Tetrabutylammonium fluoride (TBAF)-catalyzed addition of substituted trialkylsilylalkynes to aldehydes, ketones, and trifluoromethyl ketones

Article abstract of DOI:10.1021/jo200314g

Herein we report that tetrabutylammonium fluoride (TBAF) is a very efficient catalyst for the addition of trialkylsilylalkynes to aldehydes, ketones, and trifluoromethyl ketones in THF solvent at room temperature. The reaction conditions are mild and oper

Full text of DOI:10.1021/jo200314g

ARTICLE
pubs.acs.org/joc
Tetrabutylammonium Fluoride (TBAF)-Catalyzed Addition of
Substituted Trialkylsilylalkynes to Aldehydes, Ketones, and
Trifluoromethyl Ketones
Venkat Reddy Chintareddy, Kuldeep Wadhwa, and John G. Verkade*
Department of Chemistry, Gilman Hall, Iowa State University, Ames, Iowa 50011, United States
S Supporting Information
b
ABSTRACT: Herein we report that tetrabutylammonium
fluoride (TBAF) is a very efficient catalyst for the addition of
trialkylsilylalkynes to aldehydes, ketones, and trifluoromethyl
ketones in THF solvent at room temperature. The reaction
conditions are mild and operationally simple, and a variety of
aryl functional groups, such as chloro, trifluoromethyl, bromo,
and fluoro groups, are tolerated. Impressively, using our protocol, useful CF3-bearing tertiary propargylic alcohols can be
synthesized. Product yields are generally better than or comparable to those in the literature. 1-Phenyl-2-trimethylsilyl acetylene,
trimethyl ((4-(trifluoromethyl)phenyl)ethynyl)silane, 1-trimethylsilyl-1-hexyne, and trimethyl(thiophen-3-ylethynyl)silane under-
went clean conversion to their corresponding propargylic alcohols as products under our conditions. Heterocyclic carbonyl
compounds, such as furan-3-carboxaldehyde, thiophene-3-carboxaldehyde, and 2-pyridyl ketone, gave good yields of propargylic
alcohols.
’ INTRODUCTION
10 mol % KOEt in THF as solvent at 0 °C was reported by
Scheidt et al. to provide good yields of alkynylated product when
triethoxysilylacetylenes bearing alkyl substituents on the acetylene
were used as reagents with aldehydes, ketones and imines.10b In
2006, Mukaiyama et al. disclosed that 10 mol % of [Bu4N][OPh]
at ꢀ78 °C in THF solvent gave 39ꢀ100% isolated alkynylated
product yields with aldehydes and four ketone substrates, but
unfortunately, alkyl-substituted acetylenes did not work well in
their methodology.10c Using trimethylsilylethers and aldehydes
as reaction partners, Shioiri et al. reported the use of KOtBu as a
catalyst for the formation of Z-selective β-branched Moritaꢀ
BaylisꢀHillman-type adducts.10d Recently we reported the use of
the proazaphosphatrane, P(PhCH2NCH2CH2)3N, asa catalyst for
the synthesis of propargylic alcohols at room temperature with
aldehydes, although this method did not work for ketones.11,12
Most importantly, β-branched MoritaꢀBaylisꢀHillman (MBH)
type adducts were isolated when electron-deficient aromatic
aldehydes were employed.12 This result prompted us to broaden
our investigation of TBAF in an effort to generalize its use as an
efficient catalyst for aldehyde and ketone alkynylation using
alkyl-substituted terminal silylated acetylenes.
Development of simple and efficient methodologies for CꢀC
bond formation is important to the advancement of synthetic
organic chemistry, and the formation of such bonds to multiple
carbonꢀcarbon bonds is an important route to the creation of
complex structures. Propargylic alcohols are key building blocks
for the synthesis of many natural products and biologically
important molecules,1,2 and not surprisingly, many methods
have been developed for the efficient synthesis of such species.
A common approach to propargylic alcohol synthesis involves
the use of an equivalent of a strong metal-base (e.g., n-BuLi) to
generate acetylide ions from terminal alkynes for nucleophilic
addition to carbonyl groups.3 Other methods for synthesizing
propargylic alcohols employ heavy metal catalysts such as zinc or
indium in the presence of bulky ligands.4ꢀ8 However, the latter
method suffers from the drawback that enolizable aldehydes and
ketones do not function in these reactions.
