Masked α-Arylalkenyllithium reagents for efficient syntheses of functionalized monosubstituted and 1,1-disubstituted ethylenes

Full text of DOI:10.1021/ja972037y

J. Am. Chem. Soc. 1997, 119, 9321-9322
9321
Scheme 1
Masked r-Arylalkenyllithium Reagents for Efficient
Syntheses of Functionalized Monosubstituted and
1,1-Disubstituted Ethylenes
Alan R. Katritzky* and Dorin Toader
Center for Heterocyclic Compounds
Department of Chemistry
UniVersity of Florida, GainesVille, Florida 32611-7200
ReceiVed June 20, 1997
Due to its ability to favor R-carbanion formation, benzotria-
zole has proven to be a good tool for the introduction of silicon
into organic molecules.1 The potentially powerful transforma-
tions attributed to the presence of silicon in organic molecules,
thus, become available. One of the most useful transformations
in this category is the formation of an alkene by vicinal
elimination of silicon (for comprehensive reviews of these types
of reactions see ref 2). We now present a versatile method for
the introduction of 1-arylethenyl moieties into organic molecules
by the vicinal elimination of silicon from (2-benzotriazolyl-2-
arylethyl)silanes. These intermediates act as masked 1-arylethen-
yl units that can be transformed into the corresponding alkene
when needed (cf. the concept of “silicon-masked enones”
introduced by Fleming3 ). The vicinal elimination of silicon
can be accomplished by several protocols including pyrolysis,
[1,4]-Brook rearrangement, and fluoride ion induced â-elimina-
tion. Examples are documented illustrating potentially general
methods for the preparation of styrenes, 1,2-disubstituted allyl
alcohols, R-substituted acrylamides, 1,3-disubstituted homoallyl
alcohols, and γ,δ-unsaturated ketones.
Previous methods for generating alkenyllithiums use either
the Shapiro reaction, applied to carbonyl compounds,4,5 or
lithium-halogen exchange, applied to the corresponding vinyl
halides.6 Our approach utilizes 1-(arylmethyl)benzotriazoles (1)
that can be easily prepared from the corresponding arylmethyl
chlorides in high yields (Scheme 1). Compounds 1 can be
deprotonated to give the corresponding benzyllithiums and then
reacted with electrophiles in high yields (for leading examples
see 7). The nucleophilic displacement of chlorine in (chloro-
methyl)trimethylsilane (2) by the carbanion derived from 1 gives
rise to reagents 3a-e in high yields (Scheme 1). The reagents
3a-e are highly stable solid compounds which can be distilled
under reduced pressure without decomposition.8
Scheme 2
corresponding styrene 6 (Scheme 2) in high yield. The main
reason why TBAF shows a higher elimination rate is the higher
concentration of “naked” fluoride ions (for recent discussion
see ref 9 and references therein). 18-Crown-6 was used to
increase the solubility of cesium fluoride in DMF.10 However,
the elimination rate is still slower compared to that of TBAF.
Upon deprotonation, reagents 3 react with electrophiles
regiospecifically R to the benzotriazole to give the corresponding
adducts. Thus, with alkyl halides, compounds of type 4 are
obtained cleanly (Scheme 2). Heating these adducts at 120 °C
affords the corresponding 1,1-disubstituted ethylenes in excellent
yields as illustrated by the transformation 4 f 5 (Scheme 2).
Addition of the carbanions derived from 3 to non-enolizable
aldehydes is a facile process. Aryl and tertiary alkyl aldehydes
gave trimethylsilyl allyl ethers by a [1,4]-Brook rearrangement
(Scheme 3).11,12 This process is most likely intramolecular,
since the stereochemistry of the intermediate alkoxides 7
dramatically influences the reaction conditions required. Thus,
when the phenyl group of the incoming nucleophile possesses
no substituents in the 2- or 6-position, the rearrangement of the
alkoxide 7 takes place on simple warming from -78 °C to room
temperature (rt), as is the case with compounds 8a-c (Scheme
3). For 3a, heating the alkoxide 7 under reflux in THF for 3 h
was necessary to yield the corresponding 8d. Upon treatment
of 8d with TBAF, the free allyl alcohol 9 was isolated in 70%
yield (Scheme 3).
The vicinal elimination of silicon in compounds 3 can be
accomplished by treatment with fluoride ion. Both tetrabutyl-
ammonium fluoride (TBAF, 1 M solution in THF) and cesium
fluoride in dimethylformamide work well with 3d to give the
(1) (a) Katritzky, A. R.; Kuzmierkiewicz, W. J. Chem. Soc., Perkin.
Trans. 1 1987, 819-823. (b) Katritzky, A. R.; Lam, J. N. Heteroat. Chem.
1990, 1, 21-31. (c) Katritzky, A. R.; Toader, D.; Xie, L. Synthesis 1996,
1425-1427.
(2) (a) Ager, D. J. Org. React. (N. Y.) 1990, 38, 1-223. (b) Kocienski,
P. In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon Press: Oxford, 1991; Vol. 6, pp 1000-1007. (c) Maguire, A.
R. In ComprehensiVe Organic Functional Group Transformations; Katritzky,
A. R., Meth-Cohn, O., Rees, C. W., Eds.; Pergamon Press: Cambridge,
1995; Vol. 1, pp 648-656.
(3) (a) Fleming, I.; Goldhill, J. J. Chem. Soc., Chem. Commun. 1978,
176-177. (b) Ager, D. J.; Fleming, I. J. Chem. Soc., Chem. Commun. 1978,
177-178.
(4) Kende, A. S.; Jungheim, L. N. Tetrahedron Lett. 1980, 21, 3849-
3852.
The reaction of 3b with phenyl isocyanate gave the inter-
mediate alkoxide 10 which upon aqueous workup afforded the
(9) Christe, K. O.; Wilson, W. W.; Wilson, R. D.; Bau, R.; Feng, J. J.
Am. Chem. Soc. 1990, 112, 7619-7625.
(10) Wynn, D. A.; Roth, M. M.; Pollard, B. D. Talanta 1984, 31, 1036-
1040.
(11) Brook, A. G.; Bassindale, A. R. Molecular Rearrangements of
Organosilicon Compounds. In Rearrangements in Ground and Excited
States; De Mayo, P., Ed.; Academic Press: New York, 1980; Vol. 2, pp
149-227.
(12) Tsukamoto, M.; Iio, H.; Tokoroyama, T. Tetrahedron Lett. 1985,
26, 4471-4474.
(5) Chamberlin, A. R.; Bloom, S. H. Org. React. (N. Y.) 1990, 39, 1-83.
(6) Wakefield, B. J. Organolithium Methods; Academic Press: London,
1988; pp 27-32.
(7) (a) Katritzky, A. R.; Xie, L.; Toader, D.; Serdyuk, L. J. Am. Chem.
Soc. 1995, 117, 12015-12016. (b) Katritzky, A. R.; Toader, D.; Xie, L. J.
Org. Chem. 1996, 61, 7571-7577.
(8) When centimolar amounts of compounds 3a-e were prepared,
purification by distillation with a Kugelrohr apparatus at 0.1 Torr and 100-
120 °C was found to be more convenient than flash column chromatography.
S0002-7863(97)02037-4 CCC: $14.00 © 1997 American Chemical Society

