P(PhCH2NCH2CH2)3N: An efficient Lewis base catalyst for the synthesis of propargylic alcohols and Morita-Baylis-Hillman adducts via aldehyde alkynylation

Article abstract of DOI:10.1021/jo9012332

(Chemical Equation Presented) Proazaphosphatrane P(PhCH₂NCH ₂CH₂)₃N (1a) is an efficient catalyst for the addition of aryl trimethylsilyl alkynes to a variety of aromatic, aliphatic, and heterocyclic aldehydes i

Full text of DOI:10.1021/jo9012332

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P(PhCH2NCH2CH2)3N: An Efficient Lewis Base Catalyst for the
Synthesis of Propargylic Alcohols and Morita-Baylis-Hillman Adducts
via Aldehyde Alkynylation
Kuldeep Wadhwa, Venkat Reddy Chintareddy, and John G. Verkade*
Department of Chemistry, 1275 Gilman Hall, Iowa State University, Ames, Iowa 50011
jverkade@iastate.edu
Received June 10, 2009
Proazaphosphatrane P(PhCH2NCH2CH2)3N (1a) is an efficient catalyst for the addition of aryl
trimethylsilyl alkynes to a variety of aromatic, aliphatic, and heterocyclic aldehydes in THF at room
temperature. The reaction conditions are mild and employ a low catalyst loading (ca. 5 mol %). Only
propargylic alcohols were isolated in good to excellent isolated yields when electron-rich, electron-
neutral, heterocyclic, and aliphatic aldehydes were employed, whereas β-branched Morita-Baylis-
Hillman (MBH) type adducts were isolated with electron-deficient aromatic aldehydes after
conventional acid hydrolysis of the TMS ether products. Alkynes containing heterocyclic and
aromatic groups bearing electron-withdrawing or -donating substituents underwent clean addition
to cyclohexanecarboxaldehyde and to electron-rich aromatic aldehydes to give propargylic alcohols
in excellent isolated yields. β-Branched Morita-Baylis-Hillman (MBH) type adducts were isolated
when electron-deficient aromatic aldehydes were employed. Reaction pathways to both types of
products are proposed.
Introduction
(+)-sterpurene, and (-)-chlorothricolide, via carbon-car-
bon bond forming reactions.1-3 Several methods have been
described in the literature over the decades for the synthesis
of propargylic alcohols,4-7 and the most common technique
for their synthesis is via the use of metal bases (e.g., n-BuLi)
to generate the acetylide ion.4-6 Heavy metals have also been
Propargylic alcohols are useful in the synthesis of complex
multifunctional natural products, such as (-)-reveromycin
B, aspinolide B, (()-blastmycinone, (-)-methylenolactocin,
*To whom correspondence should be addressed. Phone: +1 515 294 5023.
Fax: +1 515 294 0105
(1) For a review, see: Cozzi, P. G.; Hilgraf, R.; Zimmermann, N. Eur. J.
Org. Chem. 2004, 4095-4105.
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Roush, W. R.; Spada, A. P. Tetrahedron Lett. 1982, 23, 3773–3776. (c)
Cheon, S. H.; Christ, W. J.; Hawkins, L. D.; Jin, H.; Kishi, Y.; Taniguchi, M.
Tetrahedron Lett. 1986, 27, 4759–4762. (d) Nicolaou, K. C.; Webber, S. E. J.
Am. Chem. Soc. 1984, 106, 3734–3736. (e) Chemin, D.; Linstrumelle, G.
Tetrahedron Lett. 1992, 48, 1943–1952. (f) Vourlournis, D.; Kim, K. D.;
Peterson, J. L.; Magriotis, P. A. J. Org. Chem. 1996, 61, 4848–4852. (g)
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DOI: 10.1021/jo9012332
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Wadhwa et al.
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used in the preparation of propargylic alcohols.5,6 For exam-
ple, Carreira et al. have worked extensively on stereoselective
alkynylations of aldehydes, mainly with Zn metal-based cat-
alytic systems.5 In addition, Ag-, In-, and Ru-based catalyst
systems for terminal alkyne addition have also been reported.6
In recent years, several reports on the Lewis base activa-
tion of a variety of organosilyl reagents associated with the
synthesis of important organic intermediates have ap-
peared.8 Pertinent to the present work on activation of
silyl-terminated alkynes to generate the corresponding acet-
ylide nucleophiles are past examinations of this process.7 In
1976, Kuwajima et al. first reported the use of tetrabutylam-
monium fluoride (3-5 mol %) for the reaction between
1-trimethylsilyl-2-phenylacetylene with aldehydes and
ketones, providing products in yields ranging from 5% to
87%.7a,7b Shioiri et al. reported the use of a quaternary
ammonium fluoride salt derived from cinchonine (10 mol
%) at -20 °C to facilitate the reaction of 1-trimethylsilyl-
2-phenylacetylene with aldehydes, and Morita-Baylis-
Hillman (MBH) type adducts were isolated in 23-92%
yields. Among the eleven aldehydes screened, alkynylation
product was obtained in the case of benzaldehyde and
o-phthalaldehyde in minor quantities, whereas alkynylation
was observed as a major product with p-anisaldehyde and
3,4-dimethoxybenzaldehyde.7c The use of 10 mol % of KOEt
in THF as solvent at 0 °C was reported by Sheidt et al. to
provide good yields of alkynylated product when triethoxy-
silylacetylenes were used as reagents with aldehydes,
ketones, and imines.7d In 2006, Mukaiyama et al. reported
that 10 mol % of [Bu4N][OPh] at -78 °C in THF as solvent
gave 39-100% isolated alkynylated product yields with
aldehydes and four ketone substrates.7e Matsukawa et al.
reported the synthesis of propargylic alcohols using tris-
(2,4,6-trimethoxyphenyl)phosphine (10 mol %) as a catalyst
for reaction between 1-trimethylsilyl-2-phenylacetylene and
various aldehydes in DMF as solvent at 100-120 °C provid-
ing products in 74-96% isolated yield.7f Tetrabutylammo-
nium triphenyldifluorosilicate (10 mol %) was reported to
promote the reaction between 1-trimethylsilyl-2-phenylace-
tylene and benzaldehyde, giving the alkynylated product in
81% yield.7g However, the generality of this process remains
to be established.7g The use of tetraphenylphosphonium
FIGURE 1. Proazaphosphatranes.
