Table 1, entry 10).
With the optimized conditions in hand, a series of disubstituted MCBs 1 were
employed, and the corresponding cyclobutyl ketones 2 were synthesized. It is obvi-
ous that the NIS-promoted reaction has wider application scope than the
NBS-promoted one (Table 2, entries 7–12).
Although the literature has reported the preparation of cyclobutyl ketones
through the reactions of MCBs with an I2–AgOAc system,[5c] the employment of
300% equivalent of expensive silver salt makes that method uneconomical and limits
its further applications. Herein, we have developed a more economic method for the
preparation of cyclobutyl ketones, avoiding the use of silver salt.
Table 2. Synthesis of substituted cyclobutyl ketones 2
Entry
R1, R2
X
Yield of 2 (%)a
1
2
C6H5, H (1a)
C6H5, H (1a)
CH3, H (1b)
Br
I
86 (2a)
83 (2a)
62 (2b)
70 (2b)
68 (2c)
76 (2c)
0
3
Br
I
4
CH3, H (1b)
5
C2H5, H (1c)
C2H5, H (1c)
p-FC6H4, F (1d)
p-FC6H4, F (1d)
CH3, CH3 (1e)
CH3, CH3 (1e)
CH3, Cl (1f)
Br
I
6
7
Br
I
8
53 (2d)
0
9
Br
I
10
11
12
13
14
80 (2e)
0
Br
I
CH3, Cl (1f)
C2H5, Br (1g)
C2H5, Br (1g)
58 (2f)
0
67 (2g)
Br
I
aIsolated yields based on 1.

3240
L. YU ET AL.
Table 3. Synethsis of substituted halohydroxylation adducts
Entry
Ar
X
Yield of 5 (%)a
1
2
3
4
5
6
C6H5 (1h)
p-ClC6H4 (1i)
o-BrC6H4 (1j)
p-BrC6H4 (1k)
C6H5 (1 h)
Br
Br
Br
Br
I
88 (5a)
52 (5b)
90 (5c)
70 (5d)
0
p-BrC6H4 (1k)
I
0
aIsolated yields based on 1.
We then examined the reaction of mono-aryl-substituted MCBs with NBS, and
the products were quite different. Instead of the rearranged products cyclobutyl
ketones 2, direct halohydroxylation adducts 5 were obtained (Table 3, entries
1–4). When NIS was employed, only a series of unidentified complexes were
observed (Table 3, entries 5 and 6). Interestingly, when the reaction was taken with-
out nitrogen atmosphere protection, a-bromo-substituted cyclobutyl ketone 6 was
obtained (Scheme 1).
On the basis of the literature and previous experimental results, a possible
mechanism of this reaction is suggested in Scheme 2. The electrophilic addition of
halogen (Br or I) cation to MCBs 1 first generated the intermediate cation 7. When
monosubstituted MCBs were employed, the reaction of 7 with water offered the
halo-hydroxylation adduct 5. Correspondingly, when disubstituted MCBs were
employed, water did not attack the intermediate cation 7 immediately (probably
because of the steric hindrance factor), and rearrangement happened to give the
intermediate 8.[5c] The nucleophilic attack of water to 8 gave 9, which could be trans-
formed to the final product 2 by dehydrohalogenation.
In conclusion, we have investigated the reactions of MCBs with NXS-H2O sys-
tem and found that the results were quite different from similar reactions with MCP.
When disubstituted MCBs were employed, an interesting aryl-transfer reaction
happened to give the substituted cyclobutyl ketones in moderate to good yields. Cor-
respondingly, when monosubstituted MCBs were employed, halo-hydroxylation
Scheme 1. Reaction of 1k with NBS in air.

REACTION OF METHYLENECYCLOBUTANES AND NXS-H2O
3241
Scheme 2. Proposed mechanism for the reaction.
adducts were obtained in moderate to good yields. All of these analogs have potent
application value in organic synthesis.
