Ethynyl MIDA boronate: A readily accessible and highly versatile building block for small molecule synthesis

Article abstract of DOI:10.1016/j.tet.2010.04.020

Ethynyl N-methyliminodiacetic acid (MIDA) boronate is a very useful building block for small molecule synthesis. This compound can serve as both a bifunctional acetylene equivalent with the capacity for terminus-selective bis-functionalization and a versatile starting material for the preparation of a wide range of other MIDA boronate building blocks.

Full text of DOI:10.1016/j.tet.2010.04.020

Tetrahedron 66 (2010) 4710e4718
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Ethynyl MIDA boronate: a readily accessible and highly versatile building block for
small molecule synthesis
*
Justin R. Struble, Suk Joong Lee, Martin D. Burke
Howard Hughes Medical Institute, Roger Adams Laboratory, Department of Chemistry, University of Illinois at UrbanaeChampaign, 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:
Ethynyl N-methyliminodiacetic acid (MIDA) boronate is a very useful building block for small molecule
synthesis. This compound can serve as both a bifunctional acetylene equivalent with the capacity for
terminus-selective bis-functionalization and a versatile starting material for the preparation of a wide
range of other MIDA boronate building blocks.
Received 19 March 2010
Received in revised form 1 April 2010
Accepted 2 April 2010
Available online 9 April 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Dedicated to Professor Brian Stoltz with
congratulations for his receipt of the Tetra-
hedron Young Investigator Award
Keywords:
MIDA boronates
Iterative cross-coupling
Small molecule synthesis
Alkynes Sonogashira coupling
DielseAlder
1. Introduction
conditions but can be readily hydrolyzed with mild aqueous base to
yield a reactive boronic acid.4,5 This enables the iterative cross-
Many powerful strategies have been developed to advance the
facility with which small molecules can be prepared in the labo-
ratory. Of these, that which is sometimes called ‘the building block
approach’1 can be particularly enabling. In one idealized version of
this strategy,2 a collection of pre-assembled building blocks having
all of the required functional groups pre-installed in the correct
oxidations states and with the desired stereochemical relationships
are brought together using only one stereospecific reaction in an
iterative fashion. The inherent modularity of most small molecule
natural products and pharmaceuticals suggests that the theoretical
scope of this approach is substantial.
With the goal of maximally enabling such a strategy, we are
developing a platform of N-methyliminodiacetic acid (MIDA) boro-
nate3 building blocks.2 MIDA boronates have a wide range of
favorable chemical and physical properties that collectively render
them highly useful in this context. Specifically, these compounds are
air-stable, monomeric, highly crystalline, free-flowing solids that
can be stored indefinitely on the benchtop under air, are soluble in
many organic solvents, and are uniformly compatible with silica gel
chromatography.2,4e8 With respect to reactivity, the MIDA boronate
functional group is inert toward cross-coupling under anhydrous
coupling (ICC) of bifunctional MIDA boronates bearing a halide or
pseudohalide. MIDA boronates are also stable to a wide range of
other common reaction conditions, making it possible to utilize
multistep synthesis pathways to prepare complex organoborane
building blocks from simple MIDA boronate starting materials.6,7 In
addition, the in situ rate-controlled hydrolysis of MIDA boronates in
the presence of aqueous base can produce dramatic improvements
in the yields of cross-coupling reactions.8 This ‘slow-release’ meth-
odology has transformed even some of the most notoriously
unstable boronic acids into air-stable and highly effective cross-
coupling partners. Given the favorable features of this platform, the
development of highly versatile MIDA boronate building blocks
represents an important goal.
In this vein, ethynyl MIDA boronate 1 was very attractive. First, the
ethyne subunit appears in wide range of natural products, pharma-
ceuticals, and materials. Thus, a simple, non-toxic, and air-stable
bifunctional ethyne equivalent with the capacity for terminus-selec-
tive bis-functionalization would be of substantial utility (Fig. 1A).
Moreover, given the compatibility of MIDA boronates with many
common reaction conditions6,7 and the considerable versatility of the
alkyne functional group, we recognized that 1 could potentially serve
as a very effective starting material for the preparation of many other
types of useful MIDA boronate building blocks (Fig. 1B).9
* Corresponding author. E-mail address: burke@scs.uiuc.edu (M.D. Burke).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.04.020

J.R. Struble et al. / Tetrahedron 66 (2010) 4710e4718
4711
MeN
A
MeN
B
O
O
B
O
O
O
O
O
O
1
MeN
MeN
B
B
B
O
O
O
O
O
O
O
O
MeN
MeN
MeN
B
O
O
B
O
O
B
1
O
O
O
O
O
O
O
O
MeN
MeN
B
O
O
B
O
O
O
O
O
O
Figure 1. A. Ethynyl MIDA boronate 1 is an air and chromatographically stable, highly crystalline solid that can serve as a bifunctional surrogate for acetylene. B. This compound also
represents a highly versatile starting material for the preparation of a range of other types of useful MIDA boronate building blocks.
As part of our efforts to prepare a wide range of bifunctional
haloalkenyl MIDA boronate building blocks for the stereospecific
synthesis of polyene motifs via ICC, we recently reported that 1 can
be prepared via the trimethylborate salt derived from reacting
ethynylmagnesium bromide 2 with trimethylborate (Scheme 1).10
We further discovered that running this MIDA transligation
reaction at >115 ꢀC11 can provide good yields of 1 on the decagram
scale.10 Importantly, all of the reagents used in this synthesis are
environmentally friendly and can be accessed on very large scale for
very low cost, including the MIDA ligand. Specifically, MIDA can be
prepared on the kilogram scale from the commodity chemicals
iminodiacetic acid, formic acid, and formaldehyde.12,13 Iminodi-
acetic acid is a starting material used to make herbicides (e.g.,
Round-upÒ), environmental metal chelating reagents, and surfac-
tants. As a result, tens of thousands of metric tons of iminodiacetic
acid are produced annually14 and this material is very inexpensive.15
MIDA is also biodegradable.16
observed when 1 was coupled to 1-bromo-4-cyano benzene using
Pd(PPh3)4 as catalyst and piperidine as base in THF (Table 1, entry
1). Alternatively, switching to PdCl2(PPh3)2 and triethylamine led to
a substantial improvement in yield (entry 2). A survey of solvents
revealed that while both DMSO and CH3CN led to inferior results
(entries 3 and 4), an excellent isolated yield (93%) was observed
when this reaction was performed in DMF (entry 5).