SCHEME 1. 1a-Catalyzed Alkynylation and MBH Reactions
hydrogen difluoride (3-8 mol %) to catalyze the reaction
of 1-trimethylsilyl-2-phenylacetylene with one aldehyde and
three ketones in DMF solvent at 50 °C provided moderate
product yields (46-64%).7h Corey et al. utilized a 1:1 mix-
ture of CsF and CsOH for silyl activation of 1-trimethylsilyl-
2-phenylacetylene in the alkynylation of two aldehydes,
which gave good product yields (85 and 90%), although
1.6 equiv of fluoride ion was required.7i
Discovered for the first time in our laboratories, proaza-
phosphatranes of the type shown in Figure 1 are strongly
basic, with pKa values of 32-34 in CH3CN for their P-
protonated Nbasal f P transannulated conjugated acids.9 If
such transannulation occurs during a catalytic cycle, the
nucleophilicity of the phosphorus center would be enhanced.
The catalytic activation of silicon centers by the phosphorus
of proazaphosphatranes has been invoked, for example, for
silylation of alcohols with silyl chloride,10a,10b for the synth-
esis of cyanohydrins by the addition of trimethylsilyl nitrile
to carbonyl compounds,10c,10d for desilylation of TBDMS
ethers,10e for nucleophilic aromatic substitution of aryl
fluorides with aryl silylethers,10f,10g for allylation of aromatic
aldehydes,10h and for the reduction of aldehydes and ketones
with poly(methylhydrosiloxane).10i
(4) (a) Viehe, H. G.; Reinstein, M. Chem. Ber. 1962, 95, 2557–2562.(b)
Brandsma, L. Preparative Acetylenic Chemistry, 2nd ed.; Elsevier: Amsterdam,
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1984, 49, 1728–1732.
€
(5) (a) Frantz, D. E.; Fassler, R.; Tomooka, C. S.; Carreira, E. M. Acc.
Results and Discussion
Chem. Res. 2000, 33, 373–381. (b) Anand, N. K.; Carreira, E. M. J. Am.
€
Chem. Soc. 2001, 123, 9687–9688. (c) Frantz, D. E.; Fassler, R.; Carreira, E.
M. J. Am. Chem. Soc. 2000, 122, 1806–1807. (d) Boyall, D.; Frantz, D. E.;
Carreira, E. M. Org. Lett. 2002, 4, 2605–2606.
In the present work, we report the use of proazapho-
sphatrane 1a as an efficient catalyst for the synthesis of
(6) (a) Takita, R.; Fukuta, Y.; Tsuji, R.; Ohshima, T.; Shibasaki, M. Org.
Lett. 2005, 7, 1363–1366. (b) Wei, C.; Li, C.-J. Green Chem. 2002, 4, 39–41. (c)
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New Aspects of Phosphorus Chemistry II. In Top. Curr. Chem. 2002, 233, 1-44.
(b) Verkade, J. G.; Kisanga, P. B. Tetrahedron 2003, 59, 7819–7858. (c) Verkade,
J. G.; Kisanga, P. B. Aldrichim. Acta 2004, 37, 3–14. (d) Urgaonkar, S.; Verkade,
J. G. Spec. Chem. 2006, 26, 36–39.
(10) (a) D’Sa, B. A.; Verkade, J. G. J. Am. Chem. Soc. 1996, 118, 12832–
12833. (b) D’Sa, B. A.; McLeod, D.; Verkade, J. G. J. Org. Chem. 1997, 62,
5057–5061. (c) Wang, Z.; Fetterly, B.; Verkade, J. G. J. Organomet. Chem.
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TABLE 1. Survey of Proazaphosphatranes as Catalysts for the Synthesis of Propargylic Alcoholsa
entry
catalyst
mol (%)
2 (equiv)
temp (°C)
yield of 3a (%)b
yield of 3b (%)b
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1b
1c
1d
none
5
3
5
5
5
5
5
-
1.5
1.5
2.0
2.0
2.0
2.0
2.0
2.0
25
25
25
0
25
25
25
25
79
20
6
-
2
82 (27-100)c-i
81
72
2
10j
42
69
-
-
n.r.k
n.r.k
aReaction conditions: aldehyde (2.0 mmol), THF (2 mL), 24 h, followed by 1 N HCl (3 mL). bIsolated yield after silica gel column chromatography.
c76% yield with 3 mol % of nBu4NF (ref 7a). d76% yield with 5 mol % of nBu4NF (ref 7b). e27% yield with 10 mol % of the quaternary ammonium
fluoride salt derived from cinchonine (ref 7c). f100% yield with 10 mol % of NBu4(OPh) (ref 7e). g95% yield with 10 mol % of tris(2,4,6-
i
trimethoxyphenyl)phosphine (ref 7f). h81% yield with 10 mol % of nBu4N(Ph3SiF2) (ref 7g). 64% yield with 3 mol % of Ph4P(HF2) (ref 7h).
jDetermined by 1H NMR spectroscopic integration. kNo reaction.
propargylic alcohols using electron-rich, electron-neutral,
heterocyclic, and aliphatic aldehydes with trimethylsilyl-
acetylenes, whereas β-branched Morita-Baylis-Hillman
(MBH) type adducts are obtained as the sole products in
the case of electron-deficient aromatic aldehydes (Scheme 1).
We first screened the reaction between benzaldehyde and
1-trimethylsilyl-2-phenylacetylene (2) (as shown in the reac-
tion scheme in Table 1) using 1a as a catalyst. With 5 mol %
catalyst and 1.5 equiv of alkyne 2 in THF solvent, complete
of alkynylation products, except in the case of m-tolualdehyde,
wherein 6% of the MBH adduct was isolated. Pleasingly,
excellent isolated yields with no observable MBH side pro-
duct were obtained when sterically hindered aldehydes, such
as o-phenylbenzaldehyde (Table 2, entry 5), o-tolualdehyde
(Table 2, entry 6), and 2,6-dimethylbenzaldehyde (Table 2,
entry 7), were employed under our conditions. The versatility
of our protocol was extended to the heterocyclic aldehyde,
thiophene-2-carboxaldehyde, providing a 91% yield of alky-
nylation product (Table 2, entry 8). Unfortunately, pyridine-
and furan-2-carboxaldehyde gave complicated mixtures, the
reason for which is not presently clear (Table 2, entries 9 and
10, respectively).
After screening aromatic aldehydes, we tested several
aliphatic examples (Table 3). All the substrates in this table
selectively gave propargylic alcohols, and MBH-type adduct
formation was not observed. We conjecture that this is
because the intermediate E (shown in Scheme 2) required
for MBH-type adduct formation cannot be stabilized by
aliphatic aldehydes (vide infra). Cyclohexanecarboxalde-
hyde (Table 3, entry 1), isobutyraldehyde (Table 3, entry 2)
and heptaldehyde (Table 3, entry 3) led to generally excellent
isolated yields of alkynylated product (96%, 94%, and 84%,
respectively). Interestingly, catalyst 1a was efficient in pro-
ducing a high yield of alkynylation product with a long-chain
unsaturated aliphatic aldehyde (Table 3, entry 4).