In 1976, Kuwajima et al. reported the first use of tetrabuty-
lammonium fluoride (TBAF) for the reaction of 1-phenyl-2-
trimethylsilyl acetylene with aldehydes and ketones, providing
products in yields ranging from 5 to 87% using a 3ꢀ5 mol %
loading of catalyst. However, they screened only an acetylene
substrate with a phenyl substituent.9a,b Lerebours et al. reported
that TBAF is an efficient catalyst for the arylation of aldehydes,9c
and Yoshizawa et al. reported reactions aimed at the synthesis of
MoritaꢀBaylisꢀHillman type adducts using quaternary ammo-
nium fluorides derived from cinchonine as the catalyst.10a In
these reactions, propargylic alcohols were formed as byproduct.
In fact, when TBAF was used as the catalyst, the proportion of
side product surpassed that of the expected product. The use of
Here we report a mild method for alkynylating aldehydes with
trialkylsilylalkynes using TBAF as the catalyst (see scheme in the
abstract). TBAF is a well-known desilylating agent and its use as a
catalyst for Michael reactions, intramolecular aldolizations, alcohol
silylations and aldehyde arylations has been described in the
literature.9c,13 The uniqueness of TBAF stems from its bulky n-butyl
Received: February 13, 2011
Published: April 25, 2011
r
2011 American Chemical Society
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Table 1. Screening of Fluoride Salts as Catalysts for Aldehyde
Alkynylation
Table 2. Reactions of Aldehydes with 1-Trimethylsilyl-1-
hexyne (2) using TBAF as the Catalysta
entry
catalyst
2 (equiv.) catalyst (mol %) yield (%)
1
2
3
4
5
6
7
8
9
TBAF
TBAF
TBAF
TBAF
TBAF
TBAF
1.1
1.1
1.1
1.1
1.5
2.0
2.0
2.0
2.0
2.0
1
2
50
57
63
65
71
75
5
10
10
10
10
10
10
10
a
MF (M = Na, K or Cs)
Me4NF
ꢀ
a
ꢀ
a
Bu3SnF
ꢀ
10b Bu3SnF
a No detectable yield. b Toluene as solvent at 80 °C.
ꢀ
a
groups which render this catalyst highly soluble in polar organic
solvents to function simultaneously as a nucleophilic fluoride
source and also as a possible source of electrophilic bulky
quaternary ammonium cations that act as a Lewis acid for
activating carbonyl groups via oxygen coordination.8 These
notions are supported by the superior performance of TBAF
over alkali fluoride salts in the arylation of aldehydes8 and by our
results in entry 7 of Table 1 in which alkali fluorides were
ineffective in facilitating formation of the desired product.
Initially, the reaction of o-methoxybenzaldehyde (1) with
1-trimethylsilyl-1-hexyne (2) was screened with various fluoride
salts for the synthesis of 3 (Table 1). Because of the good
solubility of TBAF in THF, this solvent was chosen for further
study. As anticipated, only TBAF efficiently catalyzed the screen-
ing reaction, thus corroborating previously reported results.10
Other fluoride salts produced no significant conversions
(Table 1, entries 7ꢀ10). The use of tetramethylammonium
fluoride (Table 1, entry 8) was not beneficial, apparently because
of its poor solubility in THF. Tributyltin fluoride was tested to
determine if its greater Lewis acidity promoted carbonyl group
activation in THF or toluene as solvent. However, no product
was detected by 1H NMR spectroscopy in either case. As shown
in Table 1, entries 1ꢀ6, 10 mol % of TBAF in the presence of
2 equiv of 1-trimethylsilyl-1-hexyne (2) at room temperature
gave the best results.
We then examined various aldehydes under the conditions
given in Table 1, entry 6. From the data in Table 2, it is seen that
our method has advantages over existing methods which include
good efficiency at ambient temperature and significantly shorter
reaction times (15 min). Thus, literature references report tem-
peratures of ꢀ50ꢀ100 °C and reaction times of 30 min to 48 h.