The scope of aryl halides amenable to Sonogashira coupling
with 1 under these standard conditions is very good. Specifically,
as shown in Table 2, a series of electron-deficient aryl bromides
4aeg (entries 1e7), electron neutral or rich aryl iodides 4iel
(entries 9e12), as well as 2-heterocyclic bromides 4m and 4n
(entries 13 and 14) all provided good to excellent yields of the
desired coupling products 5aem. Under these conditions, electron
rich aryl bromides (e.g., 4h, entry 8) were competent electrophiles
but were less effective than the corresponding iodides (e.g., 4i,
entry 9).
Scheme 1. (Ref. 10).
Consistent with many other MIDA boronates that we have
prepared and studied, 1 is an air-stable, monomeric, highly
crystalline, free-flowing solid that is soluble in many common
organic solvents and fully compatible with silica gel chromatog-
raphy.10 We attribute the stability of this building block (in con-
trast to the corresponding highly unstable boronic acid) to the
pyramidalized and rigid MIDA boronate functional group lacking
a reactive p-orbital on the boron atom4,6 (see Scheme 1 for
crystal structure). We herein describe the utility of 1 in both ICC
and building block synthesis applications.
Table 1
NC
Br
4a
1.15 equiv
5 mol% Pd catalyst
MeN
MeN
10 mol% CuI
B
O
O
NC
B
O
O
base (3 equiv)
0.20 M in solvent
23 °C, 3–6 h
O
O
O
O
5a
1
1.00 equiv
2. Results
Entry
Pd catalyst
Base
Solvent
% Yield
The utility of 1 as a bifunctional acetylene equivalent with the
capacity for sequential, distinct derivitization of the two alkyne
termini was first explored.17 There are a few prior reports of
Sonogashira couplings with ethynyl boranes that proceed with
specialized substrates.18 As shown in Table 1, only low yields were
1
2
3
4
5
Pd(PPh3)4
Piperidine
ET3N
ET3N
ET3N
ET3N
THF
THF
DMSO
CH3CN
DMF
30
78
47
59
93
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2

4712
J.R. Struble et al. / Tetrahedron 66 (2010) 4710e4718
Table 2
To complete the proposed sequential bis-functionalization of 1,
we tested the capacity of alkynyl MIDA boronates to undergo cross-
coupling with organohalides. SuzukieMiyaura couplings with
alkynyl boronic acids are rare,19 presumably due to the instability of
these intermediates. However, there are several reports with more
stable alkynyl boronic esters,20 alkynyl(triisopropoxy)borate
salts,21,22 and trifluoroborate salts.23 We wanted to determine
whether it might be possible to achieve good yields in the cross-
coupling of alkynyl boronic acids via employment of the corre-
sponding alkynyl MIDA boronates such as 5j under ‘slow-release’
cross-coupling conditions.8 Specifically, we have determined that
exposure of MIDA boronates to K3PO4 in organic solvent/water
mixtures leads to a slow hydrolysis of the MIDA boronate over the
course of several hours producing a constant supply of fresh boronic
acid in the reaction mixture. If the rate of cross-coupling is fast rel-
ative to the rate of boronic acid release, then the boronic acid is
rapidly consumed in a productive coupling reaction thereby avoid-
ing its undesired in situ decomposition.
To test the hypothesis that alkynyl boronic acids could also
benefit from this slow-release methodology, 5h and p-nitroben-
zene were treated with Pd(OAc)2, SPhos, and aq K3PO4 in dioxane:
H2O 5:1 at 60 ꢀC for 6 h (Scheme 2), and an 86% isolated yield was
observed. Thus, building block 1 has the potential to serve as a very
useful bifunctional acetylene equivalent.
The utility of 1 as a versatile starting material for the prepara-
tion of other MIDA boronate building blocks was also explored. As
described above, in addition to being unreactive under a wide
range of anhydrous cross-coupling conditions, the MIDA boronate
functional group is stable to many common synthetic reagents.6,7,24
Previous reports have demonstrated that these reagents include
oxidants, reductants, soft nucleophiles, electrophiles, acids, and
a wide range of anhydrous bases. Given these compatibilities and
the remarkable versatility of alkynes, we investigated whether
a range of previously unexplored reactions could be performed on
the ethyne subunit of 1 while similarly leaving the MIDA boronate
functional group intact.
X
MeN
B O
MeN
B O
4
O
O
PdCl2(PPh3)2
DMF, Et3N
23 C, 4Š7 h
O
O
O
O
1
5
Entry
1
4
5
Isolated yield (%)
93
MeN
B O
NC
Br
4a
NC
NC
O
O
O
5a
MeN
B O
NC
2
3
4
5
6
7
95
92
69
80
65
72
Br
4b
CN
O
O
O
5b
CN
MeN
B O
Br
4c
O
O
O
5c
MeN
F3C
Br
4d
F3C
B O
O
O
O
5d
MeN
O
O
Br
4e
B O
O
Me
O
O
Me
5e
MeN
B O
O2N
Br
O2N
O
O
O
4f
5f
O2N
O2N
MeN
Me
Br
4g
Me
B O
O
O
O
5g
MeN
MeO
Br
4h
8
9
33
80
MeO
B O
O
O
O
5h
MeO
I
5h
As shown in Scheme 3, dicyclohexyl borane-catalyzed hydro-
boration with pinacol borane25 proceeded smoothly to generate the
very useful bis-borylated ethylene equivalent 7.5,26 This differen-
tially ligated diboron reagent has the capacity for selective cross-
coupling of the sp2-hybridized pinacol ester terminus while the
sp3-hybridized MIDA boronate remains inert.5,27 Relative to that
previously reported,5 the hydroboration of 1 to generate 7 repre-
sents a more efficient and practical route to this very useful
building block. As communicated recently,10 1 can also be trans-
formed into trans-1-iodo-2-ethenyl MIDA boronate via a one-pot
hydrostannylation/iododestannylation sequence. We herein dem-
onstrate that intermediate, 1-tributylstannyl-2-ethenyl MIDA bor-
onate 8, can be isolated in excellent yield. Lynchpin reagents 7 and
8 both possess substantial potential for terminus-selective double
functionalizations via ICC.
