Cyanuric chloride-dimethylformamide mediated cleavage of cyclopropylcarbinols-synthesis of phenolic antioxidant and construction of a new vinylcyclopropane skeleton

Article abstract of DOI:10.1016/j.tetlet.2014.07.053

Differently substituted cyclopropylcarbinols underwent ring cleavage with easily accessible cyanuric chloride-N,N-dimethylformamide adduct to produce homoallylic chlorides or dienes depending on the nature and location of the substituents. A mechanistic explanation of the aforesaid observations has been provided. A promising antioxidant compound was prepared following this protocol and studied against Fenton's reagent. This methodology was utilized to construct hitherto unreported vinylcyclopropane frameworks bearing homoallylic chloride and diene moieties.

Full text of DOI:10.1016/j.tetlet.2014.07.053

Tetrahedron Letters 55 (2014) 5019–5024
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Cyanuric chloride–dimethylformamide mediated cleavage
of cyclopropylcarbinols-synthesis of phenolic antioxidant
and construction of a new vinylcyclopropane skeleton
Sagar Khan a, Sanchita Roy b, Rimi Roy a, Avishek Ghatak a, Amit Pramanik c, Sanjay Bhar a,
⇑
a Department of Chemistry, Organic Chemistry Section, Jadavpur University, Kolkata 700 032, India
b Department of Chemistry, Basanti Devi College, Kolkata 700 029, India
c Department of Chemistry, Taki Government College, North 24 Pgs 743 429, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Differently substituted cyclopropylcarbinols underwent ring cleavage with easily accessible cyanuric
chloride–N,N-dimethylformamide adduct to produce homoallylic chlorides or dienes depending on the
nature and location of the substituents. A mechanistic explanation of the aforesaid observations has been
provided. A promising antioxidant compound was prepared following this protocol and studied against
Fenton’s reagent. This methodology was utilized to construct hitherto unreported vinylcyclopropane
frameworks bearing homoallylic chloride and diene moieties.
Received 10 April 2014
Revised 14 July 2014
Accepted 15 July 2014
Available online 19 July 2014
Keywords:
Ó 2014 Elsevier Ltd. All rights reserved.
Cyclopropylcarbinol
Cyanuric chloride
Cleavage
Homoallylic chloride
Diene
Cyclopropane framework has drawn considerable interest in
recent times among the synthetic organic chemists not only due
to its occurrence as a subunit of numerous natural products1 but
also for its unique reactivity2 associated with ring strain. Several
important molecular skeletons have been efficiently constructed
utilizing the cleavage of appropriately constituted cyclopropane
motifs in well-defined fashions using a plethora of classical and
upcoming reagents.3 Various electrophilic reagents promote the
so-called ‘edge opening’ of cyclopropane where an electron
deficient centre is initially developed on the cyclopropylcarbinyl
carbon followed by a ring scission.4 As a result, a homoallylic moi-
ety is generated which undergoes subsequent reactions (either
similar kind. This reagent was used over the last few years as an
activator6a during the reduction of carboxylic acid to primary alco-
hol, as a chlorinating agent6b in the preparation of sulfonyl chlo-
rides from sulfonic acids, as
a
coupling agent6c during the
synthesis of hydroxamic acids from carboxylic acids, as a catalyst
for ammonium thiocyanate-mediated solvent-free conversion of
thiiranes6d from oxiranes, as
p
-spacer6e during the synthesis and
photovoltaic studies of donor-p
-acceptor dyes, as a promoter6f
for the labelling of mouse anti-quail IgY with horseradish peroxi-
dase, as a catalyst6g for the Pictet–Spengler reaction with elec-
tron-donating aldehydes and as a reagent6h for activating DMSO
during the structure-dependent conversion of various alcohols to
methylene acetal, thioether, and ene-thioether. TCT in combination
with DMF was utilized as a mild chlorinating agent for the conver-
sion of alcohols and b-aminoalcohols to the corresponding alkyl
chlorides,7a regioselective synthesis of unsymmetrical allyl
chlorides through ipso- and tele-substitution7b and construction
of 2-azetidinone7c moieties. Inspired by the aforesaid literature
precedence we initiated a detailed investigation on the cleavage
of differently substituted cyclopropylcarbinols with TCT–DMF
adduct7a at room temperature.
attack by the nucleophiles4a–c or reductive transformations4d
)
depending on the composition of reagents. Dehydrative ring open-
ing of cyclopropylcarbinols under thermal,5a ionic liquid-catalysed
sonochemical condition5b and indium triflate catalysed reaction5c
produce 1,3-dienes.