EXPERIMENTAL
1H NMR spectra were recorded on a Bruker Avance (600-MHz) spectrometer
in CDCl3 with tetramethylsilance (TMS) as the internal standard. 13C NMR spectra
were recorded on a Bruker Avance (150-MHz) spectrometer in CDCl3. Infrared (IR)
spectra were recorded on a Shimadzu IR-408 spectrometer. Election impact mass
spectra (EIMS) were run on a HP 5989B mass spectrometer.
General Procedure for the Preparation of 2
Under N2 atmosphere protection, a solution of 1 (0.3 mmol in 1 mL of
CH3CN-H2O) was added to NBS or NIS (0.6 mmol). The mixture was stirred at
room temperature, and the reaction was monitored by thin-layer chromatography
(TLC) (eluent: petroleum ether). When the reaction terminated, the solvent was
evaporated by vacuum, and the residue was separated by preparative TLC (eluent:
petroleum ether=EtOAc 6:1) to give the corresponding product 2.
General Procedure for the Preparation of 5
Under N2 atmosphere protection, a solution of 1 (0.3 mmol in 1 mL of
CH3CN-H2O) was added to NBS (0.6 mmol). The mixture was stirred at room tem-
perature, and the reaction was monitored by TLC (eluent: petroleum ether). When
the reaction terminated, the solvent was evaporated by vacuum, and the residue

3242
L. YU ET AL.
was separated by preparative TLC (eluent: petroleum ether=EtOAc 5:1) to give the
corresponding product 5.
Data
Compound 2a. Oil, IR (film): 3060, 2985, 2946, 2867, 1756, 1675, 1597, 1494,
1
1446, 1247, 912, 754, 702 cmꢁ1. H NMR (600 MHz, CDCl3): d ¼ 7.20–7.73 (m,
10 H), 2.91–2.96 (m, 2H), 2.54–2.58 (m, 2H), 2.07–2.09 (m, 1H), 1.90–1.92 (m,
1H). 13C NMR (150 MHz, CDCl3): d ¼ 16.0, 32.3, 57.2, 125.6, 126.5, 128.1, 129.0,
129.7, 132.3, 134.2, 143.2, 201.1. MS (EI, 70 eV): m=z (%) ¼ 236 (2) [Mþ], 235 (13)
[Mþ ꢁ 1], 55 (100). The spectral data were consistent with Ref. 5c.
Compound 2b. Oil, IR (film): 2982, 2948, 1704, 1492, 1437, 1353, 1235, 1188,
1106, 798, 757, 701 cmꢁ1
.
1H NMR (600 MHz, CDCl3): d ¼ 7.24–7.36 (m, 5H),
2.73–2.77 (m, 2H), 2.40–2.45 (m, 2H), 1.93 (s, 3H), 1.85–1.91 (m, 2H). 13C NMR
(150 MHz, CDCl3): d ¼ 15.9, 24.4, 30.5, 59.3, 126.2, 126.7, 128.7, 143.2, 208.7. MS
(EI, 70 eV): m=z (%) ¼ 174 (8) [Mþ], 131 (100), 102 (78). Anal. calcd. for C12H14O:
C, 82.72; H, 8.10. Found: C, 82.97; H, 7.81.
Compound 2c. Oil, IR (film): 2979, 2940, 1706, 1493, 1447, 1343, 1094, 1072,
959, 913, 756, 701 cmꢁ1
.
1H NMR (600 MHz, CDCl3): d ¼ 7.23–7.35 (m, 5H),
2.73–2.77 (m, 2H), 2.40–2.45 (m, 2H), 2.22–2.26 (m, 2H), 1.85–1.91 (m, 2H), 0.90
(t, J ¼ 7.2 Hz, 3H). 13C NMR (150 MHz, CDCl3): d ¼ 8.4, 16.0, 29.7, 30.7, 58.8,
126.3, 126.6, 128.6, 143.5, 211.5. MS (EI, 70 eV): m=z (%) ¼ 188 (11) [Mþ], 131
(100), 103 (94). Anal. calcd. for C13H16O: C, 82.94; H, 8.57. Found: C, 82.65; H,
8.30.
