Preparation of silyl-protected γ-hydroxylated α,β-unsaturated acetylenic ketones and their reactions with some nucleophiles

Article abstract of DOI:10.1080/00397911.2016.1172236

A number of 5-siloxylated 1,1-diethoxy-3-alkyn-2-ones were prepared from the corresponding ketals. The t-butyldiphenylsiloxy derivatives were stable, whereas the trimethylsilyl analogs were unstable. The former compounds were reacted with diethylamine, li

Full text of DOI:10.1080/00397911.2016.1172236

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
Preparation of silyl-protected γ-hydroxylated
α,β-unsaturated acetylenic ketones and their
reactions with some nucleophiles
Weidong Shang, Magnus E. Fairhurst & Leiv K. Sydnes
To cite this article: Weidong Shang, Magnus E. Fairhurst & Leiv K. Sydnes (2016)
Preparation of silyl-protected γ-hydroxylated α,β-unsaturated acetylenic ketones and
their reactions with some nucleophiles, Synthetic Communications, 46:9, 775-792, DOI:
10.1080/00397911.2016.1172236
To link to this article: http://dx.doi.org/10.1080/00397911.2016.1172236
View supplementary material
Accepted author version posted online: 11
Apr 2016.
Published online: 11 Apr 2016.
Submit your article to this journal
Article views: 12
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=lsyc20
Download by: [University of Cambridge]
Date: 02 June 2016, At: 04:42

SYNTHETIC COMMUNICATIONS®
2016, VOL. 46, NO. 9, 775–792
http://dx.doi.org/10.1080/00397911.2016.1172236
Preparation of silyl-protected γ-hydroxylated α,β-unsaturated
acetylenic ketones and their reactions with some nucleophiles
Weidong Shang, Magnus E. Fairhurst, and Leiv K. Sydnes
Department of Chemistry, University of Bergen, Bergen, Norway
ABSTRACT
ARTICLE HISTORY
Received 2 March 2016
A number of 5-siloxylated 1,1-diethoxy-3-alkyn-2-ones were prepared
from the corresponding ketals. The t-butyldiphenylsiloxy derivatives
were stable, whereas the trimethylsilyl analogs were unstable. The
former compounds were reacted with diethylamine, lithium dimethyl-
cuprate, and 1,3-propanedithiol and gave Michael adducts in good to
very good yields. The amine and cuprate gave the conjugated
alkenones, the former in a stereospecific manner (Z), the latter
stereospecifically (E) in one case but otherwise stereoselectively with
an E preponderance. With the dithiol bisaddition occurred, and the
corresponding 1,3-dithiane was obtained in excellent yield. Attempts
to make 1,3-dithianes from 1,3-propanedithiol and 1,1-diethoxy-
4-diethylaminoalk-3-en-2-ones failed.
KEYWORDS
Conjugate addition;
conjugated acetylenic
ketones; dimethylcopper
lithium; 1,3-dithianes;
propargylic alcohols; silyl
protection
GRAPHICAL ABSTRACT
Introduction
α,β-Unsaturated acetylenic ketones have proved to be valuable starting materials for
the preparation of a wide range of organic compounds.[1–5] A key reaction in many
of these transformations is Michael addition, which primarily leads to formation of
α,β-unsaturated alkenones,[6] an important structural motif in its own right, but also
excellent starting materials for the synthesis of more complex molecules. When a
specific conjugated alkynone is reacted the final outcome depends on a number of
factors, of which the presence of another reactive moiety in a favorable position relative
to the ynone has appeared to be a useful feature. We have studied the reactions between
a number of nucleophiles and a series of such alkynones, viz. 5-substituted 1,1-diethoxy-
3-alkyn-2-ones, with this opportunity in mind, and we indeed observed that substituents
at C-5 may facilitate multistep transformations leading to the formation of interesting
stable secondary products.[2–4]
An illustrative example of such a substituent is the hydroxyl group, which has appeared
to enable 1 to form furans in good yields when treated with secondary amines.[4] As
CONTACT Leiv K. Sydnes
leiv.sydnes@kj.uib.no
Department of Chemistry, University of Bergen, Allégt 41, NO-5007
Bergen, Norway.
Supplemental data for this article can be published on the publisher’s website.
© 2016 Taylor & Francis

776
W. SHANG ET AL.
Scheme 1. Synthesis of 2-alkyl-3-dialkylamino-5-diethoxymethylfuran (3) by addition of dialkylamine
to 1,1-diethoxy-5-hydroxy-3-alkyn-2-ones.
outlined in Scheme 1, the reaction is believed to involve conjugated enone 2, which is con-
sumed quickly due to intramolecular hemiketalization, made possible by its E geometry
and the resulting proximity of the OH and carbonyl groups, followed by dehydration.
Thus, furan 3 is formed by default, not as a result of a reaction initiated by a controlled
intervention with a specific outcome in mind. Consequently, if products other than furans
are going to be formed, the OH group has to be protected so that no reaction occurs before
the structural modifications required to facilitate the formation of other products have
been carried out.
A large number of groups are available for protection of the hydroxyl group.[7] Among
the most versatile ones are the silyl ethers, which in general are easy to make and capable of
surviving a range of reaction conditions prevailing during the application of many of the
useful reagents.[8] A single reaction performed some years ago indicated that this approach
is promising,[2] and we therefore wanted to convert a selection of 1,1,2,2,-tetraethoxy-
5-hydroxyalk-3-ynes (4) into the corresponding silyl ether (5) and then 5-siloxylated
1,1-diethoxy-3-alkyn-2-ones (6) and investigate the reactivity of the α,β-unsaturated
ketones. The results of this study are reported here.
Results and discussion
At the outset the plan was to convert 4 [obtained from 3,3,4,4-tetraethoxybutyne (TEB)[9]
]
into silyl ethers 5 following the three-step synthesis summarized in Scheme 2.[2] Attempts
were first made to synthesize some trimethylsilyl (TMS) ethers to estimate the robustness
of the silylation (step 2) and the stability of the siloxy group during the deketalization
(step 3). The outcome of step 2 appeared to be very sensitive to the method applied and
the yields were often poor; thus, when 1,1,2,2-tetraethoxyundec-3-yn-5-ol (4d) and
6,6,7,7-tetraethoxy-5-ethylhept-4-yn-3-ol (4 g) were reacted, yields in the 6–84% range
Scheme 2. Synthesis of 5-siloxylated 1,1-diethoxyalk-3-yn-2-ones (6) from TEB.

SYNTHETIC COMMUNICATIONS®
777
were obtained. The best results were achieved when a small amount of dimethylsulfoxide
(DMSO) was added, a measure recommended by Visser et al.,[11] and under these
conditions the tetramethylsilane (TMS)–ether derivatives of 4d and 4 g were easily available
in around 80% yield. Next, deketalization was carried out following several literature
procedures,[2,12] but unfortunately, without exception, the desired reaction was
accompanied by simultaneous desilylation so that the corresponding alcohols were
completely regenerated in both cases. A solution to this problem was envisaged to be to
switch steps 2 and 3, and when this strategy was implemented using 4 g, the corresponding
protected ketone, 1,1-diethoxy-5-ethyl-5-trimethylsiloxyhept-3-yn-2-one (6 g), was indeed
obtained in 78% overall yield.
On the basis of these results it was decided to apply t-butyldiphenylsilyl (TBDPS) ethers
instead since such ethers are about 100 times more stable to hydrolysis than t-butyldi-
methylsilyl ethers, which in turn are about 104 times more stable than the TMS analogs.[13]
That change turned out to be a success; not only were the propargylic alcohols converted to
the corresponding TBDPS ethers in better than 80% yield in all cases but one, but also the
deketalization proceeded smoothly and furnished 5-siloxylated conjugated alkynones 6, in
almost quantitative yield in the best cases (Table 1).
With silyl-ether-protected 1,1-diethoxy-5-hydroxy-3-alkyn-2-ones at hand Michael
additions were performed with diethylamine, lithium dimethylcuprate (the Gilman cup-
rate), and 1,3-propanedithiol, all of which have been shown to react smoothly with similar
alkyones.
The highest selectivity was achieved with the amine, which appeared to undergo
monoaddition and afford the corresponding 4-diethylamino-3-alken-2-ones (7) in a stereo-
specific manner in excellent yields whether reacted with 5-trimethylsiloxy- or 5-(t-butyldi-
phenyl)siloxy-substituted 1,1-diethoxyalk-3-yn-2-ones (6) (Scheme 3). Comparison of the
1H NMR data for 7 (chemical shifts and allylic coupling constants between the protons
attached to C-3 and C-5) with available literature data[14] gave no basis to draw a con-
clusion regarding the stereochemistry of these Michael adducts, but by performing nuclear
Overhauser spectroscopy (NOESY) experiments it was unequivocally proved that 7 exhib-
ited Z configuration in all cases. On one hand, this conclusion is founded on the presence
of mutual enhancement of the signals due to the olefinic proton, hydrogen atoms in the
alkyl group(s) attached to C-5, and all the hydrogens in the diethoxymethyl moiety; on
the other hand, it is founded on the complete absence of any nuclear Overhauser enhance-
ment of the signals due to the diethylamino group attached to C-4.
Me2CuLi[15] also underwent monoaddition to 6 and gave the corresponding
1,1-diethoxy-4-methyl-3-alken-2-ones (8) in up to excellent yield (Table 2). The reaction
Table 1. Isolated yields of siloxylated acetylenic ketals 5 and ketones 6
with R3Si ¼ t-BuPh2.
Step 2 product/
isolated yield (%)
Step 3 product/
isolated yield (%)
R1,R2
H,H
5a/94
5b/82
5c/82
5d/81
5e/82
5f/53
6a/56
6b/80
6c/97
6d/94
6e/92
6f/70
Me,H
i-Pr,H
n-Hex,H
Me,Me
CH2(CH2)3CH2

