Rhodium-Catalyzed Methylenation of Aldehydes

Article abstract of DOI:10.1021/ja038112o

The rhodium-catalyzed methylenation of aldehydes using trimethylsilyldiazomethane and triphenylphosphine produces a variety of terminal alkenes in excellent yields. These mild and nonbasic reaction conditions allow the conversion of enolizable substrates (keto aldehydes and nonracemic α-substituted aldehydes) to terminal alkenes without epimerization. Optimization of the reaction conditions led to the conclusion that a variety of rhodium(I) sources can be used as catalysts. The effect of the solvent on the reaction has also been studied, and it indicates that although the THF is the best solvent, other solvents may be used. The reactivity of the system is very much dependent on the nature of the phosphine reagent. The use of an easily removable phosphine is also described. Spectroscopic studies indicate that the reaction proceeds via an unusual mechanism which leads to the in situ formation of the salt-free phosphorus ylide, methylenetriphenylphosphorane.

Full text of DOI:10.1021/ja038112o

Rhodium-Catalyzed Methylenation of Aldehydes.
Hélène Lebel* and Valérie Paquet.
Département de chimie, Université de Montréal, Montréal, Québec, Canada, H3C 3J7
Supporting Information
Table 1. Rhodium-Catalyzed Methylenation of Cinnamaldehyde..............................................3
Table 2. Solvent Effect on the Rhodium-Catalyzed Methylenation
of 6-(tert-Butyldimethylsilyloxy)-1-pentanal with Trimethylsilyldiazomethane......... 4
Table 3. Rhodium-Catalyzed Methylenation of 6-(tert-Butyldimethylsilyloxy)-1-pentanal
with Various Trimethylsilyldiazomethane Solutions....................................................5
Table 4. Rhodium-Catalyzed Methylenation of Aldehydes with commercial solution
and freshly prepared trimethylsilyldiazomethane solution...........................................6
General Information....................................................................................................................7
Trimethylsilyldiazomethane Synthesis....................................................................................... 8
Phosphine Synthesis....................................................................................................................8
Olefination Procedures A to C....................................................................................................11
Characterization of Alkene Products..........................................................................................11
GC Trace of Various Trimethylsilyldiazomethane Solutions.....................................................23
S1

An investigation of other rhodium complexes shows that the requisite catalyst may also be
generated in-situ from a number of rhodium sources, due to the presence of an excess of
triphenylphosphine in the reaction mixture (Table 1). For instance, rhodium (III) chloride hydrate1
may react directly with triphenylphosphine under the methylenation reaction conditions. Since the
formation of the Wilkinson’s catalyst does not proceed at room temperature, the reaction run at 50
°C (entry 2). Alternatively, we can also preformed in-situ the desired catalyst from rhodium (III)
chloride hydrate and triphenylphosphine at 50 °C, and then cooled the reaction mixture to room
temperature, prior to the addition of the substrate and the other reagents (2-propanol and
trimethylsilyldiazomethane) required to carry out the methylenation reaction (entry 3). Rhodium (I)
dimer complexes are also suitable precursors for the in-situ generation of the Wilkinson’s catalyst.
While the reaction of chloro[1,5-cyclooctadiene] rhodium (I) dimer and triphenylphosphine also
proceeded only at 50 °C (entries 4-6), the use of a more labile diene, such as norbornadiene allowed
the reaction to occur at room temperature (entries 7-8).2 In comparison, the corresponding cationic
complexes derived from silver tetrafluoroborate and sodium tetraphenylborate were less reactive
and the olefination reaction took place only at 50 °C (entries 9-12). Formally the rhodium (0)
complex Rh(NO)(PPh3)3 seems also to be an active catalyst, although a very long latent period was
observed prior to the beginning of the olefination reaction (entry 13). This latent period and the
many color variations of the reaction mixture are consistent with the hypothesis that a redox process
initially occurs, leading to an active rhodium (I) species. In contrast, no reaction was observed with
the rhodium (II) acetate dimer, although this complex has found many applications in carbene
chemistry (entry 14).3
1
Due to solubility issues, it is required to use rhodium (III) chloride hydrate (instead of rhodium (III) chloride
anhydrous) to prepare the chlorotris(triphenylphosphine)rhodium (I).
2
The formation of the desired chlorotris(triphenylphosphine)rhodium (I) was monitored by phosphorus NMR.
(a) Paulissen, R.; Reimlinger, H.; Hayez, E.; Hubert, A. J.; Teyssie, P. Tetrahedron Lett. 1973, 2233-2236. (b) Doyle,
3
M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods for Organic Synthesis with Diazo Compounds: From
Cyclopropanes to Ylides.; Wiley: New York, 1998. (c) Timmons, D. J.; Doyle, M. P. J. Organomet. Chem. 2001, 617,
98-104. (d) Doyle, M. P.; Ren, T. Prog. Inorg. Chem. 2001, 49, 113-168. (e) Lebel, H.; Marcoux, J. F.; Molinaro, C.;
Charette, A. B. Chem. Rev. 2003, 103, 977-1050. (f) Merlic, C. A.; Zechman, A. L. Synthesis 2003, 1137-1156.
S2

Table 1. Rhodium-Catalyzed Methylenation of Cinnamaldehyde.
N2
(1.4 equiv)
TMS
H
Ph
Ph
O
Catalyst (2.5 mol%) / THF
i-PrOH (1.1 equiv), PPh (1.1 equiv)
3
1
Entry
1
Catalyst
Conv.a
≥98%
≥98%
≥98%
19%
RhCl(PPh3)3; 25 °C, 0.5 h
RhCl3•H2O; 50 °C, 1 h
RhCl3•H2O; 25 °C, 1 hb
2
3
4
[Rh(COD)Cl]2; 25 °C, 4 h
[Rh(COD)Cl]2; 25 °C, 0.5 hb
[Rh(COD)Cl]2; 50 °C, 1 h
[Rh(NBD)Cl]2; 25 °C, 1.5 h
[Rh(NBD)Cl]2; 50 °C, 0.5 h
[Rh(COD)2]+BF4-; 25 °C, 16 h
5
≥98%
≥98%
≥98%
≥98%
≤5%
6
7
8
9
10
11
12
13
14
[Rh(COD)2]+BF4-; 50 °C, 0.3 h ≥98%
[Rh(COD)]+BPh4-; 25 °C, 16 h
[Rh(COD)]+BPh4-; 50 °C, 3 h
Rh(NO)(PPh3)3; 25 °C, 8 h
Rh2(OAc)4; 25 °C, 16 h
≤5%
≥98%
≥98%
≤5%
aDetermined by GC. bCatalyst was premixed with PPh3 at 50
°C for 15 min prior to the methylenation reaction.
S3

Table 2. Solvent Effect on the Rhodium-Catalyzed Methylenation of 6-(tert-
Butyldimethylsilyloxy)-1-pentanal with Trimethylsilyldiazomethane.
1.RhCl(PPh ) (2.5 mol%)
3 3
i-PrOH (1.1 equiv),
PPh (1.1 equiv) / Solvent
3
TBSO
TBSO
O
3
3
2.TMSCHN (1.4 equiv)
2
THF, 25 °C
8
Entry
Solvent
Conv. a
≥98%
≥98%
≥98%
≥98%
80%
1
2
3
4
5
6
7
THF, 1 h
THFb, 1 h
Dioxane, 3 h
Ether, 16 h
Toluene, 16 h
CH2Cl2, 3 h
≥98%
≤5%
1,2-Dichloroethane, 16 h
b
aDetermined by GC. Freshly opened bottle of ACS
reagent-grade THF.
S4

Table 3. Rhodium-Catalyzed Methylenation of 6-(tert-Butyldimethylsilyloxy)-1-pentanal with
Various Trimethylsilyldiazomethane Solutions.
1.RhCl(PPh ) (2.5 mol%)
3 3
i-PrOH (1.1 equiv),
PPh (1.1 equiv) / THF
3
TBSO
TBSO
O
3
3
2.TMSCHN (1.4 equiv)
2
Solvent, 25 °C
8
Entry
TMSCHN2 Solution
Conv. a
≥98%
≥98%
≥98%
61%
1
2
10 M, Hexanes, 3 h
5.0 M, Hexanes, 6 h
2.0 M, Hexanes, 8 h
0.5 M, Hexanes, 8 h
2.0 M, THF, 1 h
3
4
5
≥98%
≥98%
72%
6
2.0 M, CH2Cl2, 7 h
2.0 M, Et2O, 2 h
7
8
2.0 M, Et2O, 5 hb
2.0 M, Et2O, 1 hb,c
50%
9
≥98%
≥98%
10
6.0 M, Et2O, 1.5 hd
b
c
aDetermined by GC. Solution from Aldrich. 1.7 equiv.
were used. dSolution from Aldrich that was concentrated.
S5

Table 4. Rhodium-Catalyzed Methylenation of Aldehydes with commercial solution and freshly
prepared trimethylsilyldiazomethane solution.
1. RhCl(PPh ) (2.5 mol%) / THF
3 3
i-PrOH (1.1 equiv), PPh (1.1 equiv)
3
R
O
R
2. TMSCHN / THF, 25 °C
2
a
2
TMSCHN
TMSCHN
2
2.0 M / THF
1.4 equiv.
2.0 M / ether
1.7 equiv.
Entry
Product
1
2
77% y. 1 h
87% y. 1 h
TBSO
2
b
(85% y. 2h)
83% y. 1 h
88% y. 0.5 h
Ph
1
3
4
5
87% y. 1 h
93% y. 1 h
27
THPO
O
79% y. 5 h
(94% ee)
86% y. 4 h
(92% ee)
NBOC
20
O
87% y. 3 h
87% y. 3 h
Ph
30
4
aCommercially available solution.aThe concentrated 5M solutionwas used.
S6