Compound 2d. Oil, IR (film): 2948, 2870, 1675, 1598, 1508, 1236, 1136, 833,
1
613, 539, 506 cmꢁ1. H NMR (600 MHz, CDCl3): d ¼ 6.95–7.74 (m, 8H), 2.92–2.93
(m, 2H), 2.50–2.53 (m, 2H), 2.05–2.08 (m, 1H), 1.91–1.94 (m, 1H). 13C
NMR (150 MHz, CDCl3) : d ¼ 15.9, 32.4, 56.5, 115.4 (d, JC-F ¼ 21.7 Hz), 115.9
(d, JC-F ¼ 21.2 Hz), 127.2 (d, JC-F ¼ 7.8 Hz), 130.4 (d, JC-F ¼ 2.9 Hz), 132.3 (d,
JC-F ¼ 9.2 Hz), 138.8 (d, JC-F ¼ 3.3 Hz), 161.6 (d, JC-F ¼ 244.5 Hz), 165.1 (d,
JC-F ¼ 253.1 Hz), 199.3. MS (EI, 70 eV): m=z (%) ¼ 272 (2) [Mþ], 149 (100). The
spectral data were consistent with Ref. 5c.
Compound 2e. Oil, IR (film): 2946, 2866, 1706, 1512, 1430, 1352, 1244, 1189,
1107, 827, 610, 562, 533 cmꢁ1. 1H NMR (600 MHz, CDCl3): d ¼ 7.12 ꢁ 7.17 (m, 4H),
2.70–2.74 (m, 2H), 2.39–2.42 (m, 2H), 2.34 (s, 3H), 1.92 (s, 3H), 1.85–1.87 (m, 2H).
13C NMR (150 MHz, CDCl3): d ¼ 15.9, 21.0, 24.3, 30.5, 58.9, 126.2, 129.4, 136.4,
140.2, 208.9. MS (EI, 70 eV): m=z (%) ¼ 188 (16) [Mþ], 145 (90), 117 (100). The spec-
tral data were consistent with Ref. 5c.
Compound 2f. Oil, IR (film): 2946, 1738, 1706, 1491, 1353, 1190, 1094, 1013,
1
833, 720 cmꢁ1. H NMR (600 MHz, CDCl3): d ¼ 7.17–7.33 (m, 4H), 2.72–2.76 (m,
2H), 2.35–2.40 (m, 2H), 1.92 (s, 3H), 1.86–1.89 (m, 2H). 13C NMR (150 MHz,
CDCl3): d ¼ 15.8, 24.4, 30.6, 58.8, 127.7, 128.9, 132.7, 141.7, 208.1. MS (EI,
70 eV): m=z (%) ¼ 208 (9) [Mþ], 167 (35), 165 (100). Anal. calcd. for C12H13ClO:
C, 69.07; H, 6.28. Found: C, 68.84; H, 5.99.

REACTION OF METHYLENECYCLOBUTANES AND NXS-H2O
3243
Compound 2g. Oil, IR (film): 2979, 2939, 2874, 1707, 1487, 1460, 1344, 1170,
1077, 1009, 960, 831, 793, 727 cmꢁ1. 1H NMR (600 MHz, CDCl3): d ¼ 7.11–7.47 (m,
4H), 2.72–2.77 (m, 2H), 2.35–2.40 (m, 2H), 2.22–2.26 (m, 2H), 1.84–1.91 (m, 2H),
0.91 (t, J ¼ 7.5 Hz). 13C NMR (150 MHz, CDCl3): d ¼ 8.4, 16.0, 29.8, 30.7, 58.4,
120.6, 128.1, 131.7, 142.5, 210.8. MS (EI, 70 eV): m=z (%) ¼ 267 (3) [Mþ þ 1], 211
(96), 130 (100). Anal. calcd. for C13H15BrO: C, 58.44; H, 5.66. Found: C, 58.17;
H, 5.80.