We next screened several electron-poor aldehydes and
observed that β-branched MBH-type adducts formed exclu-
sively under our conditions (Table 4). This may be attributed
to the formation of the stabilized intermediate E shown in
Scheme 2 (vide infra). Acid-sensitive electron-deficient meth-
yl 4-formylbenzoate selectively gave the MBH adduct in
good isolated yield (Table 4, entry 1). Electron-poor halo-
gen-containing 3-iodobenzaldehyde (Table 4, entry 2) and
4-bromobenzaldehyde (Table 4, entry 4) also stereoselectively
afforded the MBH-type adducts in good isolated yields and
electron-deficient 4-(trifluoromethyl)benzaldehyde yielded
the MBH adduct in excellent isolated yield (Table 4, entry 3).
We then screened alkynes with various electron-withdraw-
ing, electron-donating, and heterocyclic functionalities.
Gratifyingly they all tolerated our reaction conditions well,
1
conversion to a mixture of 3a and 3b was observed by H
NMR spectroscopy. Silica gel column chromatography
allowed 3a to be isolated in 79% yield and the MBH-type
adduct 3b in 6% yield (Table 1, entry 1). We then attempted
to minimize formation of the MBH product 3b by lowering
the catalyst 1a loading to 3 mol % (Table 1, entry 2).
Unfortunately, the corresponding alkynylation product 3a
was isolated in only 20% yield and only starting aldehyde
was recovered from the remainder of the reaction mixture.
Gratifyingly, increasing the trimethylsilyl alkyne to 2 equiv
(Table 1, entry 3) increased the yield of the alkynylation
product 3a to 82% with only a 2% yield of the MBH side
product 3b. Lowering the temperature to 0 °C had no
significant effect on the ratio of the two products (Table 1,
entry 4). We then screened proazaphosphatranes 1b-d in the
reaction in Table 1 using the best catalytic conditions
reported in this table (entry 3) and the results are recorded
in Table 1, entries 5-7. From these results, it is seen that 1a
functioned best for making 3a under the conditions in entry 3
of Table 1. No reaction was observed under our conditions in
the absence of catalyst (Table 1, entry 8).
To examine the scope of this methodology a wide variety
of aldehydes consisting of electron-rich, electron-poor, het-
erocyclic, and aliphatic examples were screened under the
optimized conditions in Table 1, entry 3, and the results are
summarized in Tables 2 and 3. Electron-deficient o-fluoro-
benzaldehyde reacted efficiently with alkyne 2 to yield
the desired alkynylation product in an excellent isolated
yield (Table 2, entry 1). Aldehydes with electron-donating
substituents, such as p-tolualdehyde (Table 2, entry 2),
m-methoxybenzaldehyde (Table 2, entry 3), and m-tolualde-
hyde (Table 2, entry 4), resulted in very good isolated yields
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TABLE 2. Reactions of Electron-Rich Aromatic and Heterocyclic Aldehydes with 1-Trimethylsilyl-2-phenylacetylene (2), Using Proazaphosphatrane 1a
as the Catalysta
aReaction conditions: aldehyde (2.0 mmol), 2 (4.0 mmol), 1a (5 mol %), THF (2 mL), rt, 24 h, followed by 1 N HCl (3 mL). bIsolated yield after column
chromatography. c10 mol % of NBu4(OPh) (ref 7e). dA complex mixture was observed that we were unable to separate.
giving good to excellent isolated yields of alkynylation
products (Table 5). We also examined substituents on the
alkyne phenyl group. With an electron-donating methoxy
group, an excellent isolated product yield of 92% was
realized (Table 5, entry 1). An electron-deficient trifluoro-
methyl group at the para position (Table 5, entry 2) led to a
good isolated yield of the desired product and halogens (both
bromo and chloro at ortho and meta positions, respectively)
resulting in good isolated product yields (Table 5, entries
4 and 5). Heterocyclic functionalities (such as pyridyl or thio-
phenyl) on the alkynes also underwent complete conversion,
giving good to excellent isolated yields of the desired pro
duct under our reaction conditions (Table 5, entries 3 and 6).
The use of terminally silylated aliphatic alkynes, such as hex-
1-ynyltrimethylsilane (Table 5, entry 7), produced no ob-
servable product with the reaction conditions reported in
Table 5, footnote a.
Electron-rich aromatic aldehydes were also evaluated in
the presence of a variety of aromatic-substituted alkynes
(Table 6). Bulky 2,6-dimethylbenzaldehyde reacted with the
electron-rich alkyne in entry 1 of Table 6 giving a quantitative
conversion to the alkynylated product in excellent isolated
yield (92%). A terminal silylated aromatic alkyne substituted
with a bromine at the ortho or a chloro group at the meta
position afforded the desired products with 2-biphenylcar-
boxaldehyde and o-tolualdehyde (Table 6, entries 2-4) in
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TABLE 3. Reactions of Aliphatic Aldehydes with 1-Trimethylsilyl-2-
TABLE 4. Reactions of Electron-Deficient Aldehydes with 1-Tri-
phenylacetylene (2), Using Proazaphosphatrane 1a as the Catalysta
methylsilyl-2-phenylacetylene (2), Using 1a as the Catalysta
aReaction conditions: aldehyde (2.0 mmol), 2 (4.0 mmol), 1a (5 mol %),
THF (2 mL), rt, 24 h, followed by 1 N HCl (3 mL). bIsolated yield after
column chromatography. cWith 10 mol % of NBu4(OPh) (ref 7e). dWith
3.2 equiv of a 1:1 mixture of CsOH/CsF (ref 7i). e88% yield with 10 mol %
of tris(2,4,6-trimethoxyphenyl)phosphine (ref 7f).
aReaction conditions: aldehyde (2.0 mmol), 2 (4.0 mmol), 1a (5 mol
%), THF (2 mL), rt, 24 h, followed by 1 N HCl (3 mL). bIsolated yield
after column chromatography.
SCHEME 2. Proposed Mechanism for the Alkynylation and
MBH Reactions
good to moderate isolated yields. o-Tolualdehyde in the
presence of an electron-deficient or electron-rich alkyne
(having a p-trifluoromethyl group or a p-methoxy group on
the terminal phenylacetylene) gave good isolated yields of the
alkynylated product (Table 6, entries 5 and 6, respectively).
Heterocyclic alkynes, such as thiophenyl and pyridyl, also
underwent complete conversion to give modest to good
isolated yields of the desired product with o-tolualdehyde
under our reaction conditions (Table 6, entries 7 and 8,
respectively).
In accord with the results shown in Table 4, we obtained
MBH-type adducts stereoselectively as the cis-isomer (as
determined by 2D NOESY NMR, Table 4, entry 2) when
the reaction was carried out between electron-deficient alde-
hydes and substituted terminally silylated alkynes (Table 7).