General: Unless otherwise noted, all non-aqueous reactions were performed under an oxygen-free
atmosphere of argon with rigid exclusion of moisture from reagents and glassware. The solvents
were dried using standard methods prior to use. RhCl(PPh3)3 is commercially available, but was
prepared from RhCl3•3H2O and 4 PPh3 according to the literature.4 Methanol, ethanol, 2-propanol,
benzyl alcohol, 2-butanol and 2-methyl-1-propanol was distilled over calcium hydride. All the
cationic complexes of rhodium (I) were prepared according to the literature procedure,5 except for
+
the preparation of [Rh(COD)2 BF4-].6 The commercially available aldehydes were purified using
standard methods prior to use. The following compounds were received from commercial suppliers
(Aldrich Chemical Co, Strem Chemicals Inc.) and used without further purification:
triphenylphosphine, tris(4-methoxyphenyl)phosphine, tributylphosphine, 4-(diphenylphosphino)
benzoic acid, tris(4-fluorophenyl)phosphine, tris(4-trifluoromethylphenyl)phosphine, 2-methyl-2-
propanol, phenol, chloro(1,5-cyclooctadiene) rhodium (I) dimer, chloronorbornadiene rhodium (I)
dimer. Analytical thin layer chromatography (TLC) was performed using EM Reagent 0.25 mm
silica gel 60-F plates. Visualization of the developed chromatogram was performed by UV
absorbance, aqueous cerium molybdate, ethanolic phosphomolybdic acid, or aqueous potassium
permanganate. Flash chromatography was performed using EM Silica Gel 60 (230-400 mesh) with
the indicated solvent system. Optical rotations were measured on a Perkin-Elmer 341 digital
polarimeter at 589 nm. Data are reported as follows: [a]ltemp., concentration (c g/100mL), and
solvent. Infrared spectra were recorded on a Perkin Elmer Spectrum One FTIR spectrometer
equipped with a Golden Gate Diamond ATR and are reported in reciprocal centimeters (cm-1).
1
Only the most important and relevant frequencies are reported. H NMR spectra were recorded in
deuteriochloroforme, unless otherwise noted, on a Bruker AV-400, a Bruker ARX-400, a Bruker
AMX-300 or a Bruker AV-300 spectrometers (400, 400, 300 and 300 MHz respectively).
Chemical shifts are reported in ppm on the d scale from an internal standard of residual chloroform
(7.27 ppm). Data are reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t =
triplet, q = quartet, qn = quintet, m = multiplet and br = broad), coupling constant in Hz, integration.
13C NMR spectra were recorded in deuteriochloroforme, unless otherwise noted, on a Bruker AV-
400, a Bruker ARX-400, a Bruker AMX-300 or a Bruker AV-300 spectrometers (100, 100, 75 and
75 MHz respectively) with complete proton decoupling. Chemical shifts are reported in ppm from
the central peak of deuteriochloroform (76.9 ppm) on the d scale. 19F NMR spectra were recorded
in deuteriochloroforme, unless otherwise noted, on a Bruker ARX-400 spectrometer (376,5 MHz)
with complete proton decoupling. Chemical shifts are reported in ppm from the peak of
trifluoroacetic acid (-78.5 ppm) on the d scale. 31P NMR spectra were recorded in
deuteriochloroforme, unless otherwise noted, on a Bruker ARX-400 spectrometer (162 MHz) with
complete proton decoupling. Chemical shifts are reported in ppm from the peak of 85% H3PO4 in
D2O (0 ppm) on the d scale. Mass spectra were obtained on a KRATOS MS-50 TC TA (FAB) or a
Micromass Autospec-TOF (MAB) high resolution magnetic sector mass spectrometer by the Centre
régional de spectrométrie de masse de l’Université de Montréal. The elementary analyses were
performed by the Laboratoire d’analyse élémentaire de l’Université de Montréal or by the Canadian
Microanalytical Service ltd. High performance liquid chromatography (HPLC) analyses were
performed on a Hewlett Packard 1100 Series quaternary gradient pump with diode-array detector
interfaced with HP Chemstation software. Values for enantiomeric excess were determined using a
Chiracel OJ column. Data are reported as follows: column type, flow, solvent used, and retention
time (tr). Analytical gas chromatography (GLC) was carried out on a Hewlett Packard 6890 series
gas chromatograph equipped with a split mode capillary injector and a flame ionization detector.
Unless otherwise noted, injector and detector temperatures were 250 °C and the carrier gas was
hydrogen. Data are reported as follows: column type, oven temperature, and retention time (tr).
4
Osborn J. A.; Wilkinson, G. Inorg. Synth. 1990, 28, 77-79.
5
Osborn, J. A.; Schrock, R. R. J. Am. Chem. Soc. 1971, 93, 2397-2407.
Schenck, T. G.; Downes, J. M.; Milne, C. R. C.; Mackenzie, P. B.; Boucher, T. G.; Whelan, J.; Bosnich, B. Inorg.
6
Chem. 1985, 24, 2334-2337.
S7

8
,,
Synthesis of Trimethylsilyldiazomethane.7 A dry, 1L, three-necked round-bottomed flask is
equipped with a 250 mL pressure-equalizing dropping funnel, a stirring bar and two septum. The
apparatus is flame-dry under argon. When the system is cooled at room temperature, a solution of
diphenylphosphorazidate9 (46.0 g, 167 mmol) in 200 mL of anhydrous diethyl ether is transfered to
the flask via a cannula. The ether solution of the Grignard reagent4 (200 mL, 200 mmol) is
measured in a graduate cylinder via cannula under argon and then transferred to the dropping
funnel. The flask is cooled with a dry-ice/acetone bath. When the internal temperature reaches –10
°C (measured with an electronic thermometer), the Grignard reagent is added dropwise at such a
rate that the internal temperature is maintained below 0 °C (some ether can be added for better
stirring). After the addition is completed, the reaction is stirred for 2 hours with an ice bath. The
funnel is replaced by a septum and the flask is then placed in the fridge for 14 hours. The reaction
mixture is opened to air and cooled again to –15 °C with a dry-ice/acetone bath. Water (50 mL) is
carefully added dropwise at such a rate that the internal temperature is maintained below 0 °C
(stirring can be done manually). The reaction mixture is filtered with a Buckner filter and the white
solid is washed with ether (100 mL). The yellow filtrate is washed with water (100 mL) and dried
over MgSO4. The filtrate is placed in a 1L round-bottomed flask with a magnetic stirrer and
equipped with a distillation apparatus (the vigreux column must be between 5 to 10 cm). The
solution is slowly distilled under argon until no more volatile comes over (oil bath temperature
below 50 °C). The oil bath is removed and the distillation apparatus is replaced by a “U” glass tube
connected to a 250 mL round-bottomed flask placed in a dry-ice/acetone bath. The solution is
transferred under vacuum (0.1 mmHg). At the end, the oil bath at 50 °C can be used to transfer the
remaining trimethylsilyldiazomethane. The yellow solution is dried over Na2SO4 at room
temperature. After the filtration in a 100 mL flask, the solution is concentrated slowly, until the
vapors reached 80 °C. The remaining trimethylsilyldiazomethane can be used as it is and transfer in
an amber bottle under argon (the product is light sensitive).
Purification from a commercially available solution. The Aldrich solution of
trimethylsilyldiazomethane in ether (25.0 mL, 50.0 mmol) was concentrated into a 6M solution.10
The distillation was performed over a period of 2 hours under argon with a vigreux column of 5 cm
and the oil bath temperature has raised from 40 °C to 100 °C.
Synthesis of Phosphines
SiMe
3
P
2
4-(Trimethylsilyl)phenyldiphenylphosphine (2). The title compound was prepared according to
the procedure described by van Koten.11 A solution of 1-bromo-4-(trimethylsilyl)benzene (3.44 g,
15.0 mmol) in diethyl ether (10 mL) was added to a suspension of magnesium turning in diethyl
ether (10 mL). This solution of the Grignard reagent was then added to a solution of
chlorodiphenylphosphine (3.30 g, 15.0 mmol) in diethyl ether (150 mL) at -78 °C. The cooling
7
Modified procedure according to : Shioiri, T.; Aoyama, T.; Mori, S. Org. Synth. 1990, 68, 1-7.
In contrast to diazomethane, trimethylsilyldiazomethane has been shown to be non-explosive and non-mutagenic, thus
the very careful operations used for the preparation of diazomethane are not necessary. See reference 7.
8
9
Shioiri, T.; Yamada, S. Org. Synth. 1984, 62, 187-190.
10
Although no risk is associated with the distillation of trimethylsilyldiazomethane (see reference 7), the presence of
peroxide from the ether should be considered as a potential danger. The purity of the solution and the presence of
peroxide from ether should be always checked prior to perform the distillation.
11
Richter, B.; de Wolf, E.; van Koten, G.; Deelman, B. J. J. Org. Chem. 2000, 65, 3885-3893.
S8

