(1-Bromovinyl)-MIDA boronate: A readily accessible and highly versatile building block for small molecule synthesis Dedicated to Professor Paul Wender with deepest admiration on his receipt of the 2012 Tetrahedron Prize for Creativity in Organic Chemistry

Article abstract of DOI:10.1016/j.tet.2013.05.050

Iterative cross-coupling represents a potentially general approach for the simple, efficient, and flexible construction of a wide range of functional small molecules. In this context, (1-bromovinyl)-N-methyliminodiacetic acid (MIDA) boronate is a very useful building block for small molecule synthesis. This compound can serve as a starting material for the preparation of a wide range of 1,1-disubstituted olefin-containing MIDA boronates. This compound can also be used for the iterative cross-coupling-based synthesis of various 1,1-disubstituted olefin-containing targets. Collectively, these results contribute to the expanding generality of the MIDA boronate platform.

Full text of DOI:10.1016/j.tet.2013.05.050

Tetrahedron 69 (2013) 7732e7740
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
(1-Bromovinyl)-MIDA boronate: a readily accessible and highly
versatile building block for small molecule synthesisq
*
Eric M. Woerly, Jonathan E. Miller, Martin D. Burke
Howard Hughes Medical Institute, Roger Adams Laboratory, Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801,
USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Iterative cross-coupling represents a potentially general approach for the simple, efficient, and flexible
construction of a wide range of functional small molecules. In this context, (1-bromovinyl)-N-methyl-
iminodiacetic acid (MIDA) boronate is a very useful building block for small molecule synthesis. This
compound can serve as a starting material for the preparation of a wide range of 1,1-disubstituted olefin-
containing MIDA boronates. This compound can also be used for the iterative cross-coupling-based
synthesis of various 1,1-disubstituted olefin-containing targets. Collectively, these results contribute to
the expanding generality of the MIDA boronate platform.
Received 9 March 2013
Received in revised form 10 May 2013
Accepted 13 May 2013
Available online 18 May 2013
Dedicated to Professor Paul Wender with
deepest admiration on his receipt of the
2012 Tetrahedron Prize for Creativity in
Organic Chemistry
Ó 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
Keywords:
MIDA boronates
Iterative cross-coupling
1,1-Disubstituted boronates
1,1-Disubstituted olefins
1. Introduction
methyltriphenylphosphonium bromide and a ketone,4 the Heck
reaction of an organohalide or triflate and monosubstituted olefin,5
The substantial level of inherent modularity present in most
small molecules suggests that a generalized building block based
approach may be applicable to the laboratory synthesis of many of
these compounds. In an idealized form of this approach, stable
subunits having all of the required functional groups preinstalled in
the correct oxidation states and with the desired stereochemical
relationships are linked using only one reaction. As a roadmap for
creating a general strategy for small molecule synthesis, we aim to
identify common substructural motifs that are prevalent in a wide
range of natural products and transform them into shelf-stable
building blocks that are compatible with iterative assembly.
In this vein, 1,1-disubstituted olefins are prevalent in small
molecule pharmaceuticals1 and natural products derived from
a wide range of biosynthetic pathways (Fig.1).2 In addition, they are
useful synthetic intermediates.3 Some common strategies for the
synthesis of 1,1-disubstituted olefins include the Wittig reaction of
and other metal catalyzed couplings between a halide or halide
surrogate and an organometallic reagent.6
Of particular interest, the 1,1-disubstituted alkenyl boronate
motif is an attractive intermediate for the preparation of 1,1-
disubstituted olefins because of the versatility of the vinyl boron
moiety.7 While methods for the synthesis of 1,2-disubstituted
alkenyl boronates are abundant,8 the methods for the preparation
of 1,1-disubstituted alkenyl boronates have been limited.9 Recent
methods for the preparation of these motifs include the copper
catalyzed hydroboration of aryl and heteroaryl substituted alky-
nes.9a Alternatively, aryl substituted vinyl boronates can be pre-
pared from the corresponding vinyl halide via
a Miyaura
borylation9c or a lithiation/trap sequence.9d,e However, the syn-
thesis of the requisite vinyl halide can be challenging and often uses
conditions that are not compatible with acid-sensitive functional-
ities. To address these challenges, we envision that a B-protected
1,1-disubstituted halo boronate building block would be extremely
useful for the modular synthesis of targets containing a 1,1-
disubstituted olefin motif (Scheme 1).
q
This is an open-access article distributed under the terms of the Creative
Commons Attribution-NonCommercial-No Derivative Works License, which per-
mits non-commercial use, distribution, and reproduction in any medium, provided
the original author and source are credited.
Along these lines, we are developing a platform of N-methyl-
iminodiacetic acid (MIDA) boronate building blocks.10e24 MIDA
boronates have many desirable properties that render them
* Corresponding author. E-mail address: burke@scs.uiuc.edu (M.D. Burke).
0040-4020/$ e see front matter Ó 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.05.050

E.M. Woerly et al. / Tetrahedron 69 (2013) 7732e7740
7733
Fig. 1. 1,1-Disubstituted olefins are abundant in pharmaceuticals and natural products.
Scheme 1. A 1,1-disubstituted halo boronate building block as a useful reagent for the preparation of 1,1-disubstituted olefins.
exceptionally useful as synthetic intermediates. They are uniformly
air-stable, non-toxic, highly crystalline, and monomeric free-
flowing solids that are fully compatible with silica gel chromatog-
raphy. Many methods now exist for preparing MIDA boronates
from a wide range of different starting materials, including boronic
acids,10e13,19,25 haloboranes,11,13 boronic esters,16 trialkoxyborate
salts,14e17,19 organohalides,19 organolithium reagents,19,23 and
Grignard reagents.15,16 The MIDA boronate functional group is inert
to anhydrous cross-coupling conditions, yet can be readily trans-
formed into a fully reactive boronic acid or ester using mild con-
ditions.10,14,17 These features enable the simple, efficient, and highly
flexible synthesis of a wide range of complex small molecules via
in MeCN provides a very convenient route to (1-bromovinyl)-MIDA
boronate 2 in 67% overall yield. Moreover, 2 can be prepared on the
decagram scale and isolated in pure form without the use of column
chromatography. Building block
2 is also now commercially
available.26
iterative
cross-coupling
of
MIDA-protected
haloboronic
acids.10e12,16,17,21,22,24 Finally, a large and growing collection of
MIDA boronates are now commercially available.26 Taking advan-
tage of all of these properties, we herein report a 1,1-disubstituted
halo MIDA boronate building block, which upon selective func-
tionalization, allows ready access to a variety of 1,1-disubstituted
alkenyl boronate motifs with the potential for iterative cross-
coupling for the preparation of 1,1-disubstituted olefins.