Recently, cyanuric chloride (2,4,6-trichloro-1,3,5-triazine, to be
called TCT hereafter) has come out as an efficient solid reagent for
important organic transformations. It can be conveniently handled
and it is relatively less toxic compared to many other reagents of
Different chalcones were prepared through the base-promoted
condensation of substituted aryl methyl ketones with various aryl
aldehydes in the presence of alcoholic NaOH8a and subsequently
cyclopropanated using dimethylsulfoxonium methylide which
⇑
Corresponding author.
E-mail addresses: sanjaybharin@yahoo.com, sanjay_bhar@chemistry.jdvu.ac.in
(S. Bhar).
http://dx.doi.org/10.1016/j.tetlet.2014.07.053
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

5020
S. Khan et al. / Tetrahedron Letters 55 (2014) 5019–5024
OH
Homoallylic chlorides have attracted the attention of synthetic
organic chemists due to their versatility as substrates in organic
synthesis,12a occurrence as sub-units of many natural and unnatu-
ral products12b–e and important applications in pharmaceutical
and agrochemical industries.12f But there are only a few reports13
for the synthesis of homoallylic chlorides which have limited
applicability due to the tedious experimental set-up and vulnera-
bility of the products to further side reactions. Preparation of
homoallylic chlorides from appropriate homoallylic alcohols often
leads to the formation of complex mixture of products due to
allylic rearrangement and polymeric decomposition. The present
method provides an easy access to unsymmetrical homoallylic
chlorides from easily accessible precursors using commercially via-
ble reagents.
G1
O
G2
1a - 1r
Cl
N
NMe2
H
,
N
N
CH2Cl2 , rt
Cl
Cl
G2
G2
or
G1
G1
3a - 3h
Cl
2a - 2j
Scheme 1. Reaction of 1 with TCT–DMF.
was generated by the deprotonation of trimethylsulfoxonium
iodide with alkali under phase transfer condition using a phase
transfer catalyst.8b Further reduction of the cyclopropyl ketones
with methanolic sodium borohydride at room temperature pro-
duced the cyclopropylcarbinols 1 with appropriately substituted
aryl rings at the carbinol carbon as well as one of the cyclopropyl
carbons. Differently substituted cyclopropylcarbinols 1 reacted
with easily accessible TCT–DMF adduct7a in anhydrous dichloro-
methane to produce the homoallylic chlorides or dienes depending
on the electronic nature and location of the substituents
(Scheme 1). Results are presented in Table 1.
