Quick installation of a 1,4-difunctionality via regioselective nickel-catalyzed reductive coupling of ynoates and aldehydes

Article abstract of DOI:10.1021/jo301790q

The development of efficient methods for the synthesis of molecules with 1,4-difunctionalities has been a dire need of the synthetic community. In this work, intermolecular reductive coupling of ynoates and aldehydes (in the presence of a silane) has been accomplished for the first time using catalytic amounts of Ni (COD)₂, an N-heterocyclic carbene ligand, and PPh ₃. High regioselectivity has been demonstrated for the multicomponent coupling reactions, and more than a dozen invaluable silyl-protected γ-hydroxy-α,β-enoates have been synthesized. This methodology provides a quick entry to many other 1,4-difunctional compounds and oxygen-containing five-membered rings. The intermediacy of metallacycles in the catalytic process has been established by deuterium-labeling experiments.

Full text of DOI:10.1021/jo301790q

Article
pubs.acs.org/joc
Quick Installation of a 1,4-Difunctionality via Regioselective Nickel-
Catalyzed Reductive Coupling of Ynoates and Aldehydes
Sanjeewa K. Rodrigo and Hairong Guan*
Department of Chemistry, University of Cincinnati, P.O. Box 21072, Cincinnati, Ohio 45221-0172, United States
S
* Supporting Information
ABSTRACT: The development of efficient methods for the synthesis of
molecules with 1,4-difunctionalities has been a dire need of the synthetic
community. In this work, intermolecular reductive coupling of ynoates and
aldehydes (in the presence of a silane) has been accomplished for the first time
using catalytic amounts of Ni(COD)2, an N-heterocyclic carbene ligand, and
PPh3. High regioselectivity has been demonstrated for the multicomponent
coupling reactions, and more than a dozen invaluable silyl-protected γ-hydroxy-
α,β-enoates have been synthesized. This methodology provides a quick entry to
many other 1,4-difunctional compounds and oxygen-containing five-membered
rings. The intermediacy of metallacycles in the catalytic process has been established by deuterium-labeling experiments.
INTRODUCTION
■
One of the challenges that chemists often encounter in target-
directed synthesis is how to construct a 1,4-difunctionality in an
efficient manner. Disconnecting this structural moiety using a
retrosynthetic analysis typically results in “unnatural” synthons
such as acyl anions and homoenolates. Accordingly, most
strategies for making molecules with a 1,4-difunctionality
involve reactivity umpolung of heteroatom-containing carbon
chains through tedious protection−deprotection sequences.1
More recent efforts, aimed at improving the efficiency of the
synthesis, have focused on polarity reversal induced by N-
heterocyclic carbenes (NHCs)2 or transition metals,3 homo-
coupling4 or heterocoupling5 of enolates by metal-based
oxidants, and carbonylation of carbonyl derivatives via C−H
bond activation.6 Despite this progress, concise and efficient
long sought as a versatile precursor to many biologically active
molecules.13
methods for the installation of a 1,4-difunctionality are still in
high demand, particularly if the resulting products can be
conveniently transformed into a wide variety of compounds.
RESULTS AND DISCUSSION
■
We initiated our studies (Table 1) following Sato’s protocols
that had been previously optimized for catalytic reductive
coupling of ynamides and aldehydes.11c To prevent the
trimerization of ynoate, the solution of 1 in THF had to be
added last and carried out very slowly (syringe-pump addition
over 8 h) to the reaction mixture. When IMes (see Chart 1)
was employed as the ligand, two coupling products (3a:3a′ =
95:5) were detected by GC; however, the combined yield was
merely 14% (entry 1). Replacing IMes with other commonly
used NHCs did not give satisfactory yields (entries 2−4), but
SIPr was identified as our best ligand. Interestingly, when SIPr
was generated from its NHC precursor with a BF4− counterion
instead of the chloride salt, the yield was improved to 61%
(entry 5). Although the reason behind the counterion effect
One conceptually different approach is to use a low-valent
metal species to catalyze regioselective coupling of ynoates and
aldehydes in the presence of a reducing agent such as a silane
(eq 1). Among various metal complexes for the reductive
coupling of alkynes and aldehydes,7,8 catalytic systems involving
Ni(COD)2/L (COD = 1,5-cyclooctadiene, L = a phosphine or
an NHC), developed by Montgomery,9 Jamison,10 and
others,11 have stood out due to their excellent reactivity and
regioselectivity. Of the alkynes applied in these studies,
however, very few of them contain functionalities that are
adjacent to the CC bonds. In these rare cases, 1,3-
difunctional products have been obtained as the major
regioisomers (eqs 2 and 3).9g,11c We hypothesized that the
electron-withdrawing nature of the ester group in ynoates
might promote C−C bond forming reactions at the β-carbon,12
leading to the desired silyl-protected γ-hydroxy-α,β-enoates (eq
1). This specific type of 1,4-difunctional compound has been
Received: August 21, 2012
Published: August 29, 2012
© 2012 American Chemical Society
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Table 1. Optimization of the Reaction Conditions
Table 2. Reactions of 1 with Various Aldehydes
c
entry
NHC·HX
additive
yield (%)
14
1
2
3
4
5
6
IMes·HCl
SIMes·HCl
IPr·HCl
d
15
27
38
61
37
SIPr·HCl
SIPr·HBF4
SIPr·HBF4
SIPr·HBF4
SIPr·HBF4
SIPr·HBF4
IIPr·HBF4
ICy·HBF4
BAC·HBF4
NaCl
a
d
7
trace
8
PPh3
PPh3
PPh3
PPh3
100
41
0
b
9
10
11
12
a
Yield of purified product; the regioselectivity (in parentheses) was
b
0
1
determined by H NMR. The solution of 1 in THF was added over
PPh3
0
16 h rather than 8 h.
a
b
The reaction was conducted at 50 °C. 20 mol % PPh3 was added.
c
d
Combined GC yield for 3a and 3a′. A significant amount of
PhCH2OSiEt3 was detected.
that are fluorinated at different positions of the aromatic ring.
Of particular interest is that coupling of o-fluorobenzaldehyde
gave the 1,4-difunctional product 3h with a 95:5 regioselectiv-
ity. This high selectivity is not unique to fluorine, as the
reaction of o-tolualdehyde similarly yielded 3i as the
predominant product. Other aromatic aldehydes such as 2-
naphthaldehyde are also viable substrates for the synthesis of
1,4-difunctional products. However, reactions with aliphatic
aldehydes, including heptaldehyde and isovaleraldehyde,
afforded not only 1,3-difunctional compounds as the major
isomers (a 2:1 ratio favoring the 1,3-product) but also some
trimerization byproducts from 1.