4i
MeN
B O
Me
I
10
11
12
75
88
88
Me
O
O
O
4j
5i
Me
Me
MeN
I
B O
O
O
O
5j
4k
MeO
MeO
MeN
I
B O
O
O
O
5k
MeN
4l
Br
13
14
67
55
S
B O
O
O
O
S
4m
5l
The compatibility of 1 with alkyne reduction was also explored
(Scheme 3).28 For example, providing an alternative synthesis of
vinyl MIDA boronate 9,7,8 1 underwent efficient semireduction in
the presence of Lindlar’s catalyst and 1 atm of hydrogen without
MeN
Br
4n
B
O
O
N
O
O
N
5m
Br
NO2
MeN
4f
MeO
NO2
MeO
B
O
O
Pd(OAc)2, SPhos
K3PO4 (excess)
dioxane:H2O 5:1
60 °C, 6 h
O
O
6
5h
86%
Scheme 2.

J.R. Struble et al. / Tetrahedron 66 (2010) 4710e4718
4713
Scheme 3.
perturbing the MIDA boronate functional group. Alternatively,
complete reduction to the corresponding alkane 10 was achieved
with unpoisoned Pd under a H2 pressure of 200 psi. When com-
bined with the capacity for Sonogashira coupling described above,
this demonstrated compatibility of the MIDA boronate functional
group with hydrogenative reduction might prove useful in the
preparation of a range of new alkenyl and alkyl MIDA boronate
building blocks.
As a final example, we found that 1 also smoothly undergoes
DielseAlder cycloaddition9 with diene 1129 followed by spontane-
ous extrusion of carbon monoxide to generate the pentasubstituted
aryl MIDA boronate 12 (Scheme 3, the structure of 12 was con-
firmed via single crystal X-ray analysis). It is notable that the MIDA
boronate proved to be stable even when this cycloaddition was
executed at 160 ꢀC for 16 h. Collectively, the compatibility of 1 with
hydroboration, radical-mediated hydrostannylation, hydrogenative
reduction, and cycloaddition demonstrate that this MIDA boronate
possesses substantial utility in the synthesis of building blocks for
small molecule synthesis.
platform for the synthesis of a wide range of pharmaceuticals,
natural products, and materials.
4. Experimental
4.1. Materials
Commercial reagents were purchased from SigmaeAldrich,
Fisher Scientific, Alfa Aesar, TCI America, or Frontier Scientific,
and were used without further purification unless otherwise
noted. Palladium(II) acetate and trans-dichlorobis(triphenyl-
phosphine) palladium(II) were purchased from Strem and used
without further purification. Copper(I) iodide was purchased
from Strem and purified according to Ref. 34. Solvents were
purified via passage through packed columns as described by
Pangborn and co-workers31 (THF, Et2O, 1,4-dioxane, CH3CN,
CH2Cl2/dry neutral alumina; hexane, benzene, and toluene, dry
neutral alumina and Q5 reactant; DMSO, DMF/activated molec-
ular sieves). All water was deionized prior to use. Triethylamine
was freshly distilled under an atmosphere of nitrogen from
CaH2.
3. Summary and conclusions
Maximally harnessing the building block approach for small
molecule synthesis requires access to a range of air-stable, highly
versatile, and ideally commercially-available building blocks rep-
resenting the substructural elements that most commonly appear
in natural products and pharmaceuticals. MIDA boronates repre-
sent a very promising platform for this type of synthesis strategy.
The results disclosed herein demonstrate that ethynyl MIDA boro-
nate 1 can serve as a bifunctional acetylene equivalent for the
controlled assembly of disubstituted alkynes via ICC. Moreover,
executing a range of transformations on the alkyne subunit while
leaving the MIDA boronate functionality intact represents a prom-
ising approach for preparing a range of other useful building blocks.
Several of the MIDA boronates described herein, including 1, are
now commercially-available.30 Collectively, these findings help
expand the utility of ICC with MIDA boronates as a versatile
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 in oven-dried (125 ꢀC, >2 h)
vials under an atmosphere of argon. Organic solutions were con-
centrated via rotary evaporation under reduced pressure with
a bath temperature of 40 ꢀC. Reactions were monitored by analyt-
ical thin layer chromatography (TLC) performed using the indicated
solvent on E. Merck silica gel 60 F254 plates (0.25 mm). Compounds
were visualized by exposure to a UV lamp (
l¼254 nm), a solution of
KMnO4 or an acidic solution of p-anisaldehyde, followed by brief
heating using a Varitemp heat gun. MIDA boronates are compatible
with standard silica gel chromatography,32 including standard
loading techniques.

4714
J.R. Struble et al. / Tetrahedron 66 (2010) 4710e4718
4.3. Structural analysis
4.5.1. MIDA boronate (5a). Prepared according to general pro-
cedure A using CuI (6.1 mg, 0.0320 mmol, 0.106 equiv), PdCl2(PPh3)4
(11.6 mg, 0.0165 mmol, 0.0546 equiv), ethynyl MIDA boronate 1
(54.7 mg, 0.302 mmol, 1.00 equiv), 4-bromobenzonitrile (61.7 mg,
0.339 mmol, 1.12 equiv), DMF (1.50 mL), and NEt3 (0.125 mL,
0.898 mmol, 2.97 equiv). The reaction was allowed to stir at 23 ꢀC
for 4 h. Purification via flash chromatography (SiO2; gradient:
1:1/3:1 EtOAc/Et2O) afforded 5a as a white crystalline solid
(80 mg, 93%).
1H NMR spectra were recorded at 20 ꢀC on one of the following
instruments: Varian Unity 400, Varian Unity 500, Varian Unity
Inova 500NB. Chemical shifts (
(ppm) downfield from tetramethylsilane and referenced to residual
protium in the NMR solvent (CD2HCN,
¼1.93, center line; acetone-
d6 ¼2.05, center line). Data are
¼2.04, center line; DMSO-d6,
d) are reported in parts per million
d
d
d
reported as follows: chemical shift, multiplicity (s¼singlet,
d¼doublet, t¼triplet, q¼quartet, quint¼quintet, sext¼sextet,
sept¼septet, m¼multiplet, b¼broad, app¼apparent), coupling
constant (J) in Hertz (Hz), and integration. 13C NMR spectra were
recorded on a Varian Unity 500 or 13C NMR spectra for compounds
5aem, 6, and 12 were recorded at 20 ꢀC on a Varian Unity 600 using
1H NMR (500 MHz, acetonitrile-d3)
(d, J¼8.0 Hz, 2H), 4.04 (d, J¼17.0 Hz, 2H), 3.92 (d, J¼17.0 Hz, 2H),
d
7.71 (d, J¼8.0 Hz, 2H), 7.62
3.09 (s, 3H). 13C NMR (150 MHz, acetone-d6)
d
168.4, 133.3, 133.0,
128.5, 118.8, 112.7, 98.6, 62.4, 48.5. HRMS (EIþ) calculated for
C14H11BN2O4 (M)þ: 282.0812, found: 282.0804.
a d1 relaxation time of 20 s. Chemical shifts (
per million downfield from tetramethylsilane and referenced to
carbon resonances in the NMR solvent (CD3CN,
¼1.30, center line,
acetone-d6, ¼39.50, center line).