As with 1a having no substituent at the aromatic ring (entry 1),
cyclopropylcarbinols (1b, 1c, 1g and 1h) bearing electron-donating
groups at the aromatic ring of the carbinol centre produced the
corresponding homoallylic chlorides 2b, 2c, 2g and 2h in good
yields (entries 2, 3, 7 and 8). It is important to note that 1d (with
electron-withdrawing substituent at the aromatic ring connected
to the carbinyl carbon) underwent the cleavage of cyclopropane
ring to produce 2d. Compounds 1e–1h bearing electron-withdraw-
ing groups at the aromatic ring attached to the cyclopropane ring
also produced the corresponding homoallylic chlorides 2e–2h in
good yields. Homoallylic chlorides 2i and 2j were also obtained
from the compounds 1i and 1j, carrying an electron donating group
(OMe) at the m- and o-positions respectively of the aromatic sub-
stituent of the cyclopropane motif. Notable advantages of the pres-
ent method seem to be an exclusive formation of ring-cleaved
products without detectable (by 1H NMR) formation of the cyclo-
propyl products arising out of normal substitution and cyclobutyl
derivatives by the Demjanov rearrangement through the interme-
diacy of non-classical carbonium ions.11
Interestingly, in the substrates where the cyclopropyl moiety
carried an aromatic ring with the electron-donating group at p-
position (1k–1r), conjugated dienes (3a–3h) were obtained exclu-
sively instead of the homoallylic chlorides (entries 11–18 in
Table 1). Conjugated dienes and polyenes are not only present as
a structural sub-unit in many bio-active natural products14a but
also have immense potential for the design of optical power limit-
ing organic materials used to manufacture various laser safety
devices.14b,c 1,3-Butadiene moiety serves as a versatile building
block for the construction of complicated molecular skeletons
through the Diels–Alder reaction.14d Although there are literature
reports5,10,15 for the synthesis of 1,3-dienes, yet many of them
involve exotic and toxic reagents. As shown in Table 1, the present
protocol provides a facile and cost-effective access to a number of
structurally and functionally important10a–e dienes [entries 11, 12,
14–16] without using exotic reagents5 and complicated experi-
mental procedure. The acid-labile moieties like benzyl (entry 13)
and methylenedioxy (entries 16–18) survived during the said
transformation. In every occasion, the diene 3 was obtained from
the cyclopropylcarbinol with the aromatic ring carrying an O-alkyl
substituent at p-position irrespective of whether the carbinyl car-
bon carries an aromatic ring with electron-donating (entries 12,
13, 17) or electron withdrawing (entries 14, 15, 18) substituents
at p-position. The cyclopropylcarbinol 1g produced the homoallylic
chloride 2g on treatment with TCT–DMF (entry 7). In contrast to
the aforesaid observation, the isomeric cyclopropylcarbinol 1o
(with the positions of electron-donating and electron-withdrawing
groups interchanged) produced the diene 3e (entry 15) instead of
the corresponding homoallylic chloride. Apart from the distinction
by 1H NMR signals, the formation of diene 3e was further
Table 1
Reaction of cyclopropylcarbinol 1 with TCT–DMF
Entry
G1, G2
Substrate (1)
Product (2/3)
Time (h)/yielda (%)
1
2
3
4
5
H, H
4-OMe, H
4-Me, H
4-NO2, H
H, 4-Cl
H, 4-NO2
1a
1b
1c
1d
1e
1f
2a
2b
2c
2d
2e
2f
4/889
5/82
5/84
4/80
7/79
6
4/81
7
8
9
4-OMe, 4-NO2
4-OMe, 4-Cl
H, 3-OMe
1g
1h
1i
2g
2h
2i
4/87
5/86
6/80
10
11
12
13
14
15
16
17
18
H, 2-OMe
H, 4-OMe
1j
1k
1l
1m
1n
1o
1p
1q
1r
2j
6/79
3a
3b
3c
3d
3e
3f
12/8310a
12/8110b
15/76
14/8010c
14/8210d
12/7510e
12/78
11/81
4-OMe, 4-OMe
4-OMe; 3-OMe, 4-OCH2Ph
4-Cl, 4-OMe
4-NO2, 4-OMe
H, 3,4-OCH2O–
4-OMe, 3,4-OCH2O–
4-NO2, 3,4-OCH2O–
3g
3h
a
Yield refers to isolated pure products fully characterized spectroscopically.

S. Khan et al. / Tetrahedron Letters 55 (2014) 5019–5024
5021
OH
OH
established from the UV analysis, which showed a strong band
with kmax at 401.83 nm ( 15,210) for
p⁄ transition due to the
development of extended conjugation. So, it is evident that
although the initial cleavage pattern of the cyclopropane ring
remains uniform irrespective of the nature and location of the sub-
stituents in the aryl rings yet the final outcome of the reaction is
critically dictated by the two aforesaid factors.
TCT-DMF
CH2Cl2, rt
OMe
e
p–
OMe
MeO
1s
OTBDMS
8
MeO
Scheme 3. Synthesis of compound 8.