bath was removed after 2 hours and the reaction mixture was stirred for another 2 hours. When at
room temperature, the mixture was quenched with saturated aqueous NH4Cl (25 mL). The two
layers were separated and the aqueous layer was further extracted with diethyl ether (3 x 50 mL).
The combined organic fractions were then dried over MgSO4 and the solvent was removed under
reduced pressure. The desired phosphine 2 (2.70 g, 54%) was obtained as a white solid after flash
chromatography (5% EtOAc/hexanes). Rf 0.47 (5% EtOAc/hexanes); 1H NMR (400 MHz, CDCl3)
d 7.36-7.35 (m, 14H), 0.29 (s, 9H); 13C NMR (100 MHz, CDCl3) d 140.9, 137.6 (d, J = 11 Hz),
137.0 (d, J = 10 Hz), 133.7 (d, J = 20 Hz), 133.2 (d, J = 7 Hz), 132.7 (d, J = 19 Hz), 128.6, 128.4
(d, J = 7 Hz), -1.30; 31P NMR (162 MHz, CDCl3) d -5.07; IR (neat) 3052, 2953, 1583, 1479, 1435,
1250, 1122, 839, 744, 696, 631 cm-1; HMRS (MAB) calcd for C21H23PSi [M-H+]+: 334.130668.
Found: 334.130051.
O
O
P
3
4-(Methoxymethoxy)phenyldiphenylphosphine (3). The title compound was prepared according
to the procedure described by Janda.12 A solution of n-butyl lithium in hexanes (2.70 mL, 6.80
mmol) was added dropwise, to a stirred solution of 1-bromo-4-methoxymethoxybenzene (0.74 g,
3.40 mmol) in ether (25 mL) at 0 °C over 15 min. The resulting mixture was warmed to room
temperature and stirred for 3h, then cooled to 0 °C. Chlorodiphenylphosphine (0.73 g, 3.50 mmol)
was then added dropwise and the resulting mixture was stirred at room temperature for 16 hours.
The reaction was quenched by careful addition of saturated aqueous NH4Cl (50 mL) to the reaction
mixture at 0 °C. The two layers were separated and the aqueous layer was further extracted with
diethyl ether (3 x 50 mL). The combined organic fractions were then dried over MgSO4, and the
solvent was removed under reduced pressure. The desired phosphine 3 (0.45 g, 41%) was obtained
as a white solid after flash chromatography (5% EtOAc/hexanes). Rf 0.24 (5% EtOAc/hexanes); 1H
NMR (400 MHz, CDCl3) d 7.35-7.31 (m, 10H), 7.02-7.07 (m, J = 4H), 5.21 (s, 2H), 3.50 (s, 3H);
13C NMR (100 MHz, CDCl3) d 157.9, 137.6 (d, J = 11 Hz), 135.4 (d, J = 21 Hz), 133.4 (d, J = 19
Hz), 129.1 (d, J = 46 Hz), 128.9, 128.3 (d, J = 7 Hz), 116.2 (d, J = 8 Hz), 94.1, 56.0; 31P NMR (162
MHz, CDCl3) d -6.45; IR (neat) 3052, 2895, 1593, 1496, 1434, 1236, 1152, 1079, 997, 744, 697,
631 cm-1; HMRS (MAB) calcd for C20H19O2P [M-H+]+: 322.112268. Found: 322.111786.
O
O
P
4
4-(Diphenylphosphanyl)benzoic acid methyl ester (4).13 The title compound was prepared
according to the procedure described by Yoakim.14 To a solution of 4-(diphenylphosphino)benzoic
12
Sieber, F.; Wentworth, P.; Toker, J. D.; Wentworth, A. D.; Metz, W. A.; Reed, N. N.; Janda, K. D. J. Org. Chem.
1999, 64, 5188-5192.
13
Kwong, F. Y.; Lai, C. W.; Chan, K. S. Tetrahedron Lett. 2002, 43, 3537-3539.
Yoakim, C.; Guse, I.; O'Meara, J. A.; Thavonekham, B. Synlett 2003, 473-476.
14
S9

acid (398 mg, 1.30 mmol) in dichloromethane (15 mL) at 0 °C, was added methanol (0.05 mL, 1.40
mmol) and N,N-dimethylaminopyridine (37.0 mg, 0.30 mmol). A solution of diisopropylcarbo-
diimide in dichloromethane (1.40 mL, 1.40 mmol) was then added over 15 min. The resulting light
yellow suspension was stirred at room temperature for 16 hours. The reaction mixture was filtered
and concentrated to dryness. The filtrate was diluted with EtOAc (30 mL), washed successively
with aqueous 10% HCl (15 mL), aqueous saturated NaHCO3 (15 mL) and brine (15 mL). The
organic layer was dried over MgSO4, filtered and evaporated to dryness. The desired phosphine 4
(325 mg, 78%) was obtained as a white solid after flash chromatography (5% EtOAc/hexanes). Rf
1
0.4 (5% EtOAc/hexanes); H NMR (400 MHz, CDCl3) d 7.97 (d, J = 7 Hz, 2H), 7.32-7.38 (m,
12H), 3.91 (s, 3H); 13C NMR (100 MHz, CDCl3) d 166.7, 143.9 (d, J = 14 Hz), 136.0 (d, J = 11
Hz), 133.8 (d, J = 20 Hz), 133.0 (d, J = 19 Hz), 129.9, 129.1 (d, J = 7 Hz), 129.0, 128.6 (d, J = 7
Hz), 52.0; 31P NMR (162 MHz, CDCl3) d -4.65.
O
O
P
5
4-(Diphenylphosphanyl)benzoic acid ethyl ester (5). The title compound was prepared from
ethanol (0.07 mL, 1.4 mmol) according to the procedure described for the synthesis of phosphine 4.
The desired phosphine 5 (0.312 mg, 72%) was obtained as a white solid after flash chromatography
1
(5% EtOAc/hexanes). Rf 0.45 (5% EtOAc/hexanes); H NMR (400 MHz, CDCl3) d 7.99 (d, J = 8
Hz, 2H), 7.32-7.38 (m, 12H), 4.38 (q, J = 7 Hz, 2H), 1.39 (t, J = 7 Hz, 3H); 13C NMR (100 MHz,
CDCl3) d 166.3, 143.7 (d, J = 14 Hz), 136.1 (d, J = 11 Hz), 133.8 (d, J = 20 Hz), 133.0 (d, J = 19
Hz), 130.2, 129.1 (d, J = 7 Hz), 129.0, 128.5 (d, J = 7 Hz), 60.9, 14.2; 31P NMR (162 MHz, CDCl3)
d -4.70; IR (neat) 3053, 2980, 1716, 1597, 1435, 1272, 1108, 1086, 1019, 744, 696 cm-1; HMRS
(MAB) calcd for C21H19O2P [M-H+]+: 334.112268. Found: 334.111978.
O
TMS
O
P
6
4-(Diphenylphosphanyl)benzoic acid 2-trimethylsilanylethyl ester (DPPBE) (6).10 The title
compound was prepared from 2-(trimethylsilyl)ethanol (0.50 mL, 3.80 mmol) according to the
procedure described for the synthesis of phosphine 4. The desired phosphine 6 (1.16 g, 82%) was
obtained as a colorless viscous oil after flash chromatography (5% EtOAc/hexanes). The reagent
1
was used as a THF solution (0.5 M). H NMR (400 MHz, CDCl3) d 7.99 (d, J = 7 Hz, 2H), 7.32-
7.38 (m, 12H), 4.44 (t, J = 8 Hz, 2H), 1.14 (t, J = 8 Hz, 2H), 0.10 (s, 9H); 13C NMR (100 MHz,
CDCl3) d 166.4, 143.6 (d, J = 14 Hz), 136.1 (d, J = 11 Hz), 133.8 (d, J = 20 Hz), 133.0 (d, J = 22
Hz), 130.4, 129.1 (d, J = 6 Hz), 129.0, 128.5 (d, J = 7 Hz), 63.2, 17.3, -1.54; 31P NMR (162 MHz,
CDCl3) d -4.67; IR (neat) 3054, 2952, 2896, 1715, 1597, 1435, 1270, 1250, 1108, 1085, 838, 696,
631 cm-1; HMRS (MAB) calcd for C24H27O2PSi [M-H+]+: 406.151797. Found: 406.152982.
S10

General procedure for the methylenation of aldehydes.
Method A. Triphenylphosphine.
To a solution of chlorotris(triphenylphosphine)rhodium (0.023 g, 0.025 mmol) and
triphenylphosphine (0.29 g, 1.10 mmol) in THF (10 mL), was added 2-propanol (75.0 µL, 1.00
mmol) followed by the aldehyde (1.00 mmol). To the resulting red mixture, was then added a
solution of trimethylsilyldiazomethane in THF (0.82 mL, 1.40 mmol). Gas evolution was observed
and the resulting dark orange mixture was stirred at room temperature. When the reaction is
completed by GC or TLC analysis, 3% H2O2 (10 mL) was added and the organic layer was
extracted with dichloromethane (3 x 10 mL). The combined organic layers were washed with brine
(10 mL) and dried over MgSO4. The solvent was removed under reduced pressure and the crude
alkene was purified by flash chromatography on silica gel or by distillation. It is also possible to
evaporate directly the reaction mixture and performed a flash chromatography with a pre-absorption
on silica.
General procedure for the methylenation of aldehydes.
Method B. DPPBE (6).
To a solution of chlorotris(triphenylphosphine)rhodium (0.023 g, 0.025 mmol) in THF (10 mL) was
added a solution of DPPBE (6) in THF (2.20 mL, 1.10 mmol), followed by 2-propanol (75.0 µL,
1.00 mmol) and by the aldehyde (1.00 mmol). To the resulting red mixture, was then added a
solution of trimethylsilyldiazomethane in THF (0.82 mL, 1.40 mmol). Gas evolution was observed
and the resulting dark orange mixture was stirred at room temperature until the reaction is
completed by GC or TLC analysis. The reaction mixture was cooled to 0 °C, prior to the addition
of a solution of TBAF in THF (5.00 mL, 5.00 mmol). The resulting mixture was warmed to room
temperature and stirred for 12 hours. The mixture was then diluted with dichloromethane (30 mL),
washed with 10% aqueoux NaOH (15 mL) and brine (15 mL). The organic layer was dried over
MgSO4 and the solvent was removed under reduced pressure. The crude alkene was purified by
flash chromatography on silica gel or by distillation.
Wittig procedure for the methylenation of aldehydes.
Method C. Methyltriphenylphosphonium bromide and NaHMDS.
To a solution of methyltriphenylphosphonium bromide (393 mg, 1.10 mmol) in THF (10 mL), was
added sodium hexamethyldisilazide (202 mg, 1.10 mmol). The resulting yellow mixture was stirred
for 1 hour at room temperature. The aldehyde (1.00 mmol) was then added and the solution was
stirred at room temperature until the reaction is completed by GC analysis or by TLC. The solvent
was removed under reduced pressure and the crude alkene was purified by flash chromatography on
silica gel or by distillation.
Ph
Ph
O
1
4-Phenyl-1,3-butadiene (1). The title compound was prepared from trans-cinnamaldehyde (250
uL, 2.00 mmol) according to the general procedure A (reaction time: 0.5 h). The desired alkene 1
(230 mg, 88%) was obtained as a colorless oil after flash chromatography (1% ether/pentane). Rf
1
0.63 (1% EtOAc/hexanes); H NMR (400 MHz, CDCl3) d 7.43-7.41 (m, 2H), 7.35-7.31 (m, 2H),
7.26-7.22 (m, 1H), 6.80 (dd, J = 16, 10 Hz, 1H), 6.58 (d, J = 16 Hz, 1H), 6.52 (dd, J = 17, 10 Hz,
13
1H), 5.35 (d, J = 17 Hz, 1H), 5.19 (d, J = 10 Hz, 1H) ); C NMR (100 MHz, CDCl3) d 137.0,
136.96, 132.7, 129.5, 128.5, 127.5, 126.3, 117.5; IR (NaCl, film) 3080, 3060, 3030, 1800, 1630,
S11