¼29.80, center line, DMSO-d6,
d) are reported in parts
NC
d
MeN
d
d
B
O
O
Carbons bearing boron substituents were not observed (quad-
rupolar relaxation). High resolution mass spectra (HRMS) were
performed by Furong Sun and Dr. Steve Mullen at the University of
Illinois School of Chemical Sciences Mass Spectrometry Laboratory.
X-ray crystallographic analyses of 1 and 12 were carried out by Dr.
Danielle Gray and Amy Fuller at the University of Illinois George L.
Clark X-ray facility.
O
O
5b
4.5.2. MIDA boronate (5b). Prepared according to general pro-
cedure using CuI (6.4 mg, 0.0336 mmol, 0.114 equiv),
A
PdCl2(PPh3)4 (10.1 mg, 0.0144 mmol, 0.0490 equiv), ethynyl MIDA
boronate 1 (53.2 mg, 0.294 mmol, 1.00 equiv), 3-bromobenzonitrile
(64.8 mg, 0.356 mmol, 1.21 equiv), DMF (1.50 mL), and NEt3
(0.125 mL, 0.898 mmol, 3.05 equiv). The reaction was allowed to
stir at 23 ꢀC for 4.5 h. Purification via flash chromatography (SiO2;
gradient: 1:1/3:1 EtOAc/Et2O) afforded 5b as a white crystalline
solid (79 mg, 95%).
4.4. General procedure A: Sonogashira coupling
In a glove box, a 7-mL vial equipped with a stir-bar was
charged with CuI (10 mol %), PdCl2(PPh3)4 (5 mol %), ethynyl
MIDA boronate 1 (0.300 mmol, 1.00 equiv), and the aryl halide
(0.345 mmol, 1.15 equiv). The vial was sealed with a PTFE-lined
septum screw-cap and removed from the glove box. Under
a positive pressure of Ar(g), DMF (1.50 mL), and NEt3 (0.125 mL,
8.98 mmol, 2.99 equiv) were added via syringe. The reaction was
allowed to stir at 23 ꢀC for 4e7 h, absorbed onto silica gel using
acetone, loaded onto a silica gel column and purified by flash
column chromatography to afford the desired compound. When
necessary, recrystallization was performed by layering Et2O onto
a concentrated solution of the MIDA boronate in CH2Cl2. The
crystalline solid was collected by vacuum filtration and washed
with Et2O.
1H NMR (500 MHz, acetonitrile-d3)
d 7.87e7.86 (m, 1H), 7.77 (dt,
J¼8.0,1.2 Hz,1H), 7.73 (td, J¼1.2, 8.0 Hz,1H), 7.55e7.52 (m,1H), 4.04
(d, J¼17 Hz, 2H), 3.93 (d, J¼17 Hz, 2H), 3.10 (s, 3H). 13C NMR
(150 MHz, acetonitrile-d3)
d 168.7, 136.9, 136.1, 133.2, 130.6, 124.9,
118.9, 113.5, 98.5, 62.5, 48.8. HRMS (EIþ) calculated for C14H11BN2O4
(M)þ: 282.0812, found: 282.0815.
CN
MeN
B
O
O
O
O
5c
4.5. General procedure B: Sonogashira coupling
4.5.3. MIDA boronate (5c). Prepared according to general pro-
cedure using CuI (6.1 mg, 0.0320 mmol, 0.108 equiv),
In a glove box, a 7-mL vial equipped with a stir-bar was
charged with CuI (10 mol %), PdCl2(PPh3)4 (5 mol %), and ethynyl
MIDA boronate 1 (0.300 mmol, 1.00 equiv). The vial was sealed
with a PTFE-lined septum screw-cap and removed from the glove
A
PdCl2(PPh3)4 (10.5 mg, 0.0150 mmol, 0.0507 equiv), ethynyl MIDA
boronate 1 (53.5 mg, 0.296 mmol, 1.00 equiv), 2-bromobenzonitrile
(70.0 mg, 0.384 mmol, 1.30 equiv), DMF (1.50 mL), and NEt3
(0.125 mL, 0.898 mmol, 3.05 equiv). The reaction was allowed to
stir at 23 ꢀC for 5 h. Purification via flash chromatography (SiO2;
gradient: 1:1/3:1 EtOAc/Et2O) afforded 5c as an off-white solid
(77 mg, 92%).
box. Under
a positive pressure of Ar(g), the aryl halide
(0.345 mmol, 1.15 equiv), DMF (1.50 mL), and NEt3 (0.125 mL,
0.898 mmol, 2.99 equiv) were added via syringe. The reaction
was allowed to stir at 23 ꢀC for 4e7 h, absorbed onto silica gel
using acetone, loaded onto a silica gel column and purified by
flash column chromatography to afford the desired compound.
When necessary, recrystallization was performed by layering
Et2O onto a concentrated solution of the MIDA boronate in
CH2Cl2. The crystalline solid was collected by vacuum filtration
and washed with Et2O.
1H NMR (500 MHz, acetonitrile-d3)
d
7.74 (d, J¼7.5 Hz, 1H),
7.68e7.63 (m, 2H), 7.54e7.50 (m, 1H), 4.08 (d, J¼17.0 Hz, 2H), 3.95
(d, J¼17.0 Hz, 2H), 3.18 (s, 3H). 13C NMR (150 MHz, acetonitrile-d3)
d
168.6, 133.9, 133.8, 133.5, 130.3, 127.0, 118.5, 115.8, 96.8, 62.5, 49.0.
HRMS (EIþ) calculated for C14H11BN2O4 (M)þ: 282.0812, found:
282.0818.
