Direct preparation of monoarylidene derivatives of aldehydes and enolizable ketones with DIMCARB

Article abstract of DOI:10.1021/ol0351145

(Matrix presented) Aryl α,β-unsaturated ketones and aldehydes were synthesized, in moderate to excellent yields, with use of dimethylammonium dimethyl carbamate (DIMCARB) as a recyclable reaction medium and as a catalyst.

Full text of DOI:10.1021/ol0351145

ORGANIC
LETTERS
2003
Vol. 5, No. 17
3107-3110
Direct Preparation of Monoarylidene
Derivatives of Aldehydes and Enolizable
Ketones with DIMCARB
Ulf P. Kreher,* Anthony E. Rosamilia, Colin L. Raston, Janet L. Scott, and
Christopher R. Strauss*
Centre for Green Chemistry, Monash UniVersity, Clayton, Victoria 3800, Australia
chris.strauss@sci.monash.edu.au
Received June 17, 2003
ABSTRACT
Aryl r,â-unsaturated ketones and aldehydes were synthesized, in moderate to excellent yields, with use of dimethylammonium dimethyl
carbamate (DIMCARB) as a recyclable reaction medium and as a catalyst.
For other research, we required mono-2-arylidene derivatives
of ketones, particularly of cyclohexanone and cyclopenta-
none. Direct access to these compounds from the parent
ketones and aryl aldehydes by Claisen-Schmidt condensa-
tions1 was not straightforward. Several publications,2,1b
including from our laboratory,3 have demonstrated that
typically, such reactions proceed beyond mono-condensation.
Diadducts such as E,E-2,6-dibenzylidenecyclohexanone or
E,E-2,5-dibenzylidenecyclopentanone can be formed exclu-
sively, even when the molar ratio of starting aldehyde to
ketone is substantially below 1:1.2a Consequently, preparation
of the monoarylidene adducts usually requires at least two
steps, i.e. aldol addition followed by a separate elimination.4
Aldol addition is readily reversible5 and to avoid this, the
Mukaiyama approach starting from the trimethylsilyl enol
ether of the ketone6 has gained favor.7 Silylation of the ketone
introduces another step and lowers the atom economy.8 We
now report that in or with DIMCARB (N,N-dimethyl-
ammonium N′,N′-dimethylcarbamate),9 the monoarylidene
derivatives of ketones and enolizable aldehydes can be
prepared directly, with high selectivity, in moderate to
excellent yields.
DIMCARB is an adduct of CO2 and Me2NH, both of
which are gases under ambient conditions. It is a relatively
stable liquid up to 50 °C and can be produced in bulk, readily
and inexpensively.9 It has substantial ionic character and can
dissolve salts such as LiCl, NaCl, NaBr, KCl, and KI at levels
between 2 and 5% w/v.10 While lower than that of water
and higher than that of hydrophobic organic solvents, such
polarity is comparable with that of ionic liquids,11 which have
(1) (a) Le Gall, E.; Texier-Boullet, F.; Hamelin, J. Synth. Commun. 1999,
29, 3651. (b) Toda, F.; Tanaka, K.; Hamai, K. J. Chem. Soc., Perkin Trans.
1 1990, 28, 3207. (c) Noyce, D. S.; Pryor, W. A. J. Am. Chem. Soc. 1955,
77, 1397.
(2) (a) Zheng, M.; Wang, L.; Shao, J.; Zhong, Q. Synth. Commun. 1997,
27, 351. (b) Iranpoor, N.; Kazemi, F. Tetrahedron 1998, 54, 9475.
(3) Raston, C. L.; Scott, J. L. Green Chem. 2000, 2, 49.
(6) Olah, G. A.; Gupta, B. G. B.; Narang, S. C.; Malhotra, R. J. Org.
Chem. 1979, 44, 4272.
(7) (a) Mukaiyama, T.; Banno, K.; Narasaka, K. J. Am. Chem. Soc. 1974,
96, 7503. (b) Denmark, S. E.; Wong, K.-T.; Stavenger, R. A. J. Am. Chem.
Soc. 1997, 119, 2333. (c) Denmark, S. E.; Stavenger, R. A. Acc. Chem.
Res. 2000, 33, 432. (d) Denmark, S. E.; Wong, K.-T.; Stavenger, R. A.;
Su, X. J. Am. Chem. Soc. 1999, 121, 4982.
(8) Trost, B. M. Pure Appl. Chem. 1992, 64, 315.
(9) Schroth, V. W.; Andersch, J.; Scha¨dler, H.-D.; Spitzner, R. Chem.-
Ztg. 1989, 113, 261.
(4) (a) Light, R. J.; Hauser, C. R. J. Org. Chem. 1961, 26, 1716. (b)
Billimoria, J. D. J. Chem. Soc. Abstr. 1955, 1126.
(5) (a) Guthrie, J. P. Can. J. Chem. 1974, 52, 2037. (b) French, C. C. J.
Am. Chem. Soc. 1929, 51, 3215. (c) Heathcock, C. H. ComprehensiVe
Organic Synthesis: SelectiVity, Strategy & Efficiency in Modern Organic
Chemistry; Trost, B. M., Fleming, I., Eds; Pergamon Press: Oxford,
England, 1991; Vol. 2, Chapter 1.5, pp 133-179.
(10) Schroth, W.; Scha¨dler, H.-D.; Andersch, J. Z. Chem. 1989, 29, 56.
10.1021/ol0351145 CCC: $25.00 © 2003 American Chemical Society
Published on Web 07/25/2003