Scheme 2. Synthesis of (1-bromovinyl)-MIDA boronate 2.
With a readily scalable synthesis of 2 in hand, we have pre-
liminarily explored its utility in the preparation of a range of new
1,1-disubstituted alkenyl boronate building blocks en route to 1,1-
disubstituted olefins. In this vein, our initial attempt to couple 2
with phenyl boronic acid under anhydrous cross-coupling condi-
tions surprisingly formed a mixture of products identified as the
2. Results
Brominationeelimination reactions provide
a convenient
method for the synthesis of vinyl halides.27 In particular, 1,1-
disubstituted olefins can be prepared from terminal alkenes via
this type of transformation.28 With this strategy in mind, vinyl
MIDA boronate 1 is an attractive starting point. This building block
can easily be prepared on large scale from inexpensive starting
materials (Scheme 2), and is now commercially available on both
the gram and kilogram scales.29 Bromination of 1 followed by
treatment of the resulting vicinal dibromide intermediate with DBU
desired 1,1-disubstituted boronate
3
and the trans-1,2-
disubstituted product 4 in a 1:4 ratio (Scheme 3).
We hypothesized that 4 is formed through a competitive re-
action pathway involving oxidative addition of the palladium cat-
alyst to 2 followed by
b-hydride elimination, reinsertion of the
PdeH species to form a trans-1,2-disubstituted olefin, trans-
metalation with the boronic acid, and reductive elimination (Fig. 2,

7734
E.M. Woerly et al. / Tetrahedron 69 (2013) 7732e7740
Scheme 3. The unoptimized coupling of building block 2 with phenyl boronic acid provides a mixture of products.
Fig. 2. Proposed mechanism for the formation of 1,1-disubstituted product 3 and 1,2-disubstituted product 4.
pathway 2). Guided by this hypothesis, we explored reaction con-
ditions that could limit the -hydride elimination pathway (path-
way 2) and/or accelerate the rate of the desired transmetalation
reaction that leads to pathway 1 (Fig. 2).
Along these lines, silver salts have been proposed to increase the
rate of transmetalation in the SuzukieMiyaura cross-coupling re-
action.30 To test if this could favor pathway 1 over pathway 2, we
employed silver oxide as the base (Table 1, entry 1) in combination
with Pd(OAc)2 and tricyclohexylphosphine (Cy3P) and observed 3
as the major product (3:1), although with low conversion (30%).
Alternatively, the use of silver carbonate (entry 2) produced 3 in
a slightly better ratio (4:1) and with greater conversion (60%). As
a second variable, bidentate ligands, such as 1,10-bis(diphenyl-
These optimized conditions for the formation of 1,1-
disubstituted boronate 3 have proven to be scalable. On a 1 mmol
scale, cross-coupled product 3 was obtained in 61% isolated yield as
a single isomer (Scheme 4). We further explored the utility of 2 as
a substrate for iterative cross-coupling (ICC) reactions. The in situ
hydrolysis of 3 followed by cross-coupling of the resulting boronic
acid with aryl iodide 5 yielded 6 as a single isomer.
We next tested the generality of the optimized cross-coupling
conditions with a variety of aryl, heteroaryl, and vinyl boronic
acids (Table 2). Good to moderate conversions were observed in all
cases. The coupling of boronic acids with electron neutral (entries
1e3), withdrawing (entries 4e6), and donating (entries 7 and 8)
groups formed the desired product in all cases. Specifically, the
coupling of 4-vinylphenylboronic acid 7a and m-tolylboronic acid
7b proceeded with excellent selectivity (>20:1), high conversion
(>95%), and an 81% isolated yield for 8a and 90% isolated yield for
8b. Furthermore, boronic acids with ortho-substituents, such as 7c,
are tolerated, providing the cross-coupled product 8c in >20:1
selectivity and 50% isolated yield. However, the presence of elec-
tron withdrawing groups, including 4-methoxycarbonyl, 4-cyano,
4-fluoro, and 4-trifluoromethoxy (entries 4e6), resulted in mod-
erate selectivities (10:1 to 4:1) albeit still with good conversions
(70e90%). The electron withdrawing groups on the boronic acid
may reduce the rate of the desired transmetalation reaction (Fig. 2,
b
phosphino)ferrocene (dppf), have been used to limit
b-hydride
elimination pathways in cross-coupling reactions.31 Use of
PdCl2dppf (entry 3) with silver carbonate provided 3 as the major
product (4:1) with greatly improved conversion over previous re-
action conditions. A survey of other bidentate phosphine ligands
revealed 1,5-bis(diphenylphosphino)pentane (dppp, entry 4) as
a ligand that provided 3 in a 10:1 ratio. As a final variable, ancillary
ligands were investigated. A survey of various palladium sources
revealed that Pd2dba3 combined with 1,6-bis(diphenylphosphino)
hexane (dpph, entry 6) provided 3 in a >20:1 ratio and with ex-
cellent conversion. Interestingly, during the course of this study, we
also found that exclusive formation of the trans-product 4 can be
achieved in 85% conversion using Pd(OAc)2, SPhos, and K3PO4 in
THF (entry 7).
pathway 1), therefore making the b-hydride elimination pathway
more competitive (pathway 2). In contrast, electron-donating
groups, including 3,5-dimethoxy and 4-dimethylamino (entries 7
and 8) provided the cross-coupled products with excellent selec-
tivity (>20:1) and a 66% isolated yield for 8g. Additionally, the
coupling of 2-heterocyclic boronic acids, including 2-
benzofuranboronic acid 7i and 2-thiopheneboronic acid 7j pro-
duced the 1,1-product in >20:1 in both cases and an 82% isolated
yield for 8i. Finally, the coupling of vinyl boronic acids also pro-
duced the 1,1-product in >20:1 and 76% isolated yield for 8k and
65% isolated yield for 8l.