778
W. SHANG ET AL.
Scheme 3. Addition of diethylamine to silyl ether-protected 1,1-diethoxy-5-hydroxy-3-alkyn-2-ones (6).
was stereospecific in one case only, when 5-(t-butyl)diphenylsiloxy-1,1-diethoxypent-3-
yn-2-one (6a) was reacted; otherwise the transformation was stereoselective with a
preponderance, up to six times at the most (for 6f), for the isomer with the lower Rf value
(Table 2). This lack of specificity is not surprising because the accepted intermediates, cop-
per enolates, have been shown to equilibrate at a rate that is sensitive to solvent, tempera-
ture, concentration, complexation, and reaction time.[16] As a result α,β-unsaturated olefinic
carbonyl compounds with E/Z ratios approaching 1:1 have been obtained even in cases
when the cuprate addition to the C-C triple bond is believed to be stereospecific.[17]
Two of the three substituents attached to the C-C double bond in 8 are quite polar, and
the overall polarity of the E isomer and the Z isomer of 8b–8f should therefore be so
different that separation of the isomers should be feasible. Screening of a number of
solvents and solvent mixtures showed that such separation was indeed possible, but some
eluents resulted in such a significant loss of material when flash chromatography (FC) was
performed that they were unsuitable. Dichloromethane appeared to be the best choice in
our case, and when this eluent was used, the isomers were easily separated, even on a gram
scale, without loss of significant amounts.
For two of the alkenes, 8b and 8f, the stereochemistry could be settled based on the
=
coupling constant for the CH3-C C-H structural motif. In such a spin system the allylic
coupling (4J) is expected to have a larger absolute value when the olefinic hydrogen atom
and the methyl group have a cis relationship than a trans, i.e., |4Jcis|> |4Jtrans|.[14,18] Since the
coupling is larger for the minor isomer for both 8b and 8f, viz., 1.2 Hz compared to 0.9 Hz
Table 2. Synthesis of E and Z isomers of 1,1-diethoxy-4-methyl-3-alken-2-ones (8) by treating 6 with
Me2CuLi.
8, smaller Rf
8, larger Rf
6 (R1,R2)
Product/isolated yield (Rf)
Product/isolated yield (Rf)
ΔRf
E/Z
a
6a (H,H)
E-8a/39% (0.22)
E-8b/49% (0.16)
E-8c/55% (0.24)
E-8d/48% (0.35)
E-8e/73% (0.23)
E-8f/63% (0.27)
—
—
100:0
59:41
57:43
52:48
73:27
85:15
6b (Me,H)
6c (i-Pr,H)
6d (n-Hex,H)
6e (Me,Me)
6f ((CH2)5)
Z-8b/34% (0.34)
Z-8c/41% (0.45)
Z-8d/45% (0.62)
Z-8e/27% (0.44)
Z-8f/11% (0.45)
0.18
0.21
0.27
0.21
0.18
aThis isomer was not detected.

SYNTHETIC COMMUNICATIONS®
779
for 8b and 1.1 Hz compared to < 0.5 Hz for 8f, it was concluded that the E isomer predo-
minates for both these olefins.
For the other alkenes the signals due to the allylic moiety appeared as broad singlets, con-
=
ceivably caused by van der Waal interactions between the CH3-C C-H structural motif and
the two sterically demanding substituents attached to the olefinic carbon atoms, so no coup-
ling constants could be extracted from the spectra. However, due to the fact that the polarity
of the Z isomers ought to be similar for 8a–8f and larger than the polarity of the correspond-
ing E isomers of 8a–8f, it is reasonable to assume that the relative retention for the E and Z
isomers of each compound should be roughly the same under identical chromatographic
conditions. That is the case for 8b and 8f, which, respectively, show Rf values 0.34 and
0.45 for the Z isomers and 0.16 and 0.27 for the corresponding E isomers. As argued above,
8c–8e are expected to show the same relationship, and on the basis of the data in Table 2 it is
concluded that these compounds as well are formed with E isomer predominance.
As mentioned, the reaction between 6a and Me2CuLi appears to be a special case. When
this compound was reacted, thin-layer chromatographic (TLC; CH2Cl2) analysis of the resi-
due after workup showed one spot, which suggested that one product had been formed. How-
ever, when the 1H NMR spectrum of the product mixture was recorded it became clear that at
least two major products were obtained. Attempts to separate the products were only partially
successful; whereas the main product was obtained essentially pure in 39% yield the second
product had to undergo several purifications, with significant loss of material, before a
reasonably pure sample became available. When the 1H NMR spectrum of the purified sam-
ple of the main product was compared with the spectra of the E and Z isomers of 8b–8f, the
chemical shifts of the most NMR-sensitive protons in the main product (the protons at C-3
and C-5) are much closer to those exhibited by the E isomers of the analogs than to those of
the Z isomers. This indicates that 6a furnishes only E-8a, and this conclusion is supported by
the fact that the methyl group and the olefinic proton both give rise to a narrow singlet, which
precludes the presence of allylic coupling. Finally, it is noteworthy that the Rf value for the
compound under standard conditions (SiO2, CH2Cl2) is close to the values exhibited by
the E isomers of 8b–8f but much smaller than the values for the Z isomers (Table 2).
The other major product from 6a gave MS, IR, and NMR spectra, which deviated in an
indicative way from those obtained for the E and Z isomers of 8. First, its molecular
formula is reduced with C2H6O, which, according to the NMR spectra, is due to loss of etha-
nol. Second, prominent absorptions in the IR spectrum (1714 cmÀ 1) and the 13C spectrum
(203 ppm) are well off the values found in the spectra for E/Z-8, viz. 1688–1699 cmÀ 1 and
193–196 ppm, respectively. These differences are very informative; not only do
they clearly indicate that the other product is cyclic, they also suggest that the product is a
1
2-cyclopentenone derivative.[19,20] On the basis of this insight, the interpretation of the H
NMR, 13C NMR, COSY, and heteronuclear single quantum coherence (HSQC) spectra
becomes rather straightforward and leads to the unequivocal conclusion that the other main
product is 4-(t-butyl)diphenylsiloxy-5-ethoxy-3-methylcyclopent-2-enone (9) (Scheme 4).
The reason for the exceptional behavior of 6a in the reaction with Me2CuLi is not clear,
but it might be due to conformational effects caused by the presence of a methylene group
at C-5 instead of the alkylated methylene group present in this position in 6b–6f. When C-
5 is not alkylated, a methylene proton in this position becomes much more available for
abstraction, and this opens up for the reaction sequence summarized in Scheme 5. The first
step is cis attack of lithium dimethylcuprate on the triple bond, which presumably gives

780
W. SHANG ET AL.
Scheme 4. Treatment of 6a with lithium dimethylcuprate; TBDPS ¼ (t-butyl)diphenylsilyl.
C-copper enolate I.[16,17] This intermediate equilibrates with its trans isomer (II), which is
capable of abstracting a propargylic proton directly or via its O-copper enolate (III), and
forms carbanion IV. This carbanion will give E-8a upon hydrolysis, but it can also
isomerize, because of its allylic nature, to its geometrical isomer V, which can undergo
cyclization by intramolecular carbanion attack of the acetal moiety in an SN2 type reaction
with ethoxide as the leaving group and furnish 9 as a by-product. Since similar substitu-
tions usually require borontrifluoride activation,[21] the nucleophilicity of the carbanion
in V is enhanced by the α-alkoxy group whereas the electrophilicity of C-1 is increased
by the neighboring conjugated keto moiety.
The last nucleophile to be applied was 1,3-propanedithiol, which has been proved to
undergo bis-addition with a range of α,β-unsaturated acetylenic ketones and give the
corresponding 1,3-dithiane in very good yields.[5] Again 5-(t-butyl)diphenylsiloxy-1,1-
diethoxylhex-3-yn-2-one (6b) was used as a test case and as previously observed, the
primary product was unstable due to an intramolecular reaction which furnished 3-(2-
(1-(t-butyl)diphenylsiloxyethyl)-1,3-dithian-2-yl)-1,1-diethoxypropan-2-one (10b) in 82%
yield (Scheme 6). This and similar 1,3-dithianes will now be used to prepare modified
carbohydrates following the strategy applied for some time in our research group.
A final comment regarding the ability of 1,3-propanedithiol to undergo conjugate
addition with conjugated ketones is warranted. From the literature,[22] it is known that this
dithiol can react with β-amino-substituted α,β-unsaturated ketones in a process encom-
passing three consecutive steps, viz. intermolecular sulfide addition, amine elimination,
and intramolecular sulfide addition, which gives the corresponding 1,3-dithianyl ketone.
If this is a general, robust reaction it is reasonable to believe that 5-(t-butyldiphenyl)
siloxy-4-diethylamino-1,1-diethoxyhex-3-en-2-one (7b) would react smoothly and give
10b, but this was not achieved even under conditions recommended for Michael additions
to conjugated alkenyl and alkynyl ketones.[5] Obviously, the reactivity is critically influ-
enced by the properties of the amino group, an observation that merits further study.
Scheme 5. A sequence of equilibrations and transformations explaining the formation of E-8a and 9
upon treatment of 6a with Me2CuLi; TBDPS ¼ (t-butyl)diphenylsilyl.

SYNTHETIC COMMUNICATIONS®
781
Scheme 6. Bisaddition of 1,3-propanedithiol to conjugated ketone 6b.
Experimental
Infrared (IR) spectra were run on a Nicolet Impact 410 IR spectrophotometer or Nicolet
380 FT-IR spectrophotometer. NMR spectra were recorded on Bruker Spectrospin spectro-
meters (DPX 400 MHz and DPX 500 MHz). Chemical shifts are reported in parts per
million (ppm) downfield from internal tetramethylsilane (TMS). Thin-layer chromato-
graphic (TLC) analyses of the reaction mixtures were performed with silica gel (60
F254) on aluminum sheets with mixtures of hexanes (a commercial mixture of isomeric
hexanes) and ethyl acetate as the mobile phase. Flash chromatography (FC) was carried
out with silica gel (230–400 mesh) as the stationary phase and pure solvents or various
mixtures of solvents as the mobile phase. When autoflash was was carried out, a Grace
Reveleris instrument was used. The eluent composition is given for each compound. Mass
spectra were obtained on a JEOL AccuTOF T100GC spectrometer. The instruments were
operated in the DART/ESIþmode at 10–15 eV.
Synthesis of propargylic alcohols 4 from TEB
All the propargylic alcohols, viz. 4,4,5,5-tetraethoxypent-2-yn-1-ol (4a), 5,5,6,6-
tetraethoxy-hex-3-yn-2-ol (4b), 6,6,7,7-tetraethoxy-2-methylhept-4-yn-3-ol (4c), 1,1,2,
2-tetraethoxyundec-3-yn-5-ol (4d), 5,5,6,6-tetraethoxy-2-methylhex-3-yn-2-ol (4e),
1-(3,3,4,4-tetraethoxybut-1-ynyl)cyclo-hexanol (4f), and 6,6,7,7-tetraethoxy-2-ethylhept-
4-yn-3-ol (4 g) were synthesized as described in the literature.[2]
Syntheses of trimethylsilyl (TMS) ethers from 4
5-Trimethylsiloxy-1,1,2,2-tetraethoxyundec-3-yne was prepared from 4d. The alcohol
(0.826 g, 2.40 mmol) was dissolved in dimethylformamide (DMF, 25 mL) under an N2
atmosphere at rt. DMSO (0.045 g, 0.578 mmol) and triethylamine (TEA, 0.439 g,
4.34 mmol) were added and the mixture was stirred before trimethylchlorosilane
(0.314 g, 2.89 mmol) was added dropwise over 5 min. The mixture was left stirring at rt
for 3.5 h before it was quenched with water (25 mL). The phases were then separated,
the aqueous phase was extracted with dichloromethane (DCM, 3 � 20 mL), and the organic
extracts were combined and dried (MgSO4). Filtration and evaporation of the solvent was
followed by isolation by FC (mixture of hexanes). In order to reduce silica-induced
decomposition of the product (desilylation) autoflash separation was applied; this gave
the title compound (0.617 g, 79%) as a slightly brown liquid. IR (ATR): 2922 (s), 2853
(s), 1457 (m), 1377 (w), 1335 (w), 1250 (m), 1117 (s), 1079 (s), 1019 (m), 842 (s), 753
1
(w) cmÀ 1; H NMR (CDCl3, 400 MHz): δ 4.40 (t, J ¼ 6.6 Hz, 1H), 4.36 (s, 1H), 3.65–3.78
(m, 8H), 1.17–1.70 (m, 22H), 0.86 (m, 3H), 0.16 (s, 9H); 13C NMR (CDCl3, 100 MHz): δ