1600, 1495, 1450, 1000, 950, 900, 755, 690 cm-1; Anal. Calcd for C10H10: C, 92.26; H, 7.74.
Found: C, 92.20; H, 8.04.
4-Phenyl-1,3-butadiene (1). The title compound was prepared from trans-cinnamaldehyde (132
mg, 1.00 mmol) according to the general procedure B (reaction time: 2 h). The desired alkene 1
(107 mg, 82%) was obtained as a colorless oil after flash chromatography (1% ether/pentane).
4-Phenyl-1,3-butadiene (1). The title compound was prepared from trans-cinnamaldehyde (132
mg, 1.00 mmol) according to the general procedure C (reaction time: 2 h). The desired alkene 1
(107 mg, 82%) was obtained as a colorless oil after flash chromatography (1% ether/pentane).
O
7
(S)-4-Isopropenyl-1-vinyl-cyclohexene (7). The title compound was prepared from (S)-(-)-
perillaldehyde (750 mg, 5.00 mmol) according to the general procedure B (reaction time: 5 h). The
desired alkene 7 (585 mg, 79%) was obtained as a colorless oil after kugelrhor distillation (b.p. 95
°C). R f 0.60 (1% EtOAc/hexanes); 1H NMR (400 MHz, CDCl3) d 6.38 (dd, J = 17, 11 Hz, 1H),
5.78 (m, 1H), 5.08 (d, J = 17 Hz, 1H), 4.92 (d, J = 11 Hz, 1H), 4.75 (s, 1H), 4.74 (s, 1H), 2.36-2.07
(m, 6H), 1.94-1.89 (m, 1H), 1.76 (s, 1H); 13C NMR (100 MHz, CDCl3) d 149.6, 139.5, 135.6, 129.0,
109.9, 108.6, 41.1, 31.1, 27.2, 24.1, 20.6; IR (neat) 3066, 3086, 2920, 1645, 1436, 989, 890, 835
cm-1; HMRS (MAB) calcd for C11H16 [M]+: 148.125201. Found: 148.125212.
TBSO
TBSO
O
8
6-(tert-Butyldimethylsilyloxy)-1-hexene (8). The title compound was prepared from 6-(tert-
butyldimethylsilyloxy)-1-pentanal (216 mg, 1.0 mmol) according to the general procedure A
(reaction time: 1 h). The desired alkene 8 (186 mg, 87%) was obtained as a colorless oil after flash
1
chromatography (2% EtOAc/hexanes). Rf 0.48 (2% EtOAc/hexanes); H NMR (400MHz, CDCl3)
d 5.84-5.78 (m, 1H), 5.00 (d, J = 17 Hz, 1H), 4.94 (d, J = 11 Hz, 1H), 3.61 (t, J = 6 Hz, 2H), 2.09-
13
2.04 (m, 2H), 1.55-1.50 (m, 2H), 1.47-1.41 (m, 2H), 0.90 (s, 9H), 0.05 (s, 6H); C NMR (100
MHz, CDCl3) d 138.8, 114.2, 62.9, 33.4, 32.1, 25.8, 25.0, 18.2; IR (NaCl, film) 3080, 2935 (br),
1640, 1470, 1390, 1360, 1255, 1110, 910, 840, 775, 660 cm-1; Anal. Calcd for C12H26OSi :
C, 67.22; H, 12.22. Found: C, 65.94; H, 12.41.
6-(tert-Butyldimethylsilyloxy)-1-hexene (8). The title compound was prepared from 6-(tert-
butyldimethylsilyloxy)-1-pentanal (216 mg, 1.00 mmol) according to the general procedure C
(reaction time: 7 h). The desired alkene 8 (152 mg, 71%) was obtained as a colorless oil after flash
chromatography (2% EtOAc/hexanes).
BnO
BnO
O
9
S12

6-(Benzyloxy)-1-hexene (9). The title compound was prepared from 5-benzyloxy-1-pentanal15 (192
mg, 1.00 mmol) according to the general procedure A (reaction time: 0.5 h). The desired alkene 9
(141 mg, 74%) was obtained as a colorless oil after flash chromatography (1% EtOAc/hexanes). Rf
1
0.42 (1% EtOAc/hexanes); H NMR (300 MHz, CDCl3) d 7.37-7.26 (m, 5H), 5.90-5.76 (m, 1H),
5.06-4.94 (m, 2H), 4.52 (s, 2H), 3.50 (t, J = 6 Hz, 2H), 2.13-2.05 (m, 2H), 1.69-1.62 (m, 2H), 1.55-
13
1.47 (m, 2H); C NMR (75 MHz, CDCl3) d 139.2, 139.1, 128.8, 128.0, 127.9, 114.9, 73.3, 70.7,
34.0, 29.6, 25.9; IR (neat) 3066, 3032, 2933, 2858, 1641, 1455, 1362, 1103, 909, 734, 631 cm-1;
HMRS (MAB) calcd for C13H18O [M]+: 190.135765. Found: 190.135287.
6-(Benzyloxy)-1-hexene (9). The title compound was prepared from 5-benzyloxy-pentanal11 (192
mg, 1.00 mmol) according to the general procedure B (reaction time: 0.5 h). The desired alkene 9
(169 mg, 89%) was obtained as a colorless oil after flash chromatography (1% EtOAc/hexanes).
OBn
OBn
Ph
Ph
O
10
7-Benzyloxy-4-phenyl-1-octene (10). The title compound was prepared from 7-benzyloxy-4-
phenyl-1-heptanal (583 mg, 1.97 mmol) according to the general procedure A (reaction time: 1h).
The desired alkene 10 (570 mg, 98%) was obtained as a colorless oil after flash chromatography
1
(2% EtOAc/hexanes). Rf 0.70 (2% EtOAc/hexanes); H NMR (400 MHz, CDCl3) d 7.39-7.26 (m,
6H), 7.21-7.18 (m, 4H), 5.87-5.77 (m, 1H), 5.05-4.95 (m, 2H), 4.54 (d, J = 12 Hz, 1H), 4.51 (d, J =
12 Hz, 1H), 3.47-3.41 (m, 1H), 2.81-2.73 (m, 1H), 2.70-2.63 (m, 1H), 2.10-2.04 (m, 2H), 1.94-1.80
(m, 2H), 1.68-1.44 (m, 4H); 13C NMR (100 MHz, CDCl3) d 142.3, 138.8, 138.6, 128.3, 128.2 (2),
127.7, 127.4, 125.6, 114.4, 78.0, 70.6, 35.5, 33.7, 33.0, 31.5, 24.4; IR (NaCl, film) 3065, 3030,
2935, 2860, 1640, 1495, 1455, 1360, 1095, 1070, 910, 840, 735, 700 cm-1; Anal. Calcd for
C21H26O: C, 85.67; H, 8.90. Found: C, 85.09; H, 8.95.
O
11
(R)-2,6-Dimethyl-2,8-nonadiene (11). The title compound was prepared from (R)-citronellal (360
uL, 2.00 mmol) according to the general procedure A (reaction time: 7 h). The desired alkene 11
(256 mg, 84%) was obtained as a colorless oil after flash chromatography (2% EtOAc/hexanes). Rf
1
0.48 (2% EtOAc/hexanes); H NMR (400MHz, CDCl3) d 5.84-5.74 (m, 1H), 5.13-5.09 (m, 1H),
5.03-4.96 (m, 2H), 2.13-1.86 (m, 4H), 1.69 (s, 3H), 1.61 (s, 3H), 1.57-1.47 (m, 1H), 1.40-1.30 (m,
1H), 1.20-1.11 (m, 1H), 0.89 (d, J = 7 Hz, 6H); 13C NMR (100 MHz, CDCl3) d 137.5, 131.0, 124.7,
115.3, 41.2, 36.5, 32.2, 25.6, 25.4, 19.2, 17.5; IR (NaCl, film) 3080, 2965, 2915, 1640, 1455, 1380,
995, 910 cm-1; Anal. Calcd for C11H20: C, 86.76; H, 13.24. Found: C, 86.81; H, 13.23.
(R)-2,6-Dimethyl-2,8-nonadiene (11). The title compound was prepared from (R)-citronellal (180
uL, 1.00 mmol) according to the general procedure B (reaction time: 5 h). The desired alkene 11
(131 mg, 86%) was obtained as a colorless oil after flash chromatography (2% EtOAc/hexanes).
15
Crimmins, M. T.; Katz, J. D.; McAtee, L. C.; Tabet, E. A.; Kirincich, S. J. Org. Lett. 2001, 3, 949-952.
S13

