Potassium tert-butoxide catalyzed addition of carbonyl derivatives to styrenes

Article abstract of DOI:10.1021/ol000174l

(matrix presented) A catalytic amount of t-BuOK in DMSO allows the addition of ketones or imines to styrenes at 40 °C in good to excellent yield. Nitriles add to styrenes in NMP or in DMSO at room temperature.

Full text of DOI:10.1021/ol000174l

ORGANIC
LETTERS
2
000
Vol. 2, No. 21
285-3287
Potassium tert-Butoxide Catalyzed
Addition of Carbonyl Derivatives to
Styrenes
3
Alain Louis Rodriguez, Tanasri Bunlaksananusorn, and Paul Knochel*
Ludwig-Maximilians-UniVersit a¨ t M u¨ nchen, Institut f u¨ r Organische Chemie,
Butenandtstrasse 5-13, Haus F, 81377 M u¨ nchen, Germany
paul.knochel@cup.uni-muenchen.de
Received July 3, 2000
ABSTRACT
A catalytic amount of t-BuOK in DMSO allows the addition of ketones or imines to styrenes at 40 °C in good to excellent yield. Nitriles add
to styrenes in NMP or in DMSO at room temperature.
The regioselective addition of organometallics to moderately
activated olefins such as styrenes is of great importance in
butoxide (10-30 mol %) in dimethyl sulfoxide (DMSO) or
NMP leading to the corresponding products 5-7 (Scheme
1 and Table 1). The crude reaction mixture is, under optimum
1
,2
polymer chemistry and in carbometalation reactions. The
scope of these additions is however limited to reactive allylic
2b
or alkyl organometallics. Scarce reports on these reactions
can be found in the literature, and only the base-catalyzed
Scheme 1
3
,4
addition of cyclic amides to styrene has been reported.
Recently, we found that highly reactive cesium and potassium
alkoxides in N-methylpyrrolidinone (NMP) allow the per-
5
formance of catalytic addition reactions to alkynes. Herein,
we wish to report a new general procedure for adding various
carbonyl compounds (nitriles (1), ketones (2), imines (3))
to styrenes 4 using a catalytic amount of potassium tert-
(
1) (a) For review articles, see: Hoveyda, A. H.; Heron, N. M. In
ComprehensiVe Asymmetric Catalysis, Vol. I; Springer: Berlin, 1999; pp
4
31-454. (b) Marek, I. J. Chem. Soc., Perkin Trans. 1 1999, 535. (c)
Knochel, P. In ComprehensiVe Organic Synthesis, Vol. 4; Trost, B. M.,
Fleming, I., Semmelhack, M. F., Eds.; Pergamon Press: Oxford, 1991; p
8
65.
2) (a) Priddy, D. B. AdV. Polym. Sci. 1994, III, 67. (b) Lemkuhl, H.;
McLane, R. Liebigs Ann. Chem. 1980, 736.
3) (a) Pines, H.; Kannan, S. V.; Simonik, J. J. Org. Chem. 1971, 36,
311. (b) For an addition to styrene in the presence of dispersed potassium
or sodium, see: Pines, H.; Sartoris, N. E. J. Org. Chem. 1969, 2618.
4) For the stoichiometric PdCl2-mediated addition of ketones to styrenes,
(
(
2
conditions, remarkably clean, and the addition products are
readily purified. Nitriles are the most reactive substrates, and
most reactions are complete at room temperature within
(
see: Hegedus, L. S.; Williams, R. E.; McGuire, M. A.; Hayashi, T. J. Am.
Chem. Soc. 1980, 102, 4973.
5
-15 h in NMP using t-BuOK (10-30 mol %) as catalyst,
(
5) (a) Tzalis, D.; Knochel, P. Angew. Chem., Int. Ed. 1999, 38, 1463.
(
b) Tzalis, D.; Koradin, C.; Knochel, P. Tetrahedron Lett. 1999, 40, 6193.
providing the expected regioselective addition products 5a-g
in 74-91% yields (see entries 1-7 of Table 1). On the other
hand, the presence of an additional substituent at the double
(
c) For a new indole synthesis, see: Rodriguez, A. L.; Koradin, C.; Dohle,
W.; Knochel, P. Angew. Chem., Int. Ed. In press. (d) Caubere, P. Chem.
ReV. 1993, 93, 2317. (e) Schlosser, M. Mod. Synth. Methods 1992, 6, 227.
1
0.1021/ol000174l CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/21/2000