Table 1. Synthesis of Aryl R,â-Unsaturated Ketonesa
a Conditions: DIMCARB removed by (a) distillation under CO2 atmosphere, (b) in vacuo, (c) after acidification with 0.5 M H2SO4. Workup by (d)
extraction into 1:1 hexane/EtOAc and adsorption onto silica gel and (e) extraction with organic solvent. (f) Yield determined by NMR. (g) 1.2 mol equiv
of ketone used.
attracted interest as synthetic media through their negligible
vapor pressure, solvent properties, and lack of flammability.12
The isolation of nonvolatile products from ionic liquids can
be difficult. In contrast, at 60 °C, DIMCARB dissociates to
CO2 and Me2NH, which can be condensed and reassociated.9
Thus, since DIMCARB can be recycled during reactions or
recovered afterward for reuse, in many respects it could be
considered as a self-associated, “distillable” ionic medium.
First, condensations were carried out in DIMCARB as
solvent at temperatures up to 50 °C for times ranging from
2 to 32 h. Yields, usually on the order of 60-80%, were
obtained almost routinely (see Table 1). Under these condi-
tions a range of enolizable ketones and an enolizable aliphatic
aldehyde afforded monoarylidene products. Methods for
workup included recovery of DIMCARB by distillative
dissociation-reassociation in vacuo or under an atmosphere
(11) Aki, S. N. V. K.; Brennecke, J. F.; Samanta, A. Chem. Commun.
2001, 413.
(12) (a) Wassercheid, P.; Keim, W. Angew. Chem., Int. Ed. 2000, 39,
3772. (b) Welton, T. Chem. ReV. 1999, 99, 2071. (c) Earle, M. J.; Seddon,
K. R. Pure Appl. Chem. 2000, 72, 1391.
3108
Org. Lett., Vol. 5, No. 17, 2003