Cyclopropylcarbinol 416 carrying the COOCH3 group (an elec-
tron-withdrawing substituent) at the ring carbon under similar
treatment neither produce any homoallylic chloride nor the diene
(as evident from its 1H NMR spectrum); rather, cyclopropane ring
remained intact with the formation of chloro substituted product
5 (Scheme 2).
initially developed electron-deficient centre from the cyclopropane
ring in 6, the electron-withdrawing group (like –COOCH3) cannot
assist in this way; rather it impedes this initial electron donation.
So the cyclopropane ring in 4 survives in this reaction and it is con-
verted to the corresponding chloride 5 (Scheme 2) through usual
nucleophilic substitution.7a
A plausible mechanism is presented in Figure 1 to account for
the effect of the substituents towards the reaction outcome. The
relief of strain in the cyclopropane ring due to its opening to the
acyclic system along with the attainment of the extended conjuga-
tion of the newly developed double bond with the aromatic moiety
seems to be the driving force for this transformation. According to
Figure 1, cyclopropylcarbinol 1 reacts with TCT–DMF adduct7a to
produce 6 where a partial electron deficiency at the carbinol centre
is developed. Concomitant cleavage of the cyclopropane ring in 6
with departure of DMF as a leaving group forms carbocation 7 as
an intimate ion pair. Compound 2 is obtained from 7 through the
capture of Clꢀ. When the carbocation 7 is mesomerically stabilized
by the electron-donating substituent G2 located at the p-position
(canonical 70), development of more positive charge on a carbon
makes the adjacent C–H bonds of the –CH2– moiety in 7 more
acidic. Therefore, subsequent deprotonation even under weakly
basic condition yields the diene 3. As the cleavage of the cyclopro-
pane ring is triggered by the supply of electron density to the
Development of various cardiovascular and malignant diseases
is often linked to the processes associated with damages of biolog-
ical systems caused by reactive oxygenated species. Naturally
occurring phenolic antioxidants such as vitamin E,17a curcumin17b,c
and resveratrol17d as well as synthetic analogues such as BHT17a
prevent radical reactions by terminating radical chain mechanisms
which are responsible for cellular damage and oxidative spoilage
both in vivo and in vitro. Radicals abstract a hydrogen atom from
the phenolic OH group of the antioxidant and form a resonance-
stabilized phenoxy radical which halts the oxidation process. The
antioxidative17e and antiproliferative17f properties and inhibitory
capacity of such compounds are critically dictated by the number
and position of hydroxyl groups as well as the presence of certain
chemical groups and double bond(s) at particular locations. A phe-
nolic compound where the resultant phenoxy radical would be fur-
ther stabilized due to extended conjugation through a diene
moiety along with an aptly placed dative OMe group might be
Cl
NMe2
H
,
N
N
OH
Cl
N
Cl
Cl
O
COOMe
COOMe
CH2Cl2 , rt
5
4
Scheme 2. Survival of cyclopropane ring.
OH
Cl NMe2
H
NMe2 Cl
H
N
N
O
N
OH
N
Cl
Cl
Cl
N
NMe2
O
+
N
N
+
G1
N
N
G2
1
G1
H
O
Cl
Cl
G2
Cl
Cl
6
H
H
G2
NMe2
G2
+
G1
G1
Cl
H
O
7
2
Cl
OH
N
N
G2 is +R group
at p-position
N
Cl
Cl
..
G2
G2
OH
H
H
+
N
N
Cl
Cl
G1
G1
Cl
7'
N
H
3
Cl
Figure 1. Mechanistic explanation for the substituent effect.

5022
S. Khan et al. / Tetrahedron Letters 55 (2014) 5019–5024
Figure 2. (a) Fluorescence spectrum of 8 and (b) UV spectra of A: 8 and B1 to B14: 8 after treatment with Fenton’s reagent at 10 sec interval.
OH
damage to almost any biomolecule such as proteins, lipids and
nucleic acid. So the reactivity of compound 8 was studied against
(CH2)n
9a-9i
Fenton’s reagent mimicking the biological generation of radicals.