Moreover, the addition of strong bases and metal/ligand combina-
tions4ꢀ8 is avoided with our approach. A variety of functional groups
were tolerated under our conditions, providing good to excellent
yields as shown in Table 2. Electron donating groups such as
methoxy and methyl resulted in good isolated yields (Table 2,
entries 1, 6 and 7) and as expected, halogen-containing alde-
hydes, such as o-chlorobenzaldehyde and p-bromobenzaldehyde,
also afforded good product yields (entries 4 and 5). Since our
a TBAF (10 mol %), THF (4 mL), room temperature for 15 min.
c
Isolated yields after column chromatography. b Reference 4. Refer-
ence 5c. d Reference 6c. e Reference 5d. f Reference 7c. g Reference 5e.
h Reference 5f. i Reference 5g. j Reference 6g. k Reference 8e.
procedure does not involve the use of strong bases to generate
acetylide ions, enolizable aldehydes also gave excellent product
yields (Table 2, entries 8 and 9). Although quantitative conver-
sion was observed in the case of heterocyclic 3-furaldehyde
(entry 10), the yield was only 72%. Even bulky 1-naphthaldehyde
(Table 2, entry 3) gave a good product yield, and the sterically
hindered alkyl aldehyde in Table 2, entry 11 provided a better
yield of product than that obtained using a quaternary ammo-
nium hydroxide as a catalyst (10 mol %).7c Higher yields for this
alkyl aldehyde were also reported with the use of potassium
ethoxide (10 mol %) and cesium hydroxide (10 mol %) as bases,
respectively.6c,10b
Since Kuwajima et al. screened only 1-phenyl-2-trimethylsilyl
acetylene,9a,b we broadened our protocol by screening three
different terminally silylated alkynes (Table 3). The electron-rich
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Table 3. Screening of Trimethylsilyl Aryl Alkynes with Aromatic and Aliphatic Aldehydesa
a TBAF (10 mol %), THF (4.0 mL), room temperature, 15 min. Isolated yields after column chromatography. b Reference 6d. c Reference 6e. d Reference
6f. e Reference 5c. f Reference 6c. g Reference 7c. h Reference 7e.
alkyne 1-phenyl-2-trimethylsilyl acetylene, afforded a good pro-
duct yield with both an aromatic and an enolizable aldehyde
(entries 1 and 2, respectively). Electron deficient trimethyl
((4-(trifluoromethyl)phenyl)ethynyl)silane (entries 3 and 4)
and the functionalized alkyne trimethyl(thiophen-3-ylethynyl)silane
(entries 5 and 6) were also screened with the aforementioned
aromatic and enolizable aldehyde, providing generally good
yields of product.
There are many literature examples of trifluoromethyl-con-
taining analogs of biologically active molecules14 featuring an
alkyne motif, for example, the anti-HIV drug Efavirenz,14 in
which the trifluoromethyl substituent substantially changes the
electronic properties, leading to a different drug candidate. In this
context, Shibasaki, and Kanai et al. developed an elegant method
for the synthesis of CF3-functionalized propargylic alcohols using
CuOtBu-xantphos or phenanthroline with alkyne substrates at
60ꢀ100 °C.15 Thus, we focused our attention on achieving a
gratifying synthesis of CF3-containing alkynes using commer-
cially available materials in a simple metal-free protocol. From
our results in Table 4, it is seen that electron-neutral (entries 1,
and 2) and electron-donating (entry 3) CF3-containing aceto-
phenones with aromatic alkyne, 1-phenyl-2-trimethylsilyl acet-
ylene give rise to excellent isolated yields affording CF3-
substituted tertiary propargyl alcohols at room temperature.
We then turned our attention to screening various hetero-
cyclic, aromatic and aliphatic ketones with 1-phenyl-2-tri-
methylsilyl acetylene (Table 5). Nitrogen-containing 2-pyridyl
ketone afforded an excellent isolated product yield (Table 5,
entry 1) in the TMS as well as in the alcohol form. Long chain
aliphatic ketone (entry 4) also provided good yields of the
corresponding TMS-protected propargylic alcohols. How-
ever, 4-bromobenzophenone gave an excellent isolated
product yield (entry 2) in TMS form. Nonetheless, the syn-
theses of these molecules have not been reported previously
in the literature. A heterocyclic ketone did not participate
in alkyne addition reaction under our reaction conditions
(entry 5).
The mechanism we suggest in Scheme 1 parallels that
proposed by Scheidt et al. in 2005 for aldehyde and ketone
alkynylation using triethoxysilylalkynes in the presence of 10%
KOEt.10b Activation of the silyl group of the alkyne by TBAF
forms the activated pentacoordinated silicon species A which is
followed by silicon coordination of the aldehyde leading to B.
