Intramolecular gold(III) catalysed Diels-Alder reaction of 1-(2-furyl)-hex-1-en-5-yn-3-ol derivatives: A short and generalised route for the synthesis of hydroxyphenanthrene derivatives

Article abstract of DOI:10.1016/j.tetlet.2012.01.018

Gold(III) catalysed intramolecular Diels-Alder reaction of various 1-(2-furyl)-hex-1-en-5-yn-3-ol derivatives has been studied to synthesise hydroxyphenanthrenes and other polynuclear aromatic hydroxyl compounds. The required precursors were synthesised by indium mediated propargylation of suitable β-furyl-α,β-unsaturated aldehydes.

Full text of DOI:10.1016/j.tetlet.2012.01.018

Tetrahedron Letters 53 (2012) 1376–1379
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Intramolecular gold(III) catalysed Diels–Alder reaction of 1-(2-furyl)
-hex-1-en-5-yn-3-ol derivatives: a short and generalised route
for the synthesis of hydroxyphenanthrene derivatives
⇑
⇑
Khokan Samanta, Gandhi K. Kar , Achintya K. Sarkar
Department of Chemistry and Biochemistry, Presidency University (Formerly Presidency College), 86/1 College Street, Kolkata 700073, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Gold(III) catalysed intramolecular Diels–Alder reaction of various 1-(2-furyl)-hex-1-en-5-yn-3-ol deriva-
tives has been studied to synthesise hydroxyphenanthrenes and other polynuclear aromatic hydroxyl
compounds. The required precursors were synthesised by indium mediated propargylation of suitable
Received 16 November 2011
Revised 3 January 2012
Accepted 5 January 2012
Available online 14 January 2012
b-furyl-a,b-unsaturated aldehydes.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Hydroxyphenanthrene derivatives
Polynuclear aromatic hydroxyl compound
Intramolecular Diels–Alder reaction
Gold(III) catalysed reaction
Homopropargylic alcohols
Since the discovery of phenanthrene in coal tar and the elucida-
tion of its structure1a many synthetic strategies and methodologies
have been explored for the preparation of it and its derivatives.
Motivation for these studies has been provided by the fact that
many naturally occurring compounds of biological and therapeutic
interest contain a phenanthrene or reduced phenanthrene moiety.
Ample methods have been developed for their synthesis, but per-
haps the most convenient method is the classical Haworth1b
synthesis.
Retro synthetic analysis of these phenanthrene/dihydrophenanth-
rene derivatives reveals that an intramolecular Diels–Alder reaction
of furan and alkene functionality in 4 may be a key step for the con-
struction of the tricyclic arene moiety. b-Furyl-a,b-unsaturated
aldehydes (3) are the suitable precursors of such compounds (4)
(Scheme 1). Synthesis of such aldehydes has already been described
in our earlier publication3a and herein we report the utilisation of
the process for the synthesis of substituted phenanthrene
derivatives.
A large number of new polyhydroxy or polymethoxyphenanth-
renes and their 9,10-dihydro derivatives, phenanthropyrans and
pyrones and their 9,10-dihydroderivatives, etc. have been isolated
by Majumder and his co-workers2 from high altitude Himalayan
orchids. The polyoxygenated phenanthrene derivatives are poten-
tial antimitotic compounds, while some of these were found to
be endogenous plant growth regulators.2 Several of the 9,10-
dihydrophenanthrene derivatives were also found to exhibit pro-
nounced phytoalexin properties.2 Some of the representative
examples of naturally occurring phenanthrene and their 9,10-
dihydro derivatives are given in Figure 1.
Indium mediated allylation of aldehyde derivatives is well
established in the literature4 for the synthesis of homoallylic alco-
hols. Using this method the homoallylic alcohols 4(a–d), precur-
sors for intramolecular Diels–Alder reaction, were prepared
(Scheme 2). Thus reaction of b-furyl-a,b-unsaturated aldehydes
3(a–d) with allylbromide in the presence of indium metal and
NaI in DMF afforded the alcohols 4(a–d) in a very good yield. The
results have been summarised in Table 1. But the intramolecular
Diels–Alder reaction5 of the homoallyl alcohols 4 to produce the
Diels–Alder adduct was unsuccessful even after several attempts
including heating in sealed tubes. The product mixture contained
a large number of components which, however we failed to isolate
in pure form for characterisation. Thus the scheme was abandoned.
Recently Hashmi and his co-workers6 reported AuCl3 catalysed
intramolecular Diels–Alder reaction between a furan ring and a
terminal alkyne unit to produce highly substituted phenols. Then
we have successfully applied this protocol on the corresponding
homopropargylic alcohols (7) to achieve the synthesis of various
substituted hydroxyphenanthrenes (Scheme 3).
Having been inspired by the importance of this naturally occur-
ring phenanthrene and their 9,10-dihydro derivatives our aim was
to synthesise substituted phenanthrene derivatives including the
naturally occurring phenanthrene derivatives in our laboratory.
⇑
Corresponding authors.
E-mail address: gandhikar41@hotmail.com (G.K. Kar).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2012.01.018

