Silylformylation - Fluoride-assisted aryl migration of acetylenic derivatives in a versatile approach to the synthesis of polyfunctionalised compounds

Article abstract of DOI:10.1002/ejoc.200500883

Polyfunctionalised aldehydes and dihydropyrans are prepared from easily available functionalised 1-alkynes through a two-step silylformylation/aryl migration sequence. The silylformylation process is performed under mild experimental conditions and affords the corresponding β-silylalkenals in high yields. The fluoride-promoted migration step occurs instantaneously with quantitative conversion. The chemo-, regio- and stereoselectivity can be modulated according to the nature and the position of the functional group on the acetylene precursors. When a good leaving group is present in the ω position of the aliphatic chain of the alkyne a cyclisation product is obtained, while α,β-unsaturated aldehydes are generated from propargylic tosylamides. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

Full text of DOI:10.1002/ejoc.200500883

FULL PAPER
DOI: 10.1002/ejoc.200500883
Silylformylation – Fluoride-Assisted Aryl Migration of Acetylenic Derivatives
in a Versatile Approach to the Synthesis of Polyfunctionalised Compounds
Laura Antonella Aronica,[a] Patrizio Raffa,[a] Giulia Valentini,[a] Anna Maria Caporusso,[a]
and Piero Salvadori*[a]
Keywords: Alkynes / Carbonylation / Rearrangement / Aldehydes
Polyfunctionalised aldehydes and dihydropyrans are pre-
pared from easily available functionalised 1-alkynes through
a two-step silylformylation/aryl migration sequence. The si-
lylformylation process is performed under mild experimental
conditions and affords the corresponding β-silylalkenals in
high yields. The fluoride-promoted migration step occurs in-
stantaneously with quantitative conversion. The chemo-, re-
gio- and stereoselectivity can be modulated according to the
nature and the position of the functional group on the acety-
lene precursors. When a good leaving group is present in the
ω position of the aliphatic chain of the alkyne a cyclisation
product is obtained, while α,β-unsaturated aldehydes are
generated from propargylic tosylamides.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
strates and the preparation of different classes of com-
pounds (linear, cyclic, unsaturated) according to the nature
and the position of the functional group on the aliphatic
chain of the alkyne.
Introduction
Carbon–silicon bond-formation reactions are of great
importance and are widely used in organic synthesis.
Among a variety of methods developed for such transfor-
mations, transition metal-promoted silylations[1] provide
useful routes to organosilicon compounds, currently sub-
jects of much attention owing to their low cost, low toxicity,
generality, selectivity and ease of handling. Rhodium-medi-
ated silylformylation of acetylenic substrates, for instance,
has been being intensively studied for over ten years,[2] since
it generates β-silylalkenals, polyfunctionalised compounds
that can be subjected to Peterson olefination,[3] Nazarov-
and Trost-type annulations,[4] isomerization of the double
bond, reduction and Wittig transformation of the carbonyl
group.[5]
Scheme 1.
Results and Discussion
Recently, taking advantage of the high chemical affinity
(BDE Si–F = 135 kcal) between silicon and fluorine,[6] we
were able to convert 2-(dimethylphenylsilylmethylene)hexa-
nal into the corresponding 2-benzylhexanal through aro-
matic ring migration from the dimethylphenylsilyl moiety
to the adjacent carbon atom of the β-silylalkenal (Scheme 1,
step 2).[7] The two-step silylformylation/phenyl migration
sequence was successfully applied to several terminal acety-
lenes and arylsilanes to yield 2-(arylmethyl)alkanals, useful
building blocks for organic chemistry[8] and important in-
dustrial products.[9] Here we report the extension of this
tandem process to variously functionalised acetylenic sub-
An important condition for the synthetic utility of a two-
step approach based on such a Si–C migration is ready ac-
cess to the requisite (Z)-β-silylalkenals. Silylformylations of
terminal acetylenes can be easily performed at room tem-
perature in a stainless steel autoclave. In a typical run, a
toluene solution of equimolar amounts of silane and alkyne
and a catalytic quantity of Rh4(CO)12 was introduced into
the autoclave, the reactor was pressurized with carbon
monoxide, and the mixture was stirred for the required time
(Table 1, Table 2, step 1).
As would be expected, the reactions proceeded with com-
plete regioselectivity, since the silicon is usually introduced
onto the terminal position of the acetylene. The pressure of
carbon monoxide was chosen according to the steric hin-
drance of both the unsaturated substrates and the silanes.