MeN
MeN
F3C
B
O
O
NC
B O
O
O
O
O
O
5a
5d

J.R. Struble et al. / Tetrahedron 66 (2010) 4710e4718
4715
4.5.4. MIDA boronate (5d). Prepared according to general pro-
cedure B using CuI (5.8 mg, 0.0304 mmol, 0.100 equiv), PdCl2(PPh3)4
(10.9 mg, 0.0155 mmol, 0.0512 equiv), ethynyl MIDA boronate 1
(57.3 mg, 0.317 mmol, 1.00 equiv), 4-bromo-2-nitrotoluene
(86.5 mg, 0.400 mmol, 1.26 equiv), DMF (1.50 mL), and NEt3
(0.125 mL, 0.898 mmol, 2.83 equiv). The reaction was allowed to stir
at 23 ꢀC for 6 h. Purification via flash chromatography (SiO2, 1:1
EtOAc/Et2O) followed by recrystallization afforded 5g as an orange
crystalline solid (72 mg, 72%).
(54.8 mg, 0.303 mmol,1.00 equiv), 4-bromobenzotrifluoride (48 mL,
0.348 mmol, 1.15 equiv), DMF (1.50 mL), and NEt3 (0.125 mL,
0.898 mmol, 2.96 equiv). The reactionwas allowed to stir at 23 ꢀC for
5.5 h. Purification via flash chromatography (SiO2, 1:1 EtOAc/Et2O)
followed by recrystallization afforded 5d as a white crystalline solid
(68 mg, 69%).
1H NMR (500 MHz, DMSO-d6)
d
8.08 (d, J¼1.0 Hz, 1H), 7.73
(dd, J¼8.0, 1.5 Hz, 1H), 7.53 (d, J¼8.0 Hz, 1H), 4.33 (d, J¼17.0 Hz, 2H),
4.15 (d, J¼17.0 Hz, 2H), 3.08 (s, 3H), 2.51 (s, 3H). 13C NMR (150 MHz,
1H NMR (500 MHz, acetone-d6)
d
7.71 (app s, 4H), 4.36
DMSO-d6) d 168.7, 148.9, 135.8, 133.4, 133.2, 127.1, 121.3, 96.9, 61.5,
(d, J¼17.0 Hz, 2H), 4.20 (d, J¼17.0 Hz, 2H), 3.35 (s, 3H). 13C NMR
47.9, 19.4. HRMS (EIþ) calculated for C14H13BN2O6 (M)þ: 316.0867,
found: 316.0862.
(150 MHz, acetone-d6)
128.0, 126.2 (q, J¼4 Hz), 125.0 (q, J¼270 Hz), 98.8, 62.4, 48.5. HRMS
d
168.5,133.2 (t, J¼16 Hz),130.5 (q, J¼32 Hz),
(EIþ) calculated for C14H11BF3NO4 (M)þ: 325.0733, found: 325.0748.
MeN
MeO
B
O
O
MeN
O
O
O
Me
5h
B
O
O
O
O
5e
4.5.8. MIDA boronate (5h). Prepared according to general pro-
cedure using CuI (5.7 mg, 0.0299 mmol, 0.100 equiv),
PdCl2(PPh3)4 (10.2 mg, 0.0145 mmol, 0.0486 equiv), ethynyl MIDA
boronate (54.0 mg, 0.298 mmol, 1.00 equiv), 4-iodoanisole
(81.7 mg, 0.349 mmol, 1.17 equiv), DMF (1.50 mL), and NEt3
(0.125 mL, 0.898 mmol, 3.01 equiv). The reaction was allowed to
stir at 23 ꢀC for 6.5 h. Purification via flash chromatography (SiO2,
1:1 EtOAc/Et2O) followed by recrystallization afforded 5h as a tan
crystalline solid (69 mg, 80%).
A
4.5.5. MIDA boronate (5e). Prepared according to general procedure
A using CuI (5.9 mg, 0.0310 mmol, 0.102 equiv), PdCl2(PPh3)4
(15.5 mg, 0.0192 mmol, 0.0634 equiv), ethynyl MIDA boronate 1
(54.9 mg, 0.303 mmol,1.00 equiv), 4-bromoacetophenone (55.0 mg,
0.476 mmol, 1.57 equiv), DMF (1.50 mL), and NEt3 (0.125 mL,
0.898 mmol, 2.96 equiv). The reactionwas allowed to stir at 23 ꢀC for
4 h. Purification via flash chromatography (SiO2, 1:1 EtOAc/Et2O)
afforded 5e as a light yellow solid (72 mg, 80%).
1
1H NMR (500 MHz, acetonitrile-d3)
d
7.54 (d, J¼8.5 Hz, 2H), 7.01
1H NMR (500 MHz, DMSO-d6)
(d, J¼8.5 Hz, 2H), 4.33 (d, J¼17.0 Hz, 2H), 4.16 (d, J¼17.0 Hz, 2H),
d
7.96 (d, J¼8.5 Hz, 2H), 7.63
(d, J¼8.5 Hz, 2H), 4.14 (d, J¼17.0 Hz, 2H), 4.02 (d, J¼17.0 Hz, 2H),
3.90 (s, 3H), 3.19 (s, 3H). 13C NMR (150 MHz, acetonitrile-d3)
d 168.8,
161.0, 134.2, 115.5, 115.0, 101.1, 62.4, 56.0, 48.7. HRMS (ESIþ) calcu-
3.09 (s, 3H), 2.58 (s, 3H). 13C NMR (150 MHz, DMSO-d6)
d 197.3,
lated for C14H15BNO5 (MþH)þ: 288.1043, found: 288.1043.
168.7, 136.4, 131.8, 128.4, 126.1, 98.5, 61.5, 48.0, 26.8. HRMS (EIþ)
calculated for C15H14BNO5 (M)þ: 299.0965, found: 299.0970.
MeN
MeN
Me
B
O
O
O
O
O2N
B
O
O
5i
O
O
5f
4.5.9. MIDA boronate (5i). Prepared according to general pro-
cedure using CuI (5.2 mg, 0.0273 mmol, 0.0872 equiv),
PdCl2(PPh3)4 (10.8 mg, 0.0154 mmol, 0.0492 equiv), ethynyl MIDA
boronate (56.7 mg, 0.313 mmol, 1.00 equiv), 4-iodotoluene
4.5.6. MIDA boronate (5f). Prepared according to general pro-
cedure using CuI (5.5 mg, 0.0289 mmol, 0.0973 equiv),
a
A
PdCl2(PPh3)4 (10.3 mg, 0.0147 mmol, 0.0495 equiv), ethynyl MIDA
boronate 1 (53.7 mg, 0.297 mmol, 1.00 equiv), 4-bromoacetophe-
none (40.7 mg, 0.340 mmol, 1.14 equiv), DMF (1.50 mL), and NEt3
(0.125 mL, 0.898 mmol, 3.02 equiv). The reaction was allowed to
stir at 23 ꢀC for 4 h. Purification via flash chromatography (SiO2;
gradient: 1:1/3:1 EtOAc/Et2O) followed by recrystallization
afforded 5f as an orange crystalline solid (58 mg, 65%).