Chart 1. NHCs Employed in This Study
The scope of the reaction was further investigated by varying
the structures of the ynoates (Table 3). In addition to the
methyl ester 1, ethyl or 2-naphthyl propiolate can be utilized to
synthesize the corresponding 1,4-regioisomer with a similar
remains unclear to us at the moment, we did observe
diminished yield with externally added Cl− (entry 6). In all
of the experiments mentioned above, unreacted PhCHO was
seen, which made us suspect that the active catalyst might
already be decomposed. Gratifyingly, an attempt to extend the
lifetime of the catalyst14 by adding 10 mol % of PPh3 (with
respect to 1) showed a quantitative conversion with a 85:15
ratio of 3a and 3a′ (entry 8). Adding more PPh3, however, had
a detrimental effect on the yield (entry 9), perhaps by
saturating the nickel center to inhibit the reaction. A control
experiment with 10 mol % of PPh3 and no NHC ligand showed
no reaction, suggesting that the NHC ligand is a necessity. A
few other NHCs were also tested (entries 10−12), but none of
them promoted the coupling reaction. The choice of solvent
proved to be critical; reaction in CH2Cl2, 1,4-dioxane, or DMF
under otherwise the same conditions (as those described in
entry 8) did not produce any of the coupling products.
Table 3. Scope of Ynoates and Aldehydes
To explore the generality of the reaction, reductive coupling
of 1 with various aldehydes under the optimized conditions was
performed. As shown in Table 2, the methodology is amenable
to aldehydes bearing functional groups such as OMe, Cl, and
CO2Me (2c−e). In all cases, the 1,4-difunctional compounds
were produced as the major isomers and isolated in good yields.
The regioselectivity does not appear to be greatly influenced by
the electronic property of the substituent at the para position of
benzaldehyde. In view of recent intense interest in the synthesis
of fluorine-containing molecules, we also examined substrates
a
Yield of purified product; the regioselectivity (in parentheses) was
1
determined by H NMR.
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selectivity. In contrast, the coupling of tert-butyl propiolate is
not selective at all, producing equal amounts of two isomeric
products. Ynoates bearing an internal CC bond are also
feasible coupling partners. As a matter of fact, their reactions
are generally more regioselective, and in some cases as high as a
98:2 ratio favoring the 1,4-product (e.g., 3n) was observed.
More importantly, with these internal alkynes, aliphatic
aldehydes can now be successfully incorporated in the synthesis
of 1,4-difunctional compounds. Trimethylsilyl (TMS)-substi-
tuted ynoates can also be coupled with both aromatic and
aliphatic aldehydes to yield the 1,4-difunctional compounds
(3r,s) with excellent regioselectivity. It should be mentioned
that syringe-pump addition of these bulky ynoates is no longer
needed, because under the reaction conditions their trimeriza-
tion or oligmerization is noncompetitive. Having the TMS
groups in these molecules can be advantageous; further
modification at the β position should be possible through
Hiyama coupling reactions.15
Scheme 2. Deuterium-Labeling Studies
sequential insertions of ynoate and aldehyde, would be
inconsistent with our deuterium-labeling studies. Transition-
metal-catalyzed hydrosilylation of ynoates that involves
analogous silane activation and alkyne insertion typically leads
to the addition of silane hydrogen to the β-carbon.20
As mentioned earlier, silyl-protected γ-hydroxy-α,β-enoates
are important building blocks for a diverse array of compounds.
To demonstrate their synthetic utility, compound 3h was
subjected to saturation of the CC bond followed by
lactonization to furnish 5 (Scheme 3). Given the fact that γ-
The aforementioned regioselectivity could be rationalized by
the mechanistic hypothesis outlined in Scheme 1 (using 1 and
Scheme 1. Proposed Reaction Mechanism
Scheme 3. Synthetic Application of Silyl-Protected γ-
Hydroxy-α,β-enoates
butyrolactones are present in about 10% of all natural
products,21 we anticipate that the method described here may
open a new synthetic path to these molecules. Another
important class of compounds is substituted tetrahydrofurans,22
and as illustrated in Scheme 3, they are readily accessible from
silyl-protected γ-hydroxy-α,β-enoates following deprotection of
the silyl group, reduction of the carbonyls, and cyclo-
dehydration of the resulting diols.
PhCHO as representative substrates). A similar mechanism has
been proposed in related systems for the coupling of alkynes
and aldehydes, where it has been supported by computational
studies,16 kinetics,17 and even a crystal structure.18 The
electron-withdrawing ester group in our reactions should
provide a sufficient electronic bias so that, driven by the
formation of a stronger Ni−C bond,19 C−C bond formation
takes place at the β-carbon of 1. The metallacyclic intermediate
A would be destabilized when the methyl ester is replaced by a
tert-butyl ester, possibly due to the increased steric clash
between the ester moiety and the ancillary ligand on nickel.
This analysis is in agreement with the nonregioselectivity
observed for 3m (Table 3). For internal alkynes, the formation
of A is expected to be more favorable on the basis of both
electronic and steric arguments, resulting in enhanced
selectivity for the 1,4-difunctional products. In the case of
benzaldehyde bearing an ortho substituent (2h,i), the
intermediate B should be even less favorable, owing to the
interaction between the ester group and the aryl ring.
CONCLUSION
■
In summary, we have developed a nickel-based catalytic system
for multicomponent coupling of ynoates, aldehydes, and
silanes. Labeling studies are in accordance with the formation
of metallacycles as the key intermediates. The reactions are
applicable to a broad range of substrates and enable
regioselective synthesis of a wide variety of silyl-protected γ-
hydroxy-α,β-enoates. Further manipulations of these 1,4-
difunctional compounds allow for convenient access to
oxygen-containing five-membered rings, which are important
cores of natural products.
EXPERIMENTAL SECTION
■
Consistent with the proposed mechanism, selectively labeling
the silane hydrogen with deuterium gave rise to 3a-D with
deuterium exclusively at the α-position (Scheme 2). A similar
experiment using PhCDO yielded 3a-D with deuterium at the
carbon center originating from the aldehyde. An alternative
mechanism involving the activation of silane first, followed by
General Experimental Methods. All the reactions were carried
out in flame-dried glassware under an argon atmosphere using
standard glovebox and Schlenk techniques. Dry and oxygen-free
solvents (THF and CH2Cl2) were collected from an Innovative
Technology solvent purification system and used throughout the
experiments. DMF was dried over molecular sieves (4 Å) and then
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1
degassed by three freeze−pump−thaw cycles. Anhydrous 1,4-dioxane
was obtained from Sigma-Aldrich in a Sure/Seal bottle. Aldehydes
were purchased from commercial sources and freshly distilled prior to
use. BAC·HBF4 was prepared as described in the literature.23
Compound 3e (colorless oil, 135 mg, 74% yield): H NMR (400
MHz, CDCl3, δ) 8.01 (d, J = 7.9 Hz, 2H), 7.40 (d, J = 7.9 Hz, 2H),
6.96 (dd, J = 15.4, 4.5 Hz, 1H), 6.15 (dd, J = 15.4, 1.8 Hz, 1H), 5.36
(dd, J = 4.5, 1.8 Hz, 1H), 3.91 (s, 3H), 3.72 (s, 3H), 0.90 (t, J = 7.9
Hz, 9H), 0.63−0.53 (m, 6H); 13C{1H} NMR (101 MHz, CDCl3, δ)
167.0, 166.9, 149.7, 146.9, 130.0, 129.7, 126.3, 119.3, 73.6, 52.2, 51.8,
6.8, 4.9; IR (neat, cm−1) 2953, 2912, 2876, 1721 (νCO), 1658, 1610,
1458, 1435, 1413, 1242, 1191, 1164, 1108, 1018, 971, 888, 857, 825,
807, 769, 725, 566; HRMS-ESI (m/z) [M + Na]+ calcd for
C19H28O5SiNa 387.1604, found 387.1595.
