Indium mediated allylation of β-chloro-/β-alkoxy vinylaldehyde: A facile one pot synthesis of 1-chloro-/1-alkoxy hexa-1,5-diene-3-ol derivatives

Article abstract of DOI:10.1081/SCC-120015553

Indium mediated allylation of β-chloro- or β-alkoxy vinylaldehydes in the presence of sodium iodide produce homoallylic alcohol derivatives (1-chloro-/1-alkoxy hexa-1,5-diene-3-ol derivatives) in good yields.

Full text of DOI:10.1081/SCC-120015553

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
Indium Mediated Allylation of β-Chloro-/β-Alkoxy
Vinylaldehyde: A Facile One Pot Synthesis of 1-
Chloro-/1-Alkoxy Hexa-1,5-diene-3-ol Derivatives
Dipanjan Pan , Gandhi K. Kar & Jayanta K. Ray
To cite this article: Dipanjan Pan , Gandhi K. Kar & Jayanta K. Ray (2003) Indium Mediated
Allylation of β-Chloro-/β-Alkoxy Vinylaldehyde: A Facile One Pot Synthesis of 1-Chloro-/1-
Alkoxy Hexa-1,5-diene-3-ol Derivatives, Synthetic Communications, 33:1, 1-9, DOI: 10.1081/
SCC-120015553
To link to this article: http://dx.doi.org/10.1081/SCC-120015553
Published online: 20 Aug 2006.
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 1, pp. 1–9, 2003
Indium Mediated Allylation of
b-Chloro-/b-Alkoxy Vinylaldehyde: A Facile
One Pot Synthesis of 1-Chloro-/1-Alkoxy
Hexa-1,5-diene-3-ol Derivatives
Dipanjan Pan, Gandhi K. Kar, and Jayanta K. Ray*
Department of Chemistry, Indian Institute of Technology,
Kharagpur, India
ABSTRACT
Indium mediated allylation of b-chloro- or b-alkoxy vinylaldehydes
inthe presecne of sodium iodide produce homoallylic alcohol
derivatives (1-chloro-/1-alkoxy hexa-1,5-diene-3-ol derivatives) in
good yields.
The synthesis of homoallyl alcohol by reaction of allylic organo-
metallic compounds has received wide spread attention.[1] Inthe last
few years indium has emerged as most attractive metal for allyl group
*Correspondence: Jayanta K. Ray, Department of Chemistry, Indian Institute of
Technology, Kharagpur 721 302, India; E-mail: jkray@chem.iikgp.ernet.in.
1
DOI: 10.1081/SCC-120015553
Copyright & 2003 by Marcel Dekker, Inc.
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Pan, Kar, and Ray
Scheme 1.
transfer.[2] In the context of our general interest in the chemistry of
b-chlorovinylaldehydes[3] and exploration of indium mediated allylation
of such compounds, we studied to develop a general method for
1-chloro-/1-alkoxy hexa-1,5-diene-3-ol derivatives.
We have found that an allyl indium reagent generated in situ readily
undergoes regioselective addition to the carbonyl group of the
b-chloro-/b-alkoxy vinylaldehydes in DMF solvent at ambient tempera-
ture (Sch. 1).
Thus when1-chloro-3,4-dihydroanphthaleen-2-aldehyde (
1a) was
treated in DMF, with indium and allyl bromide in presence of NaI, it
produced 15a as a white solid in 64% yield (Entry no. 1). Various other
alkoxy/chloroaldehydes[4] have beensubjected to the same allylation
protocol[5] inorder to assess the generality of our method. The results
are summarised inTable 1.
Inall these cases, the chloroaldehydes ( 2–11) (Entry nos. 4–15) and
alkoxy aldehydes (12–14) (Entry nos. 16–18) undergo facile allylation
when subjected to similar reaction condition. Alkoxy aldehydes (12/14)
could be easily synthesised from b-chloro vinyl aldehydes by treating it
with the corresponding alkoxides (MeOꢀ/allyl-Oꢀ).[4] Ina similar way, b-
allyloxy-2,3-diphenyl-2-propenal (14) onreactionwith allyl idnium
iodide afforded 28 in 61% yield (Entry no. 18). Compound 25 (Entry
no. 13) is obtained in about 4:1 (E:Z) diastereomeric mixture in72%
yield starting from compound 10a. Compound 26 (Entry no. 14) exists
in1:5 ( E:Z) inseparable diastereomeric mixture as indicated by 1H NMR
spectra. Interestingly we found that this reaction provides a very effective
access to novel bis homoallyl alcohols 20–23 (Entry no. 8–11) starting
from appropriate bis chlorovinylaldehydes in moderate to high yield.
1
All the compounds gave satisfactory H NMR, 13C NMR, DEPT, and
elemental analysis data.[6] Studies are inprogress to exploit these
compounds for the synthesis of some novel receptor molecule by ring
closure metathesis reaction.
We have also studied the behavior of propargyl bromide inthis
reaction. It has been observed that chloroaldehydes under the same