Table 1
Optimization studies for the coupling of 2
Entry
Pd/ligand
Base
% Conversiona
3/4a
3:1
4:1
4:1
10:1
12:1
>20:1
1
2
3
4
5
6
7
Pd(OAc)2/Cy3P
Pd(OAc)2/Cy3P
PdCl2dppf
Pd(OAc)2/dppp
Pd2dba3/dppp
Pd2dba3/dpph
Pd(OAc)2/SPhos
Ag2O
30
60
>95
70
70
>95
85
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2Co3
K3PO4
3. Summary and conclusions
Access to a wide range of bifunctional building blocks repre-
senting motifs that commonly appear in small molecules stands to
greatly increase the efficiency and flexibility of the synthesis of this
broadly important class of compounds. The 1,1-disubstituted olefin
represents a very important substructure that appears in a wide
1:20
a
The reaction conversion and ratio of 3/4 was determined based on the 1H NMR
of the crude reaction mixture.

E.M. Woerly et al. / Tetrahedron 69 (2013) 7732e7740
7735
Scheme 4. MIDA boronate 2 is a substrate for iterative SuzukieMiyaura coupling reactions.
Table 2
Substrate scope under the optimized reaction conditions
Entry
1
7
8
8/9
% Conversiona (isolated yield)
>20:1
>95 (81%)
>95 (90%)
2
3
>20:1
>20:1
>95 (50%)
4
10:1
85 (45%)b
5
6
8:1
4:1
70 (39%)b
90 (43%)b
7
>20:1
85 (66%)
8
>20:1
>20:1
>20:1
50 (28%)
95 (82%)
50 (24%)
9
10
(continued on next page)

7736
E.M. Woerly et al. / Tetrahedron 69 (2013) 7732e7740
Table 2 (continued )
Entry
7
8
8/9
% Conversiona (isolated yield)
90 (76%)
11
>20:1
12
>20:1
80 (65%)
a
The reaction conversion and ratio of 8/9 was determined based on the 1H NMR of the crude reaction mixture.
Isolated yield as an inseparable mixture of isomers.
b
range of pharmaceuticals and natural products. We herein de-
(ppm) downfield from tetramethylsilane and referenced to residual
protium in the NMR solvent (CHCl3, ¼1.94,
¼7.26; CD2HCN,
center line; acetone-d6,
¼2.05, center line) or to added tetrame-
thylsilane (
multiplicity (s¼singlet, d¼doublet, t¼triplet, q¼quartet,
quint¼quintet, sext¼sextet, sept¼septet, m¼multiplet, br¼broad,
app¼apparent), coupling constant (J) in Hertz (Hz), and integration.
13C NMR spectra were recorded at 23 ꢀC on a Varian Unity 400 or
scribed a very practical and scalable synthesis of the bifunctional
building block 2 and demonstrated its utility for the synthesis of
a wide range of 1,1-disubstituted boronates. Collectively, these
findings expand the utility of ICC with MIDA boronates as a simple
and flexible platform for the efficient synthesis of a wide range of
functional small molecules.
d
d
d
d
¼0.00). Data are reported as follows: chemical shift,
Varian Unity 500. Chemical shifts (
million (ppm) downfield from tetramethylsilane and referenced to
carbon resonances in the NMR solvent (CDCl3,
¼77.0, center line;
CD3CN, ¼29.80, center line) or to
¼1.30, center line; acetone-d6,
added tetramethylsilane (
¼0.00). Carbons bearing boron sub-
d) are reported in parts per
4. Experimental
4.1. Materials
d
d
d
d
Commercial reagents were purchased from SigmaeAldrich,
Fisher Scientific, Alfa Aesar, TCI America, Strem Chemicals Inc., or
Frontier Scientific and were used without further purification un-
less otherwise noted. Solvents were purified via passage through
packed columns as described by Pangborn and co-workers32 (THF,
Et2O, CH3CN, CH2Cl2/dry neutral alumina; hexane, benzene, and
toluene/dry neutral alumina and Q5 reactant; DMSO, DMF/acti-
vated molecular sieves). All water was deionized prior to use.
stituents were not observed (quadrupolar relaxation). High0-
resolution mass spectra (HRMS) were performed by Furong Sun,
Haijun Yao, and Beth Eves at the University of Illinois School of
Chemical Sciences Mass Spectrometry Laboratory. X-ray crystallo-
graphic analyses were carried out by Dr. Danielle Gray at the Uni-
versity of Illinois George L. Clark X-ray facility.
4.4. MIDA boronate 1
4.2. General experimental procedures
Unless noted, all reactions were performed in flame-dried round
bottom or modified Schlenk flasks fitted with rubber septa under
a positive pressure of argon or nitrogen. Organic solutions were
concentrated via rotary evaporation under reduced pressure with
a bath temperature of 35e40 ꢀC. Reactions were monitored by
analytical thin layer chromatography (TLC) performed using the
indicated solvent on E. Merck silica gel 60 F254 plates (0.25 mm).
To a 3 L three-neck round bottom flask equipped with a stir bar
were added B(OMe)3 (94 mL, 840 mmol) and THF (600 mL). The
solution was cooled to ꢁ78 ꢀC. Vinylmagnesium bromide (1.0 M in
THF, 800 mL, 800 mmol) was added dropwise via cannula over 2 h
45 min. The resulting solution was stirred at ꢁ78 ꢀC for 15 min,
followed by stirring at 23 ꢀC for 2 h 30 min. In a separate 2 L three-
neck round bottom flask equipped with a stir bar, internal ther-
mometer, and distillation apparatus were added dry MIDA (235.0 g,
1.6 mol) and DMSO (600 mL). The solution was heated with an oil
bath to an internal temperature of 110e115 ꢀC. The borate sus-
pension was added dropwise to the hot MIDA solution via a Teflon
cannula dropwise over 2 h 10 min, keeping the internal tempera-
ture between 105 and 115 ꢀC. After full addition of the borate so-
lution, the reaction solution was cooled to 23 ꢀC. The resulting
solution was transferred to a separatory funnel containing H2O
(1 L), brine (1 L), EtOAc (1.5 L), and acetone (1 L). The mixture was
shaken and the aqueous layer was removed and extracted with
EtOAc/acetone (2:1, 2ꢂ600 mL). The combined organic layers were
washed with H2O (2ꢂ500 mL). The combined water washes were
back extracted with EtOAc/acetone (2:1, 2ꢂ300 mL). The combined
organic phases were dried over MgSO4, filtered, and concentrated
in vacuo. The resulting solid was suspended in 300 mL acetone and
4 L Et2O was added to precipitate the product. The resulting solid
was collected by vacuum filtration to yield vinyl MIDA boronate 1 as
Compounds were visualized by exposure to a UV lamp (
l
¼254 nm)
and/or a solution of basic KMnO4 followed by brief heating using
a Varitemp heat gun. MIDA boronates are compatible with standard
silica gel chromatography, including standard loading techniques.