The reaction was monitored with UV spectroscopy and the result
is presented in Figure 2b. Compound 8 gave a strong UV absorption
G
G
Cl
NMe2
H
N
N
CH2Cl2 , rt
(A) at k 348 nm (e 7464) due to p–
p⁄ transition which immediately
N
,
Cl
Cl
O
disappeared after adding Fenton’s reagent (B1). This clearly indi-
cates that compound 8 reacts instantly with Fenton’s reagent and
bears the promise of showing strong antioxidant activity against
radical generating species analogous to biological system. It might
have the potential to be used as a preventive for lipid peroxidation
and preservation of fat molecules to increase their shelf lives.
As a continuation of the aforesaid investigations and to elabo-
rate the synthetic potential of the present protocol, symmetrical
bis-cyclopropylcarbinols (9) with differently substituted aryl moi-
eties were reacted with TCT–DMF complex. One of the cyclopro-
pane rings in 9 was selectively cleaved leaving behind the other
intact (Scheme 4) and resulted in novel structural backbones with
vinylcyclopropane motif. The products were either homoallylic
chlorides (10) or dienes (11) depending on the electronic nature
of the substituents (Table 2). Neither such cyclopropyl-substituted
homoallylic chlorides (10) nor the cyclopropyl dienes (11) have
any literature precedence till date to the best of our knowledge.
The presence of cyclopropane rings in 10 and 11 was confirmed
from their 1H and 13C NMR spectra (See Supplementary material).
The novel structural framework of these compounds was conclu-
sively established by the single crystal X-ray diffraction study of
11d (Fig. 3), where the simultaneous occurrence of the cyclopro-
pane (C6–C7–C20) and the diene (C8–C11) moieties is clearly evi-
dent. Compounds 10b, 10d, 11b and 11d carried structurally
important spiro [2.5]-oct-4-ene framework with immense
possibility for further synthetic transformations leading to the
G
G
Cl
or
(CH2)n
11a-11e
(CH2)n
10a-10d
G
G
Scheme 4. Cleavage of bis-cyclopropylcarbinols.
expected to act as an efficient radical chain terminator. Such a
compound 8, which did not have any literature precedence, has
been elegantly synthesized following the aforesaid protocol as
delineated in Scheme 3. In general, TBDMS remains unaffected
with TCT–DMF for phenol. But it is cleaved in the present system
due to the higher nucleophilicity of Clꢀ in aprotic nonpolar med-
ium and greater nucleofugality of the resultant phenol 8 due to
extended conjugation.
Compound 8 was strongly fluorescent at k 403 nm with fluores-
cent intensity 250 a.u. (Fig. 2a).
Fenton’s reaction18a is important in biology as it involves the
creation of free radicals by chemicals present in vivo.18b Transition
metal ions like iron and copper donate or accept free electrons via
intracellular reactions and create free radicals promoting free rad-
ical damage.
Hydrogen peroxide is weakly active to initiate lipid peroxida-
tion, but its activity as an ‘active oxygen’ species is profoundly
increased due to the production of highly reactive hydroxyl radical
through the Fenton’s reaction which is responsible for oxidative
Table 2
Cleavage of bis-cyclopropylcarbinols 9 with TCT–DMF
Entry
n, G
Substrate (9)
Product (10/11)
Time (h)/yielda (%)
1
2
3
4
5
6
7
8
9
0, 4-Cl
3, 4-Cl
0, 4-Me
3, 4-Me
0, 4-OMe
3, 4-OMe
0, 3,4-(OMe)2
3, 3,4-(OMe)2
0, 3, 4(–OCH2O–)
9a
9b
9c
9d
9e
9f
9g
9h
9i
10a
10b
10c
10d
11a
11b
11c
11d
11e
12/86
12/82
14/85
14/86
15/82
15/87
15/86
15/89
15/83
a
Yield refers to isolated pure products fully characterized spectroscopically.

S. Khan et al. / Tetrahedron Letters 55 (2014) 5019–5024
5023
Figure 3. Ortep diagram of compound 11d.19
3. (a) Min, S.-J.; Danishefsky, S. J. Tetrahedron Lett. 2008, 49, 3496–3499; (b)
Sethofer, S. G.; Staben, S. T.; Hung, O. Y.; Toste, F. D. Org. Lett. 2008, 10, 4315–
4318; (c) Simone, F. D.; Andres, J.; Torrosantucci, R.; Waser, J. Org. Lett. 2009, 11,
1023–1026; (d) Tsuritani, T.; Yamamoto, Y.; Kawasaki, M.; Mase, T. Org. Lett.