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1-Chloro-/1-Alkoxy Hexa-1,5-diene-3-ol Derivatives
3
condition on reaction with propargyl indium iodide afforded a mixture of
homopropargyl alcohols and allenyl alcohols (Sch. 2).
Thus compound 5 under the same reaction condition produced
compound 31 and 32 in1:1.5 ratio in67% overall yield. Similarly 10a
produced 33 and 34 inoverall 67% yield as 1:1 mixture.
Compound 27 has beenfurther silylated to the bis silyl derivatives in
62% yield with Et3SiH inpresence of Spier’s catalyst [7] (H2PtCl6) (Sch. 3).
Further investigation towards the extension of this method to the synth-
esis of novel sol-gel glass by treating allyloxy homoallyl alcohols with
triethoxy silanes [HSi(OEt)3] is underway in our laboratory.
Another advantage of this study is the generation of a tetrahedral
carbon, which could be made chiral under appropriate reaction condition
in presence of chiral ligands such as (ꢀ) sparteine or (ꢀ) cinchonidine. An
initial study shows that reaction of compound 5 with 2 equiv. of indium,
and 3 equiv. of allylbromide in presence of 2 equiv. of (ꢀ) sparteine,
produced respective homoallyl alcohol derivative and the specific rotation
25
d
of the compound ½ꢀŠ was found to be þ35 (c ¼ 0.2, CHCl3). However
this result is not yet optimised and systematic studies on the enantiose-
lective indium mediated allylation of b-chlorovinylaldehydes is under
progress inour laboratory. Furthermore homoallyl alcohols could be
dehydrated by using PTSA in dry benzene to produce novel hexatriene
derivatives. (Sch. 4) It is worthy of mention that hexatriene derivatives
are very important class of organic molecules.
For a specific example, compound 1c whenrefluxed with p-toluene
sulphonic acid in dry benzene as a solvent afforded 36 as a yellow solid in
78% yield.
So, ingeneral we have developed a simple and efficient method for
the synthesis of mono- an dbis-homoallyl alcohols (1-chloro-/1-alkoxy-

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Pan, Kar, and Ray

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1-Chloro-/1-Alkoxy Hexa-1,5-diene-3-ol Derivatives
5

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Pan, Kar, and Ray

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1-Chloro-/1-Alkoxy Hexa-1,5-diene-3-ol Derivatives
7
Scheme 2.
Scheme 3.
Scheme 4.
Scheme 5.
hexa-1,5-diene-3-ol derivatives) which could be further functionalised to
synthesise some interesting designed molecules like macrocyclic oxa-
heterocycles (via ring closure metathesis reaction) or sol-gel glass
(via triethoxysilanes) (Sch. 5).
Our method also opens up the possibility of enantioselective
indium-mediated allylation reaction of b-substituted vinylaldehydes by
performing the reaction in presence of chiral ligands and also provide a
facile entry into the novel substituted hexatriene system.

