Superbase-catalyzed addition of ketones to propargyl and allenyl ethers in the KOH (KOBut)/DMSO system

Article abstract of DOI:10.1016/j.mencom.2013.07.008

Alkyl (het)aryl ketones undergo nucleophilic addition to propargyl or allenyl ethers in the KOH (KOBu^t)/DMSO system at 100 C either at terminal (giving 1:2 adducts) or internal (giving 1:1 adducts) positions of the propargyl or allenyl fragment

Full text of DOI:10.1016/j.mencom.2013.07.008

Mendeleev
Communications
Mendeleev Commun., 2013, 23, 204–205
Superbase-catalyzed addition of ketones to propargyl
and allenyl ethers in the KOH (KOBut)/DMSO system
Elena Yu. Schmidt, Nadezhda V. Zorina, Olga A. Tarasova, Igor A. Ushakov and Boris A. Trofimov*
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.2013.07.008
Alkyl (het)aryl ketones undergo nucleophilic addition to propargyl or allenyl ethers in the KOH (KOBut)/DMSO system at 100°C
either at terminal (giving 1:2 adducts) or internal (giving 1:1 adducts) positions of the propargyl or allenyl fragment.
Unsaturated ketones are versatile building blocks in organic
synthesis,1 among them most common being a,b-enones. Much
less accessible are b,g-unsaturated ketones which are usually
prepared by multi-step and laborious procedures.2 Recently, we
have discovered the direct stereoselective nucleophilic addition
(KOH/DMSO,3 KOH/ButOH/DMSO4 or KOBut/DMSO5 systems)
of ketones to acetylenes to afford (E)-b,g-enones in yields up
to 92%.
R1 Me
O
KOH/DMSO
100 °C, 1 h
+
OR2
1a R1 = Ph
1b R1 = 4-PhC6H4
2a R2 = Me
2b R2 = Bu
OR2
OR2
R1
This is a concise report on the extension of this finding over
propargyl ethers, the reaction being carried out in the presence of
KOH/DMSO or KOBut/DMSO systems at 100°C.
R1
+
O
O
Me
OR2
Since propargyl ethers are known to readily isomerize to the
corresponding allenyl ethers in the same superbase systems even
at room temperature within 15 min (Scheme 1),6 actually, at 100°C,
we should consider the reaction as proceeding with allenyl ethers.
3a R1 = Ph, R2 = Me, 18%
3b R1 = Ph, R2 = Bu, 14%
4a R1 = Ph, R2 = Me, 24%
4b R1 = Ph, R2 = Bu, 26%
3c R1 = 4-PhC6H4, R2 = Bu, 18% 4c R1 = 4-PhC6H4, R2 = Bu, 24%
Scheme 2
KOH/DMSO
20 °C, 15 min
O
R
O
R
should wonder why nothing of the 1:1 adduct to terminal carbon
is present in the reaction mixture. The plausible explanation is
outlined in Scheme 3.
Scheme 1
Indeed, under equal conditions we have obtained very close
results with both types of ethers. Acetophenones 1a,b add to
propargyl and allenyl ethers 2a,b both to their internal (most
expected for nucleophilic attack at allenes)7 and terminal posi-
tions to give the 1:1 adducts 3a–c in the former case and the 1:2
adducts 4a–c in the latter case (Scheme 2) approximately in the
same ratio.†
H
R1
CH2
R1
HO–
2a,b
1a,b
– H2O
O
O
OR2
A
B
R1
If the 1:1 adducts 3a–c seem to be not uncommon, the forma-
tion of the 1:2 adducts 4a–c needs special rationalization. One
2a,b, then H2O
O
4a–c
– HO–
H
†
OR2
General procedure for the reaction of ketones 1 with allenyl (or propargyl)
C
ethers 2a,b in the KOH/DMSO or KOBut/DMSO system. A mixture of
ketone 1 (2 mmol), allenyl (or propargyl) ether 2 (2 mmol), KOH·0.5H2O
(0.13 g, 2 mmol) or KOBut (0.22 g, 2 mmol) in DMSO (7 ml) was heated
(100°C) and stirred for 1 h. After cooling (20–25°C), the mixture was
diluted with H2O (10 ml), neutralized with NH4Cl and extracted with Et2O
(4×5 ml). The organic extract was washed with H2O (3×10 ml) and dried
with K2CO3. Column chromatography (SiO2, eluent hexane–Et2O with
gradient from 1:0 to 3:1) of a crude residue after removal of the solvent
gave the pure adducts 3–6.
Scheme 3
(E)-5-Methoxy-2-[(E)-(3-methoxyprop-2-en-1-yl)]-1-phenylpent-4-en-
1-one 4a: yield 0.11 g (24%), yellow oil. 1H NMR, d: 7.90–7.88 (m, 2H,
o-H), 7.53–7.48 (m, 2H, m-H), 7.45–7.41 (m, 1H, p-H), 6.25 (d, 2H,
CH=CH–OMe, 3J 12.7 Hz), 4.59 (dt, 2H, CH=CH–OMe, 3J 12.7 Hz,
3J 7.7 Hz), 3.42 (m, 1H, O=C–CH), 3.39 (s, 6H, OMe), 2.35–2.32,
2.15–2.13 (m, 4H, CH2–CH=CH–OMe). 13C NMR, d: 203.6 (C=O),
148.7 (2CH=CH–OMe), 137.7 (i-C), 132.8 (p-C), 128.6 (m-C), 128.3