The corresponding (Z)-β-silylalkenals were obtained in
high yields regardless of the electronic and steric require-
[a] Dipartimento di Chimica e Chimica Industriale, Università de-
gli Studi di Pisa,
Via Risorgimento 35, 56126 Pisa
E-mail: psalva@dcci.unipi.it
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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Table 1. Silylformylation/aryl migration reactions of terminal acetylenes and aryldimethylsilanes.
[a] Reaction conditions: 3 mmol of alkyne 1, 3 mmol of silane 2, 3 mL of toluene, 0.1 mmol% of Rh4(CO)12, room temperature, 24 h.
[b] Reaction conditions: 2 mmol of aldehydes (Z)-3 added to 5 mL of TBAF (1  in THF) in 10 mL of THF and immediately hydrolysed.
[c] Determined by GC analysis; the isolated yields are reported in parentheses (not optimised). [d] Reaction time: 41 h. [e] Reaction
performed with alkyne/silane ratio = 2:1, 0.2 mol% of catalyst; 30% of doubly silylated by-products. [f] Diastereomers mixture: Z/E =
60:40; 26% of phenyldimethylsilyloxy aldehydes. [g] The mixture of Z/E diastereomers yielded 4ea as sole product.[7a]
ments either of the alkynes or of the silanes (Table 1, strate had a great influence on how the reactions proceeded.
Table 2, step 1), confirming the trend we had observed pre- Unsaturated moieties (C=C, CϵC) or nitrile or hydroxy
viously.[7b] It is well known that the silylformylation reac- groups in the ω positions of the alkynes were not involved
tion can tolerate many functional groups on the alkynes; in the migration step but were directly transferred to the
indeed, when α-, β- and ω-substituted acetylenes were saturated aldehydic products (Table 1, entries 5–8, step 2).
treated with Me2PhSiH, chosen as model reagent, the pres- In contrast, the presence and the position of a leaving group
ence of double or triple bonds, nitrile, halogens, tosylate, on the aliphatic chain of the acetylene had a dramatic effect
hydroxy or amido groups did not markedly affect the reac- on the chemo- and regioselectivity of the process. When a
tions, which in most cases yielded the expected products halide or a tosyl substituent was positioned at the end of
quantitatively (Table 1, Table 2, Scheme 3, step 1). It is the hydrocarbon chain, exo-tet ring-closure reactions took
noteworthy that when an acetylene bearing a free amino place with the formation of three-, five- and six-membered
group was treated with the silane it was not possible to iso- ring products, all favoured according to Baldwin’s rules
late the β-silylalkenal, although complete conversion of the (Table 2, step 2).[12] Cycloalkanecarbaldehydes 7, 11, 13 and
reagents was observed, with concomitant formation of 14 (Table 2, entries 1 and 5–8, step 2) and 5-benzyl-3,4-di-
some unidentified materials. Moreover, small amounts of hydro-2H-pyran (8, Table 2, entries 2–4, step 2) were ob-
by-products of double silylation were detected when 1,7- tained as major products. In particular, aldehydes 7, 11, 13
octadiyne was used even if the reaction was carried out in and 14 were generated by intramolecular C-alkylation of
this case with excess alkyne and under high CO pressure the carbanion 15 formed after the fluoride addition to the
(Table 1, entry 5).
silicon atom and subsequent phenyl migration (Scheme 2).
With easy access to the (Z)-β-silylalkenals to hand, we In the cases of α-branched acetylenes 5g–h the cyclisation
turned to the TBAF-promoted migration step (Table 1, reactions took place with good diastereoselectivity, with
Table 2, step 2). The reactions were performed at room tem- (Z)-13 and (Z)-14 being formed as major isomers (Table 2,
perature, with addition of aldehyde (2 mmol) to TBAF (1  entries 7–8, step 2). The benzyldihydropyran 8 (Table 2, en-
in THF solution, 5 mL) and hydrolysis of the resulting solu- tries 2–4, step 2) was obtained by kinetically favoured intra-
tion with water immediately afterwards. The 1,2 rearrange- molecular O-alkylation of the enolate form of 15
ment of the aromatic ring occurred smoothly with complete (Scheme 2). Complete chemoselectivity towards 8 was ob-
retention of the original configuration of the Ar group served in the presence of an excellent leaving group such as
(Table 1, entries 1–4, step 2). In contrast, the chemical fea- tosylate (Table 2, entry 4, step 2), while the reactions of ω-
tures of the functional group situated on the acetylenic sub- chlorinated and ω-brominated β-silylalkenales (Z)-6b and
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Silylformylation – Fluoride-Assisted Aryl Migration of Acetylenic Derivatives
FULL PAPER
Table 2. Silylformylation/phenyl migration reactions of acetylenes characterised by the presence of a leaving group.
