New synthesis of α-benzylaldehydes from 2-(dimethylphenylsilylmethylene)alkanals by fluoride promoted phenyl migration

Article abstract of DOI:10.1016/S0040-4039(02)01178-4

α-Benzyl aldehydes are prepared from easily available β-silylalkenals and fluoride reagents, under mild experimental conditions; the reaction occurs instantaneously with almost quantitative yields. A plausible mechanism is suggested, which involves a 1,2-

Full text of DOI:10.1016/S0040-4039(02)01178-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 5813–5815
New synthesis of a-benzylaldehydes from
2-(dimethylphenylsilylmethylene)alkanals by fluoride promoted
phenyl migration
Laura Antonella Aronica, Francesca Morini, Anna Maria Caporusso and Piero Salvadori*
Dipartimento di Chimica e Chimica Industriale, Istituto del CNR di Chimica dei Composti Organo Metallici (ICCOM),
sezione di Pisa, Via Risorgimento, 35, 56126 Pisa, Italy
Received 16 May 2002; revised 14 June 2002; accepted 17 June 2002
Abstract—a-Benzyl aldehydes are prepared from easily available b-silylalkenals and fluoride reagents, under mild experimental
conditions; the reaction occurs instantaneously with almost quantitative yields. A plausible mechanism is suggested, which
involves a 1,2-phenyl migration from the silicon to the adjacent carbon atom. © 2002 Elsevier Science Ltd. All rights reserved.
a-Benzyl aldehydes are extremely useful intermediates
in organic synthesis1 and important industrial sub-
strates.2 They are usually prepared starting from cin-
namaldehydes by hydrogenation or selective addition of
alkyl lithium to the carbonꢀcarbon double bond,3 pro-
vided that the carbonyl group is protected. Both these
methods suffer from strong experimental conditions,
since hydrogenation requires high H2 pressure and tem-
perature (50 psi, 200–400°C) and carbolithiation must
be performed with excess of RLi at −78°C. More
complicated methodologies involve multistep sequences
starting from Fischer alkenyl carbene complexes,4
aziridines,5 pseudoephedrine derivatives6 and a-
benzyloxazolidinones.7
Various fluoride sources such as KF, BF3, TBAF were
tested and the obtained results are reported in Table 1.
KF/MeOH and TBAF/MeOH were completely ineffec-
tive (Table 1, entries 1, 2): (Z)-1 was recovered com-
pletely unreacted. This lack of activity could be due to
the strong hydrogen bonds between the hydroxy group
of methanol and the fluoride ion. As a consequence, F−
resulted shielded and could not coordinate the silicon
atom.
The reaction with BF3–acetic acid complex generated a
mixture of (E)-2-(dimethylphenylsilylmethylene)hexanal
(E)-1a and 2-benzylhexanal 2a (Table 1, entry 3). The
formation of the trans isomer (E)-1a (thermodynami-
cally more stable) can be easily explained considering
the acidic experimental conditions (CH3COOH) that
cause addition of proton to the double bond, formation
of a b-stabilised carbocation which, after rotation
through the CꢀC s bond and consequent deprotona-
tion, affords (E)-1a (Scheme 2). Indeed, when paratolu-
ensulfinic acid (p-TsH) was used, exclusive
isomerisation of the b-silylalkenal was observed (Table
1, entry 4).
In this paper we describe a new convenient synthesis of
a-benzyl aldehydes 2 starting from b-silylalkenals (Z)-1,
based on the fluoride affinity for silicon8 (Scheme 1).
F
O
C
R
R
H
H
CH CH2
OHC
SiMe2Ph
(Z)-1
When the reaction was performed at room temperature
(25°C) with tetrabutylammonium fluoride in DMSO
and hydrolysed immediately after adding TBAF, the
complete conversion of the substrate to 2-benzylhexa-
nal 2a was observed. One mole of fluoride source was
sufficient (Table 1, entries 5, 6) and the reaction pro-
ceeded in various polar aprotic solvents, such as
DMSO, THF, CH3CN (Table 1, entries 6–8), resulting
completely chemoselective: 2a was exclusively formed.
Scheme 1.
Keywords: a-benzyl aldehydes; alkynes; b-silylalkenal; silicon and
compounds.
* Corresponding author. Tel.: +39-050-918273; fax: +39-050-918260;
e-mail: psalva@dcci.unipi.it
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01178-4