(o-C), 99.5 (2CH=CH–OMe), 55.9 (2OMe), 48.5 (O=C–CH), 30.0
(2CH2–CH=CH–OMe). IR (film, nmax/cm–1): 3060, 2998, 2931, 2830,
1681, 1652, 1594, 1580, 1448, 1275, 1130, 1076, 1049, 1004, 957, 936,
757, 694. Found (%): C, 73.99; H, 7.69. Calc. for C16H20O3 (%): C, 73.82;
H, 7.74.
(Z)-4-Methoxy-3-methyl-1-phenylbut-3-en-1-one 3a: yield 0.07 g (18%),
yellow oil. 1H NMR, d: 7.89–7.87 (m, 2H, o-H), 7.53–7.49 (m, 2H, m-H),
7.42–7.39 (m, 1H, p-H), 5.88 (s, 1H, C=CH–OMe), 3.55 (s, 3H, OMe),
3.46 (s, 2H, O=C–CH2), 1.63 (s, 3H, Me). 13C NMR, d: 200.0 (C=O),
145.2 (C=CH–OMe), 136.8 (i-C), 132.6 (p-C), 128.5 (m-C), 128.3 (o-C),
101.5 (C=CH–OMe), 59.5 (OMe), 43.5 (O=C–CH2), 13.2 (Me). IR (film,
n
max/cm–1): 3059, 3000, 2933, 2832, 1680, 1654, 1597, 1580, 1448, 1376,
1275, 1211, 1132, 1076, 1049, 1002, 953, 936, 795, 757, 704. Found (%):
C, 75.64; H, 7.39. Calc. for C12H14O2 (%): C, 75.76; H, 7.42.
For characteristics of compounds 3b,c, 4b,c, 5a,b and 6a,b see Online
Supplementary Materials.
© 2013 Mendeleev Communications. All rights reserved.
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Mendeleev Commun., 2013, 23, 204–205
R3
O
Me
The primary adduct of deprotonated ketone A to the terminal
allenic carbon, the initial vinyl carbanion B, does not trap a
proton from the medium in the expected intermolecular manner.
Instead, intramolecular proton transfer from the a-CH2 group
leads to a-carbanion C which then adds to the terminal carbon
of the second molecule of the allenyl ether to deliver the final 1:2
adducts 4a–c. Similar intramolecular proton transfer does not
occur during the formation of the 1:1 adducts 3a–c because sp3-
centred carbanion D is much more basic than the sp2-centred one
(B),8 moreover, its carbanionic centre is sterically more accessible
for a medium proton (Scheme 4).
R1
OR2
K
R3 = H, Me
E
In conclusion, the previously unknown nucleophilic super-
base-catalyzed addition of ketones to available propargyl/allenyl
ethers paves a straightforward one-pot route to new families
of promising synthetic intermediates which combine the ketone
and E or Z enol ether structures in one molecule. This is just a
preliminary pioneering communication and hence the product
yields and selectivity are open for optimization.
OR2
H2O
– HO–
R1
2a,b
A
3a–c
O
CH2
This work was supported by the Russian Foundation for
Basic Research (grant no. 11-03-00270) and the grant to leading
scientific schools by the President of the Russian Federation
(grant no. NSh-1550.2012.3).
D
Scheme 4
In support of this concept, the branching at the carbanionic
centre of the ketone (carbanion A') prevents the above intramole-
cular proton transfer (Scheme 3) and thus only 1:1 adducts are
formed as it is observed for propiophenone 1c and 2-propionyl-
thiophene 1d (Scheme 5).
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.mencom.2013.07.008.
References
Me
Me
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R1
R1
HO–
2b, then H2O
– HO–
– H2O
O
O
1c R1 = Ph
A'
1d R1 = 2-thienyl
Me
OBu
Me
R1
OBu
R1
+
O
O
Me
5a R1 = Ph, 8%
6a R1 = Ph, 28%
6b R1 = 2-thienyl, 27%
3 B. A. Trofimov, E. Yu. Schmidt, I. A. Ushakov, N. V. Zorina, E. V.
Skital’tseva, N. I. Protsuk and A. I. Mikhaleva, Chem. Eur. J., 2010, 16,
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5b R1 = 2-thienyl, 9%
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Scheme 5
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Nauka, Moscow, 1980 (in Russian).
In this case, along with 1:1 adducts 6a,b to the terminal allenic
carbon, the normal 1:1 adducts 5a,b to the internal position of
allene are formed (Scheme 5).
The Z configuration of enones 3a–c, 5a,b is probably due to
the generation of the conjugated potassium dienolate stabilized
as the seven-membered ring E by the specific interaction between
potassium cation and the ether oxygen.
The E configuration of enones 4a–c, 6a,b is likely a result of
steric repulsion of the encumbered substituents.
Received: 24th April 2013; Com. 13/4113
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