Compound 5a. Oil, IR (film): 3434, 2988, 2951, 2872, 1492, 1448, 1422, 1299,
1
1243, 1193, 1079, 1025, 915, 747, 700 cmꢁ1. H NMR (600 MHz, CDCl3): d ¼ 7.32–
7.45 (m, 5H), 4.77 (d, J ¼ 4.8 Hz, 1H), 2.62–2.74 (m, 4H), 2.48–2.50 (m, 1H),
2.14–2.19 (m, 1H), 1.53–1.57 (m, 1H). 13C NMR (150 MHz, CDCl3): d ¼ 16.7,
35.6, 37.5, 73.3, 79.1, 127.5, 128.0, 128.2, 139.2. MS (EI, 70 eV): m=z (%) ¼ 240 (2)
[Mþ], 115 (10), 107 (100). Anal. calcd. for C11H13BrO: C, 54.79; H, 5.43. Found:
C, 54.56; H, 5.71.
Compound 5b. Oil, IR (film): 3441, 2993, 2953, 2874, 1491, 1406, 1383, 1091,
1
1014, 825, 798, 732, 672, 541 cmꢁ1. H NMR (600 MHz, CDCl3): d ¼ 7.33-7.39 (m,
4H), 4.75 (s, 1H), 2.64–2.69 (m, 3H), 2.58 (s, 1H), 2.46–2.52 (m, 1H), 2.18–2.22
(m, 1H), 1.59–1.61 (m, 1H). 13C NMR (150 MHz, CDCl3): d ¼ 16.7, 35.5, 37.4,
72.7, 78.5, 128.2, 128.8, 134.0, 137.7. MS (EI, 70 eV): m=z (%) ¼ 275 (1) [Mþ þ 1],
143 (38), 141 (100). Anal. calcd. for C11H12BrClO: C, 47.94; H, 4.39. Found: C,
47.71; H, 4.10.
Compound 5c. Oil, IR (film): 3443, 2991, 2952, 1736, 1469, 1436, 1384, 1240,
1079, 1020, 912, 752, 688 cmꢁ1. 1H NMR (600 MHz, CDCl3): d ¼ 7.20–7.74 (m, 4H),
5.40 (d, J ¼ 4.8 Hz, 1H), 2.63–2.75 (m, 4H), 2.45–2.47 (m, 1H), 2.19–2.23 (m, 1H),
1.67–1.69 (m, 1H). 13C NMR (150 MHz, CDCl3): d ¼ 17.3, 35.0, 37.9, 73.9, 77.3,
124.2, 127.4, 129.4, 129.7, 132.7, 138.4. MS (EI, 70 eV): m=z (%) ¼ 319 (1)
[Mþ þ 1], 187 (90), 185 (100). Anal. calcd. for C11H12Br2O: C, 41.28; H, 3.78. Found:
C, 41.03; H, 3.66.
Compound 5d. Oil, IR (film): 3442, 2992, 2952, 2872, 1638, 1592, 1486, 1424,
1
1403, 1241, 1073, 1027, 1010, 913, 822, 795, 729, 690 cmꢁ1. H NMR (600 MHz,
CDCl3): d ¼ 7.30–7.49 (m, 4H), 4.71 (s, 1H), 2.64–2.65 (m, 4H), 2.47–2.50 (m,
1H), 2.19–2.22 (m, 1H), 1.58–1.62 (m, 1H). 13C NMR (150 MHz, CDCl3):
d ¼ 16.7, 35.5, 37.4, 72.6, 78.5, 122.2, 129.2, 131.1, 138.3. MS (EI, 70 eV): m=z
(%) ¼ 319 (1) [Mþ þ 1], 187 (95), 185 (100). Anal. Calcd for C11H12Br2O: C, 41.28;
H, 3.78. Found: C, 41.08; H, 3.52.