782
W. SHANG ET AL.
104.4, 88.9, 64.8, 64.7, 62.8, 60.1, 38.7, 31.9, 29.1, 25.4, 22.8, 15.6, 15.5, 14.3, 0.31. HRMS
calcd. for C22H44O5SiNaþ[M þ Na]þ 439.6564804; found 439.38908.
5-Trimethylsiloxy-1,1,2,2-tetraethoxy-5-ethylhept-3-yne was prepared from 4 g. The
alcohol (0.281 g, 0.885 mmol) was dissolved in DMF (22 mL) under N2 atmosphere at
rt. DMSO (0.016 g, 0.20 mmol) and TEA (0.135 g, 1.33 mmol) were added and the mix-
ture was stirred, before trimethylchlorosilane (0.0961 g, 0.885 mmol) was added dropwise
over 5 min. The mixture was left stirring at rt for 3 h before it was quenched with water
(25 mL). The phases were then separated, the aqueous phase was extracted with DCM
(3 � 15 mL), and the organic extracts were combined and dried (MgSO4). Filtration
and evaporation of the solvent was followed by isolation by FC (mixture of hexanes).
In order to reduce silica-induced decomposition of the product (desilylation) autoflash
separation was applied; this gave the title compound (0.288 g, 84%) as a slightly brown
liquid. IR (ATR): 2974 (m), 2932 (w), 2881 (w), 2359 (w), 2340 (w), 1737 (w), 1457
(w), 1444 (w), 1388 (w), 1371 (w), 1324 (w), 1248 (m), 1150 (m), 1117 (s), 1058 (s),
1017 (s), 935 (w), 880 (m), 840 (s), 755 (m), 687 (w), 668 (w), 610 (w), 573 (w), 557
1
(w) cmÀ 1; H NMR (CDCl3, 400 MHz): δ 4.35 (s, 1H), 3.60–3.82 (m, 8H), 1.65 (q, J ¼ 7.4
Hz, 4H), 1.20 (m, 12H), 0.97 (t, J ¼ 7.4 Hz, 6H), 0.18 (s, 9H); 13C NMR (CDCl3,100
MHz): δ 104.6, 99.08, 90.1, 80.1, 73.6, 64.5, 60.2, 35.6, 15.6, 15.5, 8.9, 2.0. HRMS calcd.
for C20H40O5SiNaþ[M þ Na]þ 411.60332; found 411.25433.
5-Trimethylsiloxy-1,1-diethoxy-5-ethylhept-3-yn-2-one (6 g) was prepared in a two-step
synthesis from 4 g, but without purifying the ketone formed in the first step. Alcohol 4 g
(3.96 g, 11.5 mmol) was dissolved in a 7:3 mixture of THF and H2O (120 mL). p-Toluene-
sulfonic acid monohydrate (0.438 g, 2.30 mmol) was added and the mixture was refluxed
for 4 h until the starting material was consumed (followed by TLC). Most of the THF
was then evaporated on a rotary evaporator, before a saturated aqueous NaCl solution
(30 mL) and DCM (30 mL) were added to the residue. The phases were separated and
the aqueous phase was extracted with DCM (3 � 30 mL). The combined organic extracts
were washed with a saturated aqueous solution of NaHCO3 (80 mL), dried (MgSO4), fil-
tered, and concentrated under reduced pressure. 1,1-Diethoxy-5-ethyl-5-hydroxyhept-3-
yn-2-one (2.98 g, 93%) was obtained as a reddish liquid and appeared to be essentially pure
according to 1H NMR [1H NMR (CDCl3, 400 MHz): δ 4.68 (s, 1H), 3.54–3.68 (m, 4H), 1.68
(m, 4H), 1.20 (t, J ¼ 7.0 Hz, 12H), 0.99 (t, J ¼ 7.0 Hz, 6H)]. A sample of this ketone
(0.2211 g, 0.885 mmol) was dissolved in DMF (22 mL) under N2 atmosphere at rt. DMSO
(0.016 g, 0.20 mmol) and TEA (0.135 g, 1.33 mmol) were added and the mixture was stirred,
before trimethylchlorosilane (0.0961 g, 0.885 mmol) was added dropwise over 5 min. The
mixture was left stirring at rt for 3 h before it was quenched with water (25 mL). The phases
were then separated, the aqueous phase was extracted with DCM (3 � 15 mL), and the
organic extracts were combined and dried (MgSO4). Filtration and evaporation of the sol-
vent was followed by isolation by FC (mixture of hexanes), yielding 1,1-diethoxy-5-ethyl-5-
trimethylsiloxyhept-3-yn-2-one (0.288 g, 84%) as a light brown liquid. IR (ATR): 2976 (m),
2940 (w), 2881 (w), 2208 (w), 1687 (m), 1460 (w), 1374 (w), 1319 (w), 1250 (m), 1153 (m),
1059 (s), 1017 (s), 935 (w), 880 (m), 839 (s), 754 (m), 680 (w), 679 (w), 612 (w), 584 (w)
1
cmÀ 1; H NMR (CDCl3, 400 MHz): δ 4.74 (s, 1H), 3.60-3.73 (m, 4H), 1.71 (q, J ¼ 7.5 Hz,
4H), 1.25 (t, J ¼ 7.0 Hz, 12H), 0.98 (t, J ¼ 7.4 Hz, 6H), 0.20 (s, 9H); 13C NMR (CDCl3,
100 MHz): δ 182.9, 101.6, 99.1, 83.1, 73.8, 63.1, 62.9, 53.6, 34.9, 15.3, 8.8, 8.6, 2.0, 1.7.
HRMS calcd. for C16H30O4SiNaþ[M þ Na]þ 337.4817204; found 337.181121.

SYNTHETIC COMMUNICATIONS®
783
Syntheses of t-butyldiphenylsilyl (TBDPS) ethers from 4
Protection of primary and secondary propargylic alcohols: general procedure
Alcohol 4 was dissolved in anhydrous DMF under a N2 atmosphere at rt. After addition of
imidazole (3.0–5.0 equiv.) t-butyldiphenylsilyl chloride (TBDPSCl) (1.05–1.2 equiv.) was
added dropwise at rt. The reaction mixture was stirred at rt until the starting material
was consumed (monitored by TLC) and was then diluted with diethyl ether and washed
with water and brine. The organic phase was subsequently dried (MgSO4), filtered, and
concentrated to provide a crude product from which silyl ether 5 was isolated by FC.
Protection of tertiary propargylic alcohols: general procedure
TBDPSCl (1.5 equiv.) was added dropwise to the mixture of propargylic alcohol 4 (1.0
equiv.), N-methylimidazole (2.6 mL/mmol), and I2 (6.0 equiv.) at rt. The resulting mixture
was stirred at 60 °C until the starting material was consumed (monitored by TLC) and
extracted with diethyl ether (3 � 30 mL). The combined extracts were washed with aqueous
saturated Na2S2O3 solution and hydrochloric acid, dried (MgSO4), filtered, and concen-
trated to give a crude product from which silyl ether 6 was isolated by FC.
Following these procedures, six silyl ether-protected alcohols were prepared.
1-t-Butyldiphenylsiloxy-4,4,5,5-tetraethoxypent-2-yne (5a) was synthesized from 4a
(2.75 g, 10.58 mmol) and TBDPSCl (3.49 g, 12.70 mmol). FC (10% hexanes in dichloro-
methane, Rf ¼ 0.17) provided 4.95 g (94%) of the product as a colorless liquid. IR (ATR):
3072 (w), 3050 (w), 2974 (s), 2930 (s), 2893 (s), 2859 (s), 1962 (w), 1891 (w), 1827 (w),
1777 (w), 1589 (w), 1473 (m), 1462 (w), 1444 (w), 1428 (s), 1390 (m), 1371 (s), 1330
(w), 1246 (w), 1184 (s), 1107 (s), 1075 (s), 1018 (s), 998 (s), 962 (w), 938 (w), 877 (m),
1
823 (s), 789 (s), 739 (s), 701 (s), 690 (s) cmÀ 1; H NMR (CDCl3, 400 MHz): δ 7.73–7.70
(m, 4H), 7.44–7.35 (m, 6H), 4.43 (s, 2H), 4.37 (s, 1H), 3.83–3.66 (m, 8H), 1.23 (t, J ¼ 7.1 Hz,
6H), 1.21 (t, J ¼ 7.1 Hz, 6H), 1.05 (s, 9H); 13C NMR (CDCl3, 101 MHz): δ 135.6 (4C), 133.1
(2C), 129.8 (2C), 127.7 (4C), 104.21 and 104.17 (1C, the two signals belong to two confor-
mers), 98.7, 85.5, 79.5, 64.8, 52.80, 52.76, 26.63, 26.61 (2C), 19.2, 15.41, 15.40, 15.3 (2C).
HRMS calcd. for C29H42O5SiNaþ [M þ Na]þ 521.26992; found 521.26974.
2-t-Butyldiphenylsiloxy-5,5,6,6-tetraethoxyhex-3-yne (5b) was synthesized from 4b
(7.42 g, 27.08 mmol) and TBDPSCl (7.82 g, 28.43 mmol). FC (5% methanol in hexanes, Rf
¼ 0.30) provided 11.17 g (80%) of the product as a colorless liquid. IR (ATR): 3071 (w),
3049 (w), 2975 (s), 2930 (s), 2889 (s), 2858 (s), 1590 (w), 1473 (m), 1463 (w), 1443 (w),
1428 (s), 1390 (m), 1369 (m), 1338 (m), 1315 (m), 1242 (m), 1183 (s), 1103 (s), 1092
(s), 1075 (s), 1058 (s), 1016 (s), 984 (s), 937 (m), 922 (m), 869 (m), 823 (s), 762 (m),
1
739 (s), 700 (s), 689 (s), 622 (m), 613 (s), 535 (m) cmÀ 1; H NMR (CDCl3, 400 MHz): δ
7.77–7.67 (m, 4H), 7.44–7.35 (m, 6H), 4.56 (q, J ¼ 6.5 Hz, 1H), 4.33 (s, 1H), 3.81–3.60
(m, 8H), 1.41 (d, J ¼ 6.5 Hz, 3H), 1.23–1.15 (m, 12H), 1.06 (s, 9H); 13C NMR (CDCl3,
101 MHz, CDCl3) δ 136.0 (2C), 135.9 (2C), 133.8, 133.6, 129.8, 129.7, 127.7 (2C), 127.6
(2C), 104.32, 104.26, 98.6, 89.5, 78.2, 64.8, 64.74, 64.69, 64.63, 64.58, 60.2, 60.1, 60.03,
60.01, 26.92 (2C), 26.89, 25.2, 19.3, 15.55, 15.51, 15.49, 15.41. HRMS calcd. for C30H44O5SiNaþ
[M þ Na]þ 535.28557; found 535.28577.
5-t-Butyldiphenylsiloxy-1,1,2,2-tetraethoxy-6-methylhept-3-yne (5c) was synthesized
from 4c (1.88 g, 6.23 mmol) and TBDPSCl (1.80 g, 6.54 mmol). FC (5% methanol in hex-
anes, Rf ¼ 0.41) provided 2.83 g (84%) of the product as a colorless liquid. IR (ATR):
3072 (w), 3050 (w), 2973 (s), 2930 (s), 2894 (m), 2859 (m), 1958 (w), 1899 (w), 1824