General Procedure for Nickel-Catalyzed Reductive Coupling
of an Ynoate and an Aldehyde. In a flame-dried Schlenk flask was
added Ni(COD)2 (13.8 mg, 0.050 mmol), SIPr·HBF4 (23.9 mg, 0.050
mmol), PPh3 (13.1 mg, 0.050 mmol), and KOtBu (5.6 mg, 0.050
mmol). THF (4.0 mL) was then added to this flask at 0 °C, and the
resulting mixture was stirred at the same temperature for 15 min,
followed by the successive addition of Et3SiH (88 μL, 0.55 mmol) and
an aldehyde (0.55 mmol). After the mixture was stirred at 0 °C for 5
min, a solution of an ynoate (0.50 mmol) in 4.0 mL of THF was added
at room temperature (23 °C) over a period of 8 h (or 16 h for the
synthesis of 3b,i) using a syringe pump. Upon completion of the
addition, the reaction mixture was stirred at room temperature for
another 1 h before being concentrated under vacuum. The ratio of the
two isomers was determined from the 1H NMR spectrum of the crude
products. The desired 1,4-difunctional compound was separated from
the isomeric mixture using column chromatography (with diethyl
ether/hexanes as eluent). For the synthesis of 3r,s, the ynoate solution
was added over a period of 1 h and the resulting solution was stirred at
room temperature for 36 h prior to workup. Characterization data of
the isolated products are given below.
1
Compound 3f (colorless oil, 99 mg, 61% yield): H NMR (400
MHz, CDCl3, δ) 7.28−7.25 (m, 2H), 7.02−6.97 (m, 2H), 6.93 (dd, J
= 15.4, 4.6 Hz, 1H), 6.10 (dd, J = 15.4, 1.7 Hz, 1H), 5.27 (d, J = 4.6,
1.7 Hz, 1H), 3.72 (s, 3H), 0.90 (t, J = 7.9 Hz, 9H), 0.58−0.52 (m,
6H); 13C{1H} NMR (101 MHz, CDCl3, δ) 167.2, 162.5 (d, J = 246.4
Hz), 150.5, 137.8 (d, J = 2.7 Hz), 128.1 (d, J = 7.1 Hz), 118.9, 115.6
(d, J = 21.4 Hz), 73.4, 51.8, 6.9, 4.9; IR (neat, cm−1) 2954, 2912, 2877,
1722 (νCO), 1658, 1604, 1507, 1458, 1435, 1414, 1297, 1277, 1222,
1191, 1164, 1156, 1116, 1092, 1072, 1004, 974, 886, 872, 834, 821,
721; HRMS-ESI (m/z) [M + Na]+ calcd for C17H25O3FSiNa 347.144
92, found 347.144 98.
1
Compound 3g (colorless oil, 115 mg, 71% yield): H NMR (400
MHz, CDCl3, δ) 7.31−7.26 (m, 1H), 7.13−7.01 (m, 2H), 7.01−6.92
(m, 2H), 6.13 (dd, J = 15.4, 1.7 Hz, 1H), 5.30 (dd, J = 4.5, 1.7 Hz,
1H), 3.72 (s, 3H), 0.91 (t, J = 7.9 Hz, 9H), 0.63−0.53 (m, 6H);
13C{1H} NMR (101 MHz, CDCl3, δ) 167.1, 163.1 (d, J = 247.1 Hz),
149.9, 144.6 (d, J = 6.7 Hz), 130.2 (d, J = 8.3 Hz), 121.8 (d, J = 2.7
Hz), 119.1, 114.8 (d, J = 22.1 Hz), 113.2 (d, J = 22.1 Hz), 73.4, 51.8,
6.8, 4.9; IR (neat, cm−1) 2954, 2912, 2877, 1722 (νCO), 1679, 1659,
1614, 1591, 1483, 1448, 1436, 1414, 1348, 1268, 1192, 1166, 1136,
1116, 1004, 977, 945, 911, 870, 825, 789, 770, 727, 690; HRMS-ESI
(m/z) [M + Na]+ calcd for C17H25O3FSiNa 347.1455, found
347.1458.
1
Compound 3a (colorless oil, 116 mg, 76% yield): H NMR (400
MHz, CDCl3, δ) 7.33−7.24 (m, 5H), 6.99 (dd, J = 15.4, 4.5 Hz, 1H),
6.14 (dd, J = 15.4, 1.7 Hz, 1H), 5.31 (dd, J = 4.5, 1.7 Hz, 1H), 3.71 (s,
3H), 0.90 (t, J = 7.9 Hz, 9H), 0.60−0.54 (m, 6H); 13C{1H} NMR
(101 MHz, CDCl3, δ) 167.3, 150.8, 141.9, 128.7, 128.0, 126.4, 118.7,
74.1, 51.7, 6.9, 5.0; IR (neat, cm−1) 2953, 2911, 2876, 1722 (νCO),
1657, 1493, 1454, 1435, 1414, 1295, 1276, 1240, 1191, 1163, 1118,
1084, 1064, 1003, 973, 838, 817, 726, 697; HRMS-ESI (m/z) [M +
Na]+ calcd for C17H26O3SiNa 329.1549, found 329.1539.
1
1
Compound 3a′ (colorless oil): H NMR (400 MHz, CDCl3, δ)
Compound 3h (colorless oil, 138 mg, 85% yield): H NMR (400
7.37−7.20 (m, 5H), 6.26−6.25 (m, 1H), 6.10−6.09 (m, 1H), 5.61 (br
s, 1H), 3.67 (s, 3H), 0.86 (t, J = 7.9 Hz, 9H), 0.57−0.51 (m, 6H);
13C{1H} NMR (101 MHz, CDCl3, δ) 166.6, 144.1, 142.9, 128.3, 127.6,
127.3, 124.1, 72.6, 51.8, 6.9, 5.0; IR (neat, cm−1) 2953, 2911, 2876,
1720 (νCO), 1630, 1493, 1454, 1438, 1413, 1358, 1292, 1256, 1192,
1147, 1084, 1003, 953, 912, 875, 835, 815, 726, 697, 603, 540; HRMS-
ESI (m/z) [M + Na]+ calcd for C17H26O3SiNa 329.154 34, found
329.154 35.