OTBDPS
OTBDPS
O
12
1-[3-(tert-Butyldiphenylsilyloxymethyl)-1,2,2-trimethylcyclopentyl]ethane (12). The title
compound was prepared from 3-(tert-butyl-diphenyl-silanyloxymethyl)-1,2,2-trimethyl-cyclo-
pentanecarbaldehyde16 (410 mg, 1.00 mmol) according to the general procedure A (reaction time: 7
h). The desired alkene 12 (320 mg, 79%) was obtained as a colorless oil after flash chromatography
1
(5% EtOAc/hexanes). Rf 0.57 (5% EtOAc/hexanes); H NMR (400MHz, CDCl3) d 7.70-7.67 (m,
4H), 7.43-7.37 (m, 6H), 5.87 (dd, J = 17, 11 Hz, 1H), 4.97 (d, J = 11 Hz, 1H), 4.91 (d, J = 17 Hz,
1H), 3.71 (dd, J = 10, 7 Hz, 1H), 3.56 (dd, J = 10, 7 Hz, 1H), 2.22-2.14 (m, 1H), 1.94-1.82 (m, 2H),
1.40-1.25 (m, 2H), 1.06 (s, 9H), 0.95 (s, 3H), 0.90 (s, 3H), 0.66 (s, 3H); C NMR (100 MHz,
13
CDCl3) d 144.9, 135.5, 133.9, 129.4, 127.4, 111.7, 65.8, 50.9, 48.8, 44.5, 34.3, 26.7, 24.9, 22.6,
22.2, 19.4, 19.1; IR (NaCl, film) 3070, 2960, 2860, 1470, 1430, 1110, 1070, 825, 700 cm-1; Anal.
Calcd for C27H38OSi: C, 79.74; H, 9.42. Found: C, 78.35; H, 9.16. HMRS (FAB) calcd for
C27H39OSi [M+H]+: 407.27701. Found: 407.27790.
O
13
(E)-4,8-Dimethyl-nona-1,3,7-triene (13).17 The title compound was prepared from citral (152 mg,
1.00 mmol) according to the general procedure A (reaction time: 2 h). The desired alkene 13 (135
mg, 90%) was obtained as a colorless oil after flash chromatography (1% EtOAc/hexanes). Rf 0.68
1
(1% EtOAc/hexanes); H NMR (400MHz, CDCl3) d 6.59 (dt, J = 17, 10 Hz, 1H), 5.88 (d, J = 10
Hz, 1H), 5.14-5.08 (m, 2H), 5.00 (d, J = 10 Hz, 1H), 2.20-2.08 (m, 4H), 1.78 (s, 3H), 1.70 (s, 3H),
13
1.62 (s, 3H); C NMR (100 MHz, CDCl3) d 139.9, 133.8, 132.1, 125.8, 124.4, 115.0, 40.3, 26.9,
26.1, 18.1, 17.1; IR (neat) 3080, 2965, 2915, 1640, 1455, 1380, 995, 910 cm-1.
(E)-4,8-Dimethyl-nona-1,3,7-triene (13). The title compound was prepared from citral (152 mg,
1.00 mmol) according to the general procedure B (reaction time: 2 h). The desired alkene 13 (116
mg, 77%) was obtained as a colorless oil after flash chromatography (1% EtOAc/hexanes).
(E)-4,8-Dimethyl-nona-1,3,7-triene (13). The title compound was prepared from citral (152 mg,
1.00 mmol) according to the general procedure C (reaction time: 6 h). The desired alkene 13 (116
mg, 77%) was obtained as a colorless oil after flash chromatography (1% EtOAc/hexanes).
OH
O
14
OH
Dodec-1-en-5-ol (14). The title compound was prepared from 5-heptyl-tetrahydro-furan-2-ol18 (93
mg, 0.50 mmol) with 2-methyl-1-propanol (1 mL) according to the general procedure A (reaction
time: 1 h). The desired alkene 14 (58 mg, 63%) was obtained as a colorless oil after flash
chromatography (5% EtOAc/hexanes). Rf 0.22 (10% EtOAc/hexanes); 1H NMR (300 MHz,
CDCl3) d 5.82 (ddt, J = 17, 10, 7 Hz, 1H), 5.01 (d, J = 17 Hz, 1H), 4.94 (d, J = 10, Hz, 1H), 3.63-
16
Betancort, J. M.; Rodriguez, C. M.; Martin, V. S. Tetrahedron Lett. 1998, 39, 9773-9776.
17
Leopold, E. J. Org. Synth. 1986, 64, 164-174.
Brunetiere, A. P.; Lallemand, J. Y. Tetrahedron Lett. 1988, 29, 2179-2182.
18
S14

3.55 (m, 1H), 2.22-2.04 (m, 2H), 1.60-1.16 (m, 14H), 0.85 (t, J = 5 Hz, 3H); 13C NMR (75 MHz,
CDCl3) d 139.1, 115.2, 72.0, 37.9, 36.9, 32.3, 30.6, 30.1, 29.7, 26.1, 23.1, 14.6; IR (neat) 3339 (br),
2956, 2924, 2855, 1641, 1456, 1378, 909, 630 cm-1; HMRS (MAB) calcd for C12H24O [M]+:
184.182716. Found: 184.182550.
O
O
O
O
O
15
(1R*,5R*)-1-Allyl-3,3-dimethyl-2,4-dioxabicyclo[4,3,0]nonane (15). The title compound was
prepared from (1R*,2R*)-[(1,2-isopropylidenedioxy)cyclohexyl]acetaldehyde19 (56.0 mg, 0.280
mmol) according to the general procedure A (reaction time: 1.5 h). The desired alkene 15 (43.0 mg,
79%) was obtained as a colorless oil after flash chromatography (5% Ether/pentane). Rf 0.36 (5%
1
Ether/pentane); H NMR (400 MHz, CDCl3) d 5.98-5.88 (m, 1H), 5.13-5.10 (m, 2H), 3.93 (s, 1H),
2.39 (dd, J = 14, 7 Hz, 1H), 2.31 (dd, J = 14, 7 Hz, 1H), 2.10-2.07 (m, 1H), 1.71-1.48 (m, 5H), 1.52
(s, 3H), 1.35 (s, 3H), 1.21-1.11 (m, 1H), 0.90-0.87 (m, 1H); 13C NMR (100 MHz, CDCl3) d 134.3,
118.1, 107.2, 80.5, 76.6, 40.5, 34.7, 28.9, 27.4, 26.6, 23.1, 20.2.
Ph
Ph
O
O
O
16
(2S,3S)-2-Phenyl-3-vinyloxirane (16). The title compound was prepared from (2R,3S)-3-phenyl-
oxirane-2-carbaldehyde20 (228 mg, 1.50 mmol) according to the general procedure A (reaction time:
1 h). The desired alkene 16 (188 mg, 86%) was obtained as a colorless oil after flash
1
chromatography (5% EtOAc/hexanes). Rf 0.49 (5% EtOAc/hexanes); H NMR (400 MHz, C6D6) d
7.25-7.15 (m, 5H), 5.65-5.56 (m, 1H), 5.32 (d, J = 17 Hz, 1H), 5.11 (d, J = 10 Hz, 1H), 3.53 (s, 1H),
3.18 (d, J = 7 Hz, 2H); 13C NMR (100 MHz, C6D6) d 138.2, 136.2, 129.0, 128.6, 126.2, 119.1, 63.3,
60.6; IR (NaCl, film) 3080, 3025, 2980, 1495, 1460, 1440, 870, 750 cm-1; HMRS (EI+) calcd for
C10H9O [M-H+]+: 145.065340. Found: 145.065174.
O
O
O
O
O
Ph
Ph
17
(2R*,4S*)-5,5-Dimethyl-2-phenyl-4-vinyl-1,3-dioxane (17). The title compound was prepared
from (2R*,4S*)-4-formyl-5,5-Dimethyl-2-phenyl-1,3-dioxane21 (280 mg, 1.25 mmol) according to
the general procedure A (reaction time: 5 h). The desired alkene 17 (202 mg, 74%) was obtained as
1
a colorless oil after flash chromatography (5% EtOAc/hexanes). Rf 0.52 (5% EtOAc/hexanes); H
NMR (400 MHz, C6D6) d 7.67-7.64 (m, 2H), 7.18-7.07 (m, 3H), 5.71 (ddd, J = 17, 10, 6 Hz, 1H),
5.36 (s, 1H), 5.26 (d, J = 17 Hz, 1H), 5.04 (d, J = 10 Hz, 1H), 3.70 (d, J = 7 Hz, 1H), 3.50 (d, J = 11
Hz, 1H), 3.23 (d, J = 11 Hz, 1H), 1.06 (s, 3H), 0.40 (s, 3H); 13C NMR (100 MHz, C6D6) d 136.8,
131.5, 125.9, 125.4, 123.9, 114.0, 98.9, 82.9, 75.5, 30.1, 18.4, 16.1; IR (NaCl, film) 3070, 2960,
2840, 1460, 1390, 1135, 1100, 1030, 990, 750, 700 cm-1; HMRS (MAB) calcd for C14H17O2 [M-
H+]+: 217.122855. Found: 217.121927.
19
Devaux, J. M.; Gore, J.; Vatele, J. M. Tetrahedron: Asymmetry 1998, 9, 1619-1626.
20
Evans, D. A.; Williams, J. M. Tetrahedron Lett. 1988, 29, 5065-5068.
21
Ito, M.; Kibayashi, C. Synthesis 1993, 137-140.
S15