784
W. SHANG ET AL.
(w), 1590 (w), 1472 (m), 1444 (w), 1428 (s), 1389 (m), 1367 (m), 1352 (m), 1332 (w), 1240
(w), 1186 (m), 1111 (s), 1106 (s), 1073 (s), 1028 (s), 1019 (s), 999 (s), 961 (w), 939 (m),
1
920 (w), 877 (w), 833 (s), 820 (s), 739 (s), 700 (s) cmÀ 1; H NMR (CDCl3, 400 MHz):
δ 7.76–7.68 (m, 4H), 7.44–7.33 (m, 6H), 4.32 (d, J ¼ 4.6 Hz, 1H), 4.28 (s, 1H), 3.78–3.54
(m, 8H), 1.91–1.83 (m, 1H), 1.22–1.11 (m, 12H), 1.08 (s, 9H), 1.05 (d, J ¼ 6.7 Hz, 3H),
0.90 (d, J ¼ 6.8 Hz, 3H); 13C NMR (CDCl3, 101 MHz): δ 136.2 (2C), 136.0 (2C), 133.8,
133.7, 129.8, 129.6, 127.7 (2C), 127.5 (2C), 104.5, 98.8, 87.2, 80.0, 69.2, 64.5, 64.4,
60.4, 60.2, 35.4, 27.0 (3C), 19.5, 18.3, 17.1, 15.6, 15.5, 15.44, 15.42. HRMS calcd. for
C32H48O5SiNaþ [M þ Na]þ 563.31687; found 563.31670.
5-t-Butyldiphenylsiloxy-1,1,2,2-tetraethoxyundec-3-yne (5d) was synthesized from 4d
(0.37 g, 1.08 mmol) and TBDPSCl (0.36 g, 1.30 mmol). FC (5% methanol in hexanes, Rf
¼ 0.20) provided 0.51 g (82%) of the product as a colorless liquid. The spectroscopic data
were in agreement with those reported in the literature.[2]
5-t-Butyldiphenylsiloxy-1,1,2,2-tetraethoxy-5-methylhex-3-yne (5e) was synthesized
from 4e (2.15 g, 7.47 mmol) and TBDPSCl (3.08 g, 11.21 mmol). FC (10% dichloromethane
in hexanes, Rf ¼ 0.08) provided 3.15 g (80%) of the product as a colorless liquid. IR (ATR):
3071 (w), 3050 (w), 2975 (s), 2931 (s), 2891 (m), 2858 (s), 1473 (w), 1444 (w), 1428 (m),
1388 (w), 1378 (w), 1361 (w), 1331 (w), 1251 (s), 1157 (s), 1108 (s), 1074 (s), 1043 (s),
956 (w), 937 (w), 893 (w), 821 (s), 740 (s), 700 (s), 609 (s), 554 (m) cmÀ 1; 1H NMR (CDCl3,
400 MHz): δ 7.81–7.78 (m, 4H), 7.43–7.34 (m, 6H), 4.22 (s, 1H), 3.74–3.50 (m, 8H), 1.47 (s,
6H), 1.17 (t, J ¼ 7.1 Hz, 6H), 1.10 (t, J ¼ 7.1 Hz, 6H), 1.00 (s, 9H); 13C NMR (CDCl3,
101 MHz): δ 136.2 (4C), 135.2 (2C), 129.5 (2C), 127.5 (4C), 104.2, 98.4, 92.0, 77.6, 68.2,
64.5 (2C), 60.0 (2C), 32.7 (3C), 26.9 (2C), 19.3, 15.5 (2C), 15.4 (2C). HRMS calcd. for
C31H46O5SiNaþ [M þ Na]þ 549.30122; found 549.30145.
1-(1-t-Butyldiphenylsiloxycyclohexyl)-3,3,4,4-tetraethoxybut-1-yne (5f) was synthesized
from 4f (5.00 g, 15.24 mmol) and TBDPSCl (6.29 g, 22.86 mmol). FC (5% methanol in
hexanes, Rf ¼ 0.38) furnished 4.48 g (52%) of the product as a colorless liquid. IR
(ATR): 3071 (w), 3048 (w), 2973 (s), 2931 (s), 2893 (s), 2856 (s), 1589 (w), 1473 (w),
1444 (w), 1427 (m), 1389 (w), 1362 (w), 1337 (w), 1291 (m), 1258 (w), 1232 (w), 1182
(m), 1103 (s), 1076 (s), 1018 (s), 1002 (s), 937 (m), 905 (m), 870 (s), 844 (w), 821 (s),
1
773 (w), 739 (s), 700 (s), 609 (s), 560 (w) cmÀ 1; H NMR (CDCl3, 400 MHz): δ 7.80–
7.78 (m, 4H), 7.42–7.32 (m, 6H), 4.16 (s, 1H), 3.69–3.50 (m, 4H), 3.45–3.34 (m, 4H),
1.91–1.88 (m, 2H), 1.63–1.44 (m, 7H), 1.23–1.11 (m, 1H), 1.14 (t, J ¼ 7.1 Hz, 6H), 1.03
(t, J ¼ 7.1 Hz, 6H), 1.01 (s, 9H); 13C NMR (CDCl3, 101 MHz): δ 136.3 (4C), 135.3 (2C),
129.4 (2C), 127.4 (4C), 104.4, 98.6, 90.7, 80.9, 71.5, 64.2 (2C), 60.2 (2C), 41.3 (2C), 27.1
(3C), 25.4, 23.3 (2C), 19.5, 15.5 (2C), 15.4 (2C). HRMS calcd. for C34H50O5SiNaþ [M þ
Na]þ 589.33277; found 589.33252.
Synthesis of TBDPS-protected ketones 6 from ketal 5: General procedure
Siloxylated ketal 5 was dissolved in a 7:3 mixture of THF and H2O, p-TsOH monohydrate
(0.3–0.6 equiv.) was added, and the resulting mixture was refluxed until all the starting
material had reacted (monitored with TLC). The reaction mixture was then mixed with
an equal volume of CH2Cl2 and after shaking the phases were separated. The aqueous
phase was extracted with CH2Cl2 (3 �), and the combined organic phases were dried
(MgSO4), filtered, and concentrated under reduced pressure to give a crude product, from

