Domino assembly of functionalized cyclopentenols from 1,5-diphenylpentane-1,5-dione and phenylacetylene in the KOH/DMSO suspension

Article abstract of DOI:10.1016/j.mencom.2015.01.005

1,5-Diphenylpentane-1,5-dione reacts (50 mol% KOH in DMSO, 70 °C, 3 h) with phenylacetylene in a domino manner to afford 3-benzoyl-2-benzyl-1-phenylcyclopenten-1-ol and its debenzoylated derivative in 66 and 25% yields, respectively.

Full text of DOI:10.1016/j.mencom.2015.01.005

Mendeleev
Communications
Mendeleev Commun., 2015, 25, 17–18
Domino assembly of functionalized cyclopentenols from 1,5-diphenyl-
pentane-1,5-dione and phenylacetylene in the KOH/DMSO suspension
Boris A. Trofimov,* Elena Yu. Schmidt, Ivan A. Bidusenko and Natalia A. Cherimichkina
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences,
664033 Irkutsk, Russian Federation. Fax: +7 3952 419 346; e-mail: boris_trofimov@irioch.irk.ru
DOI: 10.1016/j.mencom.2015.01.005
1,5-Diphenylpentane-1,5-dione reacts (50 mol% KOH in DMSO, 70°C, 3 h) with phenylacetylene in a domino manner to afford
3-benzoyl-2-benzyl-1-phenylcyclopenten-1-ol and its debenzoylated derivative in 66 and 25% yields, respectively.
Recently, we have published the one-pot stereoselective assembly
of 7-methylidene-6,8-dioxabicyclo[3.2.1]octanes 3 from 1,5-di-
ketones 1 and acetylenes 2 in the KOH/DMSO suspension
(100–200 mol% KOH, 70°C, 0.5–4 h), the yields reaching 92%
(Scheme 1).1
Ph
O
O
Ph
KOH (50 mol%)/
DMSO
Ph
Ph
OH
+
+
OH
70°C, 3 h
Ph
2a
O
Ph
Ph
4, 66%
R5
5, 25%
Ph
1a
R4
R2
R4
KOH/
DMSO
R1
R5
R6
R3
R2
+
O
Scheme 2
R6
O
O
R3
O
3 is preceded by the formation of hemiacetal alcoholate B via
the attack of oxygen-centered anion A at the carbonyl group.
When the content of KOH is reduced to 50 mol%, alcoholate A
R1
2
1
3
R1, R5 = Ar, Het
R2, R3, R4 = H, Me, Ph
R1 + R2, R4 + R5 = (CH2)4
R6 = H, Ar, Het
Cyclopentenols 4, 5. A suspension of 1,5-diphenylpentane-1,5-dione
1a (1.50 g, 6 mmol) and KOH (water content 15%, 0.20 g, 3 mmol) in
DMSO (40 ml) was heated (70°C) with stirring. Then phenylacetylene
2a (0.79 g, 7.7 mmol) in DMSO (10 ml) was added for 20 min. The
mixture was heated for 3 h and, after cooling to room temperature, was
diluted with H2O (100 ml) and extracted with Et2O (7×20 ml). The extract
was washed with water (3×20 ml) and dried (K2CO3) for 3 h. Column
chromatography (basic Al2O3, eluent hexane–chloroform with gradient
from 1:0 to 0:1) of a crude residue after removal of the solvent (1.87 g)
gave pure products 4, 5.
3-Benzoyl-2-benzyl-1-phenylcyclopent-2-en-1-ol 4: yield 1.39 g (66%),
colorless crystals, mp 102–105°C. 1H NMR (C6D6) d: 7.83–7.81 (m, 2H,
o-HPh1), 7.41–7.39 (m, 2H, o-HPh2), 7.16–6.97 and 6.87–6.78 (m, 11H,
HPh), 3.49 (d, 1H, CH2Ph, 2J 14.8 Hz), 3.08 (d, 1H, CH2Ph, 2J 14.8 Hz),
2.78–2.73 (m, 1H, 5-H), 2.48–2.43 (m, 1H, 5-H'), 2.17–2.10 (m, 1H,
4-H), 2.06–1.99 (m, 1H, 4-H'), 1.53 (s, 1H, OH). 13C NMR (C6D6) d:
196.7 (C=O), 149.1 (1-C), 146.2 (i-CPh3), 141.3 (2-C), 139.0 (i-CPh2), 137.8
(i-CPh1), 133.0 (p-CPh1), 129.6 (o-CPh2), 129.2 (o-CPh1), 128.7 (m-CPh1),
128.5 (m-CPh2,3), 127.1 (p-CPh3), 126.4 (p-CPh2), 125.7 (o-CPh3), 89.7 (3-C),
42.8 (4-C), 33.5 (CH2Ph), 33.0 (5-C). IR (film, nmax/cm–1): 3331, 3083,