[a] Reaction conditions: 3 mmol of alkyne 1, 3 mmol of silane 2, 3 mL of toluene, 0.1 mmol% of Rh4(CO)12, room temperature, 24 h.
[b] Reaction conditions: 2 mmol of aldehydes (Z)-3 added to 5 mL of TBAF (1  in THF) in 10 mL of THF and immediately hydrolysed.
[c] Determined by GC analysis; the isolated yields are reported in parentheses (not optimised). [d] Crude product (diastereomers mixture:
Z/E = 80:20).
(Z)-6c involved the formation of relevant amounts of by-
The obtained results prompted us to extend our investi-
products (Table 2, entries 2, 3, step 2). In the case of alde- gation to the reactivity of propargyl derivatives (Scheme 2,
hyde (Z)-6b the TBAF-mediated reactions yielded the linear n = 0) characterised by a good leaving group such as acetate
1-benzylaldehyde 9 together with the cyclisation products 8, or tosylamide in the α position with respect to the triple
probably due to the poor leaving group properties of chlo- bond. As shown in Scheme 3, while treatment of propar-
rine (Table 2, entry 2, step 2). Analogously, when (Z)-6e was gylamine 5k protected as NHBOC exclusively yielded the
treated with TBAF the formation of the chloroaldehyde 12 “normal” rearrangement product 18, TBAF treatment of
was detected (Table 2, entry 5, step 2). The presence of bro- the β-silylalkenals derived from alkynes 5i and 5j resulted
mine in the ω position induced the formation of carbacyclic in the formation of α,β-unsaturated aldehydes 17.
aldehyde 10, which can be ascribed to the carbanion 16,
The observed behaviour is consistent with the mecha-
nism depicted in Scheme 4 and can be easily explained by
generated by Brook rearrangement[13] of 15 (Scheme 2).
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Scheme 2.
β-silylalkenal 20 derived from propargylamide 19 exclu-
sively afforded the stereoisomer 21 characterised by the
bulky tert-butyl substituent trans to the carbonyl moiety
(Scheme 5).
Scheme 3.
Scheme 5.
considering that in this case the carbanion generated after
the phenyl migration induces the elimination of OAc and
pTsNH and consequent double bond formation (Scheme 4).
2-Benzyl-3-methylpentenal (17) was obtained in good yields
(59–62%, pure product) but with poor stereoselectivity, as
might be expected in view of the very similar steric require-
ments of the methyl and ethyl substituents. In contrast, the
Conclusions
In conclusion, the chemo-, regio- and stereoselectivity of
the desilylation reaction in the tandem silylformylation/
fluoride-promoted SiǞC rearrangement process turned out
to be strongly dependent on the nature and the position of
the functional group present on the silylformylation prod-
uct. The ready access to functionalised β-silylalkenals
through silylformylation reactions enhances the versatility
of the procedure, which can be successfully employed in the
preparation of polyfunctionalised aldehydes and pyrans,
useful building blocks for organic chemistry.
Experimental Section
General Procedure for the Rhodium-Catalyzed Silylformylation of 1-
Alkynes with Aryldimethylsilanes: Carbonylation reactions were run
in a 25 mL stainless steel autoclave fitted with a Teflon inner cruci-
ble and a stirring bar. In a typical run, the silane (3 mmol), the
Scheme 4.
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Silylformylation – Fluoride-Assisted Aryl Migration of Acetylenic Derivatives
FULL PAPER
required 1-alkyne (3 mmol), toluene (3 mL) and Rh4(CO)12
(0.1 mol%) were placed under CO in a Pyrex Schlenk tube. This
solution was introduced into the previously evacuated (0.1 Torr)
autoclave through a steel siphon. The reactor was pressurized with
carbon monoxide and the mixture was stirred at room temperature
for 24 h, unless otherwise specified. After removal of excess CO
(fume hood), the reaction mixture was diluted with n-hexane, fil-
tered through Celite and concentrated under vacuum. The residue
was purified by column chromatography on silica gel with an ap-
propriate solvent mixture as eluent.