Here the product yields ranged from modest (65%) to
moderate (74%).
A rationale for the selectivity in the formation of the two
different types of products we observed can be given by using
a combination of mechanisms for the two reactions11
(Scheme 2). After activation of the silyl group of 2 by
proazaphosphatrane 1a to form the activated pentacoordi-
nated silicon species A, A dissociates to form the cationic
intermediate B and the acetylide counteranion. To obtain
some insight into this pathway, we carried out 29Si NMR
experiments at -40 °C in which we combined 1-trimethylsi-
lyl-2-phenylacetylene (δ 29Si NMR, -18.5 ppm in THF) with
proazaphosphatrane 1a in equimolar ratio in THF. A new
29Si peak appeared at δ 7.17 ppm, which was attributed to the
tetracoordinate silicon species B from which the acetylide
anion had been displaced. This chemical shift accords with
the previously reported value for a 1:1 mixture of TMSCN
and 1d in C6D6 (δ 29Si 7.5 ppm) in which CN- had pre-
sumably been displaced.10c If the anion had not been dis-
placed in both cases, an upfield rather than a downfield shift
from the parent TMSCN molecule would have been ob-
served since the silicon would have become 5-coordinate.10c
(11) Yoshizawa, K.; Shioiri, T. Tetrahedron Lett. 2006, 47, 757–761.
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TABLE 5. Reactions of Cyclohexanecaboxaldehyde with Substituted 1-Trimethylsilylacetylenes, Using 1a as the Catalysta
aReaction conditions: aldehyde (2.0 mmol), 2 (4.0 mmol), 1a (5 mol %), THF (2 mL), rt, 24 h, followed by 1 N HCl (3 mL). bIsolated yield after column
chromatography. cNo reaction.
We used similar reasoning to account for the formation of
both R- and γ-addition products in the reaction of crotyl-
trimethylsilane with aldehydes in the presence of 1b.10h The
acetylide ion in Scheme 2 then nucleophilically attacks
the aldehyde to give the ionic intermediate C. Transfer of
the silyl group to the alkoxide regenerates catalyst 1a and the
alkynylated product D is formed concomitantly. In the case
of electron-deficient aldehydes, D can undergo a deprotona-
tion step to form intermediate E, followed by rearrangement
of E to give the allenic anion F. Anion F could abstract a
proton from D to generate E and give allene G, which has
been previously isolated as a crude product and which, after
addition of an aldehyde, produced H, which in turn was
converted to the MBH-type adduct upon acid hydrolysis.11
the catalyst loading to 10 mol % resulted in a 1:1 ratio of
alkynylation to MBH product. We believe our protocol will
find many applications in organic syntheses, including the
synthesis of a variety of useful polyfunctional aromatics.
The use of low metal-free catalyst loading (ca. 5 mol %), the
high isolated product yields, the broad scope, and room
temperature reaction conditions are attractive features of
this protocol.
Experimental Section
General Procedure for Alkynylation and MBH Reactions. A
flat-bottomed screw-capped vial was charged with proazapho-
sphatrane catalyst 1a (44.4 mg, 0.1 mmol, 5 mol %) in a
nitrogen-filled glovebox. To the vial was added, at room tem-
perature, 2.0 mL of anhydrous THF, followed by the addition of
aldehyde (2.0 mmol). The resulting solution was stirred at room
temperature for 15 min and then aryl(trimethylsilyl)acetylene
(4.0 mmol) was added over a period of 2 min. Progress of the
reaction was monitored by TLC. The reaction mixture was
stirred for 24 h and quenched with 3 mL of an aq solution of
HCl (1 N). The mixture was stirred for an additional 1 h and
then neutralized with saturated aq NaHCO3 solution. The crude
product was extracted with CH2Cl2 (3 Â 30 mL) and the
combined organic extracts were dried over anhydrous MgSO4
(ca. 2.0 g). The crude product was purified by column chroma-
tography with 30% EtOAc/hexane as eluent.
Conclusion
We have found that the nonionic Lewis basic proazapho-
sphatrane 1a is an efficient catalyst for addition of 1-aryl-
2-(trimethylsilyl)acetylenes to aldehydes at room tempera-
ture. The selectivity of this reaction for the synthesis of
propargylic alcohols is facilitated by electron-rich, elec-
tron-neutral, heterocyclic, and aliphatic aldehydes, whereas
MBH-type adducts are isolated when electron-deficient al-
dehydes are employed, regardless of the substituents on the
propargylic alcohol and despite the use of excess alkyne.
Attempts to maximize yields of MBH-type adducts by using
a ratio of 0.5 equiv of alkyne to aldehyde and by increasing
1-(2,6-Dimethylphenyl)-3-phenylprop-2-yn-1-ol (Table 2, en-
try 7). The general reaction procedure described in the paper was
followed for the synthesis and purification; the product was
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TABLE 6. Reactions of Electron-Rich Aromatic Aldehydes with Variously Substituted 1-Trimethylsilylacetylenes, Using 1a as Catalysta
aReaction conditions: aldehyde (2.0 mmol), 2 (4.0 mmol), 1a (5 mol %), THF (2 mL), rt, 24 h, followed by 1 N HCl (3 mL). bIsolated yield after column
chromatography.
afforded as a colorless oil in 96% isolated yield. 1H NMR
(CDCl3, 400 MHz) δ 7.49-7.46 (m, 2H), 7.34-7.33 (m, 3H),
7.16-7.15 (m, 1H), 7.09-7.08 (m, 2H), 6.16 (s, 1H), 2.62 (s,
6H), 2.52 (s, 1H) ppm; 13C NMR (CDCl3, 100.6 MHz) δ 136.9,
136.6, 131.9, 129.5, 128.7, 128.5, 128.4, 123.0, 88.9, 86.1, 61.1,
20.8 ppm; HRMS m/z calcd for C17H16O 236.12011, found
236.12053.
400 MHz) δ 7.96 (d, 2H, J=8.0 Hz), 7.76 (d, 2H, J=8.0 Hz), 7.61
(d, 2H, J=8.0 Hz), 7.50 (d, 2H, J=8.0 Hz), 7.07 (s, 1H), 7.03
(s, 4H), 5.81 (s, 1H), 3.94 (s, 1H), 3.86 (s, 3H), 3.83 (s, 3H) ppm;
13C NMR (CDCl3, 100.6 MHz) δ 199.8, 166.9, 166.3 146.2,
141.1, 139.5, 134.7, 133.9, 133.9, 130.1, 129.9, 129.6, 129.3, 129.2,
128.9, 128.5, 126.6, 76.6, 52.6, 52.4 ppm; HRMS m/z calcd for
C26H22O2 430.14164, found 430.14262.