i-Pr
i-Pr
O
OTBDPS
OTBDPS
18
(3S)-3-(tert-Butyldiphenylsilyloxy)-4-methyl-1-pentene (18). The title compound was prepared
from (2S)-2-(tert-butyldiphenylsilyloxy)-3-methylbutanal (618 mg, 1.80 mmol; prepared from
enantiomerically pure L-leucine22) according to the general procedure A (reaction time: 3 h). The
desired alkene 18 (540 mg, 89%) was obtained as a colorless oil after flash chromatography (5%
EtOAc/hexanes). Rf 0.55 (5% EtOAc/hexanes); [a]D25 = +21.7 (c 0.18, CHCl3); (lit.18 [a]D25 = +22.8
1
(c 0.18, CHCl3)); H NMR (400MHz, CDCl3) d 7.69-7.74 (m, 4H), 7.36-7.46 (m, 6H), 5.81(ddd, J
= 17, 10, 7 Hz, 1H), 5.00 (d, J = 10 Hz, 1H), 4.93 (d, J = 17 Hz, 1H), 4.00 (dd, J = 7, 4 Hz, 1H),
1.73-1.78 (m, 1H), 1.12 (s, 9H), 0.89 (d, J = 7 Hz, 3H), 0.82 (d, J = 7 Hz, 3H); 13C NMR (100 MHz,
CDCl3) d 137.8, 135.9, 135.8, 134.4, 129.3, 129.2, 127.34, 127.27, 127.1, 115.6, 79.5, 34.1, 27.0,
19.4, 18.2, 16.8; IR (NaCl, film) 1070, 2960, 2860, 1475, 1430, 1110, 1060, 820, 740, 700 cm-1;
HMRS (FAB) calcd for C22H29OSi [M-H+]+: 337.19876. Found: 337.19640.
Ph
Ph
O
NHBOC
19
NHBOC
(S)-2-(tert-Butoxycarbonylamino)-1-phenylbut-3-ene (19).23 The title compound was prepared
from (S)-2-(tert-butoxycarbonylamino)-3-phenylpropan-1-al (249 mg, 1.00 mmol; prepared from
enantiomerically pure L-phenylalanine24) according to the general procedure A (reaction time: 16
h). The desired alkene 19 (131 mg, 53%) was obtained as a colorless oil after flash chromatography
(5% EtOAc/hexanes). Rf 0.22 (5% EtOAc/hexanes); [a]D25 = +5.15 (c 2.0, CHCl3); 1H NMR
(400MHz, CDCl3) d 7.15-7.33 (m, 5H), 5.80 (ddd, J = 16, 10, 5 Hz, 1H), 5.17 (dd, J = 10, 1 Hz,
13
1H), 5.12 (dd, J = 16, 1 Hz, 1H), 4.42 (s (br), 2H), 2.84 (d (br), J = 7 Hz, 2H), 1.42 (s, 9H); C
NMR (100 MHz, CDCl3) d 155.6, 138.5, 137.8, 130.0, 128.8, 126.9, 115.2, 79.9, 53.8, 41.9, 28.8;
The enantiomeric excess was determined to be 95% (39:1) following a procedure described in the
literature.19
(S)-2-(tert-Boc-amino)-1-phenylbut-3-ene (19). The title compound was prepared from (S)-2-(tert-
butoxycarbonylamino)-3-phenylpropan-1-al (249 mg, 1.00 mmol; prepared from enantiomerically
pure L-phenylalanine24) according to the general procedure B (reaction time 16 h). The desired
alkene 19 (168 mg, 68%) was obtained as a colorless oil after flash chromatography (5%
EtOAc/hexanes). The enantiomeric excess was determined to be 95% (39:1) following a procedure
described in the literature.19
22
Ina, H.; Ito, M.; Kibayashi, C. J. Org. Chem. 1996, 61, 1023-1029.
Luly, J. R.; Dellaria, J. F.; Plattner, J. J.; Soderquist, J. L.; Yi, N. J. Org. Chem. 1987, 52, 1487-1492.
23
24
Crude aldehyde prepared by TEMPO oxidation, see : Noula, C.; Loukas, V.; Kokotos, G. Synthesis 2002, 1735-
1739.
S16

O
O
O
NBOC
NBOC
20
(4R)-2,2-Dimethyl-4-vinyloxazolidine-3-carboxylic acid tert-butyl ester (20). The title
compound was prepared from (4S)-4-formyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl
ester25 (230 mg, 1.00 mmol; the enantiomeric excess was determined to be 92% (24:1) by chiral GC
analysis (20% Permethylated G-Cyclodextrin, isothermal 70 °C, tr 22,3 (minor), 24.5 (major)).
according to the general procedure A (reaction time: 4 h). The desired alkene 20 (195 mg, 86%)
was obtained as a colorless oil after flash chromatography (5% EtOAc/hexanes). Rf 0.28 (5%
1
EtOAc/hexanes); [a]25D = +12.5 (c 2.5, CHCl3); H NMR (400MHz, C6D6) d 5.85-5.82 (m (br),
1H), 5.22-5.11 (m (br), 1H), 5.08 (d, J = 10 Hz, 1H), 4.31-4.14 (m (br), 1H), 3.79 (dd, J = 9, 6 Hz,
1H), 3.59 (dd, J = 9, 2 Hz, 1H), 1.81 (s (br), 3H), 1.66 (s (br), 3H), 1.52 (s, 9H); C NMR (100
13
MHz, CDCl3) d 151.8, 137.2, 136.6, 115.5, 93.7, 80.0, 79.3, 67.9, 59.5, 28.2, 27.0, 26.3, 24.6, 23.5;
IR (NaCl, film) 2980, 2940, 2870, 1690, 1375, 1255, 1175, 1090, 1060, 920, 860, 840, 770 cm-1;
HMRS (MAB) calcd for C12H20NO3 [M-H+]+: 226.144319. Found: 226.143815. The enantiomeric
excess was determined to be 92% (24:1) by chiral GC analysis (20% Permethylated G-
Cyclodextrin, isothermal 70 °C, tr 46.4 (minor), 47.4 (major)).
TBDPSO
TBDPSO
O
21
(S)-4-[(tert-Butyldiphenylsilyl)oxy]-3-methylbut-1-ene (21).26 The title compound was prepared
from (R)-3-[(tert-butyldiphenylsilyl)oxy]-2-methylpropanal (163 mg, 1.00 mmol; [a]D25 = -9.4 (c
1.08, CHCl3); (lit.26 [a]D25 = +4.0 (c 1.28, CHCl3)) according to the general procedure A (reaction
time: 1 h). The desired alkene 21 (117 mg, 72%) was obtained as a colorless oil after flash
25
chromatography (1% EtOAc/hexanes); Rf 0.55 (1% EtOAc/hexanes); [a]D = -3.18 (c 0.71,
CHCl3); 1H NMR (300 MHz, CDCl3) d 7.69-7.66 (m, 4H), 7.43-7.38 (m, 6H), 5.81 (ddd, J = 14, 9,
7 Hz, 1H), 5.01 (m, 2H), 3.57 (dd, J = 9, 6 Hz, 1H), 3.49 (dd, J = 9, 6 Hz, 1H), 2.40 (m, 1H), 1.06
(s, 9H), 1.04 (d, J = 7 Hz, 3H); C NMR (75 MHz, CDCl3) d 141.2, 135.5, 133.8, 129.4, 127.4,
13
113.9, 68.4, 40.1, 26.7, 19.2, 16.0. The enantiomeric excess was determined to be 94% (30:1) by
chiral GC analysis (20% Permethylated G-Cyclodextrin, 40 °C, 3 min; 10 °C/min, 230 °C, tr 4.23
(major), 4.36 (minor)) of the corresponding alcohol product after treatment of the alkene 21 with
TBAF (1 M in THF).
(S)-4-[(tert-Butyldiphenylsilyl)oxy]-3-methylbut-1-ene (21).26 The title compound was prepared
from (R)-3-[(tert-butyldiphenylsilyl)oxy]-2-methylpropanal (163 mg, 1.00 mmol; [a]D25 = -9.4 (c
1.08, CHCl3); (lit.26 [a]D25 = +4.0 (c 1.28, CHCl3)) according to the general procedure C (reaction
time: 2 h). The desired alkene 21 (119 mg, 73%) was obtained as a colorless oil after flash
chromatography (1% EtOAc/hexanes); [a]D25 = -3.07 (c 0.75, CHCl3); The enantiomeric excess was
determined to be 90% (20:1) by chiral GC analysis (20% Permethylated G-Cyclodextrin, 40 °C, 3
min; 10 °C/min, 230 °C, tr 4.23 (major), 4.36 (minor)) of the corresponding alcohol product after
treatment of the alkene 21 with TBAF (1 M in THF).
BnO
BnO
O
22
25
26
Avenoza, A.; Cativiela, C.; Corzana, F.; Peregrina, J. M.; Zurbano, M. M. J. Org. Chem. 1999, 64, 8220-8225.
Konno, K.; Fujishima, T.; Maki, S.; Liu, Z.; Miura, D.; Chokki, M.; Ishizuka, S.; Yamaguchi, K.; Kan, Y.; Kurihara,
M.; Miyata, N.; Smith, C.; DeLuca, H. F.; Takayama, H. J. Med. Chem. 2000, 43, 4247-4265.
S17