5814
L. A. Aronica et al. / Tetrahedron Letters 43 (2002) 5813–5815
Table 1. Synthesis of 2-benzylaldehydes 2 from b-silylakenalsa (Z)-1
R
SiMe2Ph
R
R
H
+
OHC
H
OHC
OHC
SiMe2Ph
(E)-1
2
(Z)-1
Entry
(Z)-1
R
Reaction conditions
Reagent/substrate (molar ratio)
Yield (%)b
reagent/solvent/temp./time
(E)-1
2
1
2
3
4
5
6
7
8
9
a
a
a
a
a
a
a
a
a
nBu
nBu
nBu
nBu
nBu
nBu
nBu
nBu
nBu
KF/MeOH/rt/24 h
TBAF/MeOH/rt/24 h
10
1
1
0.2
5
1
1
1
0.1
–
–
80
100
–
–
–
–
–
–
–
BF3–2CH3COOH/CH2Cl2/rt/24 h
TsH/CH3CN/80°C/24 h
TBAF/DMSO/rt/1 min
TBAF/DMSO/rt/1 min
TBAF/THF/rt/1 min
20
–
100 (68)
100
100
100
100
TBAF/CH3CN/−60°C/1 min
TBAF/THF/rt/1 h
10
11
12
b
c
d
TBAF/DMSO/rt/1 min
TBAF/DMSO/rt/1 min
TBAF/DMSO/rt/1 min
1
1
1
–
–
–
100 (46)
100 (71)
100 (60)
a Reactions were run with 1 mmol of substrate in 10 ml of solvent. b-Silylalkenals (Z)-1a–d were prepared by rhodium catalysed silylformylation
of the corresponding acetylenes, performed in a stainless steel autoclave, under 10 atm of CO, at room temperature for 24 h.10
b Determined by GLC of the reaction mixture after work up. All new compounds were identified and characterised by FT-IR, NMR (1H and 13C),
GC–MS and elemental analysis. In parentheses the isolated yields of pure compounds are reported.
H
H
R
H
R
H
R
SiMe2Ph
H
H
OHC
SiMe2Ph
OHC
SiMe2Ph
OHC
(Z)-1
(E)-1
Scheme 2.
For instance, when (Z)-1a was reacted with an equimo-
lar amount of TBAF in CH3CN, the yield of 2-benzyl-
hexanal was quantitative within 1 minute at −60°C
(Table 1, entry 8). The reaction was successfully
extended to branched b-silylalkenals (Table 1, entries
10–12) and afforded the corresponding 2-benzylalde-
hydes 2b–d with good yields after purification (not
optimised), showing the high potentialities of this
process.
H
H
R
Ph
Si
R
H
C
H
R
H
F
Ph
H
H
Me
Me
Ph
H
C
O
Si
C
Si Me
Me
Me
F
Me
(Z)-1
O
O
F
3
4
H
R
Ph
F
R
Ph
R
H
H
H2O
Me
Me
Me
H
Si
C
O
Si
OHC
O
Me
F
5
2
To our knowledge, no data on this fluoride–silicon
mediated transformation are reported. The reaction
seems to involve a 1,2-migration of phenyl from the
silicon atom to the adjacent carbon atom. Indeed, it is
known that fluoride ion reacts with phenyltrimethylsi-
lane to generate a phenyl ion9 which could act as
nucleophile on the a,b-unsaturated aldehyde. A possi-
ble mechanism is reported in Scheme 3. Fluoride adds
to (Z)-1 forming the pentacoordinate silicon derivative
3, the phenyl group migrates generating the enolate 4
which can intramolecularly cyclise to form silyleno-
lether 5. After hydrolysis 2-benzylaldehydes 2 are
Scheme 3.
obtained. According to this mechanism, a catalytic
amount of TBAF (0.1 mol) in DMSO determines a
complete conversion of (Z)-1a to 2a, even if a longer
reaction time is necessary (Table 1, entry 9). Moreover,
when (E)-2-(dimethylphenylsilylmethylene)hexanal (E)-
1a was reacted with an equimolar amount of TBAF in
DMSO, 2-benzylhexanal 2a was exclusively obtained,
confirming the formation of enolate 4 which can rotate
through the sp3 CꢀC bond (Scheme 4).