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Pan, Kar, and Ray
ACKNOWLEDGMENT
Financial support from CSIR, New Delhi is gratefully acknowledged.
REFERENCES
1. (a) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207; (b) Roush,
W.R. In Comprehensive Organic Synthesis; Trost, B.M., Fleming, I.,
Eds.; Pergamon: Oxford, 1991; Vol. 2, Chapter 1; (c) Li, C.-J.
Tetrahedron 1996, 5643; (d) Ranu, B.C. Eur. J. Org. Chem. 2000,
2347; (e) Li, C.J.; Chan, T.H. Tetrahedron 1999, 55, 11149.
2. (a) Cintas, P. Synlett 1995, 1087; (b) Chan, T.-H.; Issac, M.B. Pure
Appl. Chem. 1996, 68, 919; (c) Marshall, J.A. Chemtract.-Org. Chem.
1997, 10, 481; (d) Chauhan, K.K.; Frost, C.G. J. Chem. Soc. Perkin
Trans. 1 2000, 3015; (d) Isaac, M.B.; Paquette, L.A. J. Org. Chem.
1997, 63, 5333; (e) Li, C.-J. Chem. Rev. 1993, 93, 2023; (f ) Yi, X.-H.;
Meng, Y.; Li, C.-J. Tetrahedron Lett. 1997, 38, 4731; (g) Loh, T.-P.,
Li, X.R. Angew. Chem., Int. Ed. Engl. 1997, 36, 980; (h) Hoppe,
H.A.; Lloyd-Jones, G.C.; Murray, M.; Peakman, T.M.; Walsh,
K.E. Angew. Chem. Int. Ed. 1998, 37, 1545; (i) Lloyd-Jones, G.C.;
Russell, T. Synlett 1998, 903.
3. Haldar, M.; Kar, G.K.; Ray, J.K. Synlett 1997, 9, 1057 and the
references cited therein.
4. (a) Ghosh, M.; Mukherjee, R.; Chatterjee, B.G.; Ray, J.K. Ind. J.
Chem. Sec. B 1981, 20, 243; (b) Ray, J.K.; Sharma, S.; Chatterjee,
B.G. Synth. Commun. 1979, 9, 727; (c) Haldar, M.; Kar, G.K.;
Gupta, S.; Ray, J.K. Tetrahedron 2000, 56, 909; (d) Ray, J.K.;
Sharma, S.; Chatterjee, B.G. Synthesis 1980, 4, 326; (e) Ramesh,
D.; Chatterjee, B.G.; Ray, J.K. Ind. J. Chem. 1986, 984; (f) Ray,
J.K.; Kar, G.K.; Chatterjee, B.G. Tetrahedron 1984, 40, 2959; (g)
Ray, J.K.; Gupta, S.; Pan, D.; Kar, G.K. Tetrahedron 2001, 57,
7213; (h) Ray, J.K. Unpublished results. (i)–(k) Chakraborty, A.;
Ray, J.K. Synth. Commun. 1995, 25, 1869; (l) Ray, J.K.
Unpublished results. (m) Sami, M.I.; Kar, G.K.; Ray, J.K.
Tetrahedron 1992, 48, 5199.
5. Typical experimental procedure: A mixture of b-chlorovinylaldehyde
(1 mmol), allyl bromide (3 mmol), indium metal (Sisco Research
Laboratory, India) (2 mmol), sodium iodide (3 mmol) in dimethyl
formamide (4–5 mL) was stirred at 25ꢀC until completion of the reac-
tion(checked by TLC). The reactionmixture was quenched with a

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1-Chloro-/1-Alkoxy Hexa-1,5-diene-3-ol Derivatives
9
few drops of 1N HCl, diluted with water and extracted with diethyl
ether. After usual work up, the crude product obtained was purified
by columnchromatography (silica gel).
6. (a) All compounds gave satisfactory elemental and spectroscopic
1
data; (b) Data of the product 15c. H NMR (CDCl3) ꢀ: 1.9 (brs,
1H), 2.26–2.53 (m, 4H), 2.53–2.74 (m, 2H), 5.04–5.20 (m, 3H),
5.71–5.92 (m, 1H), 6.96 (d, 1H, J ¼ 8.0 Hz), 7.28 (dd, 1H, J ¼ 2.0 &
8.0 Hz), 7.71 (d, 1H, J ¼ 2.0 Hz) ppm; 13C NMR 23.09, 27.12, 39.26,
70.32, 118.39, 120.23, 124.34, 127.42, 128.46, 130.64, 133.58, 134.67,
135.01, 139.27; DEPT 135: 23.09, 27.13, 39.27, 70.31, 118.41, 127.42,
128.48, 130.64, 133.57. DEPT 90: 70.31, 127.41, 128.48, 130.65,
133.57. CHN calcd: C (53.59), H (4.47). Observed: C (53.35), H
1
(4.27). Data of the product 20. H NMR (CDCl3) ꢀ: 1.85 (br, 1H),
2.37–2.50 (m, 4H), 4.81 (m, 2H), 5.16–5.24 (m, 4H), 5.87–5.95 (m,
2H), 6.13 (d, 2H, J ¼ 7.6 Hz), 7.00 (dd, 4H, J ¼ 2.2 & 6.8 Hz), 7.55
(dd, 4H, J ¼ 2.2 & 6.8 Hz) ppm. 13C NMR 40.81, 68.88, 109.90,
118.58, 118.73, 128.13, 128.69, 133.51. CHN calcd: C (66.82), H
(5.57). Observed: C (66.57), H (5.31).
7. Yamaguchi, R. Synth. Commun. 1982, 12, 1027.
Received inthe UK December 13, 2001

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