MHz, CDCl3, δ) 7.48−7.43 (m, 1H), 7.27−7.23 (m, 1H), 7.16−7.10
(m, 1H), 7.03−6.97 (m, 2H), 6.16 (dd, J = 15.4, 1.7 Hz, 1H), 5.69 (d,
J = 4.6, 1.7 Hz, 1H), 3.72 (s, 3H), 0.90 (t, J = 7.6 Hz, 9H), 0.63−0.55
(m, 6H); 13C{1H} NMR (101 MHz, CDCl3, δ) 167.2, 159.2 (d, J =
246.4 Hz), 149.2, 129.4 (d, J = 9.1 Hz), 129.0 (d, J = 14.1 Hz), 128.0
(d, J = 4.0 Hz), 124.6 (d, J = 4.0 Hz), 119.0, 115.3 (d, J = 22.2 Hz),
67.0, 51.7, 6.8, 4.8; IR (neat, cm−1) 2954, 2912, 2877, 1725 (νCO),
1659, 1573, 1458, 1456, 1435, 1296, 1271, 1242, 1223, 1164, 1130,
1087, 1004, 974, 819, 796, 725; HRMS-ESI (m/z) [M + Na]+ calcd
for C17H25O3FSiNa 347.144 92, found 347.144 92.
1
Compound 3b (colorless oil, 101 mg, 63% yield): H NMR (400
MHz, CDCl3, δ) 7.20 and 7.13 (AB pattern, J = 8.0 Hz, 4H), 6.98 (dd,
J = 15.2, 4.4 Hz, 1H), 6.12 (dd, J = 15.2, 1.6 Hz, 1H), 5.28 (dd, J = 4.4,
1.6 Hz, 1H), 3.71 (s, 3H), 2.33 (s, 3H), 0.90 (t, J = 7.6 Hz, 9H), 0.60−
0.53 (m, 6H); 13C{1H} NMR (101 MHz, CDCl3, δ) 167.4, 151.0,
138.9, 137.6, 129.4, 126.4, 118.4, 73.9, 51.7, 21.3, 6.9, 4.9; IR (neat,
cm−1) 2953, 2912, 2876, 1724 (νCO), 1657, 1512, 1458, 1435, 1413,
1276, 1239, 1192, 1162, 1118, 1104, 1072, 1004, 974, 843, 815, 720;
HRMS-ESI (m/z) [M + Na]+ calcd for C18H28O3SiNa 343.169 99,
found 343.170 07.
1
Compound 3i (colorless oil, 107 mg, 67% yield): H NMR (400
MHz, CDCl3, δ) 7.41−7.38 (m, 1H), 7.20−7.08 (m, 3H), 6.96 (dd, J
= 15.6, 4.4 Hz, 1H), 6.10 (dd, J = 15.6, 1.6 Hz, 1H), 5.49 (dd, J = 4.4,
1.6 Hz, 1H), 3.70 (s, 3H), 2.33 (s, 3H), 0.89 (t, J = 8.0 Hz, 9H), 0.60−
0.52 (m, 6H); 13C{1H} NMR (101 MHz, CDCl3, δ) 167.4, 149.8,
139.8, 134.4, 130.7, 127.8, 127.0, 126.5, 118.7, 71.4, 51.7, 19.4, 6.9, 4.9;
IR (neat, cm−1) 2952, 2911, 2876, 1723 (νCO), 1656, 1459, 1435,
1413, 1276, 1239, 1164, 1114, 1091, 1068, 1004, 970, 820, 722;
HRMS-ESI (m/z) [M + Na]+ calcd for C18H28O3SiNa 343.169 99,
found 343.170 02.
1
Compound 3c (pale yellow oil, 97 mg, 58% yield): H NMR (400
MHz, CDCl3, δ) 7.22 (d, J = 8.8 Hz, 2H), 6.97 (dd, J = 15.4, 4.5 Hz,
1H), 6.86 (d, J = 8.8 Hz, 2H), 6.11 (dd, J = 15.4, 1.8 Hz, 1H), 5.26
(dd, J = 4.5, 1.8 Hz, 1H), 3.80 (s, 3H), 3.71 (s, 3H), 0.89 (t, J = 7.9
Hz, 9H), 0.59−0.52 (m, 6H); 13C{1H} NMR (101 MHz, CDCl3, δ)
167.3, 159.3, 151.0, 134.0, 127.7, 118.3, 114.0, 73.6, 55.4, 51.7, 6.9, 4.9;
IR (neat, cm−1) 2953, 2911, 2876, 1722 (νCO), 1657, 1610, 1510,
1244, 1193, 974, 818, 724; HRMS-ESI (m/z) [M + Na]+ calcd for
C18H28O4SiNa 359.164 91, found 359.164 87.
1
Compound 3j (colorless oil, 144 mg, 81% yield): H NMR (400
MHz, CDCl3, δ) 7.82−7.76 (m, 4H), 7.48−7.42 (m, 3H), 7.06 (dd, J
= 15.4, 4.5 Hz, 1H), 6.19 (dd, J = 15.4, 1.6 Hz, 1H), 5.48 (dd, J = 4.5,
1.6 Hz, 1H), 3.71 (s, 3H), 0.91 (t, J = 7.9 Hz, 9H), 0.63−0.56 (m,
6H); 13C{1H} NMR (101 MHz, CDCl3, δ) 167.3, 150.6, 139.3, 133.5,
133.3, 128.6, 128.2, 127.9, 126.4, 126.2, 125.1, 124.5, 118.9, 74.2, 51.8,
7.0, 5.0; IR (neat, cm−1) 3056, 2952, 2910, 2875, 1721 (νCO), 1656,
1601, 1508, 1457, 1434, 1413, 1366, 1338, 1298, 1270, 1238, 1191,
1162, 1124, 1108, 1073, 1004, 975, 954, 896, 856, 816, 727; HRMS-
ESI (m/z) [M + Na]+ calcd for C21H28O3SiNa 379.169 99, found
379.170 05.
1
Compound 3d (pale yellow oil, 95 mg, 56% yield): H NMR (400
MHz, CDCl3, δ) 7.30 and 7.25 (AB pattern, J = 8.4 Hz, 4H), 6.93 (dd,
J = 15.4, 4.6 Hz, 1H), 6.11 (dd, J = 15.4, 1.6 Hz, 1H), 5.28 (d, J = 4.6
Hz, 1H), 3.72 (s, 3H), 0.90 (t, J = 7.9 Hz, 9H), 0.60−0.54 (m, 6H);
13C{1H} NMR (101 MHz, CDCl3, δ) 167.1, 150.1, 140.5, 133.7, 128.9,
127.8, 119.0, 73.4, 51.8, 6.9, 4.9; IR (neat, cm−1) 2953, 2911, 2876,
1722 (νCO), 1658, 1488, 1458, 1435, 1409, 1297, 1275, 1240, 1191,
1163, 1120, 1088, 1014, 973, 819, 725; HRMS-ESI (m/z) [M + Na]+
calcd for C17H25O3SiClNa 363.115 37, found 363.115 41.