L. A. Aronica et al. / Tetrahedron Letters 43 (2002) 5813–5815
5815
2. (a) Rhone-Poulenc, DE, 1145161, 1963; C.A. EN, 59,
9900d, 1963; (b) Soda Aromatic Co. NL, 6502482, 1964;
C.A. EN, 64, 19497g, 1966; (c) L. Givaudan and Cie DE,
2851024, 1979; C.A. EN, 91, 107808a, 1979.
Me
Me
Me
Me
Me
Me
Ph
Bu
Si
F
Bu
Si
F
Bu
Si
F
Ph
H
H
H
C
O
2a
C
O
Ph
C
O
H
(E)-1a
H
H
3
4
3. (a) Bremand, N.; Mangeney, P.; Normant, J. F. Tetra-
hedron Lett. 2001, 42, 1883–1885; (b) Bremand, N.; Man-
geney, P.; Normant, J. F. Synlett 2000, 4, 532–534.
4. Barluega, J. J. Pure Appl. Chem. 1999, 71, 1385–1391.
5. Tanner, D.; Birgersson, C.; Gogoll, A. Tetrahedron 1994,
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6. (a) Myers, A. G.; Yang, B. H.; Chen, H.; Gleason, J. L.
J. Am. Chem. Soc. 1994, 116, 9361–9362; (b) Myers, A.
G.; Yang, B. H.; Chen, H.; McKinstry, L.; Kopecky, D.
J.; Gleason, J. L. J. Am. Chem. Soc. 1997, 119, 6496–
6511.
Scheme 4.
Br
Ph
Si Me
Me
BrCH2CH2CH2CH2
H
F
Ph
H
C
Si
C
O
1e
Me
Me
O
F
Br
H2O
Ph
H
Me
C
O
Si
OHC
Me
2e
7. Bull, S. D.; Davies, S. G.; Nicholson, R. L.; Sanganee,
H. J.; Smith, A. D. Tetrahedron: Asymmetry 2000, 11,
3475–3479.
F
Scheme 5.
8. (a) Anderson, J. C.; Flaherty, A. J. Chem. Soc., Perkin
Trans. 1 2000, 3025–3027; (b) Shepard, M. S.; Carreira,
E. M. J. Am. Chem. Soc. 1997, 119, 2596–2605; (c)
Chenede´, A.; Abd.Rahamn, N.; Fleming, I. Tetrahedron
Lett. 1997, 38, 2381–2382; (d) Brasseur, D.; Marek, I.;
Normant, J. F. Tetrahedron 1996, 52, 7235–7250; (e)
Kishi, N.; Maeda, T.; Mikami, K.; Nakai, T. Tetrahedron
1992, 48, 4087–4098; (f) Jefford, C. W.; Moulin, M. Helv.
Chim. Acta 1991, 74, 336–342; (g) Bachi, M. D.; Bosch,
E. Tetrahedron Lett. 1988, 29, 2581–2584; (h) Oda, H.;
Sato, M.; Morizawa, Y.; Oshima, K.; Nozaki, H. Tetra-
hedron 1985, 41, 3257–3268.
9. DePuy, C. H.; Bierbaum, V. M.; Flippin, L. A.;
Grabowski, J. J.; King, G. K.; Schmitt, R. J.; Sullivan, S.
A. J. Am. Chem. Soc. 1980, 102, 5012–5015.
10. Aronica, L. A.; Terreni, S.; Caporusso, A. M.; Salvadori,
P. Eur. J. Org. Chem. 2001, 22, 4321–4329 and references
cited therein.
11. 2-Benzylhexanal 2a (representative procedure): 3 mmol of
Me2PhSiH, 3 mmol of 1-hexyne, 3 mL of toluene and
0.0022 g (3×10−3 mmol) of Rh4(CO)12 were put in a Pyrex
‘Schlenk’ tube, under CO atmosphere. This solution was
introduced in a 25 mL stainless steel autoclave fitted with
a Teflon inner crucible and a stirring bar, previously
placed under vacuum (0.1 mmHg), by a steel siphon. The
reactor was pressurised with 10 atm of carbon monoxide
and the mixture was stirred at room temperature for 24
h. After removal of excess CO (fume hood), the reaction
mixture was diluted with pentane, filtered (Celite) and
concentrated by bulb to bulb distillation (1 mmHg). The
residue was purified by column chromatography on silica
gel using pentane/EtOAc (95/5) as eluent, affording the
pure aldehyde10 (Z)-1a (85%). To a solution of 0.24 g (1
mmol) of (Z)-1a in 10 ml of DMSO, was added, at room
temperature, 1 ml of TBAF (1 M in THF). The reaction
mixture was hydrolysed with water, extracted with Et2O
and the organic layers were dried over Na2SO4. After
concentration under vacuum, the crude product was
purified by column chromatography on silica gel using
hexane/EtOAc (90/10) as eluent, affording the title com-
pound 2a (68%).3b
Finally, 1-benzylcyclopentancarbaldehyde 2e was
obtained when (Z)-2-(dimethylphenylsilylmethylene)-6-
bromohexanal (Z)-1e was reacted with tetra-
butylammonium fluoride (Scheme 5). In this case, after
addition of fluoride to silicon and subsequent phenyl
transposition to the alpha carbon atom, an intramolec-
ular attachment of the formed carbanion on the carbon
bearing bromine could occur. Hydrolysis of the CꢀSi
bond afforded 2e quantitatively, confirming the mecha-
nism proposed in Scheme 3.
In conclusion, this promoted fluoride regioselective
phenyl migration represents a direct methodology for
the preparation of 2-benzylaldehydes from b-silylalke-
nals (Z)-1. Considering that compounds (Z)-1 can be
easily generated by Rh-catalysed silylformylation of
1-alkynes with phenylsilanes,10 the above results open a
new route to the synthesis of 2-benzylaldehydes starting
from acetylenic substrates.11 The extension and optimi-
sation of this method to the preparation of a large
variety of aryl and heteroaryl aldehydes is in progress.
Acknowledgements
Financial support for this work was provided by the
Ministero dell’Istruzione, dell’Universita’
e
della
Ricerca (MIUR).
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