134 (100), 118 (8), 91 (5), 41 (12). IR (neat): ν = 2704 (CHO), 1720
˜
(C=O) cm–1. C15H23NO (233.18): calcd. C 77.21, H 9.93, N 6.00;
found C 77.35, H 9.90, N 5.98.
(RS)-2-Benzyloct-7-ynal (4ba): Isolated yield (n-hexane/ethyl ether,
80:20): 0.33 g, 78%. 1H NMR (200 MHz, CDCl3): δ = 1.26–1.57
(m, 6 H), 1.83 (t, J = 2.5 Hz, 1 H), 2.01–2.09 (m, 2 H), 2.47–2.60
(m, 1 H), 2.61 (dd, J = 7.0, 13.5 Hz, 1 H), 2.88 (dd, J = 6.9,
13.5 Hz, 1 H), 7.03–7.18 (m, 5 H), 9.55 (d, J = 2.6 Hz, 1 H) ppm.
13C NMR (50.3 MHz, CDCl3): δ = 18.0, 25.8, 27.8, 28.2, 34.8, 53.1,
68.4, 83.9, 126.2, 128.4, 128.8, 138.6, 204.2 ppm. IR (neat): ν =
˜
3293 (ϵC–H), 2713 (CHO), 1723 (C=O) cm–1. GC-MS (int. rel.%):
m/z = 214 [M]+, 133 (26), 105 (12), 91 (100), 65 (14). C15H18O
(214.14): calcd. C 84.07, H 8.47; found C 84.24, H 8.50.
General Procedure for the Fluoride-Promoted Migration Reaction:
In a typical run, the substrate (2 mmol), dissolved in anhydrous
THF (10 mL), was added slowly at room temperature to TBAF
(1  in THF, 5 mL). Immediately after the addition, the reaction
mixture was hydrolysed with water and extracted three times with
ether, and the organic layers were dried with Na2SO4. After concen-
tration under vacuum, the crude product was purified by column
chromatography on silica gel with an appropriate solvent mixture
as eluent.
(RS)-2-Benzylhept-6-enal (4ca): Isolated yield (n-hexane/ethyl ether,
90:10): 0.27 g, 67%. 1H NMR (200 MHz, CDCl3): δ = 1.23–1.68
(m, 4 H), 1.94 (m, 2 H), 2.45–2.60 (m, 1 H), 2.62 (dd, J = 6.8,
13.4 Hz, 1 H), 2.90 (dd, J = 7.3, 13.4 Hz, 1 H), 4.82–4.95 (m, 2 H),
5.66 (ddt J = 6.6, 10.3, 16.9 Hz, 1 H), 7.04–7.23 (m, 5 H), 9.56 (d,
J = 2.0 Hz, 1 H) ppm. 13C NMR (50.3 MHz, CDCl3): δ = 26.1,
27.9, 33.5, 34.9, 53.2, 114.8, 126.3, 128.4, 128.9, 137.9, 138.8,
(RS)-2-[(1-Naphthyl)methyl]hexanal (4ab): Isolated yield (n-hexane/
1
ethyl ether, 95:5): 0.25 g, 52%. H NMR (200 MHz, CDCl3): δ =
204.3 ppm. IR (neat): ν = 3062 (=C–H), 2708 (CHO), 1723 (C=O),
˜
1638 (C=C) cm–1. GC-MS (int. rel.%): m/z = 202 [M]+ (3), 133
(16), 117 (11), 91 (100), 78 (8), 65 (12), 41 (15). C14H18O (202.14):
calcd. C 83.12, H 8.97; found C 82.91, H 8.93.
0.87 (t, J = 7.0 Hz, 3 H), 1.23–1.78 (m, 6 H), 2.72–2.87 (m, 1 H),
3.11 (dd, J = 7.0, 14.4 Hz, 1 H), 3.46 (dd, J = 7.3, 14.4 Hz, 1 H),
7.29–7.56 (m, 4 H), 7.71–8.00 (m, 3 H), 9.70 (d, J = 2.4 Hz, 1
H) ppm. 13C NMR (50.3 MHz, CDCl3): δ = 13.8, 22.7, 29.0, 29.1,
32.3, 52.3, 123.3, 125.3, 125.6, 126.1, 127.1, 127.3, 128.9, 131.7,
(RS)-2-Benzyl-6-cyanopentanal (4da): Isolated yield (n-hexane/ethyl
acetate 50:50): 0.23 g, 58%. 1H NMR (200 MHz, CDCl3): δ = 1.50–
1.88 (m, 4 H), 2.32 (t, J = 6.7 Hz, 2 H), 2.59–2.74 (m, 1 H), 2.73
(dd, J = 7.2, 13.4 Hz, 1 H), 3.05 (dd, J = 6.4, 13.4 Hz, 1 H), 7.16–
7.33 (m, 5 H), 9.69 (d, J = 2.2 Hz, 1 H) ppm. 13C NMR (50.3 MHz,
CDCl3): δ = 17.0, 22.7, 27.1, 34.9, 2.4, 119.0, 126.5, 128.5, 128.7,
134.0, 134.9, 204.5 ppm. IR (neat): ν = 2725 (CHO), 1722
˜
(C=O) cm–1. GC-MS (int. rel.%): m/z = 280 [M]+ (15), 165 (15),
141 (100), 128 (15), 115 (22), 41 (19). C17H20O (240.15): calcd. C
84.96, H 8.39; found C 84.88, H 8.40.