3060, 3026, 2963, 2918, 2850, 1662, 1629, 1595, 1493, 1447, 1385,
1273, 1174, 1135, 1069, 1022, 923, 885, 770, 717, 703, 689. Found (%):
C, 84.68; H, 6.14. Calc. for C25H22O2 (%): C, 84.72; H, 6.26.
2-Benzyl-1-phenylcyclopent-2-en-1-ol 5: yield 0.37 g (25%), yellow oil.
1H NMR (CDCl3) d: 7.40–7.38 (m, 2H, o-HPh1), 7.35–7.32 (m, 2H,
m-HPh1), 7.25–7.24 (m, 2H, m-HPh2), 7.23–7.22 (m, 1H, p-HPh1), 7.19–7.17
(m, 1H, p-HPh2), 7.07–7.05 (m, 2H, o-HPh2), 5.45–5.44 (m, 1H, 3-H),
3.19–3.15 (m, 1H, CH2Ph), 3.10–3.06 (m, 1H, CH2Ph), 2.47–2.43 (m,
1H, 4-H), 2.32–2.30 (m, 1H, 5-H), 2.25–2.21 (m, 1H, 4-H'), 2.20–2.19
(m, 1H, 5-H'), 1.82 (s, 1H, OH). 13C NMR (CDCl3) d: 148.5 (2-C), 146.2
(i-CPh1), 139.9 (i-CPh2), 129.9 (3-C), 129.3 (o-CPh2), 128.5 (m-CPh2), 128.4
(m-CPh1), 126.7 (p-CPh1), 126.2 (p-CPh2), 125.2 (o-CPh1), 88.2 (1-C), 44.0
(5-C), 33.6 (CH2Ph), 29.6 (4-C). IR (film, nmax/cm–1): 3566, 3448, 3084,
3059, 3027, 2964, 2930, 2905, 2853, 1951, 1881, 1811, 1751, 1681, 1600,
1581, 1497, 1448, 1361, 1334, 1298, 1281, 1222, 1176, 1089, 1059, 1028,
1002, 982, 942, 912, 846, 766, 701. Found (%): C, 86.12; H, 7.10. Calc.
for C18H18O (%): C, 86.36; H, 7.25.
Scheme 1
These bicyclic acetals 3 belong to the frontalin family of
aggregate pheromones2 and mammal hormones.3 Since 1,5-di-
ketones are easily prepared by aldehyde–ketone condensation,4
further development of such a chemistry seems promising.
Although seven 1,5-diketones 1 tolerated the reaction,1 we
here report that one of them, 1,5-diphenylpentane-1,5-dione 1a
combined with phenylacetylene 2a appeared to be surprisingly
sensitive towards the change of the process conditions.
Indeed, when the KOH: 1a ratio has been decreased from
2:1 to 0.5:1, the reaction takes absolutely other direction: instead
of the expected 7-methylidene-6,8-dioxabicyclo[3.2.1]octane
3a (R1 = R5 = Ph, R2 = R3 = R4 = H, R6 = Ph), functionalized
cyclopentenes 4 and 5 were obtained in 66 and 25% yields,
respectively (Scheme 2).†
Obviously, both the syntheses of bicyclooctanes 3 and cyclo-
pentenes 4, 5 are triggered by the Favorsky reaction onto a one
of carbonyl groups to give the common intermediate, acetylenic
alcoholate A (Scheme 3).1 Then, instead of normal Favorsky
ethynylation of the second carbonyl group, domino type intra-
molecular competitive O- vs. C-vinylation occurs. As shown in
previous publication,1 the O-vinylation leading to bicyclooctanes
1H and 13C NMR spectra were recorded at 400.13 and 100.61 MHz,
†
respectively, on an instrument equipped with an inverse gradient 5 mm
probe with HMDS as an internal standard. All 2D NMR spectra were
recorded using a standard gradient Bruker pulse program. IR spectra
were taken with FT-IR. The 1,5-diketone 1a was synthesized using
published procedures.7 KOH (water content 15%), DMSO (water content
0.2–0.3%) and all other chemicals and solvents are commercially available
and were used without further purification. The elaborated procedure
does not require degassing of DMSO and use of inert atmosphere.
© 2015 Mendeleev Communications. Published by ELSEVIER B.V.
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
– 17 –

