A vinyl radical cyclization route to hydroxycyclohexene fused carbocycles

Article abstract of DOI:10.14233/ajchem.2016.19465

Some hydroxycyclohexene fused carbocycles derivatives were synthesized from 6-bromo-hepta-1,5-dien-4-ol derivatives using a mediator, tri-n-butyltin hydride (TBTH) and an initiator, azobisisobutyronitrile (AIBN) in refluxing benzene.

Full text of DOI:10.14233/ajchem.2016.19465

Asian Journal of Chemistry; Vol. 28, No. 1 (2016), 233-234
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http://dx.doi.org/10.14233/ajchem.2016.19465
NOTE
A Vinyl Radical Cyclization Route to Hydroxycyclohexene Fused Carbocycles
*
SHILADITYA CHAUDHURI, SUSAMA MAITY, MAHUA ROY, PARAMITA RAY and JAYANTA K. RAY
Department of Chemistry, Indian Institute of Technology, Kharagpur-721 302, India
*Corresponding author: Fax: +91 3222 282252; Tel: +91 3222 283326; E-mail: jkray@chem.iitkgp.ernet.in
Received: 11 July 2015;
Accepted: 11 August 2015;
Published online: 5 October 2015;
AJC-17581
Some hydroxycyclohexene fused carbocycles derivatives were synthesized from 6-bromo-hepta-1,5-dien-4-ol derivatives using a mediator,
tri-n-butyltin hydride (TBTH) and an initiator, azobisisobutyronitrile (AIBN) in refluxing benzene.
Keywords: Allylation, Radical cyclization, Hydroxycyclohexene fused carbocycles.
Radical reactions are now widely used in organic synthesis.
However, deeper insight is still required for its application to
the synthesis of the desired compounds. It is generally accepted
that the rate of homolysis depends on bond dissociation energy
and the homolytic cleavage of O-H bond demands higher
energy than that of C-H bond [1]. Therefore to perform a
radical cyclization or reduction, it is not necessary to protect a
hydroxyl group and sometime radical reaction are carried out
in protic solvent [2,3]. Radical induced cyclizations using tri-
n-butyltin hydride/azobisisobutyronitrile represent alternative
method for building alicyclic or heterocyclic ring. The initial
step of a radical cyclization is the formation of a radical center
on a molecule containing a radicophilic moiety [4].This is the
most crucial step in the process. Padwa et al. [5] have explored
vinyl radical cyclization using N-alkenyl-7-bromo-substituted
hexahydroindolinones.
There are also reports that oxidative radical cyclization
of polyolefinic β-ketoester, a precursor of corresponding ketyl
radical, yielded the steroid analogue via consecutive 6-endo
cyclization [6a].A similar reaction forming a steroidal skeleton
from acyl radical was demonstrated by Pattenden et al. [6b].
However, the preparation of cyclopentenone derivatives by
Heck reaction using Pd(OAc)2 as catalyst was reported from
our laboratory [7].
We wish to report here a TBTH/AIBN mediated cyclization
of 6-bromo-hepta-1,5-dien-4-ol derivatives, which provide a
highly efficient and novel route to hydroxyl cyclohexne fused
carbocycles.
Indium-mediated Barbier-type allylation of bromovinyl
aldehyde was reported earlier [8a-b]. We found that an allyl
indium reagent in situ readily undergoes region selective addi-
tion to the carbonyl group of β-bromo-vinylaldehydes. Here
our goal is to demonstrate an exclusive 6-endo-trig vinyl cycli-
zation of 6-bromo-hepta-1,5-dien-4-ol derivatives as shown
in Scheme-I. It is well known that a radical is commonly
obtained by means of n-Bu3SnH in presence of an initiator
azobisisobutyronitrile.
Typical procedure of cyclization: In a mixture of com-
pound 2a (279 mg, 1 mmol) in super dry and degassed benzene
(30 mL), a solution of AIBN (33 mg, 0.2 mmol) and TBTH
(0.4 mL, 1.5 mmol) in dry and degassed benzene (20 mL) was
added slowly for 2 h. After complete addition, it was refluxed
for 6 h more. The solvent was removed under vacuo and it
was diluted with saturated KF solution (50 mL) in diethylether
(50 mL). It was stirred for 24 h. The organic layer was separated
and washed with water. It was then filtered, dried over Na2SO4.
And finally it was purified by column chromatograph (flash
silica gel) using 10 % ethyl acetate in petroleum ether as eluent.
.
Br
Br
TBTH/AIBN
In/allyl bromide
NaI/DMF
/
{
{
{
{
C6H6/reflux
CHO
OH
OH
OH
Scheme-I

The product was obtained as colourless crystalline solid, m.p.
137 °C. Yield: 124 mg, 62 %.
products is a result of favourable activation enthalpy rather
than activation of entropy. This region selectivity under enthalpy
control is explained by conformation and electronic effects.
The structure of product in one case was supported by X-ray
data in case of β-tetralone as shown in Fig. 1.
We exclusively got 6-endo product when we maintaining
the concentration of the transferring reagent (n-Bu3SnH) is
1.5 mL in 30 mL benzene. The solution of AIBN and TBTH
in dry degassed benzene (20 mL) was added slowly for 2 h in
the solution of compound (1 mol) in dry, degassed benzene. It
was refluxed for 6 h more after complete addition. Purification
of the desired product is problematic, that’s why we purified
the product by flash silica gel chromatography. We took a series
of various types of keto compounds, open chain acetophenone
(Table-1, entry 3), α-tetralone (Table-1, entry 1), cyclopentanone
(Table-1, entry 5), etc. So we got a route to the preparation of
hydroxycyclohexene fused carbocyles from these types of keto
compounds as shown below in Table-1.
TABLE-1
Yield
(%)
Time
(h)
Fig. 1. ORTEP diagram
Entry
1
Substrates
Products
Br
OH
In summary, we have developed an effective TBTH/AIBN
mediated protocol for the cyclization of an un activated olefin
which may be useful for the construction of carbocycles. Further
work is currently underway and will be reported in due courses.
OH
60
62
8
8
1a
1b
HO
HO
ACKNOWLEDGEMENTS
Br
2
The authors are thankful to CSIR, New Delhi for financial
supports.
2b
3b
2a
Br
OH
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OH
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