1
Compound 3k (colorless oil, 118 mg, 74% yield): H NMR (400
MHz, CDCl3, δ) 7.33−7.24 (m, 5H), 6.97 (dd, J = 15.4, 4.5 Hz, 1H),
6.11 (dd, J = 15.4, 1.6 Hz, 1H), 5.31 (dd, J = 4.5, 1.6 Hz, 1H), 4.20−
4.14 (m, 2H), 1.27 (t, J = 7.1 Hz, 3H), 0.90 (t, J = 7.9 Hz, 9H), 0.60−
0.54 (m, 6H); 13C{1H} NMR (101 MHz, CDCl3, δ) 167.4, 159.4,
8306
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1
151.0, 134.1, 127.8, 118.4, 114.1, 73.6, 55.5, 51.7, 6.9, 5.0; IR (neat,
cm−1) 2955, 2911, 2876, 1718 (νCO), 1656, 1454, 1413, 1367, 1276,
1238, 1161, 1114, 1064, 1038, 1002, 975, 846, 819, 742, 726, 697;
HRMS-ESI (m/z) [M + Na]+ calcd for C18H28O3SiNa 343.169 99,
found 343.170 03.
Compound 3s (colorless oil, 162 mg, 81% yield): H NMR (400
MHz, CDCl3, δ) 6.61 (s, 1H), 4.39−4.37 (m, 1H), 4.17 (q, J = 7.1 Hz,
2H), 1.32−1.25 (m, 13H), 0.95 (t, J = 7.9 Hz, 9H), 0.92−0.86 (m,
3H), 0.57 (q, J = 7.9 Hz, 6H), 0.21 (s, 9H); 13C{1H} NMR (101 MHz,
CDCl3, δ) 167.8, 167.6, 128.1, 75.1, 60.2, 38.7, 32.0, 29.4, 26.0, 22.8,
14.4, 14.2, 7.0, 5.0, −0.2; IR (neat, cm−1) 2955, 2933, 2876, 1719
(νCO), 1603, 1460, 1413, 1378, 1312, 1247, 1139, 1089, 1048, 1005,
843, 740, 681; HRMS-ESI (m/z) [M + Na]+ calcd for C21H44O3Si2Na
423.2727, found 423.2723.
1
Compound 3l (colorless oil, 140 mg, 67% yield): H NMR (400
MHz, CDCl3, δ) 7.85−7.78 (m, 3H), 7.58−7.56 (m, 1H), 7.50−7.21
(m, 9H), 6.39 (dd, J = 15.3, 1.8 Hz, 1H), 5.41 (dd, J = 4.3, 1.8 Hz,
1H), 0.94 (t, J = 8.0 Hz, 9H), 0.65−0.58 (m, 6H); 13C{1H} NMR
(101 MHz, CDCl3, δ) 165.4, 152.8, 148.5, 141.6, 133.9, 131.6, 129.5,
128.8, 128.1, 127.9, 127.8, 126.6, 126.5, 125.8, 121.3, 118.7, 118.2,
74.1, 6.9, 4.9; IR (neat, cm−1) 3060, 3029, 2954, 2910, 2874, 1733
(νCO), 1653, 1630, 1600, 1493, 1463, 1356, 1269, 1237, 1208, 1154,
1122, 1078, 969, 808, 736, 697; HRMS-ESI (m/z) [M + Na]+ calcd
for C26H30O3SiNa 441.185 64, found 441.185 69.
Procedure for the Conjugate Reduction of 3h. Following a
similar procedure established for the conjugate reduction of α,β-
unsaturated carbonyl compounds,24 [1,3-bis(2,6-diisopropylphenyl)-
imidazol-2-ylidene]copper(I) chloride (9.8 mg, 0.020 mmol, 1 mol %)
and NaOtBu (2.0 mg, 0.020 mmol, 1 mol %) were mixed in an oven-
dried flask under an argon atmosphere. About 1.0 mL of toluene was
added, and the mixture was stirred at room temperature for 10 min,
followed by the addition of poly(methylhydrosiloxane) (PMHS; 0.015
mL, 0.20 mmol, 1.0 equiv). After the yellow solution was stirred at
room temperature for 5 min, more toluene (2.0 mL) and PMHS
(0.045 mL, 0.60 mmol, 3.0 equiv) were added. A solution of 3h (65
1
Compound 3m (colorless oil, 80 mg, 46% yield): H NMR (400
MHz, CDCl3, δ) 7.33−7.24 (m, 5H), 6.86 (dd, J = 15.2, 4.8 Hz, 1H),
5.99 (dd, J = 15.4, 1.6 Hz, 1H), 5.28 (dd, J = 4.8, 1.6 Hz, 1H), 1.46 (s,
9H), 0.90 (t, J = 8.0 Hz, 9H), 0.60−0.53 (m, 6H); 13C{1H} NMR
(101 MHz, CDCl3, δ) 166.0, 149.0, 142.0, 128.4, 127.6, 126.3, 120.8,
80.3, 73.9, 28.1, 6.7, 4.8; IR (neat, cm−1) 2955, 2912, 2876, 1712
(νCO), 1654, 1493, 1454, 1413, 1392, 1367, 1297, 1281, 1246, 1148,
1120, 1064, 1001, 976, 847, 818, 740, 726, 697; HRMS-ESI (m/z) [M
+ Na]+ calcd for C20H32O3SiNa 371.201 29, found 371.201 35.
t
mg, 0.20 mmol, 1.0 equiv) and BuOH (0.06 mL, 0.80 mmol, 4.0
equiv) in 1 mL of toluene was then added via a cannula. The reaction
mixture was stirred at room temperature until all the starting material
was fully converted. The reaction mixture was quenched with water
and treated with ethyl acetate. The organic layer was separated, while
the aqueous layer was extracted with ethyl acetate three times. The
combined organic layers were washed with brine, dried over anhydrous
MgSO4, and concentrated under vacuum. The crude product was
purified by column chromatography, and compound 4 was isolated as
1
Compound 3n (colorless oil, 177 mg, 91% yield): H NMR (400
MHz, CDCl3, δ) 7.32−7.23 (m, 5H), 6.26 (s, 1H), 5.10 (s, 1H), 3.70
(s, 3H), 2.67−2.61 (m, 1H), 2.06−2.01 (m, 1H), 1.29−1.18 (m, 8H),
0.89−0.83 (m, 12H), 0.57−0.51 (m, 6H); 13C{1H} NMR (101 MHz,
CDCl3, δ) 167.4, 164.9, 142.0, 128.3, 127.9, 127.2, 113.7, 77.8, 51.1,
31.6, 29.9, 29.6, 29.5, 22.7, 14.2, 6.8, 4.9; IR (neat, cm−1) 2953, 2875,
1720 (νCO), 1649, 1493, 1454, 1433, 1413, 1377, 1312, 1209, 1145,
1102, 1062, 1004, 974, 938, 915, 884, 849, 825, 725, 698; HRMS-ESI
(m/z) [M + Na]+ calcd for C23H38O3SiNa 413.2488, found 413.2492.