1-Phenyltridec-12-en-1-yn-3-ol (Table 3, entry 4). The general
reaction procedure described in the paper was followed for the
synthesis and purification; the product was afforded as a color-
less oil in 79% isolated yield. 1H NMR (CDCl3, 400 MHz)
δ 7.44-7.42 (m, 2H), 7.31-7.30 (m, 3H), 5.86-5.76 (m, 1H),
5.01-4.91 (m, 2H), 4.59 (q, 1H, J=4.0 Hz), 2.03 (q, 2H, J=
8.0 Hz), 1.85 (d, 1H, J=4.0 Hz), 1.81-1.77 (m, 2H), 1.52-1.30
(m, 12H) ppm; 13C NMR (CDCl3, 100.6 MHz) δ 139.4, 131.9,
128.6, 128.5, 122.9, 114.3, 90.4, 85.1, 63.3, 38.1, 34.1, 29.7, 29.6,
29.5, 29.4, 29.2, 25.5 ppm; HRMS m/z calcd for C19H26O
270.19835, found 270.19875.
(Z)-2-(Hydroxy(3-iodophenyl)methyl)-1-(3-iodophenyl)-3-phenyl-
prop-2-en-1-one (Table 4, entry 2). The general reaction procedure
described in the paper was followed for the synthesis and purifica-
tion; the product was afforded as a colorless oil in 78% isolated yield.
1H NMR (CDCl3, 400 MHz): δ 7.79 (s, 1H), 7.78 (s, 1H), 7.60
(d, 1H, J=8.0 Hz), 7.56-7.51 (m, 2H), 7.35 (d, 1H, J=8.0 Hz),
7.08-7.00 (m, 7H), 6.86 (t, 1H, J=8.0 Hz), 5.64 (s, 1H), 3.40 (s, 1H)
ppm; 13C NMR (CDCl3, 100.6 MHz) δ 198.8, 143.3, 142.1, 140.9,
138.4, 137.8, 137.3, 135.6, 134.7, 133.6, 130.5, 130.1, 129.2, 128.8,
128.8, 128.5, 126.0, 94.8, 94.2, 76.1 ppm; HRMS m/z calcd for
C22H16I2O2 565.92398, found 565.92536.
(Z)-2-(Hydroxy(4-(methoxycabonyl)phenyl)methyl)-3-phenyl-
1-(4-(methoxycarbonyl)phenyl)prop-2-en-1-one (Table 4, entry 1).
The general reaction procedure described in the paper was
followed for the synthesis and purification; the product was
afforded as a yellow oil in 85% isolated yield. 1H NMR (CDCl3,
(Z)-2-(Hydroxy(4-(trifluoromethyl)phenyl)methyl)-3-phenyl-1-
(4-(trifluoromethyl)phenyl)prop-2-en-1-one (Table 4, entry 3). The
general reaction procedure described in the paper was followed
for the synthesis and purification; the product was afforded as a
colorless oil in 93% isolated yield. 1H NMR (CD3CN, 400 MHz)
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TABLE 7. Reactions of Electron-Deficient Aldehydes with Substituted 1-Trimethylsilylacetylenes, Using 1a as Catalysta
aReaction conditions: aldehyde (2.0 mmol), 2 (4.0 mmol), 1a (5 mol %), THF (2 mL), rt, 24 h, followed by 1 N HCl (3 mL). bIsolated yield after column
chromatography.
δ 7.83 (d, 2H, J=8.0 Hz), 7.64 (s, 4H), 7.55 (d, 3H, J=8.0 Hz),
7.18 (s, 1H), 7.13 (s, 4H), 5.79 (s, 1H), 4.26 (d, 1H, 4.0 Hz) ppm;
13C NMR (CD3CN, 100.6 MHz) δ 198.4, 146.6, 142.4, 139.7,
135.2, 133.4 (q, J=32.0 Hz), 131.8, 131.7 (q, J=32.0 Hz), 129.9,
129.0, 128.5, 127.6, 125.4 (q, J=4.0 Hz), 125.3 (q, J=4.0 Hz),
124.5 (q, J=273.0 Hz), 123.9 (q, J=270.0 Hz), 75.2 ppm; 19F
NMR (CDCl3, 376 MHz) δ -63.4, -64.1 ppm; HRMS m/z calcd
for C24H16F6O2 450.10545, found 450.10641.
(m, 4H), 7.31-7.26 (m, 4H), 7.08-7.06 (m, 5H), 6.97 (s, 1H),
5.67 (s, 1H), 3.28 (d, 1H, J=4.0 Hz) ppm; 13C NMR (CDCl3,
100.6 MHz) δ 199.4, 141.1, 140.1, 134.9, 134.7, 133.2, 131.9,
131.8, 131.0, 129.2, 128.9, 128.8, 128.5, 128.4, 122.2, 76.4 ppm;
HRMS m/z calcd for C22H16Br2O2 469.95170, found 469.95310.
1-Cyclohexyl-3-(4-methoxyphenyl)prop-2-yn-1-ol (Table 5,
entry 1). The general reaction procedure described in the paper
was followed for the synthesis and purification; the product
was afforded as a colorless oil in 92% isolated yield. 1H NMR
(CDCl3, 400 MHz) δ 7.38 (d, 1H, J=8.0 Hz), 7.25-7.24 (m,
1H), 6.90-6.83 (m, 2H), 4.42 (d, 1H, J=4.0 Hz), 3.85 (s, 3H),
2.47 (br s, 1H), 1.94-1.66 (m, 6H), 1.24-1.17 (m, 5H) ppm;
13C NMR (CDCl3, 100.6 MHz) δ 160.2, 133.8, 129.9, 120.6,
(Z)-1-(4-Bromophenyl)-2-((4-bromophenyl)(hydroxy)methyl)-
3-phenylprop-2-en-1-one (Table 4, entry 4). The general reaction
procedure described in the paper was followed for the synthesis
and purification; the product was afforded as a colorless oil in
1
79% isolated yield. H NMR (CDCl3, 400 MHz) δ 7.48-7.42
6688 J. Org. Chem. Vol. 74, No. 17, 2009

Wadhwa et al.
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112.2, 110.8, 93.8, 82.0, 67.9, 56.0, 44.5, 28.9, 28.4, 26.7,
26.2 ppm; HRMS m/z calcd for C16H20O2 244.14632, found
244.14668.
7.51-7.40 (m, 8H), 7.34-7.17 (m, 3H), 5.74 (s, 1H), 2.47 (s, 1H)
ppm; 13C NMR (CDCl3, 100.6 MHz) δ 141.2, 140.4, 138.2,
133.8, 132.6, 130.4, 129.9, 129.8, 128.5, 128.1, 127.7, 127.2,
125.9, 124.9, 94.5, 85.3, 62.5 ppm; HRMS m/z calcd for
C21H15BrO 362.03062, found 362.03139.