1
(76.1 mg, 0.349 mmol, 1.12 equiv), DMF (1.50 mL), and NEt3
(0.125 mL, 0.898 mmol, 2.86 equiv). The reaction was allowed to
stir at 23 ꢀC for 4.5 h. Purification via flash chromatography (SiO2,
1:1 EtOAc/Et2O) followed by recrystallization afforded 5i as white
crystalline solid (64 mg, 75%).
1H NMR (500 MHz, acetone-d6)
d
7.37 (d, J¼8.0 Hz, 2H), 7.18
1H NMR (500 MHz, DMSO-d6)
(d, J¼9.0 Hz, 2H), 4.35 (d, J¼17.0 Hz, 2H), 4.17 (d, J¼17.0 Hz, 2H), 3.11
d
8.23 (d, J¼8.5 Hz, 2H), 7.76
(d, J¼8.0 Hz, 2H), 4.32 (d, J¼17.0 Hz, 2H), 4.16 (d, J¼17.0 Hz, 2H),
3.30 (s, 3H), 2.33 (s, 3H). 13C NMR (150 MHz, acetone-d6)
d 168.6,
(s, 3H). 13C NMR (150 MHz, DMSO-d6)
d 168.7, 147.0, 132.8, 129.1,
139.6, 132.4, 129.9, 120.9, 100.7, 62.2, 48.4, 21.3. HRMS (EIþ) calcu-
lated for C14H14BNO4 (M)þ: 271.1016, found: 271.1005.
123.8, 97.4, 61.6, 48.0. HRMS (EIþ) calculated for C13H11BN2O6 (M)þ:
302.0710, found: 302.0706.
Me
MeN
MeN
B
O
O
Me
O2N
B
O
O
O
O
O
O
5j
5g
4.5.10. MIDA boronate (5j). Prepared according to general pro-
cedure using CuI (5.5 mg, 0.0289 mmol, 0.0941 equiv),
PdCl2(PPh3)4 (11.1 mg, 0.0158 mmol, 0.0515 equiv), ethynyl MIDA
boronate (55.5 mg, 0.307 mmol, 1.00 equiv), 2-iodotoluene
4.5.7. MIDA boronate (5g). Prepared according to general pro-
cedure A using CuI (6.2 mg, 0.0325 mmol, 0.102 equiv), PdCl2(PPh3)4
(10.9 mg, 0.0155 mmol, 0.0489 equiv), ethynyl MIDA boronate 1
B
1

4716
J.R. Struble et al. / Tetrahedron 66 (2010) 4710e4718
(45
m
L, 0.354 mmol, 1.15 equiv), DMF (1.50 mL), and NEt3 (0.125 mL,
(34 mL, 0.349 mmol, 1.11 equiv), DMF (1.50 mL), and NEt3 (0.125 mL,
0.898 mmol, 2.92 equiv). The reaction was allowed to stir at 23 ꢀC
for 5.5 h. Purification via flash chromatography (SiO2, 1:1 EtOAc/
Et2O) afforded 5j as a white crystalline solid (73 mg, 88%).
0.898 mmol, 2.85 equiv). The reaction was allowed to stir at 23 ꢀC
for 6 h. Purification via flash chromatography (SiO2, 3:2 Et2O:
CH3CN) followed by recrystallization afforded 5m as a pale-green
crystalline solid (45 mg, 55%).
1H NMR (500 MHz, acetone-d6)
d
7.44 (d, J¼8.0 Hz, 1H),
7.27e7.24 (m, 2H), 7.19e7.17 (m, 1H), 4.34 (d, J¼17.0 Hz, 2H), 4.19
1H NMR (500 MHz, acetonitrile-d3)
d 8.58 (br s, 1H), 7.75 (dt,
(d, J¼17.0 Hz, 2H), 3.34 (s, 3H), 2.42 (s, 3H). 13C NMR (150 MHz,
J¼8.0, 1.5 Hz, 1H), 7.54 (d, J¼3.8, 1.0 Hz, 1H), 7.35e7.33 (m, 1H), 4.33
acetone-d6)
d 168.6, 140.9, 132.8, 130.2, 129.5, 126.4, 123.6, 99.3,
(d, J¼17.0 Hz, 2H), 4.18 (d, J¼17.0 Hz, 2H), 3.12 (s, 3H). 13C NMR
62.3, 48.5, 20.8. HRMS (EIþ) calculated for C14H14BNO4 (M)þ:
271.1016, found: 271.1020.
(150 MHz, DMSO-d6) d 168.7, 150.0, 142.1, 136.7, 127.6, 123.9, 98.9,
61.6, 48.0. HRMS (ESIþ) calculated for C12H12BN2O4 (MþH)þ:
259.0890, found: 259.0885.
MeO
MeN
B
O
O
MeO
NO2
O
O
5k
6
4.5.11. MIDA boronate (5k). Prepared according to general pro-
cedure using CuI (6.4 mg, 0.0336 mmol, 0.110 equiv),
PdCl2(PPh3)4 (10.7 mg, 0.0152 mmol, 0.0508 equiv), ethynyl MIDA
boronate 1 (55.2 mg, 0.305 mmol, 1.00 equiv), 3-iodoanisole (42 L,
0.353 mmol, 1.16 equiv), DMF (1.50 mL), and NEt3 (0.125 mL,
0.898 mmol, 2.94 equiv). The reaction was allowed to stir at 23 ꢀC
for 7 h. Purification via flash chromatography (SiO2,1:1 EtOAc/Et2O)
afforded 5k as a white crystalline solid (69 mg, 90%).