K. Samanta et al. / Tetrahedron Letters 53 (2012) 1376–1379
1377
H
Me
MeO
OMe
OH
O O
MeO
HO
OH
HO
OH
Coelonin
O
HO
Rotandatin
Erianthridin
MeO
OMe
OH HO
O
OH
O
OH
HO
OMe HO
OMe
OMe
OMe
Coeloginin
MeO
Coelogin
Gymnopusin
Figure 1. Naturally occurring phenanthrene and 9,10-dihydrophenanthrene derivatives.
Table 1
R
R3
R4
Synthesis of homoallylic alcohols (4)
R
R
R5
R3
R5
R3
R5
Entry
Substrate
Producta
O
R4
R1
R4
R1
R1
R6
R6
O
O
R6
1
R2
R2
R2
CHO
3a
4
6
5
HO
4a (72%)
R3
R4
R
Br
O
O
O
R3
R4
O
R1
R2
CHO
R1
R2
2
3
CHO
+
B(OH)2
R1
CHO
4b (65%)
OH
R
3b
O
1
R2
2
3
O
O
Scheme 1. Retro synthetic analysis of phenanthrene/dihydrophenanthrene
derivatives.
CHO
3c
OH
4c (75%)
In an endeavour to make the synthesis of the target molecules,
the gold(III)chloride catalysed Diels–Alder reaction6,7 between fur-
an moiety and alkyne functionality has been explored. A series of
O
O
4
b-furyl-
a
,b-unsaturated aldehydes (3) were synthesised in good
,b-
CHO
yield via Suzuki reaction3 of different substituted b-bromo-
a
HO
3d
unsaturated aldehyde derivatives and furan-2-boronic acids fol-
lowing the standard literature procedure3a already developed in
our laboratory.
4d (70%)
a
Allylation was done using allyl bromide.
O
O
O
Br
Heat
In, NaI, DMF, r.t
(Diels-Alder
reaction)
CHO
OH
4(a-d)
OH
3(a-d)
Scheme 2. Synthesis of homoallylic alcohols 4(a–d).
OH
Br
2 mol% AuCl3
CH3CN, 20 °C
O
O
CHO
O
+
In , NaI,
DMF, r.t
OH
7(a-i)
OH
9(a-i)
3(b,d-k)
8
Scheme 3. Synthesis of hydroxyphenanthrene derivatives by gold(III) catalysed Diels–Alder reaction of homopropargylic alcohols.