The subsequent dissociative equilibrium which gives rise to C
provides an acetylide ion which nucleophilically attacks the
carbonyl carbon of the coordinated aldehyde in C to create D
which in turn liberates trimethylsilated E. Acid hydrolysis of E
then provides product F.10b
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Table 4. Screening of 1-Phenyl-2-trimethylsilyl Acetylene with Trifluoromethyl Ketonesa
a TBAF (10 mol %), ketone (2.0 mmol), alkyne (4.0 mmol), THF (4 mL), room temperature. Isolated yields after column chromatography. b No acid
workup. Product hydrolyzed during column chromatography. c See ref 14b using (AgF/C6H11)3P, 1 day, 100 °C. d See ref 15 CuOtBu-xantphos or
phenanthroline complex. e See ref 14c using CuF as the catalyst (5ꢀ10 mol %).
’ CONCLUSIONS
132.2, 130.2, 128.5, 128.2, 125.4 (q, J = 3.6 Hz), 121.18, 111.2, 91.1, 84.8,
61.9, 55.9 ppm; HRMS m/z Calcd for C17H13F3O2: 306.08676. Found:
306.08724.
We have extended and broadened the alkynylation of alde-
hydes using TBAF as a catalyst in a mild and efficient protocol.
Our reactions are faster than those observed with published
methods and no organometallic reagents or metal/ligand com-
binations are required. Enolizable aldehydes participate well in
our method, with no use of strong bases (e.g., BuLi). Facile
participation of simple, heterocyclic, and trifluoromethyl ketones
in alkynylation was observed at room temperature. Our approach
is efficient for both aromatic and aliphatic aldehydes and tolerates
a wide variety of functional groups. The low catalyst loading (ca.
10 mol %), high isolated product yields, broad scope, room
temperature reaction conditions and the use of a relatively
inexpensive commercially available nonmetallic base as catalyst
are attractive features of our protocol which can serve as an eco-
friendly alternative for the synthesis of propargylic alcohols in
industrial and academic facilities.
1-Cyclohexyl-3-(4-trifluoromethylphenyl)prop-2-yn-1-ol (Table 3,
entry 4). This product was purified via flash column chromatography
with 10% ethyl acetate/hexane, yielding 79% as a yellow oil. 1H NMR
(CDCl3, 300 MHz): δ 7.49ꢀ7.56 (m, 4H), 4.39 (d, J = 6 Hz, 1H), 2.33
(s, 1H), 1.938ꢀ1.623 (m, 6H), 1.303ꢀ1.067 (m, 5H) ppm; 13C NMR
(CDCl3, 75 MHz): δ 132.1, 130.2 (q, J = 32.55 Hz), 126.8, 125.9, 125.4,
125.3, 122.3, 92.1, 84.5, 67.8, 44.4, 28.9, 28.5, 26.56, 26.08; HRMS m/z
Calcd for C16H17F3O: 244.05580. Found: 244.05630.
1-(2-Methoxyphenyl)-3-thiophen-3-yl-prop-2-yn-1-ol (Table 3, entry 5).
This product was purified via flash column chromatography with 10%
1
ethyl acetate/hexane, yielding 77% as a yellow oil. H NMR (CDCl3,
300 MHz): δ 7.643 (dd, J = 1.8 Hz, J = 7.5 Hz, 1 H) 7.485ꢀ7.461.(m,
1H) 7.330 (t, J = 7.5 Hz, 1H) 7.266ꢀ7.239 (m, 1 H) 7.145 (dd, J =
0.9 Hz, J = 5 Hz, 1 H) 7.008 (dt, J = 0.9 Hz, J = 7.5 Hz, 1 H) 6.785 (d, J =
9 Hz, 1 H) 5.918 (s, 1H) 3.904 (s, 3H) 3.171 (d, J = 5 Hz, 1H) ppm; 13C
NMR (CDCl3, 75 MHz): δ 157.0, 130.2, 129.9, 129.3, 128.9, 128.2,
125.5, 121.9, 121.1, 111.1, 88.2, 81.5, 61.8, 55.9 ppm; HRMS m/z Calcd
for C14H12O2S: 282.12315 Found: 282.12361.
’ EXPERIMENTAL SECTION
General Experimental Procedure. To a solution of TBAF (10
mol % in dry THF) was added trimethylsilyl alkyne (2.0 mmol) at room
temperature. To this was added an aldehyde or ketone (1 mmol) and
then the reaction mixture was stirred at room temperature for 15 min.
This was followed by the addition of 1 M aqueous HCl (1.0 mL) and
further stirring for 15 min at room temperature, unless otherwise stated
in the foot notes of corresponding tables. The reaction mixture was neutral-
ized with aqueous NaHCO3 and then it was extracted with ethyl acetate.
The organic layers were collected and dried with anhydrous Na2SO4
followed by solvent removal under reduced pressure. The crude product
was purified by flash chromatography (hexane/ethyl acetate = 90:10) on
silica gel to give the desired alkynylation product.