9322 J. Am. Chem. Soc., Vol. 119, No. 39, 1997
Communications to the Editor
Scheme 3
Scheme 6
Scheme 7
Scheme 4
Scheme 8
Scheme 5
elimination is accomplished with TBAF to convert 17 into the
γ,δ-unsaturated ketone 18 in 74% yield.
To synthesize enones, we needed to react the anion derived
from 3b with a carboxylic acid derivative. Esters gave complex
mixtures, but an acid chloride afforded the adduct 19 in excellent
yield. Suitable reaction conditions to accomplish the elimination
from this substrate are CsF in DMF and a crown ether to
enhance the solubility of the fluoride. These conditions afforded
a mixture of the desired enone 20 in 74% yield together with
the chalcone 21 as the E-regioisomer (Scheme 7). The
formation of compound 21 can be explained by a Grovenstein-
Zimmerman rearrangement13,14 in which the intermediate car-
banion 22 is stabilized by formation of the bridged phenonium
anion 23 or alternatively by conversion of carbanion 22 into
intermediate 24 (Scheme 8).
corresponding masked acrylamide 12 in excellent yield (Scheme
4). Attempted vicinal elimination of silicon in 12 with TBAF
afforded only the desilylation product 13, probably due to the
proximity of the acidic amide proton. However, direct heating
of intermediate 10 without a solvent at 130 °C gave the
acrylamide 11 in 64% yield (Scheme 4). To the best of our
knowledge, this silicon [1,4]-C f O rearrangement in amide
systems is unprecedented.
Phenyloxirane reacts with the carbanion derived from 3c to
give the intermediate 14, which did not rearrange to the
corresponding homoallylic alcohol by a [1,5]-Brook rearrange-
ment on refluxing in THF; instead adduct 15 was obtained in
72% yield upon aqueous workup of 14 (Scheme 5). To
accomplish the vicinal elimination of silicon, the alcohol 15
was first deprotonated to the corresponding alkoxide and then
treated with TBAF to afford the desired elimination product 16
in 81% yield (Scheme 5).
In summary, we have shown that reagents of type 3 show
high promise for the regiospecific preparation of compounds
containing a silicon-masked R-arylalkenyl moiety. These
intermediates can eliminate the protecting group under a variety
of conditions to give the corresponding terminal alkene contain-
ing compounds. More detailed studies of this methodology are
currently being pursued.
Supporting Information Available: Typical experimental proce-
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JA972037Y
Conjugate addition of alkenyllithiums is usually accomplished
Via previous conversion into the cuprate. This was not necessary
in our case, as deprotonation of 3b with n-BuLi and subsequent
reaction with an enone gave regiospecifically the conjugate
addition product 17 in 83% yield (Scheme 6). The final
(13) Grovenstein, E., Jr. Angew. Chem., Int. Ed. Engl. 1978, 17, 313-
332.
(14) Hunter, D. H.; Stothers, J. B.; Warnhoff, E. W. Rearrangements in
Carbanions. In Rearrangements in Ground and Excited States; De Mayo,
P., Ed.; Academic Press: New York, 1980; Vol. 1, pp 391-470.