Column chromatography was performed using standard methods33
or on a Teledyne-Isco CombiFlash Rf purification system using
ꢀ
Merck silica gel grade 9385 (60 A, 230e400 mesh). For loading,
compounds were adsorbed onto non acid-washed Celite in vacuo
from an acetone solution. Specifically, for a 1 g mixture of crude
material the sample is dissolved in reagent grade acetone
(25e50 mL) and to the flask is added Celite 545 Filter Aid (5e15 g).
The mixture is then concentrated in vacuo to afford a powder,
which is then loaded on top of a silica gel column. The procedure is
typically repeated with a small amount of acetone (5 mL) and Celite
(2 g) to ensure quantitative transfer.
4.3. Structural analysis
1H NMR spectra were recorded at 23 ꢀC on one of the following
instruments: Varian Unity 400, Varian Unity 500, Varian Unity
Inova 500NB. Chemical shifts (d) are reported in parts per million

E.M. Woerly et al. / Tetrahedron 69 (2013) 7732e7740
7737
a white solid (81.2 g, 55%). Spectral data for 1 were consistent with
0.05 mmol) was added THF (5.0 mL). The solution was stirred at
23 ꢀC for 30 min.
those previously reported from our laboratories.13
The freshly prepared catalyst solution was used in the following
reaction: in a glovebox, to a 20 mL vial with stir bar, charged with
MIDA boronate 2 (261.9 mg, 1.0 mmol) was added Ag2CO3 (1.10 g,
4.0 mmol). Phenyl boronic acid (182.8 mg, 1.5 mmol) was added as
a solution in THF (5.0 mL). The prepared catalyst solution was
added in one portion. The vial was sealed with a septum cap and
removed from the glovebox. The solution was stirred at 40 ꢀC for
24 h. The reaction mixture was filtered through a pad of Celite,
concentrated in vacuo, dry loaded onto Celite from an acetone so-
lution, and purified via flash chromatography on silica (Et2O/MeCN
100:0/80:20) to afford MIDA boronate 3 (158.0 mg, 61%).
4.5. MIDA boronate 2
To a 2 L round bottom flask equipped with a stir bar and charged
with vinyl MIDA boronate 1 (25.0 g, 137 mmol) was added CH2Cl2
(1.2 L). The resulting clear, colorless solution was cooled to 0 ꢀC in
an ice bath. Neat bromine (12.5 mL, 239 mmol) was added drop-
wise over 5 min to give a cloudy orange solution. The solution was
warmed to 23 ꢀC over 30 min. The resulting orange solution was
concentrated in vacuo to give a yellow solid. Residual bromine was
removed by azeotroping with CH2Cl2 (2ꢂ100 mL). The resulting
solid was suspended in MeCN (1 L).1,8-Diazabicyclo[5.4.0]undec-7-
ene (DBU, 51.0 mL, 342 mmol) was added in one portion. The
resulting mixture stirred at 23 ꢀC for 1 h. The solution was poured
into 1 M aq HCl (1 L) and diluted with EtOAc/acetone (3:1, 1 L). After
shaking, the layers were separated. The organic layer was washed
with saturated aqueous sodium bisulfite/brine (3:2, 1ꢂ500 mL) and
brine (1ꢂ250 mL). The organic layer was dried over MgSO4, filtered,
and concentrated in vacuo. The resulting residue was passed
through a plug of silica, eluting with acetone. The resulting solid
was suspended in THF (50 mL) onto which Et2O (1.8 L) was layered
to precipitate the product. The product 2 was collected by vacuum
filtration (24.0 g, 67%).
1H NMR (400 MHz, acetone-d6)
d 7.42e7.38 (m, 2H), 7.33e7.28
(m, 2H), 7.26e7.21 (m, 1H), 5.73 (br d, J¼3.0 Hz, 1H), 5.69 (br s, 1H),
4.23 (d, J¼17.0 Hz, 2H), 3.85 (d, J¼17.0 Hz, 2H), 2.82 (s, 3H). 13C NMR
(125 MHz, acetone-d6) d 168.9, 145.2, 129.1, 128.3, 128.1, 127.3, 62.6,
47.6. HRMS (ESIþ) calculated for C13H15BNO4 (MþH)þ: 260.1094.
Found: 260.1094. TLC (Et2O/MeCN 6:1) Rf¼0.44, visualized by short
wave UV. MIDA boronate 3 is commercially available.26
4.8. 1,1-Disubstituted olefin 6
In a glovebox, to a 20 mL vial with stir bar, charged with MIDA
boronate 3 (100.0 mg, 0.39 mmol, 1.0 equiv) was added 4-
iodoacetephenone (113.9 mg, 0.46 mmol, 1.2 equiv), second gen.
SPhosPd cycle (20.9 mg, 0.029 mmol, 0.075 equiv), and THF
(3.5 mL). The vial was sealed with a septum cap and removed from
the glovebox. To the reaction solution was added 1 M aq NaOH via
syringe (2.9 mL, 2.9 mmol). The solution was stirred at 23 ꢀC for 4 h.