(S)-(2-Methyl-but-3-enyloxymethyl)-benzene (22).27 The title compound was prepared from (R)-
25
3-benzyloxy-2-methylpropanal28, (178 mg, 1.00 mmol; [a]D25 = -29.4 (c 1.13, CHCl3); (lit.28 [a]D
=
+30.6 (c 1.32, CHCl3)) according to the general procedure A (reaction time 3 h). The desired alkene
22 (137 mg, 78%) was obtained as a colorless oil after flash chromatography (1% EtOAc/hexanes).
1
Rf 0.36 (1% EtOAc/hexanes); [a]D25 = -3.0 (c 1.0, CHCl3); H NMR (400MHz, CDCl3) d 7.36-7.26
(m, 5H), 5.87-5.76 (m, 1H), 5.11-4.99 (m, 2H), 4.53 (s, 2H), 3.42-3.28 (m, 2H), 2.56-2.45 (m, 1H),
13
1.05 (d, J = 7 Hz, 3H); C NMR (100 MHz, CDCl3) d 141.7, 129.3, 128.8, 128.0, 127.9, 114.5,
75.4, 73.4, 38.3, 17.0; The enantiomeric excess was determined to be 84% (12:1) by chiral HPLC
analysis (Chiracel OJ, 1mL/min, 2% 2-propanol/hexane, tr 59.3 (major), 62.7 (minor), 68.2 (major),
85.9 (minor)) of the corresponding diol product.
(S)-(2-Methyl-but-3-enyloxymethyl)-benzene (22). The title compound was prepared from (R)-3-
benzyloxy-2-methylpropanal (178 mg, 1.00 mmol; [a]D25 = -29.4 (c 1.13, CHCl3); (lit.28 [a]D
25
=
+30.6 (c 1.32, CHCl3)) according to the general procedure B (reaction time: 5 h). The desired
alkene 22 (134 mg, 76%) was obtained as a colorless oil after flash chromatography (1%
EtOAc/hexanes). Rf 0.36 (1% EtOAc/hexanes); The enantiomeric excess was determined to be
79% (8:1) by chiral HPLC analysis, (Chiracel OJ, 1mL/min, 2% 2-propanol/hexane, tr 59.3 (major),
62.7 (minor), 68.2 (major), 85.9 (minor)) of the corresponding diol product.
(S)-(2-Methyl-but-3-enyloxymethyl)-benzene (22). The title compound was prepared from (R)-3-
benzyloxy-2-methylpropanal (50.0 mg, 0.28 mmol) according to the general procedure C (reaction
time 2 h). The desired alkene 22 (26 mg, 53%) was obtained as a colorless oil after flash
chromatography (1% EtOAc/hexanes). Rf 0.36 (1% EtOAc/hexanes); The enantiomeric excess was
determined to be 80% (8:1) by chiral HPLC analysis, (Chiracel OJ, 1mL/min, 2% 2-
propanol/hexane, tr 59.3 (major), 62.7 (minor), 68.2 (major), 85.9 (minor)) of the corresponding diol
product.
OH
OH
BnO
4-Benzyloxy-3-methyl-butane-1,2-diol. The isolated alkene 22 from procedure A was treated with
AD-mix alpha in t-BuOH/H2O for 48 h.29 The desired diol was isolated as a mixture of
diastereoisomers and as a colorless oil after flash chromatography (50% EtOAc/hexanes). Rf 0.24
(50% EtOAc/hexanes); [a]D25 = -11.0 (c 1.0, CHCl3); Major diastereoisomer: 1H NMR (400MHz,
CDCl3) d 7.38-7.28 (m, 5H), 4.53 (s, 2H), 3.76-3.43 (m, 5H), 2.81-2.76 (s (br), 2H), 2.06-1.95 (m,
1H), 0.90 (d, J = 7 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 137.3, 128.4, 127.8, 127.7, 127.6, 76.1,
74.5, 74.4, 73.4, 64.5, 36.0, 13.8; IR (neat) 3370 (br), 3030, 2860, 1497, 1454, 1364, 1073, 699,
631 cm-1; HMRS (MAB) calcd for C12H18O3 [M+H+]+: 211.13342. Found: 211.13280.
OBn OBn
OBn OBn
O
O
OBn OBn
OBn OBn
23
(3R, 4R, 5R, 6S)-3,4,5,6-Tetra(benzyloxy)-1,7-octadiene (23).30 The title compound was
prepared from 2,3,4,5,-tetra-(benzyloxy)-1,6-hexanedial (50.0 mg, 0.10 mmol) and 2-methyl-1-
27
Grandguillot, J. C.; Rouessac, F. Tetrahedron 1991, 47, 5133-5148.
Kawabata, T.; Kimura, Y.; Ito, Y.; Terashima, S.; Sasaki, A.; Sunagawa, M. Tetrahedron 1988, 44, 2149-2165.
28
29
Kolb, H. C.; Andersson, P. G.; Sharpless, K. B. J. Am. Chem. Soc. 1994, 116, 1278-1291.
Ackermann, L.; El Tom, D.; Furstner, A. Tetrahedron 2000, 56, 2195-2202.
30
S18

propanol (0.2 mL) according to the general procedure A (reaction time: 2 h). The desired diene 23
(24 mg, 50%) was obtained as a colorless oil after flash chromatography (2% EtOAc/hexanes). Rf
1
0.22 (2% EtOAc/hexanes); [a]D25 = +13.0 (c 1.0, CHCl3); H NMR (400 MHz, CDCl3) d 7.32-7.24
(m, 20 H), 5.99-5.81 (m, 2H), 5.35-5.18 (m, 4H), 4.82-4.50 (m, 6H), 4.36-3.70 (m, 6H); 13C NMR
(75 MHz, CDCl3) d 139.4, 139.3, 138.9, 138.7, 136.6, 136.0, 128.7, 128.6, 128.5, 128.3, 128.1,
128.0, 127.9, 128.7, 120.1, 119.5, 81.7, 81.5, 80.9, 80.8, 75.6, 74.4, 70.8, 70.3.
O
O
O
O
O
24
5-Vinylbenzo[1,3]dioxole (24). The title compound was prepared from piperonal (75 mg, 0.50
mmol) according to the general procedure A (reaction time: 1 h). The desired alkene 24 (55 mg,
74%) was obtained as a colorless oil after flash chromatography (2% EtOAc/hexanes). Rf 0.37 (2%
EtOAc/hexanes); 1H NMR (400 MHz, CDCl3) d 6.97 (s, 1H), 6.84 (d, J = 8 Hz, 1H), 6.77 (d, J = 8
Hz, 1H), 6.63 (dd, J = 18, 11 Hz, 1H), 5.96 (s, 2H), 5.58 (d, J = 18 Hz, 1H), 5.13 (d, J = 11 Hz,
1H); 13C NMR (100 MHz, CDCl3) d 147.8, 147.2, 136.2, 132.0, 120.9, 111.8, 108.0, 105.2, 100.9;
IR (neat) 3087, 3008, 2981, 2893, 1630, 1604, 1504, 1444, 1350, 1247, 1043, 939, 915, 813 cm-1;
Anal. Calcd for C9H8O2: C, 72.96; H, 5.44. Found: C, 72.94; H, 5.49.
5-Vinylbenzo[1,3]dioxole (24). The title compound was prepared from piperonal (150 mg, 1.00
mmol) according to the general procedure B (reaction time: 2 h). The desired alkene 24 (120 mg,
81%) was obtained as a colorless oil after flash chromatography (2% EtOAc/hexanes).
5-Vinylbenzo[1,3]dioxole (24). The title compound was prepared from piperonal (150 mg, 1.00
mmol) according to the general procedure C (reaction time: 3 h). The desired alkene 24 (125 mg,
84%) was obtained as a colorless oil after flash chromatography (2% EtOAc/hexanes).
O
25
Br
Br
1-Bromo-4-vinylbenzene (25). The title compound was prepared from 4-bromo-benzaldehyde
(183 mg, 1.00 mmol) according to the general procedure A (reaction time: 1 h). The desired alkene
25 (120 mg, 66%) was obtained as a colorless oil after flash chromatography (1% ether/pentane);
1H NMR (400 MHz, CDCl3) d 7.46 (d, J = 8 Hz, 2H), 7.28 (d, J = 8 Hz, 2H), 6.67 (dd, J = 18, 11
Hz, 1H), 5.76 (d, J = 18 Hz, 1H), 5.29 (d, J = 11 Hz, 1H).
1-Bromo-4-vinylbenzene (25). The title compound was prepared from 4-bromo-benzaldehyde (183
mg, 1.00 mmol) according to the general procedure B (reaction time 2 h). The desired alkene 25
(140 mg, 77%) was obtained as a colorless oil after flash chromatography (1% ether/pentane).
O
26
MeO
MeO
1-Methoxy-4-vinylbenzene (26). The title compound was prepared from 4-methoxy-benzaldehyde
(136 mg, 1.00 mmol) according to the general procedure A (reaction time: 0.5 h). The desired
alkene 26 (107 mg, 80%) was obtained as a colorless oil after flash chromatography (1%
ether/pentane); 1H NMR (400 MHz, CDCl3) d 7.36 (d, J = 9 Hz, 1H), 6.88 (d, J = 9 Hz, 1H), 6.69
(dd, J = 18, 11 Hz, 1H), 5.62 (d, J = 18 Hz, 1H), 5.14 (d, J = 11 Hz, 1H), 3.82 (s, 3H).
S19