SYNTHETIC COMMUNICATIONS®
785
which siloxylated ketone 6 was isolated by FC. Using this procedure, the following six silyl-
ether-protected ketones were prepared.
5-(t-Butyl)diphenylsiloxy-1,1-diethoxypent-3-yn-2-one (6a) was synthesized from 5a
(0.920 g, 1.84 mmol) and p-TsOH monohydrate (0.105 g, 0.55 mmol). The reaction mixture
was refluxed for 8 h and FC purification (CH2Cl2, Rf ¼ 0.40) gave 0.440 g (56%) of the pro-
duct as a colorless oil. IR (ATR): 3072 (w), 3050 (w), 2976 (w), 2960 (w), 2931 (m), 2893
(m), 2858 (m), 2212 (m), 1686 (s), 1589 (w), 1473 (w), 1463 (w), 1443 (w), 1428 (s), 1391
(w), 1369 (m), 1317 (w), 1250 (m), 1187 (w), 1159 (m), 1105 (s), 1086 (s), 1065 (s), 1008 (s),
998 (s), 965 (m), 939 (w), 906 (m), 823 (s), 782 (s), 739 (s), 700 (s), 690 (s) cmÀ 1; 1H NMR
(CDCl3, 500 MHz): δ 7.71–7.69 (m, 4H), 7.46–7.38 (m, 6H), 4.71 (s, 1H), 4.48 (s, 2H), 3.74–
3.59 (m, 4H), 1.26 (t, J ¼ 7.1 Hz, 6H), 1.07 (s, 9H); 13C NMR (CDCl3, 126 MHz): δ 182.5,
135.7 (4C), 132.6 (2C), 130.1 (2C), 128.0 (4C), 101.6, 94.0, 82.6, 63.1 (2C), 52.7, 26.7 (3C),
19.3, 15.2 (2C). HRMS calcd. for C25H32O4SiNaþ [M þ Na]þ 5447.19675; found 447.19688.
5-(t-Butyl)diphenylsiloxy-1,1-diethoxylhex-3-yn-2-one (6b) was synthesized from 5b
(0.80 g, 1.56 mmol) and p-TsOH monohydrate (0.09 g, 0.46 mmol). The reaction mixture
was refluxed for 12 h and FC purification (5% methanol in hexanes, Rf ¼ 0.33) gave
0.55 g (81%) of the product as a colorless oil. IR (ATR): 3072 (w), 3049 (w), 2979 (m),
2962 (m), 2932 (m), 2889 (m), 2859 (m), 2214 (m), 1687 (s), 1589 (w), 1473 (m), 1463
(w), 1443 (w), 1428 (s), 1391 (m), 1370 (m), 1337 (m), 1312 (m), 1245 (m), 1187 (m),
1104 (s), 1094 (s), 1055 (s), 1008 (s), 998 (s), 980 (s), 937 (m), 921 (m), 887 (m), 822
1
(s), 760 (s), 739 (s), 700 (s), 690 (s) cmÀ 1; H NMR (CDCl3, 400 MHz): δ 7.76–7.67 (m,
4H), 7.45–7.36 (m, 6H), 4.67 (s, 1H), 4.60 (q, J ¼ 6.6 Hz, 1H), 3.71–3.54 (m, 4H), 1.45
(d, J ¼ 6.6 Hz, 3H), 1.24 (t, J ¼ 7.0 Hz, 3H), 1.23 (t, J ¼ 7.0 Hz, 3H), 1.08 (s, 9H); 13C
NMR (101 MHz, CDCl3) δ 182.6, 136.0 (2C), 135.8 (2C), 133.1, 132.9, 130.04, 129.97,
127.8 (2C), 127.7 (2C), 101.3, 97.4, 81.2, 62.9, 62.8, 59.9, 26.8 (3C), 24.3, 19.2, 15.20,
15.19. HRMS calcd. for C26H34O4SiNaþ [M þ Na]þ 461.21240; found 461.21266.
5-t-Butyldiphenylsiloxy-1,1-diethoxy-6-methylhept-3-yn-2-one (6c) was synthesized
from 5c (2.39 g, 4.42 mmol) and p-TsOH monohydrate (0.76 g, 4.0 mmol). The reaction
mixture was refluxed for 16 h and FC purification (5% methanol in hexanes, Rf ¼ 0.45) gave
2.06 g (100%) of the product as a colorless oil. IR (ATR): 3072 (w), 3050 (w), 2962 (s), 2931
(s), 2894 (m), 2859 (s), 2210 (m), 1962 (w), 1892 (w), 1686 (s), 1590 (w), 1568 (w), 1472 (s),
1446 (w), 1428 (s), 1389 (m), 1368 (m), 1362 (m), 1351 (m), 1332 (w), 1317 (w), 1244 (m),
1159 (m), 1105 (s), 1064 (s), 1007 (s), 998 (s), 961 (w), 938 (m), 904 (m), 821 (s), 740 (s), 700
(s) cmÀ 1; 1H NMR (CDCl3, 400 MHz): δ 7.74–7.67 (m, 4H), 7.46–7.35 (m, 6H), 4.60 (s, 1H),
4.33 (d, J ¼ 4.8 Hz, 1H), 3.67–3.50 (m, 4H), 1.99–1.87 (m, 1H), 1.23 (t, J ¼ 7.0 Hz, 3H), 1.21
(t, J ¼ 7.0 Hz, 3H), 1.09 (s, 9H), 1.05 (d, J ¼ 6.7 Hz, 3H), 0.92 (d, J ¼ 6.8 Hz, 3H); 13C NMR
(CDCl3, 101 MHz): δ 182.6, 136.2 (2C), 136.0 (2C), 133.1 (2C), 130.1, 129.9, 127.8 (2C),
127.6 (2C), 101.2, 95.8, 83.1, 69.1, 62.8, 62.7, 35.2, 27.0 (3C), 19.5, 18.1, 17.3, 15.25, 15.23.
HRMS calcd. for C28H38O4SiNaþ [M þ Na]þ 489.24370; found 489.24381.
5-(t-Butyl)diphenylsiloxy-1,1-diethoxylundec-3-yn-2-one (6d) was synthesized from 5d
(0.77 g, 1.32 mmol) and p-TsOH monohydrate (0.15 g, 0.79 mmol). The reaction mixture
was refluxed for 16 h and FC purification (CH2Cl2, Rf ¼ 0.48) gave 0.44 g (66%) of the pro-
duct, a colorless oil, that shows spectroscopic data in accordance with the literature.[2]
5-(t-Butyl)diphenylsiloxy-1,1-diethoxy-5-methylhex-3-yn-2-one (6e) was synthesized
from 5e (3.06 g, 5.81 mmol) and p-TsOH monohydrate (0.91 g, 4.80 mmol). The reaction
mixture was refluxed for 24 h, and FC purification (5% methanol in hexanes, Rf ¼ 0.35)

786
W. SHANG ET AL.
gave 2.47 g (94%) of the product as a colorless oil. IR (ATR): 3071 (w), 3049 (w), 2979 (s),
2932 (s), 2891 (s), 2858 (s), 2215 (m), 1689 (s), 1589 (w), 1472 (m), 1463 (m), 1445 (w),
1427 (s), 1380 (m), 1362 (m), 1319 (w), 1258 (s), 1238 (s), 1159 (s), 1104 (s), 1039 (s),
1003 (s), 953 (m), 940 (m), 919 (m), 869 (w), 821 (s), 795 (m), 741 (s), 700 (s), 609 (s),
1
559 (m), 531 (m); H NMR (CDCl3, 400 MHz): δ 7.78–7.75 (m, 4H), 7.44–7.34 (m, 6H),
4.48 (s, 1H), 3.62–3.47 (m, 4H), 1.49 (s, 6H), 1.20 (t, J ¼ 7.1 Hz, 6H), 1.04 (s, 9H); 13C
NMR (CDCl3, 101 MHz): δ 182.5, 136.3 (4C), 134.5 (2C), 129.8 (2C), 127.6 (4C), 101.0,
99.6, 80.7, 67.9, 62.7 (2C), 32.0 (2C), 27.0 (3C), 19.3, 15.2 (2C). HRMS calcd. for
C27H36O4SiNaþ [M þ Na]þ 475.22805; found 475.22816.
4-(1-(t-Butyldiphenyl)siloxycyclohexyl)-1,1-diethoxylbut-3-yn-2-one (6f) was synthe-
sized from 6f (3.69 g, 6.51 mmol) and p-TsOH monohydrate (1.48 g, 7.76 mmol). The reac-
tion mixture was refluxed for 24 h and FC purification (hexanes and ethyl acetate, 95:5,
Rf ¼ 0.46) gave 2.35 g (73%) of the product as a colorless liquid. IR (ATR): 3070 (w),
3048 (w), 2932 (s), 2892 (m), 2857 (s), 2209 (m), 1687 (s), 1589 (w), 1472 (m), 1462
(m), 1445 (m), 1427 (s), 1390 (w), 1361 (w), 1339 (w), 1317 (w), 1289 (s), 1258 (w),
1232 (w), 1152 (m), 1095 (s), 1061 (s), 1023 (s), 999 (s), 936 (m), 905 (s), 867 (s), 821
1
(s), 739 (s), 700 (s), 610 (s), 544 (m) cmÀ 1; H NMR (CDCl3, 400 MHz): δ 7.77–7.75
(m, 4H), 7.42–7.33 (m, 6H), 4.38 (s, 1H), 3.56–3.42 (m, 4H), 1.88–1.84 (m, 2H), 1.68–
1.62 (m, 4H), 1.51–1.42 (m, 3H), 1.29–1.14 (m, 1H), 1.18 (t, J ¼ 7.0 Hz, 6H), 1.05 (s,
9H); 13C NMR (CDCl3, 101 MHz): δ 182.3, 136.4 (4C), 134.7 (2C), 129.7 (2C), 127.5
(4C), 100.9, 98.9, 83.7, 71.2, 62.5 (2C), 40.5 (2C), 27.2 (3C), 25.1, 23.0 (2C), 19.5, 15.2
(2C). HRMS calcd. for C30H40O4SiNaþ [M þ Na]þ 515.25935; found 515.25966.
Addition of diethylamine to ketones 6: Formation of (Z)-4-(diethylamino)-1,1-
diethoxyalk-3-en-2-ones (7)
(Z)-5-(t-Butyldiphenyl)siloxy-4-diethylamino-1,1-diethoxyhex-3-en-2-one (7b)
To a solution of 5-(t-butyl)diphenylsiloxy-1,1-diethoxylhex-3-yn-2-one (6b) (0.556 g,
1.27 mmol) in ethanol (25 mL) was added diethylamine (0.13 mL, 94 mg, 1.27 mmol) drop-
wise by a syringe. The mixture was stirred at rt until the starting material was consumed
(2 h) (monitored by TLC). Ethanol was then evaporated on a rotary evaporator and a resi-
due was obtained, which consisted of essentially pure 7b (0.540 g, 83%). IR (ATR): 3070
(w), 3048 (w), 2970 (s), 2931 (s), 2857 (s), 1962 (w), 1892 (w), 1822 (w), 1731 (w), 1632
(s), 1590 (w), 1534 (s), 1484 (s), 1443 (s), 1427 (s), 1412 (s), 1381 (s), 1363 (s), 1313 (s),
1278 (s), 1164 (s), 1107 (s), 1077 (s), 1050 (s), 1007 (s), 959 (s), 890 (s), 819 (s), 795 (s),
1
739 (s), 699 (s), 663 (s), 606 (s), 577 (s) cmÀ 1; H NMR (500 MHz, CDCl3): δ 7.67–7.57
(m, 4H), 7.42–7.28 (m, 6H), 6.81 (q, J ¼ 6.7 Hz, 1H), 5.19 (s, 1H), 4.42 (s, 1H), 3.70 (q,
J ¼ 7.0 Hz, 2H), 3.60–3.38 (m, 6H), 1.34 (d, J ¼ 6.7 Hz, 3H), 1.24–1.14 (m, 12H), 1.08 (s,
9H); 13C NMR (126 MHz, CDCl3): δ 189.5, 167.4, 135.9 (2C), 135.8 (2C), 134.0, 133.9,
129.7, 129.6, 127.6 (2C), 127.5 (2C), 103.9, 89.2, 66.4, 62.3, 62.2, 58.5 (2C), 27.3 (3C),
26.7, 22.4, 19.4, 18.5, 15.4, 15.3. HRMS calcd. for C30H46NO4Siþ [M þ H]þ 512.31961;
found 512.31988.
(Z)-4-diethylamino-5-(t-butyldiphenyl)siloxy-1,1-diethoxy-6-methylhept-3-en-2-one (7c)
To a solution of ketone 6c (0.574 g, 1.23 mmol) in ethanol (15 mL) was added diethylamine
(0.13 mL, 94 mg, 1.27 mmol) dropwise by a syringe. The mixture was stirred at rt until the