(RS)-2-[(2-Naphthyl)methyl]hexanal (4ac): Isolated yield (n-hexane/
137.8, 203.3 ppm. IR: ν = 2716 (CHO), 2247 (CϵN), 1722
˜
1
ethyl ether, 90:10) 0.24 g, 50%. H NMR (200 MHz, CDCl3): δ =
(C=O) cm–1. GC-MS (int. rel.%): m/z = 183 [M – 18]+ (4), 172 (39),
144 (21), 133 (32), 105 (13), 91 (100), 65 (13), 51 (19), 41 (31).
C13H15NO (201.11): calcd. C 77.58, H 7.51, N 6.96; found C 77.72,
H 7.48, N 6.99.
0.84 (t, J = 7.0 Hz, 3 H), 1.19–1.62 (m, 6 H), 2.56–2.71 (m, 1 H),
2.83 (dd, J = 7.0, 13.9 Hz, 1 H), 3.11 (dd, J = 7.3, 13.9 Hz, 1 H),
7.24 (dd, J = 8.7, 1.6 Hz, 1 H), 7.34–7.45 (m, 2 H), 7.55 (t, J =
1.6 Hz, 1 H), 7.70–7.77 (m, 3 H), 9.63 (d, J = 2.6 Hz, 1 H) ppm.
13C NMR (50.3 MHz, CDCl3): δ = 13.7, 22.6, 28.2, 29.0, 35.0, 53.1,
125.3, 125.9, 127.1, 127.2, 127.3, 127.5, 128.0, 132.1, 133.4, 136.4,
(RS)-2-Benzyl-6-hydroxyhexanal (4ea): Isolated yield (dichloro-
methane/acetone 80:20): 0.22 g, 53%. 1H NMR (200 MHz,
CDCl3): δ = 1.26–1.74 (m, 6 H), 2.54–2.70 (m, 1 H), 2.73 (dd, J =
6.8, 13.0 Hz, 1 H), 2.99 (dd, J = 7.2, 13.0 Hz, 1 H), 3.22 (s, 1 H),
3.56 (t, J = 6.1 Hz, 2 H), 7.14–7.33 (m, 5 H), 9.64 (d, J = 2.4 Hz,
1 H) ppm. 13C NMR (50.3 MHz, CDCl3): δ = 22.9, 28.0, 32.2, 34.7,
204.4 ppm. IR: ν = 2722 (CHO), 1722 (C=O) cm–1. GC-MS (int.
˜
rel.%): 240 [M]+ (16), 165 (10), 155 (11), 141 (100), 128 (16), 115
(28), 41 (26). C17H20O (240.15): calcd. C 84.96, H 8.39; found C
85.00, H 8.37.
53.1, 61.8, 126.1, 128.2, 128.6, 138.5, 204.6 ppm. IR (neat): ν =
˜
(RS)-2-(4-Fluorobenzyl)hexanal (4ad): Isolated yield (n-hexane/
3384 (O–H), 2720 (CHO), 1721 (C=O) cm–1. GC-MS (int. rel.%):
m/z = 206 [M]+ (3), 188 (35), 170 (8), 144 (13), 133 (20), 117 (23),
104 (15), 91 (100), 77 (12), 65 (27), 39 (18). C13H18O2 (206.13):
calcd. C 75.69, H 8.80; found C 75.78, H 8.77.