1-Methoxy-4-vinylbenzene (26). The title compound was prepared from 4-methoxy-benzaldehyde
(136 mg, 1.00 mmol) according to the general procedure B (reaction time: 0.5 h). The desired
alkene 26 (120 mg, 90%) was obtained as a colorless oil after flash chromatography (1%
ether/pentane).
O
27
THPO
THPO
1-(Tetrahydropyran-2-yloxy)-4-vinylbenzene (27).31 The title compound was prepared from 4-
(tetrahydropyran-2-yloxy)benzaldehyde (206 mg, 1.00 mmol) according to the general procedure A
(reaction time: 1 h). The desired alkene 27 (190 mg, 93%) was obtained as a colorless oil after flash
1
chromatography (2% EtOAc/hexanes); Rf 0.42 (2% EtOAc/hexanes); H NMR (400 MHz, CDCl3)
d 7.36 (d, J = 9 Hz, 2H), 7.03 (d, J = 9 Hz, 2H), 6.68 (dd, J = 18, 11 Hz, 1H), 5.64 (dd, J = 18, 1
Hz, 1H), 5.44 (t, J = 3 Hz, 1H), 5.15 (dd, J = 11, 1 Hz, 1H), 3.92 (dd, J = 10, 3 Hz, 1H), 3.63-3.60
(m, 1H), 2.03-2.00 (m, 1H), 1.90-1.86 (m, 2H), 1.72-1.60 (m, 3H); 13C NMR (100 MHz, CDCl3) d
156.7, 136.1, 131.1, 127.1, 116.3, 111.7, 96.1, 61.8, 30.2, 25.1, 18.6.
1-(Tetrahydropyran-2-yloxy)-4-vinylbenzene (27). The title compound was prepared from 4-
(tetrahydropyran-2-yloxy)benzaldehyde (206 mg, 1.00 mmol) according to the general procedure B
(reaction time: 3 h). The desired alkene 27 (165 mg, 81%) was obtained as a colorless oil after flash
chromatography (2% EtOAc/hexanes).
MeO
MeO
NHAc
MeO
MeO
NHAc
28
O
N-[2-(4,5-Dimethoxy-2-vinylphenyl)ethyl]acetamide (28). The title compound was prepared
from N-[2-(2-formyl-4,5-dimethoxy-phenyl)-ethyl]-acetamide32 (390 mg, 1.55 mmol) according to
the general procedure A (reaction time: 0.5 h). The desired alkene 28 (233 mg, 60%) was obtained
as a yellow solid after flash chromatography (20% DCM/acetone with 1% triethylamine) and
1
recristallisation in TBME. Rf 0.27 (2% EtOAc/hexanes); H NMR (400 MHz, CDCl3) d 7.03 (s,
1H), 6.93 (dd, J = 17, 11 Hz, 1H), 6.64 (s, 1H), 5.57 (d, J = 17 Hz, 1H), 5.49 (s(br), 1H), 5.24 (d, J
= 11 Hz, 1H), 3.90 (s, 3H), 3.87 (s, 3H), 3.43 (q, J = 7 Hz, 2H), 2.85 (t, J = 7 Hz, 2H), 1.93 (s, 3H);
13C NMR (75 MHz, CDCl3) d 170.5, 149.3, 148.2, 134.2, 129.5, 129.46, 114.3, 113.1, 108.9, 56.37,
56.31, 41.1, 32.7, 23.8; IR (HATR, solid) 3245, 3075, 2935, 1630, 1510, 1460, 1260, 1220, 1100,
985, 865 cm-1; Anal. Calcd for C14H19NO3: C, 67.45; H, 7.68; N, 5.62. Found: C, 66.44; H, 7.45;
N, 5.46.
O
O
O
Ph
Ph
29
30
1-Phenylhept-6-en-1-one (30). The title compound was prepared from 6-oxo-6-phenylhexanal (29)
(630 mg, 3.31 mmol) according to the general procedure A (reaction time: 0.5 h). The desired
alkene 30 (542 mg, 87%) was obtained as a colorless oil after flash chromatography (2%
EtOAc/hexanes); Rf 0.27 (2% EtOAc/hexanes); 1H NMR (400 MHz, CDCl3) d 7.97-7.95 (m, 2H),
31
Srikrishna, A.; Sattigeri, J. A.; Viswajanani, R.; Yelamaggad, C. V. J. Org. Chem. 1995, 60, 2260-2260.
32
Wirth, T.; Fragale, G. Synthesis 1998, 162-166.
S20

7.57-7.54 (m, 1H), 7.48-7.44 (m, 2H), 5.86-5.79 (m, 1H), 5.05-4.95 (m, 2H), 2.98 (t, J = 7 Hz, 2H),
2.14-2.08 (m, 2H), 1.80-1.73 (m, 2H), 1.53-1.47 (m, 2H); C NMR (100 MHz, CDCl3) d 200.2,
13
138.4, 136.9, 132.8, 128.4, 127.9, 114.5, 38.3, 33.4, 28.4, 23.6; IR (NaCl, film) 3065, 2935, 2860,
1690, 1450, 1225, 910, 690 cm-1; Anal. Calcd for C13H16O: C, 82.94; H, 8.57. Found: C, 82.97; H,
8.55. HMRS (MAB) calcd for C13H16O [M]+: 188.120115. Found: 188.119597.
1-Phenylhept-6-en-1-one (30). The title compound was prepared from 6-oxo-6-phenylhexanal
(29) (190 mg, 1.00 mmol) according to the general procedure C (reaction time: 3 h). The desired
alkene 30 (111 mg, 59%) was obtained as a colorless oil after flash chromatography (2%
EtOAc/hexanes).
OH
OH
OH
OBn
HO
HO
6-Benzyloxy-hexane-1,5-diol. To a solution of 1,2,6-hexanetriol (670 mg, 5.00 mmol) in MeOH
(50 mL) was added dibutyltin oxide (1.24 g, 5.00 mmol). After 2 hours at reflux, the reaction
mixture was evaporated to dryness and the white solid was dissolved in benzene (100 mL).
Tetrabutylammonium iodide (2.77 g, 7.50 mmol) and benzyl bromide (0.65 mL, 5.50 mmol) were
then added to the reaction mixture at room temperature. After 16 hours at 50 °C, the solution was
concentrated down. The desired diol (0.96 g, 86%) was obtained as a colorless oil after flash
chromatography (100% EtOAc); Rf 0.39 (100% EtOAc); 1H NMR (300 MHz, CDCl3) d 7.35-7.29
(m, 5H), 4.54 (s, 2H), 3.82-3.79 (m, 1H), 3.59 (t, J = 6 Hz, 2H), 3.48 (dd, J = 9, 3 Hz, 1H), 3.33
(dd, J = 9, 8 Hz, 1H), 2.88 (br, 1H), 2.36 (br, 1H), 1.58-1.39 (m, 6H); 13C NMR (75 MHz, CDCl3) d
137.8, 128.3, 127.6, 74.5, 73.2, 70.2, 62.3, 32.5, 32.3, 21.5; IR (neat) 3370 (br), 3343, 2934, 2861,
1454, 1364, 1092, 699, 631 cm-1; HMRS (FAB) calcd for C13H20O3 [M+H+]+: 225.149070. Found:
225.148681.
O
OH
OBn
OBn
HO
O
32
6-Benzyloxy-5-oxo-hexanal. (32). Oxalyl chloride (44.0 µL, 0.50 mmol) was added to a solution
of dimethylsulfoxide (71.0 µL, 1.00 mmol) in dichloromethane (4 mL) at –78 °C. After 15 min, a
solution of the diol (22.0 mg, 0.10 mmol) in dichloromethane (1 mL) was added. The resulting
mixture was stirred for 1h at –78 °C before triethylamine (0.27 mL, 2.00 mmol) was added. The
cooling bath was then removed and the solution was stirred for another hour at room temperature.
Saturated aqueous NH4Cl (15 mL) was added and the aqueous layer was extracted with
dichloromethane (3 x 20 mL). The combined organic layers were washed with saturated aqueous
NaHCO3 (15 mL), brine (15 mL) and dried over MgSO4. After evaporation, the desired keto-
aldehyde 32 (12 mg, 55%) was obtained as a colorless oil after flash chromatography (1:2
1
EtOAc/hexanes); Rf 0.27 (1:2 EtOAc/hexanes); H NMR (300 MHz, C6D6) d 9.22 (s, 1H), 7.24-
7.10 (m, 5H), 4.22 (s, 2H), 3.61 (s, 2H), 2.05 (t, J = 7 Hz, 2H), 1.79 (t, J = 7 Hz, 2H), 1.62-1.58 (m,
2H); 13C NMR (100 MHz, C6D6) d 204.2, 197.4, 125.8, 125.4, 125.2, 125.0, 72.4, 70.4, 40.0, 34.8,
12.8; IR (neat) 3031, 2865, 1717, 1455, 1391, 1099, 739, 699, 602 cm-1; HMRS (FAB) calcd for
C13H16O3 [M-H+]+: 219.102120. Found: 219.102261.
O
O
OBn
OBn
O
32
33
S21

6-Benzyloxy-hept-6-en-2-one. (33). The title compound was prepared from keto-aldehyde 32 (163
mg, 1.00 mmol) according to the general procedure A (reaction time: 1 h). The desired alkene 33
(117 mg, 72%) was obtained as a colorless oil after flash chromatography (5% EtOAc/hexanes); Rf
1
0.18 (5% EtOAc/hexanes); H NMR (300 MHz, CDCl3) d 7.37-7.33 (m, 5H), 5.81-5.70 (m, 1H),
5.05-4.96 (m, 2H), 4.59 (s, 2H), 4.06 (s, 2H), 2.47 (t, J = 7 Hz, 2H), 2.10-2.03 (m, 2H), 1.73-1.68
(m, 2H); 13C NMR (75 MHz, CDCl3) d 208.5, 137.7, 137.1, 128.4, 127.9, 127.8, 115.2, 74.9, 73.2,
38.0, 32.9, 22.1; IR (neat) 3067, 2933, 1721, 1455, 1097, 913, 698, 630 cm-1.
D
O
35
4-phenyl-(1D)-1,3-butadiene (35). The title compound was prepared from trans-cinnamaldehyde
(250 uL, 2.00 mmol) and 2-propan(ol-d) according to the general procedure A (reaction time: 0.5
h). The desired alkene 35 (180 mg, 69%) was obtained as a colorless oil after flash chromatography
1
(1% ether/pentane); H NMR (400 MHz, CDCl3) d 7.46-7.44 (m, 2H), 7.38-7.34 (m, 2H), 7.29-7.27
(m, 1H), 6.84 (ddd, J = 16, 10, 1 Hz, 1H), 6.61 (d, J = 16 Hz, 1H), 6.60-6.51 (m, 1H), 5.40-5.19 (m,
1H); 13C NMR (100 MHz, CDCl3) d 137.1, 137.0, 132.7, 129.5, 128.5, 127.5, 126.3, 117.5; HMRS
(MAB) calcd for C10H9D [M]+: 130.078250. Found: 130.078195.
S22

GC Trace of Various Trimethylsilyldiazomethane Solutions
Synthetic
TMSCHN2
6.00
8.00
10.00
12.00
16.00
2.00
14.00
18.00
4.00
Aldrich
2M ether
TMSCHN2
6.00
8.00
10.00
12.00
16.00
2.00
14.00
18.00
4.00
S23

GC Trace of Various Trimethylsilyldiazomethane Solutions
Synthetic
TMSCHN2
6.00
8.00
10.00
12.00
16.00
2.00
14.00
18.00
4.00
Aldrich
2M hexane
TMSCHN2
6.00
8.00
10.00
12.00
16.00
2.00
14.00
18.00
4.00
S24