2009, 11, 1043–1045; (e) Stokes, S.; Spears, B.; Lascter, C.; Barker, B.; Mead, K.
T. Tetrahedron Lett. 2010, 51, 4003–4006; (f) Yuan, C.; Jiao, L.; Yu, Z.-X.
Tetrahedron Lett. 2010, 51, 5674–5676; (g) Trost, B. M.; Nguyen, H. M.; Koradin,
C. Tetrahedron Lett. 2011, 52, 2033–2036; (h) Fu, Q.; Yan, C.-G. Tetrahedron Lett.
2011, 52, 4497–4500; (i) Gopinath, P.; Chandrasekaran, S. J. Org. Chem. 2011, 76,
700–703; (j) Ganesh, V.; Sureshkumar, D.; Chandrasekaran, S. Angew. Chem.,
Int. Ed. 2011, 50, 5878–5881; (k) Kruger, S.; Gaich, T. Beilstein J. Org. Chem. 2014,
10, 163–193.
4. (a) Miller, R. D.; Mckean, D. R.; Kaufmann, D. Tetrahedron Lett. 1979, 587–590; b
Caputo, R.; Ferreri, C.; Palumbo, G.; Wenkert, E. Tetrahedron Lett. 1984, 577–
578; (c) Fu, W.; Huang, X.; Lin, Y. Synlett 2007, 321–323; (d) Krief, A.; Dumont,
W.; Baillient, D. Synlett 2005, 2688–2690.
5. (a) Patro, B.; Ila, H.; Junjappa, H. Tetrahedron Lett. 1992, 33, 809–812; (b) Ranu,
B. C.; Banerjee, S.; Das, A. Tetrahedron Lett. 2006, 47, 881–884; (c) Ranu, B. C.;
Banerjee, S. Eur. J. Org. Chem. 2006, 13, 3012–3015.
6. (a) Falorni, M.; Porcheddu, A.; Taddei, M. Tetrahedron Lett. 1999, 40, 4395–
4396; (b) Blotny, G. Tetrahedron Lett. 2003, 44, 1499–1501; (c) Giacomelli, G.;
Porcheddu, A.; Salaris, M. Org. Lett. 2003, 5, 2715–2717; (d) Bandgar, B. P.; Joshi,
N. S.; Kamble, V. T. Tetrahedron Lett. 2006, 47, 4775–4777; (e) Liu, J.; Wanga, K.;
Xu, F.; Tang, Z.; Zheng, W.; Zhang, J.; Li, C.; Yu, T.; You, X. Tetrahedron Lett. 2011,
52, 6492–6496; (f) Kassim, N.; Mtenga, A. B.; Shim, W.-B.; Chung, D.-H. J.
Microbiol. Biotech. 2013, 23, 527–533; (g) Sharma, A.; Singh, M.; Rai, N. N.;
Sawant, D. Beilstein J. Org. Chem. 2013, 9, 1235–1242; (h) Chaudhuri, S. K.;
Pramanik, A.; Roy, R.; Khan, S.; Ghatak, A.; Bhar, S. J. Ind. Chem. Soc. 2013, 90,
1773–1780.
7. (a) Luca, L. D.; Giacomelli, G.; Porcheddu, A. Org. Lett. 2002, 4, 553–555; (b) Roy,
S.; Das, T.; Saha, M.; Chaudhuri, S. K.; Bhar, S. Synth. Commun. 2007, 37, 4367–
4370; (c) Zarei, M.; Jarrahpour, A. Synlett 2011, 2572–2576.
8. (a) Vogel, A. I. A. Textbook of Practical Organic Chemistry, 5th ed.; ELBS, 1989,
1034, Longman Scientific and Technical, Longman Group UK limited, Longman
House, Essex, CM202JE, England.; (b) Patro, B.; Deb, B.; Ila, H.; Junjappa, H. J.
Org. Chem. 1992, 57, 2257–2263.