Compound 6. Oil, IR (film): 2990, 2954, 2869, 1679, 1581, 1394, 1281, 1249,
1072, 961, 849 cmꢁ1. 1H NMR (600 MHz, CDCl3): d ¼ 7.59–7.92 (m, 4H), 3.08–3.13
(m, 2H), 2.73–2.78 (m, 2H), 2.41–2.43 (m, 1H), 1.87–1.88 (m, 1H). 13C NMR
(150 MHz, CDCl3): d ¼ 16.5, 36.9, 59.3, 128.5, 131.0, 131.7(d), 193.5. MS (EI,
70 eV): m=z (%) ¼ 316 (2) [Mþ], 185 (100), 157 (26). Anal. calcd. for C11H10Br2O:
C, 41.55; H, 3.17. Found: C, 41.72; H, 3.40.

3244
L. YU ET AL.
ACKNOWLEDGMENTS
This work was supported by the University Natural Scientific Foundation of
Jiangsu Province (No. 09KJB150014), the 45th Postdoctoral Foundation of China
(No. 20090451249), the National Natural Scientific Foundation of China (No.
20633010 and 20773106), and the Natural Scientific Foundation of Jiangsu Province
(No. BK2010321).
REFERENCES
1. For reviews, see (a) Brandi, A.; Cicchi, S.; Cordero, F. M.; Goti, A. Heterocycles from
alkylidenecyclopropanes. Chem. Rev. 2003, 103, 1213–1269; (b) Nakamura, I.;
Yamamoto, Y. Transition metal–catalyzed reactions of methylenecyclopropanes. Adv.
Synth. Catal. 2002, 344, 111–129; (c) Nakamura, E.; Yamago, S. Thermal reactions of
dipolar trimethylenemethane species. Acc. Chem. Res. 2002, 35, 867–877; Selected recent
articles about MCPs, please see (d) Yu, L.; Guo, R. Recent advances on the preparation
and reactivity of methylenecyclopropanes. Org. Prep. Proc. Int. 2011, 43, 209–259; (e) Yu,
L.; Meng, J.-D.; Xia, L.; Guo, R. Lewis acid–catalyzed reaction of methylenecyclopro-
panes with 1,2-diphenyldiselane or 1,2-di-p-tolyldisulfane. J. Org. Chem. 2009, 74,
5087–5089; (f) Miao, M.-Z.; Huang, X. Organo-selenium induced radical ring-opening
intramolecular cyclization or electrophilic cyclization of 2-(arylmethylene) cyclopropylal-
dehyde: A tunable synthesis of 1-naphthaldehydes or 3-oxabicyclo[3.1.0]hexan-2-ols. J.
Org. Chem. 2009, 74, 5636–5639; (g) Hu, B.; Zhu, J.-L. Xing, S.-Y.; Fang, J.; Du, D.;
Wang, Z.-W. A highly site-, regio-, and stereoselective Lewis acid–catalyzed formal
[3 þ 3] cycloaddition of methylenecyclopropane-1,1-diesters with C,N-diarylnitrones.
Chem. Eur. J. 2009, 15, 324–327; (h) Tian, G.-Q.; Li, J.; Shi, M. Thermal rearrangement
of f[2-(arylmethylene)cyclopropyl]methylg(phenyl)sulfanes and selanes. J. Org. Chem.
2008, 73, 673–677.