SYNTHETIC COMMUNICATIONS®
787
starting material was consumed (2 h; monitored by TLC). Ethanol was evaporated on a
rotary evaporator and a residue was obtained, from which pure 7c (0.376 g, 57%) was
isolated by FC (hexanes and ethyl acetate, 95:5; then CH2Cl2). IR (ATR): 3071 (w), 3048
(w), 2966 (s), 2930 (s), 2858 (s), 1740 (s), 1634 (m), 1589 (w), 1534 (s), 1462 (s), 1441
(s), 1428 (s), 1411 (m), 1384 (s), 1362 (s), 1322 (s), 1268 (s), 1240 (s), 1182 (m), 1156
(m), 1138 (m), 1104 (s), 1057 (s), 948 (m), 907 (s), 842 (s), 819 (s), 740 (s), 699 (s), 662
1
(s), 608 (s), 579 (s) cmÀ 1; H NMR (CDCl3, 500 MHz): δ 7.68–7.57 (m, 4H), 7.41–7.28
(m, 6H), 6.55 (d, J ¼ 9.7 Hz, 1H), 5.21 (s, 1H), 4.40 (s, 1H), 3.65–2.90 (m, 8H), 1.98–
1.91 (m, 1H), 1.173 (t, J ¼ 7.0 Hz, 3H), 1.166 (t, J ¼ 7.0 Hz, 3H), 1.13 (seemingly t, J ¼ 7.2
Hz, 6H), 1.06 (s, 9H), 0.89 (d, J ¼ 6.5 Hz, 3H), 0.78 (d, J ¼ 6.9 Hz, 3H); 13C NMR (CDCl3,
126 MHz): δ 189.6, 164.5, 136.5 (2C), 136.3 (2C), 134.2, 133.7, 129.7, 129.5, 127.5 (2C),
127.2 (2C), 104.0, 91.8, 74.3, 62.1, 61.9, 60.5 (2C), 34.4, 27.5 (3C), 21.2, 20.8, 19.7, 18.1,
15.44, 15.40, 14.4. HRMS calcd. for C32H50NO4Siþ [M þ H]þ 540.35091; found 540.35098.
(Z)-4-diethylamino-5-trimethylsiloxy-1,1-diethoxy-5-ethylhept-3-en-2-one (7g)
Ketone 6 g (0.629 g, 2.02 mmol) was dissolved and stirred in EtOH (20 mL). Diethylamine
(0.15 g, 2.0 mmol) was added dropwise by syringe and the mixture was stirred at rt for
2.5 h. EtOH was then thoroughly evaporated on a rotary evaporator and gave a yellowish
1
residue, which was essentially pure 7 g (as judged from H NMR and MS), in total 0.721 g
(92%). IR (ATR): 2972 (m), 2933 (w), 2878 (w), 2208 (w), 1687 (m), 1460 (w), 1374 (w),
1319 (w), 1250 (m), 1153 (m), 1059 (s), 1017 (s), 935 (w), 880 (m), 839 (s), 754 (m),
1
680 (w), 679 (w), 612 (w), 584 (w) cmÀ 1; H NMR (CDCl3, 400 MHz): δ 5.50 (s, 1H),
4.60 (s, 1H), 3.50–3.70 (m, 8H), 1.88–1.92 (m, 2H), 1.68–2.74 (m, 2H), 1.23 (t, J ¼ 7.1 Hz,
3H), 1.10 (t, J ¼ 7.2 Hz, 6H), 0.85 (t, J ¼ 7.3 Hz, 6H), 0.16 (s, 9H); 13C NMR (CDCl3,
100 MHz): δ 100.5, 94.7, 84.9, 62.2, 47.1, 35.8, 15.5, 14.3, 9.0, 2.6. HRMS calcd. for
C16H30O4SiNaþ[M þ Na]þ 387.62934; found 388.2805.
Cuprate addition to TBDPS-protected ketones 6: General procedure
CuI (1.0 equiv.) was dispersed into dry THF under N2 and the resulting mixture was cooled
to À 30 °C before MeLi (2.0 equiv.) was added dropwise under stirring. When the addition
was complete, the resulting mixture was left stirring at bath temperature for an additional
30 min before it was cooled to À 78 °C. Ketone 6 (1.0 equiv.) in dry THF was added
dropwise to the reaction mixture, which was stirred for another 60 min before a saturated
aqueous solution of NH4Cl was added in one portion. The hydrolysate was allowed to
reach room temperature, the phases were separated, and the aqueous phase was extracted
with diethyl ether (3 �). The combined organic extracts were dried (MgSO4), filtered, and
concentrated under reduced pressure on a rotary evaporator to give the crude product,
from which the E and Z isomers of the corresponding 5-substituted 5-(t-butyldiphenylsi-
loxy)-1,1-diethoxyalk-3-en-2-one (8) was isolated pure by FC. Using this procedure the
following α,β-unsaturated alkenones were prepared.
5-(t-Butyl)diphenylsiloxy-1,1-diethoxy-4-methylpent-3-en-2-one (8a)
Ketone 6a (2.01 g, 4.73 mmol) was reacted with Me2CuLi and provided 2.27 g of a colorless
crude product, which showed only one spot when analyzed by TLC (CH2Cl2, Rf ¼ 0.22).
The 1H NMR spectrum of the residue was recorded and indicated that it mainly contained
two products. Screening of solvents to find conditions that would allow separation of the

788
W. SHANG ET AL.
compounds was rather unsuccessful. In spite of this FC separation was attempted using 5%
MeOH in hexanes as eluent and this gave essentially pure 8a (0.82 g, 39%), which turned
out to be a single isomer with E configuration (vide supra), and a small amount (0.15 g) of a
sample that contained E-8a and another product. Repeated separation gave a very small
amount of a pretty pure sample of the second product, which was given the structure
4-(t-butyl)diphenylsiloxy-5-diethoxy-3-methylcyclopent-2-enone (9).
Data for product mixture: IR (ATR): 3071 (m), 3049 (m), 2960 (s), 2931 (s), 2890 (s),
2858 (s), 1960 (w), 1893 (w), 1824 (w), 1714 (s), 1626 (s), 1589 (m), 1568 (w), 1472 (m),
1463 (m), 1428 (s), 1391 (m), 1372 (m), 1362 (m), 1315 (m), 1261 (w), 1227 (m), 1162
(s), 1103 (s), 1060 (s), 1007 (s), 998 (s), 938 (m), 908 (s), 873 (s), 854 (m), 822 (s), 740
(s), 700 (s) cmÀ 1
.
Data for (E)-8a: IR (ATR): 3070 (w), 3049 (w), 2973 (s), 2960 (s), 2930 (s), 2889 (s), 2857
(s), 1696 (s), 1627 (s), 1590 (w), 1471 (m), 1443 (m), 1427 (s), 1391 (m), 1373 (m), 1316 (s),
1263 (w), 1231 (w), 1159 (s), 1105 (s), 1059 (s), 1008 (s), 978 (m), 894 (m), 852 (s), 821 (s),
740 (s), 700 (s), 612 (s) cmÀ 1. 1H NMR (500 MHz, CDCl3): δ 7.68–7.66 (m, 4H), 7.45–7.37
(m, 6H), 7.02 (bs, 1H), 4.70 (s, 1H), 4.18 (s, 2H), 3.74–3.58 (m, 4H), 2.02 (s, 3H), 1.26 (t,
J ¼ 7.1 Hz, 6H), 1.10 (s, 9H); 13C NMR (126 MHz, CDCl3): δ 195.7, 159.4, 135.6 (4C), 133.2
(2C), 130.0 (2C), 127.93 (4C), 116.4, 102.7, 67.9, 62.8 (2C), 26.9, 19.4, 16.4, 15.34. HRMS
calcd. for C26H36O4SiNaþ [M þ Na]þ 463.22805; found 463.22812.
Data for 9: 1H NMR (500 MHz, CDCl3): δ 7.76–7.74 (m, 2H), 7.68–7.66 (m, 2H),
7.47–7.36 (m, 6H), 5.85 (s, 1H), 4.66–4.65 (m, 1H), 3.95–3.89 (m, 2H), 3.18–3.11 (m,
1H), 1.93 (s, 3H), 1.12 (s, 9H), 0.97 (t, J ¼ 7.0 Hz, 3H); 13C NMR (126 MHz, CDCl3): δ
203.2, 173.8, 136.3 (2C), 136.1 (2C), 133.4, 132.9, 130.2, 130.1, 129.2, 127.90 (2C), 127.7
(2C), 87.1, 78.7, 66.6, 27.1 (3C), 19.6, 16.7, 15.33. HRMS calcd. for C24H30O4SiNaþ
[M þ Na]þ 417.18619; found 417.18593.
5-(t-Butyldiphenylsiloxy)-1,1-diethoxy-4-methylhex-3-en-2-one (8b)
Ketone 6b (1.53 g, 3.49 mmol) was reacted with Me2CuLi to provide a colorless crude
product, from which (Z)-8b (0.55 g, 35%) and (E)-8b (0.78 g, 49%) were isolated by FC
(CH2Cl2; Rf(Z) ¼ 0.34, Rf(E) ¼ 0.16).
(Z)-8b: IR (ATR): 3071 (w), 3049 (w), 2975 (m), 2931 (m), 2888 (m), 2858 (m), 2360
(w), 1966 (w), 1890 (w), 1823 (w), 1773 (w), 1688 (s), 1615 (s), 1590 (w), 1472 (m),
1462 (w), 1443 (w), 1427 (s), 1390 (w), 1372 (m), 1362 (w), 1318 (w), 1240 (w), 1159
(m), 1107 (s), 1077 (s), 1058 (s), 1026 (s), 1008 (s), 996 (s), 951 (s), 905 (w), 892 (w),
1
852 (m), 822 (s), 739 (s), 700 (s) cmÀ 1; H NMR (CDCl3, 400 MHz): δ 7.65–7.56 (m,
4H), 7.42–7.28 (m, 6H), 6.21 (bs, 1H), 5.70 (q, J ¼ 6.3 Hz, 1H), 4.46 (s, 1H), 3.62–3.42
(m, 4H), 2.04 (d, J ¼ 1.2 Hz, 3H), 1.23–1.18 (m, 9H) 1.06 (s, 9H); 13C NMR (CDCl3,
101 MHz): δ 193.7, 167.2, 135.8 (2C), 135.7 (2C), 134.3, 134.0, 129.7, 129.6, 127.6 (2C),
127.5 (2C), 117.3, 102.6, 68.6, 62.8, 62.7, 27.1 (3C), 22.6, 19.8, 19.4, 15.3 (2C). HRMS calcd.
for C27H38O4SiNaþ [M þ Na]þ 477.24370; found 477.24375.
(E)-8b: IR (ATR): 3071 (w), 3049 (w), 2976 (s), 2931 (s), 2888 (m), 2858 (s), 1959 (w),
1893 (w), 1827 (w), 1777 (w), 1694 (s), 1622 (s), 1590 (w), 1473 (m), 1462 (w), 1444 (w),
1427 (s), 1391 (m), 1372 (s), 1318 (m), 1292 (w), 1229 (w), 1166 (s), 1110 (s), 1058 (s), 1008
(s), 998 (s), 964 (s), 939 (m), 895 (m), 872 (m), 822 (s), 778 (s), 739 (s), 700 (s), 689 (s)
1
cmÀ 1; H NMR (CDCl3, 400 MHz): δ 7.71–7.61 (m, 4H), 7.45–7.31 (m, 6H), 6.73 (bs,
1H), 4.62 (s, 1H), 4.22 (q, J ¼ 6.3 Hz, 1H), 3.71–3.52 (m, 4H), 2.06 (d, J ¼ 0.9 Hz, 3H),