3-(2-Bromophenyl)-1-o-tolylprop-2-yn-1-ol (Table 6, entry 3).
The general reaction procedure described in the paper was
followed for the synthesis and purification; the product was
afforded as a yellow solid in 78% isolated yield. 1H NMR
(CDCl3, 400 MHz) δ 7.84-7.81 (m, 1H), 7.59-7.48 (m, 2H),
7.28-7.16 (m, 5H), 5.88 (d, 1H, J=4.0 Hz), 2.53 (s, 3H), 2.46 (d,
1H, J=4.0 Hz) ppm; 13C NMR (CDCl3, 100.6 MHz) δ 138.3,
136.3, 133.8, 132.6, 131.0, 129.9, 128.8, 127.2, 127.0, 126.5,
125.9, 124.9, 93.4, 85.3, 63.3, 19.3 ppm; HRMS m/z calcd for
C16H13BrO 300.01497, found 300.01572.
3-(3-Chlorophenyl)-1-o-tolylprop-2-yn-1-ol (Table 6, entry 4).
The general reaction procedure described in the paper was
followed for the synthesis and purification; the product was
afforded as a colorless oil in 72% isolated yield. 1H NMR
(CDCl3, 400 MHz) δ 7.70 (t, 1H, J = 4.0 Hz), 7.45 (s, 1H),
7.34-7.20 (m, 6H), 5.82 (s, 1H), 2.49 (s, 4H) ppm; 13C NMR
(CDCl3, 100.6 MHz) δ 138.3, 136.2, 134.4, 131.8, 131.1, 130.1,
129.8, 129.1, 128.8, 126.8, 126.5, 124.4, 90.1, 85.3, 63.1, 19.3
ppm; HRMS m/z calcd for C16H13ClO 256.06549, found
256.06600.
1-Cyclohexyl-3-(4-(trifluoromethyl)phenyl)prop-2-yn-1-ol
(Table 5, entry 2). The general reaction procedure described in
the paper was followed for the synthesis and purification;
the product was afforded as a colorless oil in 84% isolated yield.
1H NMR (CDCl3, 400 MHz) δ 7.55-7.49 (m, 4H), 4.38 (d, 1H,
J=4.0 Hz), 2.37 (br s, 1H), 1.93-1.66 (m, 6H), 1.28-1.11 (m,
5H) ppm; 13C NMR (CDCl3, 100.6 MHz) δ 132.1, 130.2 (q, J=
30.2 Hz), 126.8, 125.4, 125.4, 125.3, 124.0 (q, J=271.6 Hz), 92.0,
84.5, 67.8, 44.4, 28.9, 28.4, 26.6, 26.1 ppm; 19F NMR (CDCl3,
376 MHz) δ -63.3 ppm; HRMS m/z calcd for C16H17F3O
282.12314, found 282.12345.
1-Cyclohexyl-3-(pyridin-3-yl)prop-2-yn-1-ol (Table 5, entry 3).
The general reaction procedure described in the paper was
followed for the synthesis and purification; the product was
afforded as a colorless oil in 88% isolated yield. 1H NMR
(CDCl3, 400 MHz) δ 8.73 (s, 1H), 8.49 (d, 1H, J = 4.0 Hz),
7.71 (d, 1H, J=8.0 Hz), 7.26-7.22 (m, 1H), 4.37 (d, 1H, J=
4.0 Hz), 4.01 (br s, 1H), 1.91-1.66 (m, 6H), 1.28-1.11 (m, 5H)
ppm; 13C NMR (CDCl3, 100.6 MHz) δ 152.2, 148.4, 139.1,
123.3, 120.5, 115.5, 94.0, 82.0, 67.5, 44.5, 28.9, 28.6, 26.6, 26.2,
26.1 ppm; HRMS m/z calcd for C14H17NO 215.13101, found
215.13147.
3-(2-Bromophenyl)-1-cyclohexylprop-2-yn-1-ol (Table 5, entry 4).
The general reaction procedure described in the paper was followed
for the synthesis and purification; the product was afforded as a
yellow oil in 86% isolated yield. 1HNMR(CDCl3, 400 MHz) δ7.56
(d, 1H, J=8.0 Hz), 7.45 (d, 1H, J=4.0 Hz), 7.23 (t, 1H, J=8.0 Hz),
7.16 (t, 1H, J=8.0 Hz), 4.44 (s, 1H), 2.30 (d, 1H, J=4.0 Hz), 1.94-
1.69 (m, 6H), 1.27-1.18 (m, 5H) ppm; 13C NMR (CDCl3, 100.6
MHz) δ 133.7, 132.6, 129.7, 127.2, 125.8, 125.1, 94.3, 84.3, 67.9,
44.5, 28.9, 28.3, 26.7, 26.2, 26.1 ppm; HRMS m/z calcd for
C15H17BrO 292.04627, found 292.04691.
3-(3-Chlorophenyl)-1-cyclohexylprop-2-yn-1-ol (Table 5, entry 5).
The general reaction procedure described in the paper was followed
for the synthesis and purification; the product was afforded as a
yellow oil in 84% isolated yield. 1HNMR(CDCl3, 400 MHz) δ7.41
(s, 1H), 7.29-7.20 (m, 3H), 4.37 (s, 1H), 2.10 (s, 1H), 1.92-1.68 (m,
6H), 1.29-1.10 (m, 5H) ppm; 13C NMR (CDCl3, 100.6 MHz)
δ 134.3, 131.7, 130.0, 129.7, 128.8, 124.7, 90.8, 84.5, 67.8, 44.5, 28.9,
28.5, 26.6, 26.1, 26.1 ppm; HRMS m/z calcd for C15H17ClO
248.09679, found 248.09739.
1-o-Tolyl-3-(4-(trifluoromethyl)phenyl)prop-2-yn-1-ol (Table 6,
entry 5). The general reaction procedure described in the paper
was followed for the synthesis and purification; the product was
afforded as a colorless oil in 83% isolated yield. 1H NMR (CDCl3,
400 MHz) δ 7.71 (t, 1H, J=4.0 Hz), 7.59-7.54 (m, 4H), 7.29-7.21
(m, 3H), 5.84 (d, 1H, J=4.0 Hz), 2.52 (d, 1H, J=8.0 Hz), 2.50 (s,
3H) ppm; 13C NMR (CDCl3, 100.6 MHz) δ 138.2, 136.2, 132.4,
131.6, 130.5 (q, J=33 Hz), 128.9, 126.8, 126.6, 125.5, 125.4, 121.3
(q, J=270 Hz), 91.3, 85.3, 63.1, 19.2 ppm; 19F NMR (CDCl3, 376
MHz) δ -63.26 ppm; HRMS m/z calcd for C17H13F3O 290.0906,
found 290.0918.