2. For selected recent articles about VCPs, please see (a) Li, W.; Shi, M. A catalytic method
for the preparation of polysubstituted cyclopentanes: [3 þ 2] cycloaddition of vinylidene-
cyclopropanes with activated olefins catalyzed by triflic imide. J. Org. Chem. 2009, 74,
856–860; (b) Su, C.-L.; Huang, X. Lewis acid-mediated selective cycloadditions of vinyli-
denecyclopropanes with aromatic aldehydes: An efficient protocol for the synthesis of
benzo[c]fluorene, furan, and furo [2,3-b]furan derivatives. Adv. Synth. Catal. 2009, 351,
135–140; (c) Yao, L.-F.; Shi, M. Nd(OTf)3-catalyzed cascade reactions of vinylidenecyclo-
propanes with enynol: A new method for the construction of the 5–7–6 tricyclic frame-
work and its scope and limitations. Eur. J. Org. Chem. 2009, 4036–4040; (d) Lu, J.-M.;
Shi, M. Lewis acid catalyzed reactions of vinylidenecyclopropanes with activated car-
bon–oxygen double bond: A facile synthetic protocol for functionalized tetrahydrofuran
and 3,6-dihydropyran derivatives. J. Org. Chem. 2008, 73, 2206–2210.
3. For a monograph on the chemistry of allenes, please see Krause, N.; Hashmi, A. S. K.
Modern Allene Chemistry; Wiley-VCH: Germany, 2004.
4. For selected recent articles about cyclopropyl allenes, please see (a) Yu, L.; Meng, B.;
Huang, X. Reaction of 1-cyclopropylallenes with phenylselenyl bromide: A highly efficient
and stereoselective method for the preparation of 2-phenylselenyl-6-bromo-1,3-hexa-
dienes. Synlett 2007, 2919–2921; (b) Yu, L.; Meng, B.; Huang, X. Electrophilic addition
to 1-cyclopropylallenes: A highly efficient and stereoselective method for the preparation
of 6-substituted-1,3-hexadienes. Synlett 2008, 1331–1334; (c) Yu, L.; Meng, B.; Huang, X.
Halohydroxylation of 1-cyclopropylallenes: An efficient and stereoselective method for the
preparation of multisubstituted olefins. J. Org. Chem. 2008, 73, 6895–6898; (d) Meng, B.;

REACTION OF METHYLENECYCLOBUTANES AND NXS-H2O
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Yu, L.; Huang, X. Difunctional additions to 1-cyclopropylallenes: An efficient and stereo-
specific method for the synthesis of 2,6-difunctional-1,3-hexadienes. Tetrahedron Lett.
2009, 50, 1947–1950.
5. MCBs could be conveniently prepared through Wittig reaction like MCPs. For details
please see (a) Stafford, J. A.; McMurry, J. E. An efficient method for the preparation
of alkylidenecyclopropanes. Tetrahedron Lett. 1988, 29, 2531–2534; Selected recent arti-
cles about MCBs, please see (b) Jiang, M.; Shi, M. Reactions of monoaryl-substituted
methylenecyclobutanes and methylenecyclopropanes with 1-hydroxybenzotriazole
(HOBt), 1-hydroxy-7-azabenzotriazole (HOAt), and 1-hydroxysuccinimide (HOSu). J.
Org. Chem. 2009, 74, 2516–2520; (c) Jiang, M.; Shi, M. Aluminum chloride-mediated acy-
lation of methylenecyclobutanes: A facile synthetic protocol for the construction of sub-
stituted cyclopentenes. Org. Lett. 2008, 10, 2239–2242; (d) Jiang, M.; Liu, L.-P.; Shi, M.
Reactions of methylenecyclobutanes with silver acetate and iodine. Tetrahedron Lett.
2007, 63, 9599–9604; (e) Li, W.; Shi, M. PhI(OAc)2-mediated additions of 2,4-dinitrophe-
nylsulfenamide with methylenecyclopropanes (MCPs) and a methylenecyclobutane
(MCB). Tetrahedron 2007, 63, 11016–11020; (f) Jiang, M.; Shi, M. Allylic lithiation of
methylenecyclobutanes. Tetrahedron 2008, 64, 10140–10147; (g) Jiang, M.; Shi, M. The
reaction of mono-aryl substituted methylenecyclobutanes with diphenyl diselenide in
the presence of iodosobenzene diacetate and H2O. Tetrahedron 2009, 65, 798–801.