Table 1. Products of Type 5-7 Obtained by the Addition of Nitriles, Ketones, or Imines to Styrenes in DMSO or NMP in the
Presence of a Catalytic Amount of t-BuOK
a
Yield of analytically pure product was determined by H and C NMR. b The reaction was performed in NMP (Method A). c The reaction was performed
1
13
in DMSO (Method B). 6-11% of double addition product is isolated. e Compound 7a was converted by acidic hydrolysis to the ketone 6b.
d
bond of the styrene, such as (E)-1-phenyl-1-butene, requires
a reaction temperature of 100 °C (4 h) for completion of the
reaction with isobutyronitrile, leading to 3-ethyl-2,2-di-
methyl-4-phenylbutanenitrile in 48% yield. The presence of
electron-withdrawing substituents such as a fluorine or a
bromine group considerably shortens the reaction time (2-5
h instead of 15 h).
The fact that an addition occurs to a 2-substituted styrene
seems to indicate that the adding species is not a radical.6
Moreover, the addition of 2,6-di-tert-butyl-4-methylphenol
did not inhibit the reaction of 1a with 4a. Treatment of
(
6) (a) Bunnett, J. F. Acc. Chem. Res. 1978, 11, 413. (b) Saveant, J. M.
Acc. Chem. Res. 1980, 13, 323. (c) Bunnett, J. F. Acc. Chem. Res. 1992,
5, 2.
7-phenyl-6-hexenenitrile 8 with t-BuOK (30 mol %) in NMP
2
(100 °C, 3 h) furnishes the cyclopentanenitrile 9 in 61% yield
3286
Org. Lett., Vol. 2, No. 21, 2000

as a 1:1 mixture of cis-trans isomers (Scheme 2). Prelimi-
nary experiments show that the amount of t-BuOK can be
reduced below 10% without a rate decrease.7
temperature is crucial for limiting the formation of double
addition products of styrene, and by conducting the reaction
between 38 and 41 °C, a smooth addition reaction occurs.
In the case of 2-tetralone (2c), cyclohexanone (2b), and
camphor (2d), only traces of double addition products were
observed and very clean crude reaction mixtures were
obtained (entries 8-11 of Table 1). In the case of phenyl
ethyl ketone (2a), 8% of 1,4-diphenyl-2-methyl-2-(2-phen-
ylethyl)-1-butanone was also isolated. An excess of the
ketone (3 equiv) compared to the styrene was used. The
addition of imine to styrene could also be achieved at 40
Scheme 2
°
C, providing the substituted imine 7 in a satisfactory yield.
In summary, we have developed a synthetic method
In the case of the addition of ketones to styrene, best results
were obtained by using DMSO as solvent since it was
observed that NMP reacts with styrene. The reaction
allowing the general addition of carbonyl compounds to
styrenes. Furthermore, the combination of t-BuOK with the
polar solvents DMSO or NMP allows the the reaction to
proceed using only a catalytic amount of base. The scope of
the reaction appears to be broad and is currently being
investigated in our laboratories.
3a
(7) Typical procedure: method A, preparation of 1-(2-phenylethyl)-
cyclohexanecarbonitrile (5g). To a stirred solution of tert-butoxide (60
mg, 0.5 mmol) in NMP (2 mL) was added under argon a mixture of
cyclohexanecarbonitrile (1c; 160 mg, 1.5 mmol) and styrene (210 mg, 2
mmol). The reaction was stirred for 15 h at rt. Water (3 mL) and CH2Cl2
Acknowledgment. We thank the DFG (Leibniz program),
the BASF AG, and the Fonds der Chemischen Industrie for
the generous financial support. A.L.R. thanks the Humboldt
Foundation for a fellowship. We thank Dr. J. Henkelmann
(BASF AG) for helpful discussions.
(
25 mL) were added, and the resulting solution was washed with brine,
dried (MgSO4), and concentrated under reduced pressure. The crude product
was purified by flash chromatography (silica gel, 1:1 CH2Cl2/pentane) to
give the desired product 5g (290 mg, 91% yield). Method B: preparation
of 2-(2-phenylethyl)-3,4-dihydro-1(2H)-naphthalenone (6c). The reaction
was carried out as above using DMSO instead of NMP as solvent. To a
stirred solution of potassium tert-butoxide (90 mg, 0.8 mmol) in DMSO
Supporting Information Available: 1H and 13C NMR
data for compounds 5a-g, 6a-d, and 9. This material is
available free of charge via the Internet at http://pubs.acs.org.
(
2.5 mL) were added R-tetralone (3a; 600 mg, 6 mmol) and styrene (210
mg, 2 mmol). The reaction mixture was vigorously stirred for 15 h at 40
C. After the same workup procedure as described above, the crude product
°
was purified by flash chromatography (silica gel, CH2Cl2) to give the desired
product 6c (340 mg, 68% yield).
OL000174L
Org. Lett., Vol. 2, No. 21, 2000
3287