3-(4-Methoxyphenyl)-1-o-tolylprop-2-yn-1-ol (Table 6, entry 6).
The general reaction procedure described in the paper was followed
for the synthesis and purification; the product was afforded as a
1
yellow oil in 86% isolated yield. H NMR (CDCl3, 400 MHz)
δ 7.82-7.80 (m, 1H), 7.43 (d, 1H, J=8.0 Hz), 7.32-7.21 (m, 4H),
6.92-6.85 (m, 2H), 5.87 (d, 1H, J=4.0 Hz), 3.85 (s, 3H), 3.70 (d,
1H, J=4.0 Hz), 2.51 (s, 3H) ppm; 13C NMR (CDCl3, 100.6 MHz)
δ 160.4, 138.7, 136.4, 133.8, 130.9, 130.2, 128.5, 127.1, 126.4, 120.6,
110.9, 93.0, 83.1, 63.3, 56.0, 19.2 ppm; HRMS m/z calcd for
C17H16O2 252.1148, found 252.1150.
3-(Thiophen-3-yl)-1-o-tolylprop-2-yn-1-ol (Table 6, entry 7).
The general reaction procedure described in the paper was
followed for the synthesis and purification; the product was
afforded as a yellow oil in 67% isolated yield. 1H NMR (CDCl3,
400 MHz) δ 7.70 (t, 1H, J=4.0 Hz), 7.28-7.20 (m, 5H), 7.98 (t,
1H, J=4.0 Hz), 5.85 (d, 1H, J=8.0 Hz), 2.49 (s, 3H), 2.22 (d, 1H,
J=8.0 Hz) ppm; 13C NMR (CDCl3, 100.6 MHz) δ 138.3, 136.2,
132.6, 131.1, 128.8, 127.6, 127.2, 126.8, 126.5, 122.6, 92.5, 80.1,
63.4, 19.3 ppm; HRMS m/z calcd for C14H12OS 228.0605, found
228.0609.
3-(Pyridin-3-yl)-1-o-tolylprop-2-yn-1-ol (Table 6, entry 8). The
general reaction procedure described in the paper was followed for
the synthesis and purification; the product was afforded as a yellow
solid in 88% isolated yield. 1H NMR (CDCl3, 400 MHz) δ 8.73
(s, 1H), 8.42 (d, 1H, J=8.0 Hz), 7.71-7.69 (m, 2H), 7.26-7.20 (m,
4H), 5.84 (s, 1H), 5.35 (br s, 1H), 2.48 (s, 3H) ppm; 13C NMR
(CDCl3, 100.6 MHz) δ 152.1, 148.4, 139.2, 138.7, 136.0, 130.9,
128.5, 126.7, 126.4, 123.4, 120.4, 93.7, 82.4, 62.5, 19.3 ppm; HRMS
m/z calcd for C15H13NO 223.0992, found 223.0997.
1-Cyclohexyl-3-(thiophen-3-yl)prop-2-yn-1-ol (Table 5, entry 6).
The general reaction procedure described in the paper was followed
for the synthesis and purification; the product was afforded as a
1
yellow oil in 91% isolated yield. H NMR (CDCl3, 400 MHz)
δ 7.24-7.19 (m, 2H), 6.97-6.94 (m, 1H), 4.38 (d, 1H, J=8.0 Hz),
2.31 (s, 1H), 1.92-1.63 (m, 6H), 1.30-1.08 (m, 5H) ppm; 13CNMR
(CDCl3, 100.6 MHz) δ 132.3, 127.1, 122.9, 93.5, 79.1, 68.0, 44.4,
28.9, 28.5, 26.6, 26.1 ppm; HRMS m/z calcd for C13H16OS
220.09218, found 220.09246.
1-(2,6-Dimethylphenyl)-3-(4-methoxyphenyl)prop-2-yn-1-ol
(Table 6, entry 1). The general reaction procedure described in
the paper was followed for the synthesis and purification; the
product was afforded as a yellow oil in 92% isolated yield. 1H
NMR (CDCl3, 400 MHz) δ 7.39 (d, 1H, J=8.0 Hz), 7.28 (t,
1H, J=8.0 Hz), 7.12-7.04 (m, 3H), 6.91-6.39 (m, 2H), 6.19 (s,
1H), 3.83 (s, 3H), 2.69 (s, 1H), 2.62 (s, 6H) ppm; 13C NMR
(CDCl3, 100.6 MHz) δ 160.4, 137.1, 136.7, 133.8, 130.2, 129.4,
128.3, 120.6, 112.2, 110.9, 93.1, 82.4, 61.2, 55.9, 20.7 ppm;
HRMS m/z calcd for C18H18O2 266.13067, found 266.13699.
1-(Biphenyl-2-yl)-3-(2-bromophenyl)prop-2-yn-1-ol (Table 6,
entry 2). The general reaction procedure described in the paper
was followed for the synthesis and purification; the product was
afforded as a colorless oil in 81% isolated yield. 1H NMR (CD-
Cl3, 400 MHz) δ 8.05 (d, 1H, J=8.0 Hz), 7.59 (d, 1H, J=8.0 Hz),
(Z)-3-(2-Bromophenyl)-2-(hydroxy(4-(trifluoromethyl)phenyl)-
methyl)-1-(4-(trifluoromethyl)phenyl)prop-2-en-1-one (Table 7,
entry 1). The general reaction procedure described in the paper
J. Org. Chem. Vol. 74, No. 17, 2009 6689

Wadhwa et al.
JOCArticle
was followed for the synthesis and purification; the product was
afforded as a colorless oil in 68% isolated yield. 1H NMR
(CDCl3, 400 MHz) δ 7.63-7.59 (m, 6H), 7.38-7.25 (m, 4H),
6.91 (br s, 3H), 5.89 (s, 1H), 3.33 (s, 1H) ppm; 13C NMR (CDCl3,
100.6 MHz) δ 198.3, 144.9, 142.3, 139.4, 135.5, 134.6, 134.2,
131.2, 130.6 (q, J=32.0 Hz), 130.3, 129.3, 127.4, 127.0, 126.8
(q, J=270.0 Hz), 126.2 (q, J=272.0 Hz), 125.9, 124.8, 123.5, 76.5
ppm; 19F NMR (CDCl3, 376 MHz) δ -63.0, -63.8 ppm; HRMS
m/z calcd for C24H15BrF6O2 528.01595, found 528.01759.