1
ethyl ether, 80:20) 0.30 g, 73%. H NMR (200 MHz, CDCl3): δ =
0.86 (t, J = 5.9 Hz, 3 H), 1.19–1.65 (m, 6 H), 2.48–2.66 (m, 1 H),
2.67 (dd, J = 6.6, 13.8 Hz, 1 H), 2.94 (dd, J = 7.1, 13.8 Hz, 1 H),
6.90–6.99 (m, 2 H), 7.06–7.14 (m, 2 H), 9.63 (d, J = 2.6 Hz, 1
H) ppm. 13C NMR (50.3 MHz, CDCl3): δ = 13.7, 22.6, 28.1, 28.9,
34.0, 53.4, 115.1 (d, J = 20.9 Hz), 130.2 (d, J = 7.6 Hz), 134.5 (d,
(RS)-2-Benzyl-5-chloropentanal (9): Isolated yield (n-hexane/ethyl
1
ether, 90:10): 0.10 g, 25% H NMR (200 MHz, CDCl3): δ = 1.58–
1.87 (m, 4 H), 2.57–2.71 (m, 1 H), 2.72 (dd, J = 6.7, 14.0 Hz, 1 H),
3.01 (dd, J = 7.0, 14.0 Hz, 1 H), 3.48 (t, J = 6.0 Hz, 2 H), 7.14–
7.33 (m, 5 H), 9.65 (d, J = 2.2 Hz, 1 H) ppm. 13C NMR (50.3 MHz,
CDCl3): δ = 25.5, 29.6, 34.9, 44.4, 52.4, 126.4, 128.4, 128.7, 138.2,
J = 3.4 Hz), 161.4 (d, J = 244.2 Hz), 204.2 ppm. IR (neat): ν =
˜
2714 (CHO), 1724 (C=O) cm–1. GC-MS (int. rel.%): m/z = 208
[M]+ (7), 166 (19), 151 (45), 109 (100), 83 (12), 41 (7). C13H17FO
(208.13): calcd. C 74.97, H 8.23, F 9.12; found C 75.15, H 8.20, F
9.09.
203.7 ppm. IR (neat):
ν =
˜
2719 (CHO), 1724 (C=O) cm–1.
C12H15ClO (210.08): calcd. C 68.40, H 7.18, Cl 16.83; found C
68.63, H 7.20, Cl 16.78.
(RS)-2-[4-(Dimethylamino)benzyl]hexanal (4ae): Isolated yield (n-
hexane/ethyl ether, 90:10): 0.32 g, 70%. 1H NMR (200 MHz,
CDCl3): δ = 0.88 (J = 6.2 Hz, 3 H), 1.22–1.72 (m, 6 H), 2.47–2.60
(m, 1 H), 2.63 (dd, J = 7.0, 20.2 Hz, 1 H), 2.90 (dd, J = 7.0,
20.2 Hz, 1 H), 2.91 (s, 6 H), 6.67 (d, J = 8.8 Hz, 2 H), 7.03 (d, J =
8.8 Hz, 2 H), 9.64 (J = 2.6 Hz, 1 H) ppm. 13C NMR (50.3 MHz,
CDCl3): δ = 13.7, 22.6, 28.2, 29.1, 35.0, 40.6, 53.6, 112.7, 126.5,
(RS)-2-Benzyl-6-chlorohexanal (12): Isolated yield (n-hexane/ethyl
ether, 90:10): 0.06 g, 13.5%. 1H NMR (200 MHz, CDCl3): δ =
1.42–1.77 (m, 6 H), 2.54–2.70 (m, 1 H), 2.72 (dd, J = 6.8, 14.0 Hz,
1 H), 3.00 (dd, J = 6.8, 14.0 Hz, 1 H), 3.48 (t, J = 6.6 Hz, 2 H),
7.13–7.30 (m, 5 H), 9.66 (d, J = 2.2 Hz, 1 H) ppm. 13C NMR
129.5, 149.2, 205.1 ppm. GC-MS (int. rel.%): m/z = 233 [M]+ (7), (50.3 MHz, CDCl3): δ = 24.1, 27.6, 32.3, 34.9, 44.5, 53.1, 126.4,
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128.5, 128.8, 138.5, 204.1 ppm. IR (neat): ν = 2720 (CHO), 1724
(E)-2-Benzyl-4,4-dimethylpent-2-enal (21): Isolated yield (CH2Cl2):
˜
1
(C=O) cm–1. C13H17ClO (224.09): calcd. C 69.48, H 7.62, Cl 15.78; 0.12 g, 31%. H NMR (200 MHz, CDCl3): δ = 1.20 (s, 9 H), 3.80
found C 69.29, H 7.60, Cl 15.83.