1378
K. Samanta et al. / Tetrahedron Letters 53 (2012) 1376–1379
Table 2
Synthesis of homopropargylic alcohols (7)
Entry
Reactant
Homopropargylic alcohols
Alkyne/allene ratio
Crude yield (%)
(containing the corresponding allene)
O
O
1
1.5:1
96
CHO
3e
7a
OH
O
O
2
3
4
5
6
1.2:1
1.2:1
1:1
92
95
90
90
95
HO
CHO
HO
3f
7b
OH
O
O
MeO
CHO
MeO
3g
7c
OH
OMe
OMe
MeO
MeO
MeO
MeO
O
O
CHO
3h
7d
OH
O
O
1:1.6
1.7:1
CHO
3b
7e
7f
OH
OH
CHO
O
O
3i
O
O
7
8
1:1.7
1:1
97
93
CHO
3d
OH
7g
O
O
CHO
3j
7h
OH
MeO
MeO
O
O
9
1:1.5
95
CHO
3k
7i
OH
b-Furyl-
a
,b-unsaturated aldehydes (3) when subjected to in-
2.07(d), 2.57(d), 2.69(d), 4.87(m), 5.43(dd), 5.87(m) in 1H NMR
and d 208.07 (sp carbon of allene) in 13C NMR spectra].
dium mediated propargylation4 (propargyl bromide, In, NaI,
DMF) afforded the corresponding hydroxyl compounds [1-(2-fur-
yl)-hex-1-en-5-yn-3-ol derivatives] (7) in 90–97% crude yield
(Table 2) along with the corresponding allenes (8) as side product
as evident from the 1H NMR spectra (ratio of alkyne and allene in
the crude reaction mixture varies within ꢀ1.7:1–1:1.7 depending
on the substrate). Formation of inseparable allene side product
along with the desired alkyne (7) was confirmed from their charac-
teristic signals in 1H NMR and 13C NMR of the crude reaction mix-
ture [one of the reaction mixture (7b) showed the signals at d
The homopropargylic alcohols when subjected to the AuCl3 cat-
alysed (2 mol %) intramolecular Diels-Alder reaction in acetonitrile
at 20 °C, furnished polycyclic aromatic hydroxyl compounds8–11 in
moderate yield (Table 3). It is important to note that compounds
7e, 7g and 7i under identical reaction condition or at higher tem-
perature afforded no isolable cyclised product (9e, 9g or 9i) (entry
no. 5, 7, 9 in Table 3) probably due to the presence of maximum
proportion of allene in crude substrate and/or due to some other
side reactions that might be taking place during intramolecular

K. Samanta et al. / Tetrahedron Letters 53 (2012) 1376–1379
1379
Table 3
Thus in conclusion, the work describes a short and generalised
approach for the synthesis of hydroxyphenanthrenes and related
polycyclic aromatic hydroxy compounds starting from easily
Synthesis of polycyclic aromatic hydroxyl compounds (9)
Entry Reactant (crude) Product
Isolated yield (%)
available b-furyl-a,b-unsaturated aldehydes. Synthesis of some
OH
natural products may be achieved by this strategy using suitably
substituted furan moiety and the work will be taken up in due
time.
1
2
3
7a
7b
7c
48
9a8
Acknowledgments
OH
Financial help from CSIR and DST acknowledged gratefully. We
are thankful to CSIR for providing NET fellowship to one of the
authors (K.S.). We are also thankful to Professor J.K. Ray, Depart-
ment of Chemistry, I.I.T Kharagpur-721302, India, for providing
us with few 1H NMR spectral data of our synthesised compounds.
42
40
HO
9b9
OH
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2012.01.018.
MeO
9c9
OH
OMe
References and notes
MeO
MeO
4
5
7d
7e
35
—
1. (a) Fittig, R.; Ostermayer, E. Justus Liebigs Ann. Chem. 1873, 166, 361; (b)
Haworth, R. D. J. Chem. Soc. 1932, 12, 1125.
9d
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No characterisable product
6
7
7f
52
—
9f10
OH
7g
No characterisable product
OH
6. (a) Hashmi, A. S. K.; Frost, T. M.; Bats, J. W. J. Am. Chem. Soc. 2000, 122, 11553;
(b) Hashmi, A. S. K.; Ata, F.; Haufe, P.; Rominger, F. Tetrahedron 1919, 2009, 65;
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Beilstein, J. Org. Chem. 2011, 7, 1075.
8
9
7h
7i
35
—
9h11
No characterisable product
´
8. Barbasiewicz, M.; Szadkowska, A.; Makal, A.; Jarzembska, K.; Wozniak, K.;
Grela, K. Chem. Eur. J. 2008, 14, 9330.
Diels–Alder reaction. The product mixture contained large number
of spots in TLC and we were unable to isolate the components in
pure form for characterisation.
9. Cornforth, J. W.; Robinson, R. J. Chem. Soc. 1942, 684.
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