(Z)-3-(3-Chlorophenyl)-2-(hydroxy(4-(trifluoromethyl)phenyl)-
methyl)-1-(4-(trifluoromethyl)phenyl)prop-2-en-1-one (Table 7,
entry 2). The general reaction procedure described in the paper
was followed for the synthesis and purification; the product was
afforded as a white solid in 74% isolated yield. 1H NMR
(CDCl3, 400 MHz) δ 7.66-7.40 (m, 8H), 7.01-6.89 (m, 5H),
5.80 (s, 1H), 3.22 (s, 1H) ppm; 13C NMR (CDCl3, 100.6 MHz)
δ 198.7, 144.5, 142.4, 138.7, 136.1, 134.8 (q, J=25.0 Hz), 134.4,
132.0, 130.7 (q, J=32.0 Hz), 129.7, 129.4, 129.0, 128.8, 126.9,
126.8 (q, J=290 Hz), 126.6 (q, J=320 Hz), 125.7, 125. 4, 75.8
ppm; 19F NMR (CDCl3, 376 MHz) δ -63.1, -63.8 ppm; HRMS
m/z calcd for C24H15ClF6O2 484.0644, found 484.0665.
100.6 MHz) δ 198.5, 144.7, 139.3, 138.9, 137.1, 134.9 (q, J =
33.0 Hz), 130.8 (q, J=33.0 Hz), 130.4, 129.8, 128.6, 128.1, 127.0,
125.7, 125.3, 124.1 (q, J=270.0 Hz), 123.6 (q, J=271.0 Hz), 76.2
ppm; 19F NMR (CDCl3, 376 MHz) δ -64.7, -65.4 ppm; HRMS
m/z calcd for C22H14F6O2S 456.06186, found 456.06315.
(Z)-1-(4-(Methoxycarbonyl)phenyl)-2-((4-(methoxycarbonyl)-
phenyl)(hydroxy)methyl)-3-(4-(trifluoromethyl)phenyl)prop-2-en-1-
one (Table 7, entry 5). The general reaction procedure described
in the paper was followed for the synthesis and purification; the
product was afforded as a yellow oil in 73% isolated yield.
1H NMR (CDCl3, 400 MHz) δ 7.97 (d, 2H, J=8.0 Hz), 7.80 (d,
2H, J=8.0 Hz), 7.63 (d, 2H, J=8.0 Hz), 7.50 (d, 2H, J=8.0 Hz),
7.30 (d, 2H, J=8.0 Hz), 7.15 (d, 2H, J=8.0 Hz), 7.03 (s, 1H), 5.84
(s, 1H), 3.87 (s, 3H), 3.85 (s, 3H), 3.35 (d, 1H, J=4.0 Hz) ppm;
13C NMR (CDCl3, 100.6 MHz) δ 198.9, 166.8, 166.1, 145.6,
143.8, 139.1, 134.4, 130.9, 130.3, 130.1 (q, J=33.0 Hz), 129.8,
129.2, 126.7, 125.5, 124.4, 123.8 (q, J=263.0 Hz), 76.2, 55.6, 52.4
ppm; 19F NMR (CDCl3, 376 MHz) δ -63.3 ppm; HRMS m/z
calcd for C27H21F3O6 498.12902, found 498.13023.
(Z)-1-(4-Bromophenyl)-2-((4-bromophenyl)(hydroxy)methyl)-
3-(4-(trifluoromethyl)phenyl)prop-2-en-1-one (Table 7, entry 6).
The general reaction procedure described in the paper was
followed for the synthesis and purification; the product was
afforded as a yellow oil in 65% isolated yield. 1H NMR (CDCl3,
400 MHz) δ 7.49-7.44 (m, 4H), 7.34-7.26 (m, 6H), 7.16 (d, 2H,
J=8.0 Hz), 6.94 (s, 1H), 5.69 (d, 1H, J=4.0 Hz), 3.08 (d, 1H, J=
4.0 Hz) ppm; 13C NMR (CDCl3, 100.6 MHz) δ 198.5, 143.8,
139.6, 138.3, 134.7, 132.2, 132.1, 132.0, 130.9, 130.4, 129.3,
128.5, 125.5, 123.9 (q, J=267 Hz), 122.5, 76.0 ppm; 19F NMR
(CDCl3, 376 MHz) δ -63.2 ppm; HRMS m/z calcd for
C23H15Br2F3O2 537.9358, found 537.9391.
(Z)-2-(Hydroxy(4-(trifluoromethyl)phenyl)methyl)-1,3-bis(4-
(trifluoromethyl)phenyl)prop-2-en-1-one (Table 7, entry 3). The
general reaction procedure described in the paper was followed
for the synthesis and purification; the product was afforded as a
yellow oil in 72% isolated yield. 1H NMR (CDCl3, 400 MHz)
δ 7.68 (d, 2H, J=8.0 Hz), 7.60-7.53 (m, 4H), 7.41 (d, 2H, J=
8.0 Hz), 7.33 (d, 2H, J=8.0 Hz), 7.16 (d, 2H, J=8.0 Hz), 7.04 (s,
1H), 5.84 (d, 1H, J=4.0 Hz), 3.18 (d, 1H, J=4.0 Hz) ppm; 13
C
NMR (CDCl3, 100.6 MHz) δ 198.5, 144.5, 143.6, 138.9, 138.1,
134.9 (q, J=32.0 Hz), 131.7, 130.7 (q, J=32.0 Hz), 130.7 (q, J=
32.0 Hz), 129.6, 129.3, 127.1, 125.8, 125.4, 125.3, 124.1 (q, J=
271.0 Hz), 123.8 (q, J=271.0 Hz), 123.4 (q, J=271.0 Hz), 75.9
ppm; 19F NMR (CDCl3, 376 MHz) δ -63.1, -63.5, -63.9 ppm;
HRMS m/z calcd for C25H15F9O2 518.09283, found 518.09409.
(Z)-2-(Hydroxy(4-(trifluoromethyl)phenyl)methyl)-3-(thiophen-
3-yl)-1-(4-(trifluoromethyl)phenyl)prop-2-en-1-one (Table 7, entry 4).
The general reaction procedure described in the paper was
followed for the synthesis and purification; the product was
afforded as a green oil in 68% isolated yield. 1H NMR (CDCl3,
400 MHz) δ 7.85 (d, 2H, J=8.0 Hz), 7.58-7.53 (m, 6H), 7.15
(d, 1H, J=8.0 Hz), 7.00 (s, 1H), 6.84-6.79 (m, 2H), 5.75 (d, 1H,
J=4.0 Hz), 3.06 (d, 1H, J=4.0 Hz) ppm; 13C NMR (CDCl3,
Acknowledgment. The National Science Foundation is
gratefully acknowledged for financial support of this re-
search in the form of grant 0750463.
Supporting Information Available: Complete experimental
details, references to the known compounds, complete charac-
terization of unknown compounds, copies of 1H and 13C NMR
spectra for all alkynylation, MBH products, and HRMS reports
for new compounds. This material is available free of charge via
the Internet at http://pubs.acs.org.
6690 J. Org. Chem. Vol. 74, No. 17, 2009