(s, 2 H), 6.58 (s, 1 H), 7.10–7.35 (m, 5 H), 9.41 (s, 1 H) ppm. 13C
NMR (50.3 MHz, CDCl3): δ = 26.4, 29.5, 30.1, 125.9, 127.9, 128.3,
1-Benzyl-2-isobutylcyclopentanecarbaldehyde (Diastereomeric Mix-
ture, Z/E = 70:30) (13): Isolated yield (n-hexane/ethyl ether, 90:10):
0.24 g, 49%. 1H NMR (200 MHz, CDCl3): δ = 1.00 (d, J = 6.2 Hz,
6 H), 1.05 (d, J = 6.2 Hz, 6 H), 1.32–2.09 (m, 20 H), 2.44 (d, J =
13.9 Hz, 0.6 H), 2.85 (d, J = 13.7 Hz, 1.4 H), 3.28 (d, J = 13.7 Hz,
1.4 H), 3.39 (d, J = 13.9 Hz, 0.6 H), 7.21–7.37 (m, 10 H), 9.51 (s,
0.6 H), 9.87 (s, 1.4 H) ppm. 13C NMR (50.3 MHz, CDCl3): δ =
20.9 and 21.5, 22.2 and 22.3, 24.1 and 23.8, 26.8 and 26.3, 30.8
and 29.8, 31.0 and 31.1, 37.9 and 32.8, 39.0 and 39.2, 46.8 and
43.1, 59.9 and 60.9, 126.1 and 125.9, 127.9, 130.0 and 130.1, 137.7
139.2, 139.3, 166.0, 196.4 ppm. IR (neat): ν = 3025 (C=C–H), 2708
˜
(CHO), 1685 (C=O), 1632 (C=C) cm–1. GC-MS (int. rel.%): m/z =
202 [M]+ (36), 159 (40), 145 (32), 131 (53), 115 (37), 91 (85), 77 (8),
55 (23), 43 (40), 41 (100), 39 (89). C14H18O (202.29): calcd. C 83.12,
H 8.97; found C 83.38, H 8.92.
Supporting Information (for details see the footnote on the first
page of this article): Procedures and spectroscopic data for the silyl-
formylation products (Z)-3ab to (Z)-3ea and (Z)-6c to (Z)-20.
and 138.6, 206.4 and 205.0 ppm. IR (neat): ν = 2710 (CHO), 1691
˜
[1] a) I. Ojima, Z. Li, J. Zhu, in: The Chemistry of Organic Silicon
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ome, Y. Ito, Chem. Rev. 2000, 100, 3221–3256; c) B. Marciniec,
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(C=O) cm–1. GC-MS (int. rel.%) (minor diastereomer): m/z = 245
[M + 1]+ (62), 227 (22), 188 (100), 171 (12), 158 (15), 120 (17). GC-
MS (int. rel.%) (major diastereomer): m/z = 245 [M + 1]+ (75), 188
(100), 171 (25), 120 (22).
1-Benzyl-2-methylcyclohexanecarbaldehyde (Diastereomeric Mix-
ture, Z/E = 70:30) (14): Isolated yield (n-hexane/ethyl ether, 90:10):
0.18 g, 41%. 1H NMR (200 MHz, CDCl3): δ = 0.98 (d, J = 7.0 Hz,
4.2 H), 1.17 (d, J = 7.0 Hz, 1.8 H), 1.26–2.02 (m, 18 H), 2.65 (d, J
= 13.8 Hz, 1.4 H), 2.78 (d, J = 13.7 Hz, 0.6 H), 3.03 (d, J = 13.7 Hz,
0.6 H), 3.08 (d, J = 13.8 Hz, 1.4 H), 7.15–7.35 (m, 10 H), 9.56 (s,
1.4 H), 9.92 (s, 0.6 H) ppm. 13C NMR (50.3 MHz, CDCl3): δ =
15.4 and 16.3, 21.1 and 22.3, 23.6 and 24.7, 27.5 and 29.7, 30.1
and 31.4, 33.3 and 34.7, 36.7 and 40.3, 53.4 and 52.4, 126.1 and
126.4, 128.0, 130.3 and 130.4, 137.4 and 136.7, 207.2 and
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207.4 ppm. IR (neat): ν = 2699 (CHO), 1721 (C=O) cm–1.