B
4.5.14. 1-Methoxy-4-((4-nitrophenyl)ethynyl)benzene
(6). Under
ambient atmosphere a 40-mL vial was equipped with a magnetic
stir-bar and charged with Pd(OAc)2 (2.8 mg, 0.0125 mmol,
0.050 equiv), SPhos (10.5 mg, 0.0256 mmol, 0.100 equiv), 1-bromo-
4-nitrobenzene (50.3 mg, 0.249 mmol, 1.00 equiv), and MIDA bor-
onate 5j (76.8 mg, 0.300 mmol, 1.20 equiv).The vial was sealed with
a PTFE-lined septum screw-cap and placed under an atmosphere of
Ar(g). To the vial was added 1,4-dioxane (9.0 mL) via syringe and
the resulting mixture stirred for 10 min at 23 ꢀC. To the vial was
added aq K3PO4 (degassed by sparging with Ar(g) for 45 min; 3.0 M,
1.8 mL, 5.4 mmol, 21.6 equiv). The vial was placed in a 60 ꢀC oil bath
with stirring for 6 h. The mixture was allowed to cool to 23 ꢀC,
transferred to a separatory funnel and diluted with aq NaOH (1.0 M,
8 mL). The mixture was extracted with Et2O (3ꢁ10 mL). The com-
bined organic fractions were washed with brine (15 mL), dried over
Na2SO4, filtered, and concentrated in vacuo. The crude orange
residue was purified via flash chromatography (SiO2; gradient:
100:0/19:1 hexanes/EtOAc) to provide 6 as a bright yellow crys-
talline solid (54 mg, 86%).
m
1H NMR (500 MHz, acetone-d6)
d
7.27 (app t, J¼8.0 Hz, 1H),
7.07e7.03 (m, 2H), 6.95 (ddd, J¼8.5, 2.5, 1.0 Hz, 1H), 4.33
(d, J¼17.0 Hz, 2H), 4.18 (d, J¼17.0 Hz, 2H), 3.80 (s, 3H), 3.31 (s, 3H).13C
NMR (150 MHz, acetone-d6) d 168.5, 160.3, 130.4, 130.3, 124.8, 117.3,
115.8, 100.5, 62.3, 55.5, 48.4. HRMS (EIþ) calculated for C14H14BNO5
(M)þ: 287.0965, found: 287.0953.
MeN
B
O
O
O
O
S
5l
1H NMR (500 MHz, acetone-d6)
(d, J¼9.0 Hz, 2H), 7.54 (d, J¼9.0 Hz, 2H), 7.00 (d, J¼9.0 Hz, 2H), 3.85
d
8.25 (d, J¼9.0 Hz, 2H), 7.75
4.5.12. MIDA boronate (5l). Prepared according to general pro-
cedure using CuI (6.0 mg, 0.0315 mmol, 0.107 equiv),
(s, 3H). 13C NMR (150 MHz, acetone-d6)
d 161.5, 147.7, 134.2, 132.9,
B
131.2, 124.5, 115.2, 114.7, 95.5, 87.2, 55.7. HRMS (EIþ) calculated for
C15H11NO3 (M)þ: 253.0739, found: 253.0744.
PdCl2(PPh3)4 (11.4 mg, 0.0162 mmol, 0.0549 equiv), ethynyl MIDA
boronate 1 (53.4 mg, 0.295 mmol, 1.00 equiv), 2-bromothiazole
(35 mL, 0.362 mmol,1.23 equiv), DMF (1.50 mL), and NEt3 (0.125 mL,
0.898 mmol, 3.04 equiv). The reaction was allowed to stir at 23 ꢀC
for 6 h. Purification via flash chromatography (SiO2, EtOAc) fol-
lowed by recrystallization afforded 5l as a light-yellow crystalline
solid (52 mg, 67%).
MeN
B O
O
O
Me
Me
Me
B
O
O
1H NMR (500 MHz, acetone-d6)
d
7.38 (dd, J¼5.0, 1.0 Hz, 1H), 7.19
O
(dd, J¼3.8, 1.0 Hz, 1H), 6.94 (dd, J¼5.0, 3.8 Hz, 1H), 4.22
7
Me
(d, J¼17.0 Hz, 2H), 4.08 (d, J¼17.0 Hz, 2H), 3.18 (s, 3H). 13C NMR
(150 MHz, acetone-d6)
d 168.5, 133.6, 128.7, 128.0, 123.6, 93.1, 62.4,
48.4. HRMS (EIþ) calculated for C11H10BNO4S (M)þ: 263.0424,
found: 263.0441.
4.5.15. MIDA boronate (7)5. To a 40-mL flame-dried vial equipped
with a magnetic stir-bar was added ethynyl MIDA boronate 1
(500 mg, 2.8 mmol, 1.0 equiv). The vial was taken into a glove box
wheresolid dicyclohexylborane33 (98 mg, 0.55 mmol, 20 mol %) was
added. The vial was capped with a PTFE-lined septa cap, removed
from the glove box, and placed under N2. To the vial was added THF
MeN
B
O
O
O
O
N
5m
(5.5 mL, 0.50 M) and neat pinacolborane (480 mL, 3.3 mmol,
1.2 equiv). The vial was sealed under N2 and placed in an 85 ꢀC
heating block. The solution turned clear, colorless within 20 min.
After stirring at 85 ꢀC for 17 h, the crude reaction solution was
concentrated in vacuo. The resulting solid was dry loaded onto Celite
from an acetone solution and purified via flash chromatography
4.5.13. MIDA boronate (5m). Prepared according to general pro-
cedure using CuI (6.0 mg, 0.0315 mmol, 0.100 equiv),
PdCl2(PPh3)4 (10.6 mg, 0.0151 mmol, 0.0479 equiv), ethynyl MIDA
B
boronate 1 (57.0 mg, 0.315 mmol, 1.00 equiv), 2-bromopyridine

J.R. Struble et al. / Tetrahedron 66 (2010) 4710e4718
4717
(SiO2; gradient: 100:0/2:1 Et2O/acetone) to afford bisborylated
MIDA boronate 7 as a white solid (717 mg, 84%).
(1.0 mL) and filtered through CeliteÒ. The resulting colorless solu-
tion was concentrated in vacuo to provide 10 as a colorless crys-
talline solid (43 mg, 93%).
1H NMR (500 MHz, acetonitrile-d3)
d
3.92 (d, J¼16.5 Hz, 2H),
MeN
3.76 (d, J¼16.5 Hz, 2H), 2.84 (s, 3H), 0.89 (t, J¼8.0 Hz, 3H), 0.58
(q, J¼8.0 Hz, 2H). 13C NMR (100 MHz, acetonitrile-d3)
d 169.1, 62.6,
B O
O
46.3, 8.0. HRMS (ESIþ) calculated for C7H13BNO4 (MþH)þ: 186.0938,
Bu3Sn
O
O
found: 186.0946.