9. Caputo, R.; Ferriri, C.; Palumbo, G. Tetrahedron Lett. 1984, 25, 577–578.
10. (a) Yamashita, M.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2010, 12, 592–595;
(b) Weber, M.; Singh, F. V.; Vieira, A.; Stefani, H. A.; Paixo, M. W. Tetrahedron
Lett. 2009, 50, 4324–4327; (c) Wang, X.; Wang, D. Z. Tetrahedron 2011, 67,
3406–3411; (d) Vangala, V. R.; Bhogala, B. R.; Dey, A.; Desiraju, G. R.; Border, C.
K.; Smith, P. S.; Mondal, R.; Howard, J. A. K.; Wilson, C. C. J. Am. Chem. Soc. 2003,
125, 14495–14509; (e) Riberio, N.; Fetzer, L.; Streiff, S.; Desaubry, L. Synlett
2010, 2928–2930.
11. March, J. Advanced Organic Chemistry, Reactions, Mechanisms and Structures,
4th ed.; John Wiley and Sons: New York, 1999–2000, pp 1075–1077.
12. (a) Jung, M. E.; Fahr, B. T.; D’Amic, D. C. J. Org. Chem. 1998, 63, 2982–2987; (b)
Aruna Verma, K. M.; Wadhawa, S. K. Curr. Sci. 1981, 50, 223–225; (c) Larson, G.
L.; Prieto, J. A.; Valle, L. Synth. Commum. 1989, 19, 1405–1412; (d) Troyanov, S.
I.; Popov, A. A. Angew. Chem., Int. Ed. 2005, 44, 4215–4218; (e) Kitagawa, T.; Lee,
Y.; Masaoka, N.; Komatsu, K. Angew. Chem., Int. Ed. 2005, 44, 1398–1401; (f)
Biernacki, W.; Gadula, A. Pol. J. Chem. 1981, 55, 849–854.
construction of novel molecular backbones. Further transforma-
tions on the remaining cyclopropane motif do not occur under
the present reaction condition owing to very mild electrophilic
character of TCT–DMF adduct. So the present protocol provides a
facile access to an unprecedented and structurally novel molecular
framework with immense synthetic potential for future
exploration.
An efficient and mild protocol for the synthesis of homoallylic
chlorides and conjugated dienes of structural and functional impor-
tance has been developed utilizing the cleavage of appropriately
substituted cyclopropylcarbinols using economically viable and
easily accessible TCT–DMF adduct. One such newly synthesized
phenolic diene described promising antioxidant activity. This
method was elegantly extended towards the construction of novel
and unprecedented molecular skeletons bearing cyclopropane ring
having immense potential for further synthetic transformations
through selective cleavage of symmetrical bis-cyclopropylcarbinols.
Acknowledgements
The authors express sincere gratitude to Dr. K. K. Rajak, Dr. A.
Sasmal, Mr. S. Saha, Mr. A. Hens and Mr. J. Poddar of Jadavpur
University and Mr. N. Dutta of IACS for instrumental, technical
and analytical assistance. Financial and infrastructural supports
from the Council of Scientific and Industrial Research, New Delhi,
Government of India (CSIR Grant No. 01(2383)/10/EMR-II),
DST-FIST programme and DST-PURSE-programme at Jadavpur
University are gratefully acknowledged. R. R. and A. G. thank CSIR
and. S. K. thank UGC, New Delhi, Government of India for senior
research fellowships. The authors thank Ms. S. Maitra and Ms. M.
Bhattacharyya for initial studies.
Supplementary data
Supplementary data (general experimental procedure and the
characterization data of the final compounds) associated with this
article can be found, in the online version, at http://dx.doi.org/
10.1016/j.tetlet.2014.07.053.
13. (a) Siriwardana, A. I.; Nakamura, I.; Yamamoto, Y. Tetrahedron Lett. 2003, 44,
985–987; (b) Wong, K. T.; Hung, Y.-Y. Tetrahedron Lett. 2003, 44, 8033–8036.
14. (a) Stille, J. K. J. Am. Chem. Soc. 1987, 109, 813–817; (b) Spangler, C. W. J. Mater.
Chem. 1999, 9, 2013–2020; (c) Elbing, M.; Bazon, G. C. Angew. Chem., Int. Ed.