˜
2-Benzyl-3-methylpent-2-enal (Diastereomeric Mixture, Z/E
=
57:43) (17): Isolated yield (n-hexane/ethyl ether, 80:20): 0.23 g,
62%. 1H NMR (200 MHz, CDCl3): δ = 1.08 (t, J = 7.8 Hz, 2.58
H), 1.26 (t, J = 7.6 Hz, 3.42 H), 2.07 (s, 3.42 H), 2.31 (s, 2.58 H),
2.41 (q, J = 7.8 Hz, 1.72 H), 2.74 (q, J = 7.6 Hz, 2.28 H), 3.73 (s,
2.28 H), 3.75 (s, 1.72 H), 7.19–7.35 (m, 10 H), 10.28 (s, 1.14 H),
10.31 (s, 0.86 H) ppm. 13C NMR (50.3 MHz, CDCl3): δ = 14.2 and
11.6, 21.5 and 16.7, 26.2 and 30.1, 30.7 and 30.7, 125.7 (2C), 128.0
(2C), 128.2 (2C), 135.3 and 135.0, 139.9 and 140.3, 162.6 and 161.5,
190.2 and 191.3 ppm. IR (neat): ν = 3021 (C=C–H), 2756 (CHO),
˜
1660 (C=O), 1616 (C=C) cm–1. GC-MS (int. rel.%) (major dia-
stereomer): m/z = 188 [M]+ (48), 159 (74), 141 (13), 131 (42), 129
(26), 117 (26), 115 (31), 105 (17), 91 (89), 77 (19), 65 (27), 53 (25),
51 (44), 46 (45), 41 (40), 39 (100). GC-MS (int. rel.%) (minor dia-
stereomer): m/z = 188 [M]+ (43), 173 (5), 159 (77), 141 (13), 131
(42), 129 (28), 115 (33), 105 (18), 91 (91), 77 (19), 65 (27), 51 (44),
43 (44), 41 (88), 39 (100).
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(Eds.: Z. Rappoport, Y. Apeilog); Wiley: Chichester, UK, 1998,
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9292–9298.
2-Benzyl-3-(tert-butoxycarbonylamino)-3-methylpentanal (18): Iso-
lated yield (CH2Cl2): 0.33 g, 54%. H NMR (200 MHz, CDCl3): δ
1
= 0.99 (t, J = 7.4 Hz, 3 H), 1.00 (t, J = 7.4 Hz, 3 H), 1.27 (s, 3 H),
1.40 (s, 3 H), 1.53 (m, 11 H), 1.55 (m, 11 H), 2.83 (t, J = 12.6 Hz,
1 H), 2.85 (t, J = 12.6 Hz, 1 H), 3.12 (t, J = 12.6 Hz, 1 H), 3.14 (t,
J = 12.6 Hz, 1 H), 3.73 (m, 1 H), 3.76 (m, 1 H), 4.74 (s, 1 H), 4.84
(s, 1 H), 7.22–7.36 (m, 10 H), 9.84 (d, J = 2.4 Hz, 1 H), 9.87 (d, J
= 2.4 Hz, 1 H) ppm. 13C NMR (50.3 MHz, CDCl3): δ = 7.6 and
7.3, 1.2 and 21.9, 28.3 and 29.5, 30.7 and 30.4, 51.1 and 53.3, 57.2
and 57.0, 60.3 and 59.6 79.2 (2C), 125.9 and 126.0, 128.3 (2C),
128.9 (2C), 139.8 and 139.7, 154.1 and 154.3, 203.9 and 204 ppm.
[8] a) L. Solà, K. S. Reddy, A. Vidal-Ferran, A. Moyano, M. A.
Pericas, A. Riera, A. Alvarez-Larena, J. F. Pinella, J. Org.
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2880; d) G. Roda, S. Riva, B. Danieli, Tetrahedron: Asymmetry
1999, 10, 3939–3949; e) Y. Ishino, Y. Kita, T. Ohno, Y. Yama-
saki, T. Miyata, I. Nishiguchi, Tetrahedron Lett. 1999, 40,
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IR (neat): ν = 3021 (N–H), 2732 (CHO), 1713 (C=O) cm–1. GC-
˜
MS (int. rel.%): m/z = 134 (37), 116 (62), 92 (48), 91 (100), 72 (46),
57 (79), 42 (40), 41 (47), 39 (33). C18H27NO3 (305.20): calcd. C
70.79, H 8.91, N 4.59; found 70.91, H 8.93, N 4.61.
1850
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 1845–1851

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Received: November 9, 2005
Published Online: February 23, 2006
Eur. J. Org. Chem. 2006, 1845–1851
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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