The reaction mixture was poured into a separatory funnel con-
taining aqueous sodium phosphate buffer (0.5 M, pH 7.0, 10 mL)
and diluted with Et2O (10 mL). The mixture was shaken and the
layers were separated. The aqueous phase was extracted with Et2O
(2ꢂ10 mL). The combined organics were dried over MgSO4, filtered,
and then concentrated in vacuo. The crude material was dry loaded
onto Celite from an acetone solution, and purified via flash chro-
matography on silica (hexane/EtOAc 100:0/90:10) to afford 1,1-
disubstituted olefin 6 (63.5 mg, 74%). Spectral data for 6 were
consistent with those previously reported.35
1H NMR (500 MHz, acetone-d6)
d 6.39 (br s, 1H), 6.19 (br s, 1H),
4.37 (d, J¼17.0 Hz, 2H), 4.16 (d, J¼17.0 Hz, 2H), 3.16 (s, 3H). 13C NMR
(125 MHz, acetone-d6)
d
168.4, 129.5, 63.4, 47.2. HRMS (ESIþ) cal-
culated for C7H10BBrNO4 (MþH)þ: 261.9886. Found: 261.9873. X-
ray quality crystals were grown by vapor diffusion of Et2O into
a dissolved solution of 2 in acetone.34 MIDA boronate 2 is com-
mercially available.26
4.6. General procedure for Table 1
In a glovebox, to a 7 mL vial containing a stir bar and silver salt
(0.4 mmol, 4.0 equiv) was added a 0.25 mL aliquot of each of the
following three stock solutions: (1) 262 mg MIDA boronate 2 in
2.5 mL THF (0.1 mmol, 1.0 equiv of 2 added to each reaction); (2)
183 mg phenyl boronic acid in 2.5 mL THF (0.15 mmol, 1.5 equiv of
boronic acid added to each reaction); (3) a solution of 0.05 mmol
palladium salt and 0.2 mmol ligand in 2.5 mL THF was prepared and
stirred at 23 ꢀC for 30 min before adding an aliquot to the reaction
vials (0.005 mmol, 0.05 equiv of palladium added to each reaction
and 0.02 mmol, 0.2 equiv of ligand added to each reaction). An
additional 0.25 mL of THF was added to each reaction. The vials
were capped, removed from the glovebox, and placed in a 40 ꢀC
heating block with stirring for 24 h. The crude reaction mixtures
were filtered through a plug of Celite, concentrated in vacuo, and
analyzed by 1H NMR.
4.9. General procedure for Table 2
Preparation of catalyst solution. In a glovebox, to a 20 mL vial
charged with dpph (136.4 mg, 0.30 mmol) and Pd2dba3 (68.7 mg,
0.075 mmol) was added THF (7.5 mL). The solution was stirred at
23 ꢀC for 30 min.
The freshly prepared catalyst solution was used in the following
reactions: in a glovebox, to a 7 mL vial with stir bar, charged with
MIDA boronate 2 (26.2 mg, 0.1 mmol) was added Ag2CO3 (110.0 mg,
0.4 mmol). Boronic acid (0.15 mmol) was added, followed by THF
(0.50 mL). An aliquot of the prepared catalyst solution (0.50 mL)
was added in one portion. The vial was sealed with a septum cap
and removed from the glovebox. The solution was stirred at 40 ꢀC
for 24 h. The reaction mixture was filtered through a pad of Celite,
concentrated in vacuo, and analyzed by 1H NMR. Select samples
were dry loaded onto Celite from an acetone solution, and purified
via flash chromatography on silica (Et2O/MeCN 100:0/80:20) to
afford the MIDA boronate 8.
4.7. MIDA boronate 3
Preparation of catalyst solution. In a glovebox, to a 7 mL vial
charged with dpph (90.9 mg, 0.20 mmol) and Pd2dba3 (45.8 mg,

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E.M. Woerly et al. / Tetrahedron 69 (2013) 7732e7740
4.9.1. MIDA boronate 8a.
an inseparable mixture of isomers to provide 60.6 mg (0.50 mmol
reaction), 45% yield.
1H NMR (400 MHz, acetone-d6)
d 7.70e7.36 (m, 4H), 5.77 (br d,
J¼3.0 Hz, 1H), 5.73 (br s, 1H), 4.25 (d, J¼17.0 Hz, 2H), 3.91 (d,
J¼17.0 Hz, 2H), 3.85 (s, 3H), 2.81 (s, 3H). 13C NMR (125 MHz, ace-
tone-d6)
d 168.8, 167.1, 134.9, 130.2, 129.2, 129.0, 128.5, 62.7, 52.2,
47.7. HRMS (ESIþ) calculated for C15H17BNO6 (MþH)þ: 318.1149.
Found: 318.1143. TLC (Et2O/MeCN 6:1) Rf¼0.32, visualized by short
wave UV.
Based on the 1H NMR of the crude reaction mixture, the reaction
proceeded to >95% conversion and a >20:1 of 8/9 was obtained.
Compound 8a was isolated by column chromatography to provide
57.8 mg (0.25 mmol reaction), 81% yield.
1H NMR (400 MHz, acetone-d6)
d 7.71e7.33 (m, 4H), 6.85e6.68
4.9.5. MIDA boronate 8e.
(m, 2H), 5.90e5.68 (m, 2H), 5.29e5.17 (m, 1H), 4.25 (d, J¼17.0 Hz,
2H), 3.88 (d, J¼17.0 Hz, 2H), 2.81 (s, 3H). 13C NMR (125 MHz, ace-
tone-d6)
d 168.9, 137.4, 136.7, 135.2, 128.5, 128.0, 127.0, 113.7, 62.6,
47.6. HRMS (ESIþ) calculated for C15H17BNO4 (MþH)þ: 286.1251.
Found: 286.1248. TLC (Et2O/MeCN 6:1) Rf¼0.44, visualized by short
wave UV.
Based on the 1H NMR of the crude reaction mixture, the reaction
proceeded to 70% conversion and an 8:1 of 8/9 was obtained.
Compounds 8e and 9e were isolated by column chromatography as
an inseparable mixture of isomers to provide 57.6 mg (0.50 mmol
reaction), 39% yield.
4.9.2. MIDA boronate 8b.
1H NMR (400 MHz, acetone-d6)
d 7.79e7.52 (m, 4H), 5.82 (br d,
J¼3.0 Hz, 1H), 5.79 (br s, 1H), 4.27 (d, J¼17.0 Hz, 2H), 3.95 (d,
J¼17.0 Hz, 2H), 2.82 (s, 3H). 13C NMR (125 MHz, acetone-d6)
d 168.8,
134.2, 132.9. 130.4, 129.3, 119.4, 111.0, 62.6, 47.7. HRMS (ESIþ) cal-
culated for C14H14BN2O4 (MþH)þ: 285.1047. Found: 285.1038. TLC
(Et2O/MeCN 6:1) Rf¼0.32, visualized by short wave UV.
Based on the 1H NMR of the crude reaction mixture, the reaction
proceeded to >95% conversion and a >20:1 of 8/9 was obtained.
Compound 8b was isolated by column chromatography to provide
61.1 mg (0.25 mmol reaction), 90% yield.