1-(2-Methoxyphenyl)-3-(4-trifluoromethylphenyl)prop-2-yn-1-ol
(Table 3, entry 3). This product was purified via flash column chroma-
tography with 10% ethyl acetate/hexane, yielding 69% as a yellow oil. 1H
NMR (CDCl3, 400 MHz): δ 7.613 (dd, J = 7.2 Hz, J = 1.2 Hz, 1H), 7.57
(s, 4H), 7.351 (dt, J = 8 Hz, J = 1.6 Hz, 1H), (bs, 1H), 7.019 (t, J = 8.4 Hz,
1H), 7.954 (d, J = 8.4 Hz, 1H), 5.936 (d, J = 6.4 Hz, 1H), 3.931 (s, 3H),
3.161 (d, J = 6.4 Hz, 1H) ppm; 13C NMR (CDCl3, 100 MHz): δ 157.0,
1-Cyclohexyl-3-thiophen-3-yl-prop-2-yn-1-ol (Table 3, entry 6).
This product was purified via flash column chromatography with 10%
ethyl acetate/hexane, yielding 73% as a yellow oil. H NMR (CDCl3,
1
300 MHz): δ 7.419 (dd, J = 0.9 Hz, J = 3 Hz, 1H), 7.092 (dd, J = 1.2 Hz,
J = 4.8 Hz, 1H) 4.349 (d, J = 6 Hz, 1H) 2.326 (bs, 1H) 1.921ꢀ1.586 (m,
6H) 1.287ꢀ1.078 (m, 5H) ppm; 13C NMR (CDCl3, 75 MHz): δ 130.1,
129.0, 125.5, 122.0, 89.2, 80.9, 67.8, 44.5, 28.9, 28.5, 26.6, 26.1 ppm;
HRMS m/z Calcd for C13H16OS: 220.09219. Found: 220.09246.
1,1,1-Trifluoro-2,4-diphenylbut-3-yn-2-ol (Table 4, entry 1). Purified
via flash column chromatography with 5% ethyl acetate/hexane, yielding
98% as yellow oil. 1H NMR (CDCl3, 300 MHz): δ 3.22 (s, 1H),
7.35ꢀ7.47 (m, 6H), 7.47ꢀ7.57 (m, 2H), 7.84ꢀ7.87 (m, 2H) ppm; 13C
NMR (CDCl3, 100 MHz): δ 73.4 (q, J = 32.2 Hz), 84.5, 88.2, 121.0,
123.5 (q, J = 283.2 Hz), 127.3, 128.3, 128.6, 129.4, 129.6, 129.7, 132.2,
135.4 ppm; HRMS m/z Calcd for C16H11F3O: 276.07620. Found:
276.07667.
2,20-(3-Phenyl-1-((trimethylsilyl)oxy)prop-2-yne-1,1-diyl)dipyridine
(Table 5, entry 1). Purified via flash column chromatography with 5%
ethyl acetate/hexane, yielding 98% as a light yellow oil. 1H NMR
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Table 5. Screening of 1-Phenyl-2-trimethylsilyl Acetylene with Ketonesa
a 10 mol % TBAF, ketone (2.0 mmol), alkyne (4.0 mmol), THF (4 mL), room temperature. Isolated yields after column chromatography. None of these
products have been reported in the literature. b No acid workup. Product hydrolyzed during column chromatography. c Catalyst (20 mol %) was used.
d No product detected.
(CDCl3, 300 MHz): δ 0.22 (s, 9H), 7.08ꢀ7.11 (m, 1H), 7.23ꢀ7.26 (m,
1H), 7.31ꢀ7.35 (m, 4H), 7.54ꢀ7.56 (m, 2H), 7.66ꢀ7.70 (m, 1H),
7.74ꢀ7.76 (m, 2H), 7.90ꢀ7.92 (m, 1H), 8.54ꢀ7.86 (m, 1H) ppm;
13C NMR (CDCl3, 100 MHz): δ 1.7, 77.3, 87.9, 91.7, 119.4, 122.1, 122.8,
126.5, 127.5, 128.1, 128.3, 128.6, 131.8, 136.7, 145.5, 149.1, 164.4 ppm;
HRMS m/z Calcd for C22H22N2OSi: 358.15013. Found: 358.15108.