of CO2. An acidic workup was effective when base-labile
monoarylidene products were formed.
Scheme 2. Reaction of Benzene-1,2-dicarboxaldehyde with
The novel one-pot processes in Table 1 were convenient,
but empirical efforts to increase the yields were unsuccessful.
Investigations into mechanistic aspects revealed that compet-
ing pathways can come into play. A aminal 1,13 which
appears to have a key role, is formed through reaction of 2
equiv of dimethylamine with 1 equiv of the arylaldehyde
(see Scheme 1). Elimination of a dimethylamino moiety from
DIMCARB in the Presence of Cyclohexanone
Scheme 1. Suggested Reaction Pathway of Benzaldehyde and
Cylohexanone in DIMCARB
monoadducts reported in Table 1. The reactions summarized
in Table 2 were performed in one pot and employed
Table 2. Synthesis of Aryl R,â-Unsaturated Cyclopentanones
entry
R1
time (h)
yield (%)
ref
15
16, 15a
15a
1
2
3
4
5
6
7
8
H
18
17
17
18
60
60
24
13
85
91
87
86
91
82
83
74
p-OCH3
o-OCH3
p-OH
p-Cl
the aminal affords a putative, transient iminium species that
can undergo Mannich reaction with the ketone. Subsequent
elimination of dimethylamine from the Mannich adduct is
facile and affords the 2-arylidene derivative.
p-Br
1-naphthaldehydea
p-CO2H
As evidenced by the evolution of CO2, in DIMCARB,
aminals were formed more rapidly from the aryl aldehydes
than were enamines from the ketones. Although the latter
processes were observed to a minor extent on occasions,
enamine chemistry was not significant in the present context.
This conclusion was supported by the failure of benzene-
1,2-dicarboxaldehyde to react with cyclohexanone under the
conditions. A cis and trans mixture of the bis-dimethylamino
ether 214 was formed instead (see Scheme 2).
Apparently, the aminal does not react directly with the
ketone. We considered that a vast excess of DIMCARB (up
to 12 mol equiv were used for experiments in Table 1) may
have helped to stabilize the aminal and could have accounted,
at least in part, for the moderate yields of arylidene
a Represents aldehyde, not R1 group.
DIMCARB in lower levels (about 5 mol equiv) as a reagent/
catalyst/cosolvent. Indeed, improved yields, between 74 and
91%, were obtained. Preparations of monoarylidene cyclo-
pentanones were particularly convenient. After removal of
the reaction medium, aqueous workup and solvent extraction,
no further purification was required. The hydroxy- and
carboxyarylaldehydes employed herein were insoluble in the
cosolvent (in this case CH2Cl2) alone. DIMCARB facilitated
their dissolution, presumably owing to the large number of
coordinating centers in a relatively small molecule. To the
best of our knowledge, all compounds in Table 2 were
obtained in higher yields than by all other reported methods
or were new.
Although the present reactions could be perceived as
mono-Claisen-Schmidt condensations, the pathway involves
Mannich reactions and elimination. As will be discussed
elsewhere, the reactions do not proceed by mixing the
reactants alone, in the presence of either an amine or a
carboxylic acid alone.
(13) (a) Katritzky, A. R.; Yannakopoulou, K.; Lang, H. J. Chem. Soc.,
Perkin Trans. 2 1994, 1867. (b) Betschart, C.; Schmidt, B.; Seebach, D.
HelV. Chim. Acta 1988, 71, 1999.
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Chem. 1977, 42, 4217.
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Perkin Trans. 1 1998, 2235. (b) Ryu, I.; Kusano, K.; Hasegawa, M.; Kambe,
N.; Sonoda, N. J. Chem. Soc., Chem. Commun. 1991, 1018. (c) Coveney,
D. J.; Patel, V. F.; Pattenden, G.; Thompson, D. M. J. Chem. Soc., Perkin
Trans. 1 1990, 2721. (d) Matsuyama, H.; Takei, Y.; Kobayashi, M. Bull.
Chem. Soc. Jpn. 1986, 59, 2657. (e) McIntyre, D.; Proctor, G. R.; Rees, L.
J. Chem. Soc. (C) 1966, 985. (f) Birkofer, L.; Kim, S. M.; Engels, H. D.
Ber. 1962, 95, 1495.
Acknowledgment. We thank the Australian Research
Council for funding the establishment and continuation of
(16) Chen, F.-E.; Liu, J.-D.; Fu, H.; Peng, Z.-Z.; Shao, L.-Y. Synth.
Commun. 2000, 30, 2295.
Org. Lett., Vol. 5, No. 17, 2003
3109

the ARC Special Research Centre for Green Chemistry
(CGC) and for postgraduate and postdoctoral scholarships
(to A.E.R. and U.P.K., respectively). C.R.S. thanks CSIRO
Molecular Science for supporting his secondment to the
CGC. Dr. Noel Dickson is thanked for technical assistance
and helpful discussion.
Supporting Information Available: Experimental pro-
cedure for the R,â-unsaturated carbonyl compounds in Tables
1 and 2 and spectral data for novel compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL0351145
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Org. Lett., Vol. 5, No. 17, 2003