1H NMR (500 MHz, acetone-d6)
d 7.24 (m, 1H), 7.21e7.18 (m, 2H),
4.9.6. MIDA boronate 8f.
7.10e7.05 (m, 1H), 5.73 (br d, J¼3.0 Hz, 1H), 5.68 (br s, 1H), 4.23 (d,
J¼17.0 Hz, 2H), 3.83 (d, J¼17.0 Hz, 2H), 2.83 (s, 3H), 2.31 (s, 3H). 13C
NMR (125 MHz, acetone-d6) d 168.7, 145.2, 138.3, 128.9, 128.8, 127.9,
127.6, 125.3, 62.6, 47.4, 21.4. 11B NMR (128 MHz, acetone-d6)
d 11.4.
HRMS (ESIþ) calculated for C14H17BNO4 (MþH)þ: 274.1251. Found:
274.1245. TLC (Et2O/MeCN 6:1) Rf¼0.44, visualized by short wave
Based on the 1H NMR of the crude reaction mixture, the reaction
proceeded to 90% conversion and a 4:1 of 8/9 was obtained. Com-
pounds 8f and 9f were isolated by column chromatography as an
inseparable mixture of isomers to provide 59.1 mg (0.50 mmol
reaction), 43% yield.
UV.
4.9.3. MIDA boronate 8c.
1H NMR (400 MHz, acetone-d6)
d 7.49e7.00 (m, 4H), 5.70 (br d,
J¼3.0 Hz, 1H), 5.67 (br s, 1H), 4.23 (d, J¼17.0 Hz, 2H), 3.88 (d,
J¼17.0 Hz, 2H), 2.80 (s, 3H). 13C NMR (125 MHz, acetone-d6)
d 163.6,
130.2, 130.1, 129.2, 128.4, 115.8, 62.6, 47.6. HRMS (ESIþ) calculated
for C13H14BFNO4 (MþH)þ: 278.1000. Found: 278.0994. TLC (Et2O/
MeCN 6:1) Rf¼0.37, visualized by short wave UV.
Based on the 1H NMR of the crude reaction mixture, the reaction
proceeded to >95% conversion and a >20:1 of 8/9 was obtained.
Compound 8c was isolated by column chromatography to provide
68.6 mg (0.50 mmol reaction), 50% yield.
4.9.7. MIDA boronate 8g.
1H NMR (400 MHz, acetone-d6)
d 7.18e7.04 (m, 4H), 5.84 (d,
J¼3.5 Hz, 1H), 5.52 (br s), 4.19 (d, J¼17.0 Hz, 2H), 3.88 (d, J¼17.0 Hz,
2H), 3.03 (s, 3H), 2.29 (s, 3H). 13C NMR (125 MHz, acetone-d6)
d
168.7, 144.9, 136.2, 130.9, 128.5, 128.3, 127.0, 126.1, 62.6, 47.4, 20.6.
HRMS (ESIþ) calculated for C14H17BNO4 (MþH)þ: 274.1251. Found:
274.1252. TLC (Et2O/MeCN 6:1) Rf¼0.44, visualized by short wave
UV.
Based on the 1H NMR of the crude reaction mixture, the reaction
proceeded to 85% conversion and a >20:1 of 8/9 was obtained.
Compound 8g was isolated by column chromatography to provide
21.1 mg (0.1 mmol reaction), 66% yield.
4.9.4. MIDA boronate 8d.
1H NMR (500 MHz, acetone-d6)
d
6.59 (d, J¼2.5 Hz, 2H), 6.38 (t,
J¼2.5 Hz, 1H), 5.75 (m, 2H), 4.24 (d, J¼17.0 Hz, 2H), 3.84 (d,
J¼17.0 Hz, 2H), 3.77 (s, 6H), 2.86 (s, 3H). 13C NMR (125 MHz, ace-
tone-d6)
d B
169.0, 161.7, 147.4, 127.8, 106.3, 99.7, 62.9, 55.5, 47.6. 11
Based on the 1H NMR of the crude reaction mixture, the reaction
proceeded to 85% conversion and a 10:1 of 8/9 was obtained.
Compounds 8d and 9d were isolated by column chromatography as
NMR (128 MHz, acetone-d6)
d
11.3. HRMS (ESIþ) calculated for
C15H19BNO6 (MþH)þ: 320.1305. Found: 320.1295. TLC (Et2O/MeCN
6:1) Rf¼0.31, visualized by short wave UV.

E.M. Woerly et al. / Tetrahedron 69 (2013) 7732e7740
7739
4.9.8. MIDA boronate 8h.
1H NMR (500 MHz, acetone-d6)
d
6.20 (d, J¼15.0 Hz, 1H), 5.90
(dt, J¼15.0 Hz, 6.5 Hz, 1H), 5.61 (br s, 1H), 5.34 (br d, J¼3.5 Hz, 1H),
4.25 (d, J¼17.0 Hz, 2H), 4.01 (d, J¼17.0 Hz, 2H), 2.97 (s, 3H), 2.06 (m,
2H), 1.41 (s, J¼7.0 Hz, 2H), 0.89 (t, J¼7.0 Hz, 3H). 13C NMR (125 MHz,
CDCl3)
(128 MHz, CDCl3)
d
167.3,132.9,132.8,125.9, 61.9, 47.0, 35.4, 22.5,13.7. 11B NMR
d
10.7. HRMS (ESIþ) calculated for C12H19BNO4
(MþH)þ: 252.1407. Found: 252.1405. TLC (Et2O/MeCN 6:1) Rf¼0.48,
Based on the 1H NMR of the crude reaction mixture, the reaction
proceeded to 50% conversion and a >20:1 of 8/9 was obtained.
Compound 8h was isolated by column chromatography to provide
40.4 mg (0.50 mmol reaction), 28% yield.
visualized by short wave UV.
4.9.12. MIDA boronate 8l.
1H NMR (400 MHz, acetone-d6)
d 7.35e7.00 (m, 4H), 5.58 (br s,
1H), 5.55 (br d, J¼3.0 Hz, 1H), 4.18 (d, J¼17.0 Hz, 2H), 3.79 (d,
J¼17.0 Hz, 2H), 3.12 (s, 6H), 2.75 (s, 3H). 13C NMR (125 MHz, ace-
tone-d6)
d 168.3, 129.5, 128.9, 128.4, 125.2, 113.2, 62.7, 47.5, 40.5.