SYNTHETIC COMMUNICATIONS®
789
1.23 (t, J ¼ 7.1 Hz, 6H), 1.17 (d, J ¼ 6.4 Hz, 3H), 1.10 (s, 9H); 13C NMR (CDCl3, 101 MHz):
δ 195.9, 164.0, 135.89 (2C), 135.87 (2C), 134.1, 133.4, 129.8 (2C), 127.68 (2C), 127.66 (2C),
116.8, 102.6, 74.1, 62.7, 62.6, 27.0 (3C), 22.9, 19.3, 16.2, 15.3 (2C). HRMS calcd. for
C27H38O4SiNaþ [M þ Na]þ 477.24370; found 477.24375.
5-(t-Butyldiphenyl)siloxy-1,1-diethoxy-4,6-dimethylhept-3-en-2-one (8c)
Ketone (6c) (1.80 g, 3.86 mmol) was reacted with Me2CuLi to provide a colorless crude
product, from which (Z)-8c (0.77 g, 41%) and (E)-8c (1.03 g, 55%) were separated by FC
(CH2Cl2; Rf(Z) ¼ 0.45, Rf(E) ¼ 0.24).
(Z)-8c: IR (ATR): 3072 (w), 3049 (w), 2962 (s), 2931 (s), 2890 (m), 2873 (m), 2858 (s),
2358 (w), 1964 (w), 1889 (w), 1824 (w), 1765 (w), 1693 (s), 1615 (s), 1471 (s), 1445 (m),
1427 (s), 1387 (s), 1372 (s), 1317 (m), 1275 (w), 1159 (m), 1104 (s), 1057 (s), 1007 (s),
1
999 (s), 960 (m), 939 (s), 908 (w), 891 (w), 860 (s), 821 (s), 739 (s), 700 (s) cmÀ 1; H
NMR (CHCl3, 400 MHz): δ 7.67–7.58 (m, 4H), 7.41–7.28 (m, 6H), 6.19 (bs, 1H), 5.57
(d, J ¼ 7.1 Hz, 1H), 4.41 (s, 1H), 3.62–3.41 (m, 4H), 1.89 (d, J ¼ 1.1 Hz, 3H), 1.84–1.76
(m, 1H), 1.210 (t, J ¼ 7.1 Hz, 3H), 1.205 (t, J ¼ 7.1 Hz, 3H), 1.09 (s, 9H), 0.87 (d, J ¼ 6.7 Hz,
3H), 0.74 (d, J ¼ 6.9 Hz, 3H); 13C NMR (CDCl3, 101 MHz): δ 193.6, 164.1, 136.20 (2C),
136.15 (2C), 134.26, 134.25, 129.57, 129.56, 127.5 (2C), 127.4 (2C), 120.2, 102.6, 75.7,
62.8, 62.6, 34.4, 27.3 (3C), 20.4, 19.8, 19.2, 18.7, 15.3 (2C). HRMS calcd. for C29H42O4SiNaþ
[M þ Na]þ 505.27500; found 505.27518.
(E)-8c: IR (ATR): 3072 (w), 3049 (w), 2961 (s), 2931 (s), 2892 (m), 2858 (s), 2355 (w),
1965 (w), 1891 (w), 1825 (w), 1776 (w), 1695 (s), 1619 (s), 1590 (w), 1471 (m), 1446 (w),
1427 (s), 1390 (m), 1367 (m), 1317 (w), 1262 (w), 1227 (w), 1160 (m), 1104 (s), 1057 (s),
1007 (s), 999 (s), 937 (w), 893 (w), 875 (m), 838 (m), 821 (s), 739 (s), 700 (s), 691 (s) cmÀ 1
;
1H NMR (CHCl3, 400 MHz): δ 7.69–7.58 (m, 4H), 7.44–7.29 (m, 6H), 6.36 (d, J ¼ 0.9 Hz,
1H), 4.52 (s, 1H), 3.84 (d, J ¼ 6.0 Hz, 1H), 3.64–3.45 (m, 4H), 2.02 (d, J ¼ 1.2 Hz, 3H),
1.85–1.77 (m, 1H), 1.203 (t, J ¼ 7.0 Hz, 3H), 1.196 (t, J ¼ 7.0 Hz, 3H), 1.08 (s, 9H), 0.84
(d, J ¼ 6.7 Hz, 3H), 0.69 (d, J ¼ 6.8 Hz, 3H); 13C NMR (CHCl3, 100 MHz): δ 195.2, 161.5,
136.24 (2C), 136.19 (2C), 134.0, 133.7, 129.7 (2C), 127.6 (2C), 127.5 (2C), 119.8, 102.5,
83.8, 62.6, 62.5, 33.0, 27.2 (3C), 19.7, 19.1, 18.4, 16.7, 15.3 (2C). HRMS calcd. for
C29H42O4SiNaþ [M þ Na]þ 505.27500; found 505.27512.
5-(t-Butyldiphenyl)siloxy-1,1-diethoxy-4-methylundec-3-en-2-one (8d)
Ketone 6d (0.56 g, 1.10 mmol) was reacted with Me2CuLi and provided a yellowish
crude product, from which (Z)-8d (0.26 g, 45%) and (E)-8d (0.28 g, 48%) were separated
by FC (CH2Cl2; Rf(Z) ¼ 0.62, Rf(E) ¼ 0.35). The spectroscopic data are in agreement with
the literature.[2]
5-(t-Butyldiphenyl)siloxy-1,1-diethoxy-4,5-dimethylhex-3-en-2-one (8e)
Ketone 6e (1.37 g, 3.02 mmol) was reacted with Me2CuLi and gave a yellowish crude pro-
duct, from which (Z)-8e (0.38 g, 27%) and (E)-8e (1.04 g, 73%) were separated by FC
(CH2Cl2; Rf(Z) ¼ 0.44; Rf(E) ¼ 0.23).
(Z)-8e: IR(ATR): 3071 (w), 3049 (w), 3015 (w), 2976 (s), 2931 (s), 2887 (m), 2857 (s),
2219 (w), 1961 (w), 1892 (w), 1826 (w), 1776 (w), 1692 (s), 1597 (s), 1472 (m), 1463
(m), 1441 (m), 1427 (s), 1385 (m), 1371 (w), 1360 (m), 1316 (m), 1237 (w), 1156 (s),
1128 (m), 1103 (s), 1058 (s), 1039 (s), 1026 (s), 1006 (s), 999 (s), 937 (m), 916 (m), 893
1
(m), 849 (m), 821 (s), 792 (m), 773 (m), 740 (s), 700 (s), 678 (s) cmÀ 1; H NMR (CHCl3,

790
W. SHANG ET AL.
400 MHz): δ 7.71 (dd, J1 ¼ 6.8 Hz, J2 ¼ 0.6 Hz, 4H), 7.42–7.34 (m, 6H), 6.33 (s, 1H), 4.51
(s, 1H), 3.69–3.49 (m, 4H), 2.26 (bs, 3H), 1.43 (s, 6H), 1.22 (t, J ¼ 7.1, 6H), 1.04 (s, 9H);
13C NMR (CDCl3, 101 MHz): δ 194.1, 170.5, 136.3 (4C), 135.7 (2C), 129.6 (2C), 127.5
(4C), 117.3, 103.6, 79.5, 63.2 (2C), 28.0, 27.5 (3C), 26.2 (2C), 19.7, 15.3 (2C). HRMS calcd.
for C28H40O4SiNaþ [M þ Na]þ 491.25935; found 491.25944.
(E)-8e: IR (ATR): 3071 (w), 3049 (w), 2977 (s), 2931 (s), 2887 (m), 2857 (s), 1965 (w),
1898 (w), 1826 (w), 1780 (w), 1694 (s), 1616 (s), 1590 (m), 1568 (w), 1472 (m), 1463 (m),
1444 (m), 1427 (s), 1384 (s), 1361 (s), 1316 (m), 1249 (s), 1171 (s), 1103 (s), 1044 (s), 1028
(s), 1007 (s), 999 (s), 935 (m), 912 (m), 900 (m), 878 (m), 821 (s), 770 (m), 741 (s), 701 (s),
1
684 (s) cmÀ 1; H NMR (CDCl3, 500 MHz): δ 7.75–7.73 (m, 4 H), 7.43–7.34 (m, 6H), 7.07
(bs, 1H), 4.67 (s, 1H), 3.72–3.56 (m, 4H), 2.17 (d, J ¼ 1.0, 3H), 1.226 (s, 6H), 1.225 (t, J ¼ 7.1
Hz, 6 H), 1.07 (s, 9H); 13C NMR (CDCl3, 126 MHz): δ 196.7, 166.7, 136.2 (4C), 135.4 (2C),
129.6 (2C), 127.6 (4C), 116.2, 102.8, 78.2, 62.7 (2C), 28.6, 27.4 (3C), 19.6, 16.3 (2C), 15.4
(2C). HRMS calcd. for C28H40O4SiNaþ [M þ Na]þ 491.25935; found 491.25944.
4-{[1-(t-Butyl)diphenylsiloxyl]cyclohex}-1,1-diethoxyl-4-methylbut-3-en-2-one (8f)
Ketone 6f (2.52 g, 5.11 mmol) was reacted with Me2CuLi and gave a yellowish crude pro-
duct, from which (Z)-8f (0.29 g, 11%) and (E)-8f (1.64 g, 63%) were separated by FC
(CH2Cl2; Rf(Z) ¼ 0.45, Rf(E) ¼ 0.27).
(Z)-8f: IR (ATR): 3071 (w), 3048 (w), 2930 (m), 2892 (m), 2856 (m), 2212 (w), 1961 (w),
1896 (w), 1830 (w), 1699 (s), 1590 (m), 1473 (m), 1446 (m), 1427 (s), 1389 (w), 1371 (w),
1360 (w), 1315 (w), 1281 (w), 1258 (w), 1226 (w), 1139 (m), 1103 (s), 1059 (s), 1027 (s), 999
1
(s), 931 (m), 902 (m), 877 (m), 846 (w), 821 (s), 740 (s), 700 (s), 689 (s) cmÀ 1; H NMR
(CDCl3, 400 MHz): δ 7.77–7.74 (m, 4H), 7.41–7.31 (m, 6H), 6.00 (d, J ¼ 1.2 Hz, 1H),
4.57 (s, 1H), 3.70–3.50 (m, 4H), 2.03–1.98 (m, 2H), 1.75 (d, J ¼ 1.1 Hz, 3H), 1.67–1.50
(m, 4H), 1.35–1.16 (m, 1H), 1.23 (t, J ¼ 7.0 Hz, 9H), 1.03 (s, 9H); 13C NMR (CDCl3,
101 MHz): δ 196.1, 155.8, 136.4 (4C), 135.7 (2C), 129.4 (2C), 127.3 (4C), 123.1, 103.3,
79.0, 63.3 (2C), 37.8 (2C), 27.4 (3C), 25.4, 24.4, 23.1 (2C), 20.1, 15.3 (2C). HRMS calcd.
for C31H44O4SiNaþ [M þ Na]þ 531.29065; found 531.29081.
(E)-8f: IR (ATR): 3071 (w), 3048 (w), 2930 (s), 2892 (m), 2856 (s), 2143 (w), 1966 (w),
1897 (w), 1825 (w), 1775 (w), 1696 (s), 1613 (s), 1473 (w), 1446 (m), 1427 (s), 1388 (w),
1360 (w), 1344 (w), 1317 (w), 1295 (m), 1259 (w), 1215 (w), 1169 (m), 1137 (m), 1003
(s), 1059 (s), 1024 (s), 998 (s), 933 (w), 900 (s), 888 (s), 857 (w), 821 (s), 740 (s), 700
1
(s), 689 (s) cmÀ 1; H NMR (CDCl3, 400 MHz): δ 7.71–7.69 (m, 4H), 7.41–7.31 (m, 6H),
6.31 (s, 1H), 4.49 (s, 1H), 3.66–3.49 (m, 4H), 2.12 (bs, 3H), 1.98–1.95 (m, 2H), 1.65–
1.58 (m, 4H), 1.40–1.37 (m, 1H), 1.28–1.10 (m, 3H), 1.22 (t, J ¼ 7.1 Hz, 6H), 0.99 (s,
9H); 13C NMR (CDCl3, 101 MHz): δ 195.8, 161.2, 136.2 (4C), 135.3 (2C), 129.5 (2C),
127.4 (4C), 119.2, 102.4, 79.1, 62.6 (2C), 37.2 (2C), 27.2 (3C), 25.7, 23.5 (2C), 19.8, 16.0,
15.3 (2C). HRMS calcd. for C31H44O4SiNaþ [M þ Na]þ 531.29065; found 531.29082.
Addition of 1,3-propanedithiol to 5-(t-butyl)diphenylsiloxy-1,1-diethoxylhex-3-yn-
2-one (6b): Formation of 3-(2-(1-(t-butyl)diphenylsiloxyethyl)-1,3-dithian-2-yl)-
1,1-diethoxy-Propan-2-one (10b)
1,3-Propanedithiol (0.186 g, 1.72 mmol) in dry THF (10 mL) was treated with NaOMe
(0.109 g, 2.02 mol) at rt, and to the resulting mixture, which was cooled to À 78 °C and