1
a yellow oil (62 mg, 95% yield): H NMR (400 MHz, CDCl3, δ)
7.51−7.47 (m, 1H), 7.23−7.18 (m, 1H), 7.14−7.09 (m, 1H), 7.00−
6.95 (m, 1H), 5.12 (t, J = 5.8 Hz, 1H), 3.63 (s, 3H), 2.44−2.29 (m,
2H), 2.06−2.00 (m, 2H), 0.88 (t, J = 7.9 Hz, 9H), 0.57−0.50 (m, 6H);
13C{1H} NMR (101 MHz, CDCl3, δ) 174.0, 159.2 (d, J = 245.4 Hz),
131.7 (d, J = 14.1 Hz), 128.7 (d, J = 7.1 Hz), 127.9 (d, J = 4.0 Hz),
124.2 (d, J = 5.1 Hz), 115.0 (d, J = 22.2 Hz), 66.8, 51.6, 34.3, 29.8, 6.8,
4.8; IR (neat, cm−1) 2954, 2912, 2877, 1740 (νCO), 1616, 1587, 1487,
1456, 1437, 1415, 1366, 1270, 1224, 1159, 1107, 1087, 1067, 1003,
889, 841, 799, 756, 725, 568, 528; HRMS-ESI (m/z) [M + Na]+ calcd
for C17H27O3FSiNa 349.1611, found 349.1611.
Procedure for the Deprotection of the Silyl Group. A similar
procedure has been described in the literature.9e To a solution of 4 (or
3h for the synthesis of 6) in 3 mL of THF was added a 1 M solution of
tetrabutylammonium fluoride in THF (2 equiv). The reaction mixture
was stirred at room temperature until all the starting material was fully
converted. The reaction mixture was then diluted with 1.2 mL of
diethyl ether and washed with a saturated aqueous solution of
NaHCO3. The organic layer was separated, dried over anhydrous
MgSO4, and concentrated under vacuum. The crude product was
purified on silica by column chromatography.
1
Compound 3o (colorless oil, 144 mg, 83% yield): H NMR (400
MHz, CDCl3, δ) 7.32−7.24 (m, 5H), 6.28 (s, 1H), 5.10 (s, 1H), 3.70
(s, 3H), 2.67−2.60 (m, 1H), 2.04−2.01 (m, 1H), 1.33−1.28 (m, 2H),
0.90−0.85 (m, 12H), 0.58−0.50 (m, 6H); 13C{1H} NMR (101 MHz,
CDCl3, δ) 167.4, 164.7, 141.9, 128.3, 127.9, 127.2, 113.8, 77.7, 51.0,
31.5, 22.9, 14.7, 6.8, 4.9; IR (neat, cm−1) 2956, 2912, 2875, 1720
(νCO), 1649, 1454, 1433, 1377, 1313, 1278, 1240, 1196, 1145, 1099,
1057, 1004, 883, 845, 726, 698; HRMS-ESI (m/z) [M + Na]+ calcd
for C20H32O3SiNa 371.201 29, found 371.201 34.
1
Compound 3p (colorless oil, 137 mg, 77% yield): H NMR (400
MHz, CDCl3, δ) 5.92 (s, 1H), 4.10 (t, J = 5.4 Hz, 1H), 3.69 (s, 3H),
2.84−2.76 (m, 1H), 2.17−2.08 (m, 1H) 1.54−1.26 (m, 12H), 1.00−
0.86 (m, 15H), 0.61−0.55 (m, 6H); 13C{1H} NMR (101 MHz,
CDCl3, δ) 167.4, 166.2, 140.3, 114.2, 75.6, 51.0, 36.7, 31.9, 29.5, 25.2,
23.1, 22.8, 14.9, 14.2, 7.0, 5.0; IR (neat, cm−1) 2954, 2933, 2875, 1721
(νCO), 1649, 1458, 1433, 1414, 1379, 1329, 1242, 1152, 1126, 1094,
1005, 978, 889, 820, 724; HRMS-ESI (m/z) [M + Na]+ calcd for
C20H40O3SiNa 379.2644, found 379.2646.
Compound 5 (colorless oil, 18.5 mg, 85% yield, for a 0.12 mmol
scale reaction): H NMR (400 MHz, CDCl3, δ) 7.43−7.39 (m, 1H),
1
1
Compound 3q (colorless oil, 123 mg, 75% yield): H NMR (400
7.37−7.31 (m, 1H), 7.20−7.16 (m, 1H), 7.12−7.06 (m, 1H), 5.75 (t, J
= 7.2 Hz, 1H), 2.79−2.65 (m, 3H), 2.25−2.15 (m, 1H); 13C{1H}
NMR (101 MHz, CDCl3, δ) 176.8, 159.7 (d, J = 248.5 Hz), 130.1 (d, J
= 8.1 Hz), 127.1 (d, J = 12.1 Hz), 126.6 (d, J = 4.0 Hz), 124.6 (d, J =
4.0 Hz), 115.8 (d, J = 21.2 Hz), 76.4 (d, J = 3.0 Hz), 29.9, 28.6; IR
(neat, cm−1) 2950 (br), 1770 (νCO), 1618, 1589, 1490, 1457, 1420,
1375, 1328, 1297, 1236, 1212, 1189, 1171, 1138, 1101, 1038, 1021,
989, 941, 891, 833, 811, 798, 755, 666, 601, 635, 602, 525; HRMS-ESI
(m/z) [M + Na]+ calcd for C10H9O2FNa 203.0484, found 203.0480.
Compound 6 (colorless oil, 19 mg, 76% yield, for a 0.12 mmol scale
reaction): 1H NMR (400 MHz, CDCl3, δ) 7.92−7.88 (m, 1H), 7.56−
7.50 (m, 1H), 7.27−7.21 (m, 1H), 7.17−7.12 (m, 1H), 3.71 (s, 3H),
3.35−3.31 (m, 2H), 2.76 (t, J = 6.4 Hz, 2H); 13C{1H} NMR (101
MHz, CDCl3, δ) 196.4 (d, J = 5.1 Hz), 173.4, 162.3 (d, J = 255.5 Hz),
134.9 (d, J = 9.1 Hz), 130.8 (d, J = 2.0 Hz), 125.2 (d, J = 13.1 Hz),
124.6 (d, J = 3.0 Hz), 116.8 (d, J = 24.2 Hz), 51.9, 38.4 (d, J = 8.1 Hz),
28.2; IR (neat, cm−1) 2953, 1737 (νCO), 1688 (νCO), 1610, 1582,
1481, 1452, 1438, 1411, 1358, 1323, 1274, 1214, 1169, 1153, 1105,
MHz, CDCl3, δ) 5.91 (s, 1H), 4.15−4.12 (m, 1H), 3.69 (s, 3H), 2.83−
2.76 (m, 1H), 2.15−2.08 (m, 1H), 1.76−1.66 (m, 1H), 1.57−1.29 (m,
4H), 1.01−0.89 (m, 18H), 0.61−0.55 (m, 6H); 13C{1H} NMR (101
MHz, CDCl3, δ) 167.3, 166.8, 114.2, 74.5, 51.0, 46.6, 31.8, 24.5, 23.7,
23.3, 22.3, 15.0, 7.0, 5.0; IR (neat, cm−1) 2955, 2875, 1720 (νCO),
1650, 1463, 1434, 1414, 1384, 1367, 1329, 1305, 1240, 1155, 1131,
1085, 1002, 961, 900, 724; HRMS-ESI (m/z) [M + Na]+ calcd for
C18H36O3SiNa 351.2332, found 351.2326.