HRMS (ESIþ) calculated for C15H20BN2O4 (MþH)þ: 303.1516. Found:
Based on the 1H NMR of the crude reaction mixture, the reaction
proceeded to 80% conversion and a >20:1 of 8/9 was obtained.
Compound 8l was isolated by column chromatography to provide
46.3 mg (0.25 mmol reaction), 65% yield.
303.1524. TLC (Et2O/MeCN 6:1) Rf¼0.31, visualized by short wave
UV.
1H NMR (400 MHz, acetone-d6)
d 7.47e7.19 (m, 5H), 5.58 (d,
4.9.9. MIDA boronate 8i.
J¼2.0 Hz, 1H), 5.31 (d, J¼2.0 Hz, 1H), 5.25 (d, J¼2.0 Hz, 1H), 5.23 (d,
J¼2.0 Hz, 1H), 4.16 (d, J¼17.0 Hz, 2H), 3.91 (d, J¼17.0 Hz, 2H), 3.05 (s,
3H). 13C NMR (125 MHz, acetone-d6)
d 168.6, 154.5, 142.3, 129.1,
128.8, 128.2, 128.1, 113.9, 62.7, 47.5. HRMS (ESIþ) calculated for
C15H17BNO4 (MþH)þ: 286.1251. Found: 286.1244. TLC (Et2O/MeCN
6:1) Rf¼0.36, visualized by short wave UV.
Based on the 1H NMR of the crude reaction mixture, the reaction
proceeded to 95% conversion and a >20:1 of 8/9 was obtained.
Compound 8i was isolated by column chromatography to provide
24.6 mg (0.1 mmol reaction), 82% yield.
Acknowledgements
We gratefully acknowledge the NIH for funding (R01
GM080436). E.M.W. is an NSF Graduate Fellow and M.D.B. is an
Early Career Scientist of the Howard Hughes Medical Institute.
1H NMR (500 MHz, acetone-d6)
d
7.59 (d, J¼8.0 Hz, 1H), 7.47 (d,
J¼8.0 Hz, 1H), 7.29 (t, J¼7.0 Hz, 1H), 7.21 (t, J¼7.0 Hz, 1H), 6.92 (s,
1H), 6.45 (s, 1H), 5.80 (d, J¼2.5 Hz, 1H), 4.41 (d, J¼17.0 Hz, 2H), 4.23
(d, J¼17.0 Hz, 2H), 3.03 (s, 3H). 13C NMR (125 MHz, acetone-d6)
References and notes
d
168.9, 158.4, 154.8, 129.8, 126.5, 125.0, 123.3, 121.7, 111.2, 104.5,
62.9, 47.7. 11B NMR (128 MHz, acetone-d6)
d
11.3. HRMS (ESIþ)
1. (a) Boehm, M. F.; Zhang, L.; Badea, B. A.; White, S. K.; Mais, D. E.; Suto, C. M.;
Goldman, M. E.; Heyman, R. A. J. Med. Chem. 1994, 37, 2930e2941; (b) Carney, J.
R.; Krenisky, J. M.; Williamson, R. T.; Luo, J. J. Nat. Prod. 2002, 65, 203e205; (c)
Borris, R. P.; Cordell, G. A. J. Nat. Prod. 1984, 47, 270e278; (d) Jarboe, C. H.; Porter,
L. A.; Buckler, R. T. J. Med. Chem. 1968, 11, 729e731.
2. (a) Arnone, A.; Dimodugno, V.; Nasini, G.; Depava, O. V. Gazz. Chim. Ital. 1990,
120, 397e401; (b) Corey, E. J.; Roberts, B. E. J. Am. Chem. Soc. 1997, 119,
12425e12431; (c) Oppolzer, W.; Thirring, K. J. Am. Chem. Soc. 1982, 104,
4978e4979; (d) Ghosh, A. K.; Wang, Y. J. Am. Chem. Soc. 2000, 122,
11027e11028.
calculated for C15H15BNO5 (MþH)þ: 300.1043. Found: 300.1049.
4.9.10. MIDA boronate 8j.
3. (a) Organ, M. G.; Bratovanov, S. Tetrahedron Lett. 2000, 41, 6945e6949; (b)
Taber, D. F.; Christos, T. E.; Neubert, T. D.; Batra, D. J. Org. Chem. 1999, 64,
9673e9678; (c) Tiefenbacher, K.; Mulzer, J. Angew. Chem., Int. Ed. 2008, 47,
2548e2555.
4. Hamze, A.; Giraud, A.; Messaoudi, S.; Provot, O.; Peyrat, J.-F.; Bignon, J.; Liu, J.-
M.; Wdzieczak-Bakala, J.; Thoret, S.; Dubois, J.; Brion, J.-D.; Alami, M. Chem-
MedChem 2009, 4, 1912e1924.
5. (a) Dounay, A. B.; Overman, L. E. Chem. Rev. 2003, 103, 2945e2963; (b) Cabri,
W.; Candiani, I.; DeBernardinis, S.; Francalanci, F.; Penco, S. J. Org. Chem. 1991,
56, 5796e5800.
6. (a) Sabarre, A.; Love, J. Org. Lett. 2008, 10, 3941e3944; (b) Hamze, A.; Brion, J.-
D.; Alami, M. Org. Lett. 2012, 14, 2782e2785; (c) Bhilare, S. V.; Darvatkar, N. B.;
Deorukhkar, A. R.; Raut, D. G.; Trivedi, G. K.; Salunkhe, M. M. Tetrahedron Lett.
2009, 50, 893e896; (d) Hashimoto, T.; Kutubi, S.; Izumi, T.; Rahman, A.; Kita-
mura, T. J. Organomet. Chem. 2011, 696, 99e105; (e) Li, R.; Wang, S. R.; Lu, W.
Org. Lett. 2007, 9, 2219e2222; (f) Reetz, M. T.; Sommer, K. Eur. J. Org. Chem.
2003, 3485e3496.
Based on the 1H NMR of the crude reaction mixture, the reaction
proceeded to 50% conversion and a >20:1 of 8/9 was obtained.
Compound 8j was isolated by column chromatography to provide
31.3 mg (0.50 mmol reaction), 24% yield.