Mendeleev Commun., 2015, 25, 17–18
Ph
Ph
Such a scheme is supported by the detection of benzoic acid in
the reaction mixture after its acidification.
KOH
O
OH
Ph
1a + 2a
O
O
– H2O
Substituted functionalized cyclopentenes are frequent motifs
in ribose-derived natural compounds5 and some modern important
drugs.6 Therefore, the one-pot domino assembly of a novel family
of these pharmaceutically promising compounds from available
materials under simple transition metal-free conditions deserves
further in-depth study.
Ph
Ph
Ph
A
C
– H2O KOH
Ph
Ph
The work was supported by the Russian Science Foundation
(grant no. 14-13-00588).
Ph
Ph
H2O
OH
Ph
O
Ph
O
O
O
O
References
Ph
Ph
Ph
Ph
1 E. Yu. Schmidt, I. A. Bidusenko, N. I. Protsuk, I. A. Ushakov and B. A.
Trofimov, Eur. J. Org. Chem., 2013, 2453.
2 (a) G. W. Kinzer, A. F. Fentiman, T. F. Page, R. L. Folz, J. P. Vite and
G. B. Pitman, Nature, 1969, 221, 477; (b) J. A. A. Renwick and J. P. Vite,
Nature, 1969, 224, 1222; (c) E. M. Suh andY. J. Kishi, J. Am. Chem. Soc.,
1994, 116, 11205.
3 (a) D. P. Wiesler, F. J. Schwende, M. Carmack and M. Novotny, J. Org.
Chem., 1984, 49, 882; (b) T. E. Perrin, L. E. L. Rasmussen, R. Gunawardena
and R. A. Rasmussen, J. Chem. Ecol., 1996, 22, 207; (c) L. E. L. Rasmussen,
H. S. Riddle and V. Krishnamurthy, Nature, 2002, 415, 975; (d) L. E.
Rasmussen and D. R. Greenwood, Chem. Senses, 2003, 28, 433.
4 (a) Y. Chi and S. H. Gellman, Org. Lett., 2005, 7, 4253; (b) R. Shankar,
A. K. Jha, U. S. Singh and K. Hajela, Tetrahedron Lett., 2006, 47, 3077;
(c) A. Yanagisawa, H. Takahashi and T. Arai, Tetrahedron, 2007, 63, 8581.
5 (a) V. E. Marquez, M. A. Siddiqui, A. Ezzitouni, P. Russ, J. Wang,
R. W. Wagner and M. D. Matteucci, J. Med. Chem., 1996, 39, 3739;
(b) E. Roulland, C. Monneret and J.-C. Floren, Tetrahedron Lett., 2003,
44, 4125; (c) J. H. Cho, D. L. Bernard, R. W. Sidwell, E. R. Kern and
Ch. K. Chu, J. Med. Chem., 2006, 49, 1140.
3a
B
D
H2O
Ph
OH
Ph
Ph
OH
O
O
Ph
Ph
Ph
4
E
–OH
+ PhCO2H
5 + PhC(O)O–
OH
Ph
F
Scheme 3
6 (a) J. L. Wood, G. Pujanauski and R. Sarpong, Org. Lett., 2009, 11, 3128;
(b) R. Krishna and R. R. Kadiyala, Tetrahedron Lett., 2010, 51, 4981;
(c) Zh. Li, M. Nakashige and W. J. Chain, J. Am. Chem. Soc., 2011, 133,
6553.
would equilibrate with the neutral acetylenic keto alcohol C. The
latter gives then enolate D, which is cyclized to benzylidenecyclo-
pentanol E, expectedly isomerizing to the final cyclopentenol 4.
Similar enolization of alcoholate A is virtually forbidden due to
the electrostatic repulsion of two negative charges.
7 M. N. Tilichenko, Zh. Obshch. Khim., 1955, 25, 2503 (in Russian).
Debenzoylation of cyclopentenol 4 likely results from the
nucleophilic attack of hydroxide anion at the carbonyl carbon
atom of the benzoyl group leading to the cleavage of the C1–C(O)
bond to form benzoic acid and to release cyclopentene carbanion F.
Received: 25th April 2014; Com. 14/4357
– 18 –