1
Compound 3r (colorless oil, 163 mg, 83% yield): H NMR (400
MHz, CDCl3, δ) 7.31−7.23 (m, 5H), 6.85 (d, J = 1.3 Hz, 1H), 5.40 (d,
J = 1.3 Hz, 1H), 4.24−4.18 (m, 2H), 1.32 (t, J = 7.1 Hz, 3H), 0.90 (t, J
= 7.9 Hz, 9H), 0.58 (q, J = 7.9 Hz, 6H), 0.00 (s, 9H); 13C{1H} NMR
(101 MHz, CDCl3, δ) 167.6, 164.9, 141.8, 129.6, 128.4, 128.0, 127.8,
78.5, 60.5, 14.5, 7.0, 5.1, 0.1; IR (neat, cm−1) 2954, 2910, 2876, 1718
(νCO), 1598, 1454, 1413, 1368, 1307, 1244, 1185, 1085, 1039, 1004,
841, 726, 698; HRMS-ESI (m/z) [M + Na]+ calcd for C21H36O3Si2Na
415.209 52, found 415.209 51.
8307
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Article
1069, 1026, 991, 950, 829, 765, 538; HRMS-ESI (m/z) [M + Na]+
calcd for C11H11O3FNa 233.0590, found 233.0588.
Rev. 2011, 40, 5336. (e) Bugaut, X.; Glorius, F. Chem. Soc. Rev. 2012,
41, 3511.
Procedure for the Reduction of 6. At 0 °C under an inert
atmosphere, a solution of 6 (200 mg, 0.95 mmol) in 2 mL of THF was
added dropwise to a suspension of LiAlH4 (144 mg, 3.80 mmol, 4
equiv) in 3 mL of THF. The reaction mixture was stirred at room
temperature until all the starting material was fully converted. The
excess LiAlH4 was carefully quenched at 0 °C with 5 mL of EtOAc
followed by 5 mL of water, at which point a white precipitate formed.
The mixture was then acidified with 15% HCl (ca. 4 mL) until it
became a clear solution, and the product was extracted with
dichloromethane. The combined organic layers were dried over
anhydrous MgSO4 and concentrated under vacuum. The crude
product was purified by column chromatography to give compound 7
as a colorless oil (167 mg, 95% yield). 1H NMR (400 MHz, CDCl3, δ)
7.42−7.38 (m, 1H), 7.19−7.14 (m, 1H), 7.08−7.04 (m, 1H), 6.96−
6.92 (m, 1H), 4.94 (t, J = 6.0 Hz, 1H), 4.29 (br s, 2H), 3.57−3.46 (m,
2H), 1.78−1.73 (m, 2H), 1.65−1.50 (m, 2H); 13C{1H} NMR (101
MHz, CDCl3, δ) 159.6 (d, J = 246.4 Hz), 131.7 (d, J = 13.1 Hz), 128.7
(d, J = 8.1 Hz), 127.4 (d, J = 4.0 Hz), 124.3 (d, J = 3.0 Hz), 115.2 (d, J
= 22.2 Hz), 67.7, 62.3, 35.0, 28.8; IR (neat, cm−1) 3311 (br, νOH),
2941, 2361, 2338, 1717, 1616, 1586, 1487, 1454, 1269, 1221, 1178,
1042, 824, 754, 619; HRMS-ESI (m/z) [M + Na]+ calcd for
C10H13O2FNa 207.0797, found 207.0792.
(3) (a) Guan, H. Curr. Org. Chem. 2008, 12, 1406. (b) Zhang, J.;
Krause, J. A.; Huang, K.-W.; Guan, H. Organometallics 2009, 28, 2938.
́
(4) Csaky, A. G.; Plumet, J. Chem. Soc. Rev. 2001, 30, 313.
̈
(5) (a) Baran, P. S.; DeMartino, M. P. Angew. Chem., Int. Ed. 2006,
45, 7083. (b) DeMartino, M. P.; Chen, K.; Baran, P. S. J. Am. Chem.
Soc. 2008, 130, 11546.
(6) (a) Giri, R.; Yu, J.-Q. J. Am. Chem. Soc. 2008, 130, 14082.
(b) Yoo, E. J.; Wasa, M.; Yu, J.-Q. J. Am. Chem. Soc. 2010, 132, 17378.
(c) Hasegawa, N.; Charra, V.; Inoue, S.; Fukumoto, Y.; Chatani, N. J.
Am. Chem. Soc. 2011, 133, 8070.
(7) Ni-catalyzed reactions: (a) Montgomery, J. Acc. Chem. Res. 2000,
33, 467. (b) Ikeda, S. Angew. Chem., Int. Ed. 2003, 42, 5120.
(c) Montgomery, J. Angew. Chem., Int. Ed. 2004, 43, 3890.
(d) Montgomery, J.; Sormunen, G. J. Top. Curr. Chem. 2007, 279,
1. (e) Moslin, R. M.; Miller-Moslin, K.; Jamison, T. F. Chem. Commun.
2007, 4441. Rh- or Ir-catalyzed reactions: (f) Rhee, J. U.; Krische, M.
J. J. Am. Chem. Soc. 2006, 128, 10674. (g) Ngai, M.-Y.; Kong, J.-R.;
Krische, M. J. J. Org. Chem. 2007, 72, 1063. (h) Skucas, E.; Ngai, M.-
Y.; Komanduri, V.; Krische, M. J. Acc. Chem. Res. 2007, 40, 1394.
(8) Ti-mediated stoichiometric reactions: (a) Reichard, H. A.;
McLaughlin, M.; Chen, M. Z.; Micalizio, G. C. Eur. J. Org. Chem. 2010,
391. Sm-mediated stoichiometric reactions: (b) Inanaga, J.; Katsuki,
J.; Ujikawa, O.; Yamaguchi, M. Tetrahedron Lett. 1991, 32, 4921.
(9) (a) Oblinger, E.; Montgomery, J. J. Am. Chem. Soc. 1997, 119,
9065. (b) Tang, X.-Q.; Montgomery, J. J. Am. Chem. Soc. 1999, 121,
6098. (c) Mahandru, G. M.; Liu, G.; Montgomery, J. J. Am. Chem. Soc.
2004, 126, 3698. (d) Sa-ei, K.; Montgomery, J. Org. Lett. 2006, 8,
4441. (e) Chaulagain, M. R.; Sormunen, G. J.; Montgomery, J. J. Am.
Chem. Soc. 2007, 129, 9568. (f) Baxter, R. D.; Montgomery, J. J. Am.
Chem. Soc. 2008, 130, 9662. (g) Malik, H. A.; Chaulagain, M. R.;
Montgomery, J. Org. Lett. 2009, 11, 5734. (h) Malik, H. A.; Sormunen,
G. J.; Montgomery, J. J. Am. Chem. Soc. 2010, 132, 6304.
(10) (a) Huang, W.-S.; Chan, J.; Jamison, T. F. Org. Lett. 2000, 2,
4221. (b) Miller, K. M.; Molinaro, C.; Jamison, T. F. Tetrahedron:
Asymmetry 2003, 14, 3619. (c) Colby, E. A.; Jamison, T. F. J. Org.
