Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 2555–2557
Boron trifluoride-catalyzed reaction of alkyl fluoride with silyl
enolate, allylsilane, and hydrosilane
Koji Hirano, Kazuya Fujita, Hideki Yorimitsu, Hiroshi Shinokubo and Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto-daigaku Katsura,
Nishikyo-ku, Kyoto 615-8510, Japan
Received 13 January 2004; revised 29 January 2004; accepted 30 January 2004
Abstract—Alkylation of silyl enolates with tert-alkyl or allylic fluorides proceeds smoothly in the presence of a catalytic amount of
boron trifluoride to afford the corresponding carbonyl compounds. Allylation and reduction of alkyl fluorides with allylsilane and
hydrosilane, respectively, occur under BF3 catalysis.
ꢀ 2004 Elsevier Ltd. All rights reserved.
Alkyl fluoride is rarely the choice of alkylation agents
because of the poor ability of fluoride as a leaving
group. Alkylation of enolate mostly utilizes alkyl chlo-
ride, bromide, and iodide.1;2 Alkylation of ketene silyl
acetal with alkyl fluoride was accomplished by using
trimethylaluminum.3 However, the considerable reac-
tivity of alkylaluminum reagent may undermine func-
tional group compatibility. Moreover, air-sensitive
alkylaluminum is bothersome to handle. Other fluoro-
philic Lewis acids can be alternatives to trimethylalu-
minum. Here we report alkylation reaction of silyl
enolate with alkyl fluoride in the presence of a catalytic
amount of boron trifluoride.
(entry 5). Reaction of 2f failed, even at elevated tem-
perature, probably due to the steric hindrance (entry 6).
On the other hand, ketene silyl acetal 2g reacted with 1a
smoothly to furnish ester 3g in spite of two methyl
groups (entry 7). Whereas tertiary alkyl fluoride 1b also
participated in the reaction (entry 8), reaction of sec-
ondary alkyl fluorides resulted in formation of alkenes.
For instance, 3-fluoro-1-phenylbutane was consumed
under the same reaction conditions to afford 2- or
3-butenylbenzene with contamination by trace of the
desired product. Primary alkyl fluorides resisted the
reaction and were completely recovered after workup.
Boron trifluoride was more effective than trimethyl-
aluminum3 as a catalyst. Treatment of a mixture of 1a
and 2a with 10 mol % of trimethylaluminum at )20 ꢁC
for 15 h afforded 3a in 46% yield, along with unchanged
1a (52%). Fluoride 1c having a ketone moiety was
subjected to the BF3-catalyzed reaction to furnish the
desired diketone 3i in 54% yield (entry 9). On the other
hand, Me3Al-catalyzed reaction (10 mol %, )20 ꢁC, 15 h)
gave no 3i and 1c remained unchanged. Ether and ester
functionalities were compatible under the reaction con-
ditions (entries 10 and 11).
Treatment of 3-fluoro-3-methyl-1-phenylbutane4 (1a,
1.0 mmol) with silyl enolate 2a (3.0 mmol) in the pres-
ence of 2 mol % of BF3ÆOEt2 in dichloromethane (3 mL)
at )20 ꢁC for 15 h afforded ketone 3a in 89% yield (Table
1, entry 1). Other enolates underwent alkylation reaction
with 1a. The enolate of propiophenone 2b was alkylated
to afford a,b,b-trimethyl ketone 3b in 65% yield (entry
2). The presence of the aromatic rings of 2a and 2b was
not essential. Alkylation of 2-siloxypropene 2c and
1-siloxycyclohexene 2d gave the corresponding ketones
in good yields (entries 3 and 4). Reaction of trimethyl-
silyl enolate of acetaldehyde 2e resulted in recovery of 1a
Besides tertiary alkyl fluoride, allylic fluoride5 under-
went the reaction to afford c,d-unsaturated ketone
(Table 2). Unfortunately, the reaction always yielded a
mixture of regioisomers 5 and 6. Moreover, 6b and 6c
were obtained as 1:1 mixtures of syn and anti isomers.
In contrast to the reaction of 2f with 1a, a,a-di-
methyl ketones 5d and 6d were obtained (entry 4).
Keywords: Alkyl fluoride; Alkylation; Silyl enolate; Boron trifluoride;
Silane.
* Corresponding author. Tel.: +81-75-383-2437; fax: +81-75-383-2438;
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.01.145