2008, 47, 834–838; (d) Dell, C. P. J. Chem. Soc. Perkin Trans. 1998, 3873–3905.
15. (a) Jin, C. K.; Yamada, T.; Sano, S.; Shiro, M.; Nagao, Y. Tetrahedron Lett. 2007, 48,
3671–3675; (b) Yamamoto, Y. Synlett 2007, 1913–1916; (c) Kirai, N.;
Yamamoto, Y. Eur. J. Org. Chem. 2009, 12, 1864–1867; (d) Dong, D.-J.; Li, H.-
H.; Tian, S. K. J. Am. Chem. Soc. 2010, 132, 5018–5020; (e) Hintermann, L.;
Schumitz, M.; Chen, Y. Adv. Synth. Catal. 2010, 352, 2411–2415.
16. Chaudhuri, S. K.; Saha, M.; Saha, A.; Bhar, S. Beilstein J. Org. Chem. 2010, 6, 748–
755.
17. (a) Burton, G. W.; Ingold, K. U. J. Am. Chem. Soc. 1981, 103, 6472–6477; (b) Ross,
C.; Barclay, L.; Vinqvist, M. R.; Mukai, K.; Goto, H.; Hashimoto, Y.; Tokunaga, A.;
Uno, H. Org. Lett. 2000, 2, 2841–2843; (c) Priyadarshini, K. I.; Maity, D. K.; Naik,
References and notes
1. (a) Donaldson, W. A. Tetrahedron 2001, 57, 8589–8627; (b) Roberts, I. O.; Baird,
M. S.; Liu, Y. Tetrahedron Lett. 2004, 45, 8685–8686; (c) Cheeseman, M.; Bull, S.
D. Synlett 2006, 1119–1121; (d) Saling, H.; Piva, O. Tetrahedron Lett. 2007, 48,
2059–2062; (e) Loannon, E.; Vagias, C.; Roussis, V. Tetrahedron Lett. 2011, 52,
3054–3056; (f) Oikawa, M.; Sasaki, S.; Sakai, M.; Sakai, R. Tetrahedron Lett.
2011, 52, 4402–4404.
2. (a) Lifchits, O.; Charette, A. B. Org. Lett. 2008, 10, 2809–2812; (b) Ding, Q.;
Wang, Z.; Wu, J. Tetrahedron Lett. 2009, 50, 198–200; (c) Meng, B.; Yu, L.;
Huang, X. Tetrahedron Lett. 2009, 50, 1947–1950; (d) Zeigler, D. T.; Steffens, A.
M.; Fung, T. W. Tetrahedron Lett. 2010, 51, 6726–6729; (e) Chagarovskiy, A. O.;
Ivanova, O. A.; Budynina, E. M.; Trushkov, I. V.; Melnikov, M. Y. Tetrahedron Lett.
2011, 52, 4421–4425.

5024
S. Khan et al. / Tetrahedron Letters 55 (2014) 5019–5024
G. H.; Sudheer Kumar, M.; Unnikrishnan, M. K.; Satav, J. G.; Mohan, H. Free
19. CCDC 990554 contains the supplementary crystallographic data for this paper.
These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/
conts/retrieving.html (or from the Cambridge Crystallographic Data Centre, 12
Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033; e-mail:
deposit@ccdc.cam.ac.uk).
Radic. Biol. Med. 2003, 35, 475–484; (d) Hussein, M. A. Int. J. Phytomed. 2011, 3,
459–469; (e) Rice-Evans, C. A.; Miller, N. J.; Paganga, G. Free Radic. Biol. Med.
1996, 20, 933–956; (f) Sartor, L.; Pexxato, E.; Dell’Aica, I.; Caniato, R.; Beggin, S.;
Garbisa, S. Biochem. Pharmacol. 2002, 64, 229–237.
18. (a) Walling, C. Acc. Chem. Res. 1975, 8, 125–131; (b) Kumar, V.; Fausto, N.;
Abbas, A. Robbins and Cotran Pathogenic Basis of Disease, 7th ed.; Elsevier,
2008, p 16, ISBN 9780808923022.