Chem. 2003, 68, 156. (d) Miller, K. M.; Huang, W.-S.; Jamison, T. F. J.
Am. Chem. Soc. 2003, 125, 3442. (e) Miller, K. M.; Luanphaisarnnont,
T.; Molinaro, C.; Jamison, T. F. J. Am. Chem. Soc. 2004, 126, 4130.
(f) Moslin, R. M.; Jamison, T. F. Org. Lett. 2006, 8, 455.
(11) (a) Takai, K.; Sakamoto, S.; Isshiki, T. Org. Lett. 2003, 5, 653.
(b) Takai, K.; Sakamoto, S.; Isshiki, T.; Kokumai, T. Tetrahedron 2006,
62, 7534. (c) Saito, N.; Katayama, T.; Sato, Y. Org. Lett. 2008, 10,
3829. (d) Yang, Y.; Zhu, S.-F.; Zhou, C.-Y.; Zhou, Q.-L. J. Am. Chem.
Soc. 2008, 130, 14052. (e) Saito, N.; Sugimura, Y.; Sato, Y. Org. Lett.
2010, 12, 3494.
Procedure for the Synthesis of 8. A similar procedure has been
described in the literature.25 Compound 7 (48 mg, 0.26 mmol) and
ZnCl2 (53 mg, 0.39 mmol, 1.5 equiv) were mixed with 5 mL of 1,2-
dichloroethane in an oven-dried flask. The reaction mixture was stirred
at 80 °C until all the starting material was fully converted. The solution
was diluted with 3 mL of CH2Cl2 and then washed with water and
brine. The organic layer was separated and dried over anhydrous
MgSO4. The crude product was purified by column chromatography
1
to give compound 8 as a colorless oil (31 mg, 72% yield): H NMR
(400 MHz, CDCl3, δ) 7.47−7.43 (m, 1H), 7.24−7.19 (m, 1H), 7.14−
7.10 (m, 1H), 7.03−6.98 (m, 1H), 5.14 (t, J = 7.1 Hz, 1H), 4.13−4.08
(m, 1H), 3.97−3.91 (m, 1H), 2.44−2.36 (m, 1H), 2.04−1.97 (m, 2H),
1.83−1.74 (m, 1H); 13C{1H} NMR (101 MHz, CDCl3, δ) 160.0 (d, J
= 246.4 Hz), 131.0 (d, J = 13.1 Hz), 128.6 (d, J = 8.1 Hz), 127.0 (d, J
= 4.0 Hz), 124.2 (d, J = 3.0 Hz), 115.3 (d, J = 21.2 Hz), 75.3 (d, J =
2.0 Hz), 68.8, 33.7, 26.2; IR (neat, cm−1) 2977, 2870, 1617, 1588,
1485, 1455, 1364, 1273, 1229, 1185, 1151, 1103, 1059, 939, 923, 821,
753, 516, 493, 461; HRMS-ESI (m/z) [M + Na]+ calcd for
C10H11OFNa 189.068 61, found 189.068 57.
ASSOCIATED CONTENT
* Supporting Information
■
S
Text and figures giving details of deuterium-labeling experi-
ments and spectroscopic data for all of the new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(12) Carbon−carbon bond formation in the Ti-mediated coupling of
ynoates and alkynes has been shown to occur at the β-carbon of
ynoates; see: Hamada, T.; Suzuki, D.; Urabe, H.; Sato, F. J. Am. Chem.
Soc. 1999, 121, 7342.
(13) (a) Nicolaou, K. C.; Pavia, M. R.; Seitz, S. P. J. Am. Chem. Soc.
1981, 103, 1224. (b) Chen, C.; Tagami, K.; Kishi, Y. J. Org. Chem.
1995, 60, 5386. (c) Naka, T.; Koide, K. Tetrahedron Lett. 2003, 44,
443. (d) Meta, C. T.; Koide, K. Org. Lett. 2004, 6, 1785.
(14) The strategy of adding a phosphine ligand to stabilize the active
catalyst has been previously used; see: Sawaki, R.; Sato, Y.; Mori, M.
Org. Lett. 2004, 6, 1131.
AUTHOR INFORMATION
Corresponding Author
*E-mail: hairong.guan@uc.edu.
Notes
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The authors declare no competing financial interest.
(15) Hiyama Cross-Coupling Reaction. In Name Reactions for
Homologations; Li, J. J., Ed.; Wiley: Hoboken, NJ, 2009; Part 1, p 33.
(16) (a) McCarren, P. R.; Liu, P.; Cheong, P. H.-Y.; Jamison, T. F.;
Houk, K. N. J. Am. Chem. Soc. 2009, 131, 6654. (b) Liu, P.; McCarren,
P.; Cheong, P. H.-Y.; Jamison, T. F.; Houk, K. N. J. Am. Chem. Soc.
2010, 132, 2050. (c) Liu, P.; Montgomery, J.; Houk, K. N. J. Am.
Chem. Soc. 2011, 133, 6956.
(17) Baxter, R. D.; Montgomery, J. J. Am. Chem. Soc. 2011, 133,
5728.
(18) Ogoshi, S.; Arai, T.; Ohashi, M.; Kurosawa, H. Chem. Commun.
2008, 1347.
ACKNOWLEDGMENTS
Financial support from the University of Cincinnati is gratefully
acknowledged.
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REFERENCES
(1) Seebach, D. Angew. Chem., Int. Ed. 1979, 18, 239.
(2) (a) Johnson, J. S. Angew. Chem., Int. Ed. 2004, 43, 1326. (b) Vora,
H. U.; Rovis, T. Aldrichim. Acta 2011, 44, 3. (c) Nair, V.; Vellalath, S.;
Babu, B. P. Chem. Soc. Rev. 2008, 37, 2691. (d) Nair, V.; Menon, R. S.;
Biju, A. T.; Sinu, C. R.; Paul, R. R.; Jose, A.; Sreekumar, V. Chem. Soc.
■
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dx.doi.org/10.1021/jo301790q | J. Org. Chem. 2012, 77, 8303−8309

The Journal of Organic Chemistry
Article
(19) Martinho Simoes, J. A.; Beauchamp, J. L. Chem. Rev. 1990, 90,
̃
629.
(20) Rooke, D. A.; Ferreira, E. M. Angew. Chem., Int. Ed. 2012, 51,
3225.
(21) Hoffmann, H. M. R.; Rabe, J. Angew. Chem., Int. Ed. 1985, 24,
94.
(22) Alali, F. Q.; Liu, X.-X.; McLaughlin, J. L. J. Nat. Prod. 1999, 62,
504.
(23) Lavallo, V.; Canac, Y.; Donnadieu, B.; Schoeller, W. W.;
Bertrand, G. Science 2006, 312, 722.
(24) Jurkauskas, V.; Sadighi, J. P.; Buchwald, S. L. Org. Lett. 2003, 5,
2417.
(25) Kim, S.; Chung, K. N.; Yang, S. J. Org. Chem. 1987, 52, 3917.
8309
dx.doi.org/10.1021/jo301790q | J. Org. Chem. 2012, 77, 8303−8309