J . Org. Chem. 1998, 63, 3745-3747
3745
Ta ble 1. Qu en ch in g of th e Rea ction betw een
Bu tylcer iu m Ch lor id e (2a ) a n d
1-(Tr im eth ylsilyl)-4-(N-p h en yla m in o)p en t-3-en -2-on e (1a )
Syn th esis of â,γ-Un sa tu r a ted Keton es via
Cer iu m -Med ia ted Ad d ition of
Or ga n olith iu m s to Silyla ted En a m in on es
w ith Va r iou s Acid ic Solu tion s
Renato Dalpozzo* and Antonio De Nino
Dipartimento di Chimica, Universita` della Calabria,
I-87030 Arcavacata di Rende (Cosenza), Italy
Giuseppe Bartoli, Marcella Bosco, and Letizia Sambri
Dipartimento di Chimica Organica “A. Mangini”, viale
Risorgimento 4, I-40136 Bologna, Italy
Enrico Marcantoni
HA
3a a (%)
4a (%)
Dipartimento di Scienze Chimiche, Universita`, via S.
HCl 10%
CH3COOH 10%
CH3COOH 5%
100b
96c
0
4
53
Agostino 1, I-62032 Camerino (Mc), Italy
47c
Received August 13, 1997
CH3COOH/CH3COONa
traces
>99
â,γ-Unsaturated ketones serve as versatile intermedi-
ates in organic synthesis.1 Their preparation is often
complicated by a proclivity toward prototropic rearrange-
ment to produce mixtures of conjugated and unconju-
gated ketones.2 Many synthetic approaches to â,γ-
unsaturated ketones have been attempted. Among these
are direct oxidation of homoallylic alcohols,3 Claisen
rearrangement of R-alkoxy ketone enolates,4 acylation of
olefins,5 allylation of borolanes,6 and reaction of butene-
diylmagnesium with esters.7 However, each suffers from
tedious procedures or limited applicability. In view of
the synthetic importance of â,γ-unsaturated ketones, it
was desirable to develop convenient methodologies for
their synthesis from readily available starting materials.
Previously, we developed a method for the almost
exclusive regiocontrolled alkylation of acyclic enaminones
(â-N-monoalkylamino R,â-unsaturated ketones) at the R′
and γ positions.8 More recently, the method was ex-
tended to the preparation of R′- and γ-(trimethylsilyl)
enaminones by addition of trimethylchlorosilane to N,R′-
and N,γ-dianions of enaminones, respectively.9 In addi-
tion, we discovered that the use of “dry”10 cerium(III)
chloride allows the addition of organolithiums to enami-
nones.11 As part of these investigations we report now a
a
b
GC ratios. Detected as 3a B. c Detected as 3a A.
facile and convenient synthesis of â,γ-unsaturated ke-
tones via silanol elimination from the adduct between
R′-(trimethylsilyl) enaminones and organocerium re-
agents.
Resu lts a n d Discu ssion
1-(Trimethylsilyl)-4-(N-phenylamino)pent-3-en-2-one (1a)
was added at -78 °C to an excess of butylcerium chloride
(2a ) prepared from equimolecular amounts of “dry”
cerium(III) chloride and organolithiums. After 2 h, the
reaction mixture was quenched with acid.
The acidic quenching is a cornerstone of the procedure
for the following reasons: (i) silanol elimination is pro-
moted, (ii) cerous salts are dissolved, (iii) acidic hydrolysis
of the silyl group is avoided.9
Some acidic quenching protocols were tested to find the
optimum conditions. All quenched mixtures were sub-
mitted to GC/MS analysis. The results, collected in Table
1, demonstrate that silanol elimination is acid catalyzed
and precedes hydrolysis of the silyl group.
Unfortunately, attempts to isolate the silanol inter-
mediate 4 (the sole product obtained in the reaction
quenched with acetic acid/sodium acetate buffer) were
unsuccessful (decomposition on silica gel, neutral alu-
mina or Florisil during chromatography) but its presence
was easily verified by MS and NMR analysis of the crude
* To whom correspondence should be addressed. E-mail: dalpozzo@
pobox.unical.it.
(1) Ohtsuka, Y.; Sasahara, T. and Oishi, T. Chem. Pharm. Bull.
1982, 30, 1106 and references therein.
(2) Pollack, R. M.; Bounds, P. L.; Bevis C. L. In The Chemistry of
Enones Part 1; Patai, S., and Zappoport, Z., Eds.; J ohn Wiley & Sons:
New York, 1989; p 599.
(3) Zaidlewicz, M. Synthesis 1988, 701.
(4) Kacinsky, J . L. C. and Solomon, R. G. J . Org. Chem. 1984, 51,
1393.
(5) (a) Beak, P.; Berger, K. R. J . Am. Chem. Soc. 1980, 102, 3848.
(b) Kang, K.-T.; U, J . S. Synth Commun. 1994, 24, 1507.
(6) Brown, H. C.; Soundararajan, R. Tetrahedron Lett. 1994, 35,
6963.
(7) Rieke, R. D.; Sell, M. S.; Xiong, H. J . Am. Chem. Soc. 1995, 117,
3429.
(8) Bartoli, G.; Bosco, M.; Cimarelli, C.; Dalpozzo, R.; Guerra, M.;
Palmieri, G. J . Chem. Soc., Perkin Trans. 2 1992, 649.
(9) Bartoli, G.; Bosco, M.; Dalpozzo R.; De Nino, A.; Iantorno, E.;
Tagarelli, A.; Palmieri, G. Tetrahedron 1996, 52, 9179.
(10) The water molecule found in “dry” cerium(III) chloride seems
to have no effect on the reagent, since the whole organolithium regent
should be destroyed by this adventitious water. cf. Evans, W. J .;
Feldman, J . D.; Ziller J . W. J . Am. Chem. Soc. 1996, 118, 4581.
(11) Bartoli, G.; Marcantoni, E.; Petrini, M.; Sambri, L. Chem. Eur
J . 1996, 2, 913.
12
reaction mixture.
The reaction of the trimethylsilyl derivatives and
organocerium reagents followed by hydrolysis to the â,γ-
unsaturated ketone with 10% HCl solution is quite
general (Table 2).
If primary alkylceriums and phenylcerium are em-
ployed, all reactions proceed in high yield, while second-
ary and tertiary alkylcerium reagents do not react (Table
2, entries 3 and 4).
Since substituents on C-1 make the R′-(trimethylsilyl)
enaminones prone to rapid hydrolysis of the silyl group,9
a one-pot reaction was carried out by adding the orga-
nocerium compound to the mixture of trimethylchlorosi-
lane and the N,R′-dianion of C-1 substituted enaminone
(Table 2, entry 13).
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Published on Web 05/13/1998