SYNTHETIC COMMUNICATIONS®
791
stirred, was added a THF solution of 5-(t-butyl)diphenylsiloxy-1,1-diethoxylhex-3-yn-2-
one (6b) (0.680 g, 1.55 mmol in 10 mL) over 15 min. The reaction mixture was stirred
for 17.5 h and allowed to reach rt. The reaction was quenched with a saturated aqueous
solution of NH4Cl (40 mL), and the mixture was extracted with DCM (3 � 50 mL), dried
(MgSO4), filtered, and concentrated to provide a crude product from which 10b
(0.691 g, 82%) was isolated as colorless liquid by FC (10% ethyl acetate in hexanes, Rf
¼ 0.21). IR (ATR): 3070 (w), 3047 (w), 2973 (s), 2929 (s), 2892 (s), 2855 (s), 1729 (s),
1589 (w), 1472 (m), 1442 (m), 1426 (s), 1390 (s), 1373 (s), 1313 (s), 1277 (m), 1240 (s),
1132 (s), 1103 (s), 1057 (s), 1004 (s), 971 (s), 957 (s), 908 (s), 871 (m), 821 (s), 740 (s),
701 (s), 609 (s) cmÀ 1 1H NMR (500 MHz, CDCl3): δ 7.79–7.75 (m, 4H), 7.44–7.36
;
(m, 6H), 4.68 (s, 1H), 4.62 (q, J ¼ 6.3 Hz, 1H), 3.74–3.54 (m, 6H), 2.95–2.84 (m, 2H),
2.74–2.69 (m, 1H), 2.59–2.54 (m, 1H), 2.02–1.95 (m, 1H), 1.86–1.78 (m, 1H), 1.27–1.23
(m, 9H), 1.03 (s, 9H); 13C NMR (126 MHz, CDCl3): δ 202.2, 136.2 (4C), 134.8, 133.3,
129.8, 129.5, 127.7 (2C), 127.4 (2C), 103.3, 73.6, 63.5, 63.3, 42.0, 27.1 (3C), 26.7, 26.2,
25.9, 24.9, 19.7, 19.2, 15.34, 15.30. HRMS calcd for C29H42O4S2SiNaþ [M þ Na]þ
569.21915; found 569.21938.
Acknowledgment
Thanks are also due to Bjarte Holmelid at the University of Bergen for skillful recording and valuable
discussions of mass spectra.
Funding
Financial support (to Shang) from the Chinese Research Council is acknowledged with gratitude.
Unfailing support from the Munin Foundation is highly appreciated.
References
[1] (a) Bol’shedvorskaya, R. L.; Vereshchagin, L. I. Russ. Chem. Rev. 1973, 42, 225–240; (b) Posner,
G. H. Org. React. 1972, 19, 1–113 (c) Kozlowski, J. A.; Trost, B. M.; Fleming, I. (Eds.); Compre-
hensive Organic Synthesis; Pergamon Press: Oxford, UK, 1991; vol. 4, ch. 1.4; (c) Tomioka, K.
Synthesis 1990, 541–549; (d) Sengee, M.; Sydnes, L. K. Synthesis 2011, 3899–3907.
[2] Sydnes, L. K.; Holmelid, B.; Sengee, M.; Hanstein, M. J. Org. Chem. 2009, 74, 3430–3443.
[3] (a) Sydnes, L. K.; Isanov, R.; Sengee, M.; Livi, F. Synth. Commun. 2013, 43, 2898–2905; (b) Nes,
I.; Sydnes, L. K. Synthesis 2015, 47, 89–94.
[4] Erdenebileg, U.; Høstmark, I.; Polden, K.; Sydnes, L. K. J. Org. Chem. 2014, 79, 1213–1221.
[5] (a) Gaunt, M. J.; Sneddon, H. F.; Hewitt, P. R.; Orsini, P.; Hook, D. F.; Ley, S. V. Org. Biomol.
Chem. 2003, 1, 15–16; (b) Sneddon, H. F.; Gaunt, M. J.; Ley, S. V. Org. Lett. 2003, 5, 1147–1150;
(a) Valdersnes, S.; Apeland, I.; Flemmen, G.; Sydnes,L. K. Helv. Chim. Acta 2012, 95,
2099–2122.
[6] (a) Perlmutter, P. Conjugate Addition Reactions in Organic Synthesis; Pergamon Press: Oxford,
1992 (b) Bergmann, E. D.; Ginsburg, D.; Pappo, R. Org. React. 1959, 10, 182–542; (b) Rossiter,
B. E.; Swingle, N. M. Chem. Rev. 1992, 92, 771–806.
[7] Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; John Wiley &
Sons: New York, 1991; ch. 2, pp. 10–143.
[8] Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; John Wiley &
Sons: New York, 1991; pp. 68–87.
[9] Kvernenes, O. H.; Sydnes, L. K. Org. Synth. 2005, 83, 184.

792
W. SHANG ET AL.
[10] Sydnes, L. K.; Holmelid, B.; Kvernenes, O. H.; Sandberg, M.; Hodne, M.; Bakstad, E.
Tetrahedron 2007, 63, 4144.
[11] Visser, R. G.; Bos, H. J. T.; Brandsma, L. Rec. Trav. Chim. Pays-Bas 1980, 99, 70.
[12] (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; John Wiley &
Sons: New York, 1991; pp. 178–198 (b) Holmelid, B.; Kvernenes, O. H.; Hodne, M.; Sydnes,
L. K. Arkivoc 2008, 6, 26–41; (c) Sydnes, L. K.; Holmelid, B.; Kvernenes, O. H.; Valdersnes,
S.; Hodne, M.; Boman, K. Arkivoc 2008, 14, 242–268.
[13] Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; John Wiley &
Sons: New York, 1991; pp. 77–83.
[14] Jackman, L. M.; Sternhell, S. Applications of Nuclear Magnetic Resonance Spectroscopy in
Organic Chemistry, 2nd ed.; Pergamon Press: Oxford, UK, 1969; pp. 316–328.
[15] (a) Gilman, H.; Jones, R. G.; Woods, L. A. J. Am. Chem. Soc. 1952, 17, 1630 (b) Jones, R. G.;
Gilman, H. Chem. Rev. 1954, 54, 847; (c) House, H. O.; Respess, W. L.; Whitsides, G. M. J. Org.
Chem. 1966, 31, 3128; (d) Taylor, R. K. Organocopper Reagents; Oxford University Press:
Oxford, UK, 1994.
[16] Posner, G. H. Organic Reactions 1972, 19, 1–114.
[17] (a) Corey, E. J.; Katzenellenbogen, J. A. J. Am. Chem. Soc. 1969, 91, 1851; (b) Siddall, J. B.;
Biskup, M.; Fried, J. H. J. Am. Chem. Soc. 1966, 91, 1853; (c) Klein, J.; Turkel, R. M. J. Am.
Chem. Soc. 1969, 91, 6186.
[18] (a) Jackman, L. M.; Wiley, R. H. J. Chem. Soc. 1960, 2881; (b) Douglas, A. W.; Goldstein, J. H.
J. Mol. Spec. 1965, 16, 1; (c) Bothner-By, A. A.; Naar-Colin, C. J. Am. Chem. Soc. 1961, 83,
231 (d) Barfield, M.; Spear, R. J.; Sternhell, S. Chem. Rev. 1976, 76, 593; (e) Sydnes, L. K.;
Hemmingsen, T. H. Acta Chem. Scand. B 1985, 39, 93.
[19] (a) Bellamy, L. J. The Infrared Spectra of Complex Molecules, 3rd ed.; Chapman and Hall:
London, UK, 1975/1978; ch. 9; (b) Jones, R. N.; Humpries, P.; Dobriner, K. J. Am. Chem.
Soc. 1950, 72, 956; (c) Fuson, N.; Josien, M. L.; Shelton, E. M. J. Am. Chem. Soc. 1954, 76, 2526.
[20] (a) Stothers, J. B. Carbon-13 NMR Spectroscopy; Academic Press: New York, 1972; pp. 289–294
(b) Barton, D. H. R.; Hulshof, L. A. J. Chem. Soc., Perkin Trans. I 1977, 1103; (c) Klunder, A. J.
H.; Zwanenburg, B. Tetrahedron Lett. 1981, 22, 4557; (d) Malmstrøm, J.; Christophersen, C.;
Barrero, A. F.; Oltra, J. E.; Justicia, J.; Rosales, A. J. Nat. Prod. 2002, 65, 364; (e) Blanco-Urgoiti,
J.; Abdi, D.; Domínguez, G.; Pérez-Castells, J. Tetrahedron 2008, 64, 67.
[21] (a) Ghribi, A.; Alexakis, A.; Normant, J. F. Tetrahedron Lett. 1984, 25, 3083; (b) Normant, J. F.;
Alexakis, A.; Ghribi, A. Tetrahedron 1989, 45, 507.
[22] Bali, A. K.; Sunnam, S. K.; Prasad, K. R. Org. Lett. 2014, 16, 4001.