6. (a) Cabanal-Duvillard, I.; Berrien, J.; Royer, J.; Husson, H. Expeditious formal synthesis
of (ꢂ)-epibatidine using diastereoselective bromohydroxylation of aminocyclohexene deri-
vatives. Tetrahedron Lett. 1998, 39, 5181–5184; (b) Rossen, K.; Reamer, R. A.; Volante,
R. P.; Reider, P. J. Mechanistic studies on the diastereoselective halohydroxylation of c-d
unsaturated carboxamides. Tetrahedron Lett. 1996, 37, 6843–6846; (c) Sawyer, D. T.;
Hage, J. P.; Sobkowiak, A. Iron(II)-induced activation of 1:1 HOOH=HCl for the
chlorohydroxylation of olefins and the chlorination of hydrocarbons: Chlorinated fenton
chemistry. J. Am. Chem. Soc. 1995, 117, 106–109.
7. (a) Ma, S.-M.; Hao, X.-S.; Huang, X. Highly regio- and stereoselective four-component
iodoamination of Se-substituted allenes. An efficient synthesis of N-(3-organoseleno-2-
iodo-2(Z)-propenyl) acetamides. Chem. Commun. 2003, 1082–1083; (b) Ma, S.-M.;
Hao, X.-S.; Huang, X. Reversed stereoselectivity in iodohydroxylation of allenyl sulfides:
An efficient synthesis of (Z)-3-organosulfur-2-iodo-2-propenols. Org. Lett. 2003, 5, 1217–
1219; (c) Ma, S.-M.; Ren, H.-J.; Wei, Q. Highly regio- and stereoselective halohydroxyla-
tion reaction of 1,2-allenyl phenyl sulfoxides. Reaction scope, mechanism, and the
corresponding Pd- or Ni-catalyzed selective coupling reactions. J. Am. Chem. Soc. 2003,
125, 4817–4830; (d) Ma, S.-M.; Wei, Q.; Wang, H. Unique selectivity of iodohydroxyla-
tion reaction of allenyl phenyl sulfoxides in aqueous MeCN. A stereodefined synthesis of
(E)-2-iodo-3-hydroxy-1-alkenyl sulfoxides. Org. Lett. 2000, 2, 3893–3895.
8. (a) Yang, Y.-W.; Huang, X. Iodohydroxylation of alkylidenecyclopropanes. An efficient
synthesis of iodocyclopropylmethanol and 3-iodobut-3-en-1-ol derivatives. J. Org. Chem.
2008, 73, 4702–4704; (b) Yang, Y.-W.; Su, C.-L.; Huang, X.; Liu, Q.-Y. Halohydroxyla-
tion of alkylidenecyclopropanes using N-halosuccinimide (NXS) as the halogen source:
An efficient synthesis of halocyclopropylmethanol and 3-halobut-3-en-1-ol derivatives.
Tetrahedron Lett. 2009, 50, 5754–5756.
9. (a) Smith, A. B.; Kanoh, N.; Ishiyama, H.; Hartz, R. A. Total synthesis of (ꢁ)-penitrem
D. J. Am. Chem. Soc. 2000, 122, 11254–11255; (b) Smith, A. B., III; Kanoh, N.; Ishiyama,
H.; Minakawa, N.; Rainier, J. D.; Hartz, R. A.; Cho, Y. S.; Cui, H.; Moser, W. H.
Tremorgenic indole alkaloids. The total synthesis of (-)-penitrem D. J. Am. Chem. Soc.
2003, 125, 8228–8237.
10. Garratt, P. J.; Neoh, S. B. 3-Thiabicyclo[3.2.0]hepta-1,4-dienes: Synthesis of tetraphenyl-
2,5-dithiabisnorbiphenylene. J. Org. Chem. 1975, 40, 970–971.