8
MeN
4.5.16. MIDA boronate (8). A dry 25-mL Schlenk flask equipped
with a magnetic stir-bar was charged with ethynyl MIDA boronate 1
(182 mg, 1.0 mmol, 1.0 equiv) and 2,20-azobis(2-methylpropioni-
trile) (16 mg, 0.10 mmol, 1.0 equiv) and was then placed under N2
atm. To the flask was added THF (5.0 mL) followed by HSnBu3
(0.40 mL, 1.5 mmol, 1.5 equiv). The flask was fitted with a reflux
condenser vented to N2 atmosphere. The solution was heated to
65 ꢀC internal temp (70 ꢀC oil bath) with stirring for 18 h. The
solutionwas allowed to cool to 23 ꢀC and was transferred to a 60-mL
separatory funnel using Et2O (15 mL). The solutionwas washed with
aq 1 M HCl (10 mL), satd aq NaHCO3 (10 mL), and brine (5 mL). The
solution was dried over MgSO4, filtered, and concentrated in vacuo
to afford a colorless oil that was purified via flash chromatography
(SiO2; gradient: 100:0/5:1 Et2O:MeCN) to afford the title com-
pound as a colorless solid (441 mg, 93%).
MeO2C
Ph
B
O
O
O
O
Ph
H
CO Me
2
12
4.5.19. MIDA boronate (12). A 5-mL round-bottom flask was
equipped with a magnetic stir-bar and charged with ethynyl MIDA
boronate 1 (172 mg, 0.950 mmol, 1.00 equiv), dimethyl 2-oxo-
4,5-diphenylcyclopenta-3,5-diene-1,3-dicarboxylate 11 (460 mg,
1.32 mmol, 1.40 equiv), and mesitylene (1.0 mL). The flask was
equipped with a water-jacketed reflux condensor and an Ar(g)
inlet. The reaction was allowed to stir in a 160 ꢀC oil bath for 16 h.
The black reaction mixture was allowed to cool to 23 ꢀC, absorbed
onto silica gel using acetone, and semi-purified via flash chroma-
tography (SiO2, 5:4 EtOAc/Et2O). The semi-purified brown powder
was dissolved in a minimal volume of acetone and then pre-
cipitated by the addition of Et2O with vigorous stirring. Collection
by vacuum filtration and washing with Et2O afforded 12 as a white
powder (269 mg, 56%).
1H NMR (500 MHz, acetone-d6)
d
6.99 (app sext, J¼22.0 Hz, 1H),
6.43 (app sext, J¼22.0 Hz, 1H), 4.19 (d, J¼17.0 Hz, 2H), 3.97
(d, J¼17.0 Hz, 2H), 2.98 (s, 3H), 1.55 (m, 6H), 1.33 (app sext, J¼7.5 Hz,
6H), 0.94 (t, J¼7.5 Hz, 6H), 0.89 (t, J¼7.5 Hz, 9H). 13C NMR (125 MHz,
acetone-d6)
d 169.2, 147.6, 62.3, 47.5, 29.9 (app hept), 27.9 (t), 14.0,
9.8 (t). HRMS (ESIþ) calculated for C19H37BNO4Sn (MþH)þ:
474.1855, found: 474.1838.
1H NMR (500 MHz, acetone-d6)
d 8.00 (s, 1H), 7.14e7.12 (m, 6H),
MeN
7.00e6.99 (m, 4H), 4.43 (d, J¼17.5 Hz, 2H), 4.25 (d, J¼17.5 Hz, 2H),
3.48 (s, 3H), 3.30 (s, 3H), 3.11 (s, 3H). 13C NMR (150 MHz, acetone-
B
O
O
d6) d 172.6, 169.4, 169.3, 142.2, 142.1, 139.9, 139.7, 139.1, 134.3, 134.1,
O
O
131.0, 130.4, 128.0, 127.9, 127.6, 127.4, 64.7, 52.4, 52.1, 50.2. HRMS
9
(EIþ) calculated for C27H24BNO8 (M)þ: 501.1595, found: 501.1586.
4.5.17. Ethenyl MIDA boronate (9)7. An oven-dried 7-mL vial
equipped with a magnetic stir-bar was charged with ethynyl MIDA
boronate 1 (45 mg, 0.25 mmol, 1.0 equiv), Lindlar’s cat. (2.5 mg),
and 1,4-dioxane (1.5 mL). Quinoline (0.015 mL, 0.125 mmol,
0.50 equiv) was added and the vial sealed with a PTFE-lined plastic
screw-cap. The vial was filled with hydrogen gas using a balloon
and the reaction mixture was stirred at 23 ꢀC for 3.5 h. The reaction
mixture was diluted with acetonitrile (1.0 mL) and filtered through
Celite Ò. The crude product was purified via flash chromatography
(SiO2, 19:1 EtOAc/MeCN) to afford 9 as a colorless crystalline solid
(37 mg, 81%).
Acknowledgements
We gratefully acknowledge E.M. Woerly and E.P. Gillis for per-
forming the synthesis of 7 and 8, respectively. We also thank the
NSF (CAREER 0747778), Howard Hughes Medical Institute, the
Arnold and Mabel Beckman Foundation, and Bristol-Myers Squibb
for financial support, Dr. Danielle Gray and Amy Fuller for X-ray
crystallographic analysis, and Dr. Steve Mullen and Furong Sun for
mass spectral analysis. M.D.B. is a Howard Hughes Medical Institute
Early Career Scientist, Beckman Young Investigator, Sloan Founda-
tion Research Fellow, Dreyfus New Faculty Awardee, Bristol-Myers
Squibb Unrestricted Grant in Synthetic Organic Chemistry
Awardee, Eli Lilly Grantee, Amgen Young Investigator, and Astra-
Zeneca Excellence in Chemistry Awardee.
MeN
Me
B
O
O
Supplementary data
O
O
10
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2010.04.020.
4.5.18. Ethyl MIDA boronate (10). An oven-dried 7-mL vial equip-
ped with a magnetic stir-bar was charged with ethynyl MIDA bor-
onate 1 (45 mg, 0.25 mmol, 1.0 equiv), Lindlar’s cat. (5.0 mg), and
1,4-dioxane (1.0 mL). The vial containing this reaction mixture was
placed in a hydrogenation bomb and the hydrogen pressure was
adjusted to 200 psi. The reaction mixture was allowed to stir at
23 ꢀC for 15 h. The reaction mixture was diluted with acetonitrile
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