1H NMR (400 MHz, acetone-d6)
d
7.80e7.00 (m, 3H), 5.83 (br s,
1H), 5.56 (br s, 1H), 4.30 (d, J¼17.0 Hz, 2H), 4.00 (d, J¼17.0 Hz, 2H),
3.13 (s, 3H). 13C NMR (125 MHz, acetone-d6)
d 168.3, 129.5, 128.5,
126.1, 125.7, 125.3, 62.9, 47.8. HRMS (ESIþ) calculated for
C11H13BNO4S (MþH)þ: 266.0658. Found: 266.0647. TLC (Et2O/
MeCN 6:1) Rf¼0.39, visualized by short wave UV.
7. (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457e2483; (b) Hall, D. G. Bo-
ronic Acids; Wiley-VCH: Weinheim, Germany, 2005.
4.9.11. MIDA boronate 8k.
8. (a) Zweifel, G.; Brown, H. C. Org. React. 1963, 13, 1e35; (b) Miyaura, N.; Maruoka,
K. Synthesis of Organometallic Compounds; Wiley: Chichester, UK, 1997.
9. (a) Jang, H.; Zhugralin, A. R.; Lee, Y.; Hoveyda, A. H. J. Am. Chem. Soc. 2011, 133,
7859e7871; (b) Gao, F.; Hoveyda, A. H. J. Am. Chem. Soc. 2010, 132,
10961e10963; (c) Takagi, J.; Takahashi, K.; Ishiyama, T.; Miyaura, N. J. Am. Chem.
Soc. 2002, 124, 8001e8006; (d) Morrill, C.; Funk, T. W.; Grubbs, R. H. Tetrahedron
Lett. 2004, 45, 7733e7736; (e) Moran, W. J.; Morken, J. P. Org. Lett. 2006, 8,
2413e2415; (f) Takahashi, K.; Ishiyama, T.; Miyaura, N. J. Organomet. Chem.
2001, 625, 47e53.
Based on the 1H NMR of the crude reaction mixture, the reaction
proceeded to 90% conversion and a >20:1 of 8/9 was obtained.
Compound 8k was isolated by column chromatography to provide
47.7 mg (0.25 mmol reaction), 76% yield.
10. Gillis, E. P.; Burke, M. D. J. Am. Chem. Soc. 2007, 129, 6716e6717.
11. Lee, S. J.; Gray, K. C.; Paek, J. S.; Burke, M. D. J. Am. Chem. Soc. 2008, 130,
466e468.

7740
E.M. Woerly et al. / Tetrahedron 69 (2013) 7732e7740
12. Gillis, E. P.; Burke, M. D. J. Am. Chem. Soc. 2008, 130, 14084e14085.
13. Uno, B. E.; Gillis, E. P.; Burke, M. D. Tetrahedron 2009, 65, 3130e3138.
14. Knapp, D. M.; Gillis, E. P.; Burke, M. D. J. Am. Chem. Soc. 2009, 131, 6961e6963.
15. Struble, J. R.; Lee, S. J.; Burke, M. D. Tetrahedron 2010, 66, 4710e4718.
16. Woerly, E. M.; Cherney, A. H.; Davis, E. K.; Burke, M. D. J. Am. Chem. Soc. 2010,
132, 6941e6943.
27. (a) See Refs. 13 and 17; (b) Brown, H. C.; Subrahmanyam, C.; Hamaoka, T.;
Ravindran, N.; Bowman, D. H.; Misumi, S.; Unni, M. K.; Somayaji, V.; Bhat, N. G.
J. Org. Chem. 1989, 54, 6068e6075; (c) Morrill, C.; Grubbs, R. H. J. Org. Chem.
2003, 68, 6031e6034.
28. For examples see: (a) Chauvelier, J. Ann. Chim. 1948, 12, 393e444; (b) Mitchell,
R. H. Can. J. Chem. 1977, 55, 210e219; (c) Ref. 7.
17. Lee, S. J.; Anderson, T. M.; Burke, M. D. Angew. Chem., Int. Ed. 2010, 49,
8860e8863.
18. Ballmer, S. G.; Gillis, E. P.; Burke, M. D. Org. Synth. 2009, 86, 344e359.
19. Dick, G. R.; Knapp, D. M.; Gillis, E. P.; Burke, M. D. Org. Lett. 2010, 12, 2314e2317.
20. Woerly, E. M.; Struble, J. R.; Palyam, N.; O’Hara, S. P.; Burke, M. D. Tetrahedron
2011, 67, 4333e4343.
21. Fujii, S.; Chang, S. Y.; Burke, M. D. Angew. Chem., Int. Ed. 2011, 50, 7862e7864.
22. Li, J.; Burke, M. D. J. Am. Chem. Soc. 2011, 133, 13774e13777.
23. Dick, G. R.; Woerly, E. M.; Burke, M. D. Angew. Chem., Int. Ed. 2012, 51,
2667e2672.
24. Gray, K. C.; Palacios, D. S.; Dailey, I.; Endo, M. M.; Uno, B. E.; Wilcock, B. C.;
Burke, M. D. Proc. Natl. Acad. Sci. U.S.A. 2012, 109, 2234e2239.
25. Mancilla, T.; Contreras, R.; Wrackmeyer, B. J. Organomet. Chem. 1986, 307, 1e6.
26. www.aldrich.com/mida. Catalog number for 2: Sigma Aldrich: MIDA009.
29. Sigma Aldrich: 704415.
30. (a) Uenishi, Y.; Beau, J.-M.; Armstrong, R. W.; Kishi, Y. J. Am. Chem. Soc. 1987, 109,
4756e4758; (b) Weibel, J.-M.; Blanc, A.; Pale, P. Chem. Rev. 2008,108, 3149e3173.
31. (a) Driver, M. S.; Hartwig, J. F. J. Am. Chem. Soc. 1996, 118, 7217e7218; (b) Al-
cazar-Roman, L. M.; Hartwig, J. F.; Rheingold, A. L.; Liable-Sands, L. M.; Guzei, I.
A. J. Am. Chem. Soc. 2000, 122, 4618e4630; (c) Birkholz, M.-N.; Freixa, Z.; van
Leeuwen, P. W. N. M. Chem. Soc. Rev. 2009, 38, 1099e1118.
32. Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K.; Timmers, F. J.
Organometallics 1996, 15, 1518e1520.
33. Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923e2925.
34. CCDC 937425 contains the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge Crystallographic
Data Centre via www.cdcc.cam.ac.uk/data_request.cif.
35. Xu, Z.-H.; McArthur, C. R.; Leznoff, C. C. Can. J. Chem. 1983, 61, 1405e1409.