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Scheme 1. Mechanism Proposed for TBAF-Catalyzed Alkynylation of Aldehydes and Ketones
((1-(4-Bromophenyl)-1,3-diphenylprop-2-yn-1-yl)oxy)trimethylsilane
(Table 5, entry 2). Purified via flash column chromatography using
hexanes yielding 98% as a light-yellow oil. 1H NMR (CDCl3, 300 MHz):
δ 0.23 (s, 9H), 7.28ꢀ7.30 (m, 1H), 7.35ꢀ7.40 (m, 5H), 7.47ꢀ7.49 (m,
2H), 7.56ꢀ7.58 (m, 4H), 7.67 (d, J = 6.0 Hz, 2H) ppm; 13C NMR
(CDCl3, 100 MHz): δ 1.9, 75.8, 88.7, 91.7, 121.5, 122.7, 126.2, 127.7,
128.1, 128.4, 128.7, 129.0, 131.4, 131.8, 146.3, 146.4 ppm; HRMS m/z
Calcd for C24H23BrOSi: 434.07014. Found: 434.07124.
’ ACKNOWLEDGMENT
The National Science Foundation is gratefully acknowledged
for financial support of this research in the form of grant
0750463.
’ REFERENCES
((5-(2,5-Dimethoxyphenyl)-3-methyl-1-phenylpent-1-yn-3-yl)oxy)-
trimethylsilane (Table 5, entry 3). Purified via flash column chroma-
tography using 10% ethyl acetate in hexanes yielding 44% as a colorless
oil. 1H NMR (CDCl3, 300 MHz): δ 0.26 (s, 9H), 1.60 (m, 3H), 1.96ꢀ
2.01 (m, 2H), 2.82ꢀ2.86 (m, 2H), 3.75 (s, 3H), 3.77 (s, 3H), 6.67ꢀ6.70
(m, 2H), 6.75ꢀ6.78 (m, 1H), 6.75ꢀ6.78 (m, 2H), 7.30ꢀ7.32 (m, 3H),
7.43ꢀ7.44) ppm; 13C NMR (CDCl3, 100 MHz): δ 2.0, 26.0, 31.1, 45.2,
55.7, 56.0, 69.8, 84.5, 93.5, 110.8, 111.3, 116.2, 123.2, 128.2, 131.5, 132.3,
152.0, 153.6 ppm; HRMS m/z Calcd for C23H30O3Si: 382.1957. Found:
382.1964.
Trimethyl((3-methyl-1-phenylundec-1-yn-3-yl)oxy)silane (Table 5,
entry 4). Purified via flash column chromatography using hexanes
yielding 76% as colorless oil. 1H NMR (CDCl3, 300 MHz): δ 0.21 (s,
9H), 0.85ꢀ0.88 (m, 3H), 1.26ꢀ1.29 (m, 10H), 1.51 (m, 5H), 1.64ꢀ
1.70 (m, 2H), 7.28ꢀ7.30 (m, 3H), 7.39ꢀ7.40 (m, 2H) ppm; 13C NMR
(CDCl3, 100 MHz): δ 2.2, 14.4, 23.0, 25.0, 29.6, 29.8, 30.0, 31.5, 32.1,
45.5, 70.1, 84.4, 94.0, 123.4, 128.3, 128.5, 131.6 ppm; HRMS m/z Calcd
for C21H34OSi: 330.2379. Found: 330.2379.
3-Methyl-1-phenylundec-1-yn-3-ol (Table 5, entry 4). Purified via
flash column chromatography using 10% ethyl acetate in hexanes
yielding 22% as a colorless oil. 1H NMR (CDCl3, 300 MHz): δ 0.87ꢀ
0.90 (s, 3H), 1.28ꢀ1.33 (m, 10H), 1.55ꢀ1.57 (m, 10H), 1.72ꢀ1.77 (m,
2H), 2.13 (s, 1H), 7.29ꢀ7.30 (m, 3H), 7.40ꢀ7.43 (m, 2H) ppm; 13C
NMR (CDCl3, 100 MHz): δ 14.4, 22.9, 25.0, 29.5, 29.8, 30.0, 30.1, 32.1,
44.0, 68.9, 83.5, 93.25, 123.0, 128.4, 131.9 ppm; HRMS m/z Calcd for
C18H26O: 258.1984. Found: 258.1981.
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’ ASSOCIATED CONTENT
S
Supporting Information. References to the known com-
b
pounds and copies of 1H and 13C NMR spectra for all alkynylation
products, and HRMS reports for new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
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’ AUTHOR INFORMATION
Corresponding Author
*jverkade@iastate.edu
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