Interrogating Pd(II) Anion Metathesis Using a Bifunctional Chemical Probe: A Transmetalation Switch

Article abstract of DOI:10.1021/jacs.7b11180

Ligand metathesis of Pd(II) complexes is mechanistically essential for cross-coupling. We present a study of halide→OH anion metathesis of (Ar)Pd^II complexes using vinylBPin as a bifunctional chemical probe with Pd(II)-dependent cross-coupling pathways. We identify the variables that profoundly impact this event and allow control to be leveraged. This then allows control of cross-coupling pathways via promotion or inhibition of organoboron transmetalation, leading to either Suzuki-Miyaura or Mizoroki-Heck products. We show how this transmetalation switch can be used to synthetic gain in a cascade cross-coupling/Diels-Alder reaction, delivering borylated or non-borylated carbocycles, including steroid-like scaffolds.

Full text of DOI:10.1021/jacs.7b11180

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Communication
Interrogating Pd(II) anion metathesis using a
bifunctional chemical probe: A transmetalation switch
John J Molloy, Ciaran P. Seath, Matthew J West, Calum McLaughlin, Neal J.
Fazakerley, Alan R. Kennedy, David James Nelson, and Allan J. B. Watson
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b11180 • Publication Date (Web): 19 Dec 2017
Downloaded from http://pubs.acs.org on December 19, 2017
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Interrogating Pd(II) anion metathesis using a bifunctional
chemical probe: A transmetalation switch
John J. Molloy,a Ciaran P. Seath,a Matthew J. West,a Calum McLaughlin,a Neal J. Fazakerley,b Alan R.
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Kennedy,a David J. Nelson,a and Allan J. B. Watsona*
aDepartment of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL, UK.
bGlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY, UK.
Supporting Information Placeholder
and/or spectroscopic methods to interrogate oxopalladium
transmetalation, with each of these studies providing key insight
into this previously ambiguous process. The Hartwig study proꢀ
vided the most detail on anion metathesis; specifically, equilibriꢀ
um constants for OH→X exchange of (R3P)2Pd(Ar)(OH) using nꢀ
ABSTRACT: Ligand metathesis of Pd(II) complexes is mechaꢀ
nistically essential for crossꢀcoupling. We present a study of halꢀ
ide→OH anion metathesis of (Ar)Pd(II) complexes using viꢀ
nylBPin as a bifunctional chemical probe with Pd(II)ꢀdependent
crossꢀcoupling pathways. We identify the variables that profoundꢀ
ly impact this event and allow control to be leveraged. This then
allows control of crossꢀcoupling pathways via promotion or inhiꢀ
bition of organoboron transmetalation, leading to either Suzukiꢀ
Miyaura or MizorokiꢀHeck products. We show how this
transmetalation switch can be used to synthetic gain in a cascade
crossꢀcoupling/DielsꢀAlder reaction, delivering borylated or nonꢀ
borylated carbocycles, including steroidꢀlike scaffolds.
Bu4NX in H2O/THF (R
= Cy, Ph; X =
I, Br, Cl).5,10
(a) Anion metathesis and oxopalladium transmetalation of organoborons
Amatore and Jutand, Hartwig
Denmark
Ar2
B
HO–
Ar2B(OR)2
L
L
Ar1
L
L
Ar1
OH
Ar1 Ar2
Pd
Pd
HO
X
OH
via
OH
X–
L
Pd
Ar1
(+ dimer)
(b) A transmetalation switch at Pd(II) via control of anion metathesis (this work)
HO–
L
L
Ar1
L
L
Ar1
Bifunctional probe for Pd(II)
Pd
Pd
X
OH
X–
Suzuki-Miyaura
Ligand metathesis at catalytically generated (Ar)Pd(II) comꢀ
plexes is an essential mechanistic event that underpins the most
widely employed catalytic processes, such as the SuzukiꢀMiyaura,
Negishi, and MizorokiꢀHeck reactions.1 A pertinent example is
the X→OH anion metathesis of (Ar)Pd(II)(X) complexes (where
X = halide), which enables oxopalladium transmetalation in the
SuzukiꢀMiyaura reaction.2ꢀ9 In seminal studies by Hartwig, stoiꢀ
chiometrically prepared (Ar)Pd(II)(OH) complexes were shown to
engage organoboron compounds and thereby provide key eviꢀ
dence to support oxopalladium transmetalation (Scheme 1a).5
Contemporaneously, Amatore and Jutand provided compelling
evidence for the same complexes and pathway in solution using
electrochemical methods.6 More recently, Denmark unequivocally
demonstrated the role of (Ar)Pd(II)(OH) complexes in oxopallaꢀ
dium transmetalation using rapid injection low temperature NMR
techniques to detect the elusive pretransmetalation intermediates.8
BPin
L
L
Ar1
L
L
Ar1
Pd
H
Pd
O
B
Mizoroki-Heck
• Pd(II)-selective reactivity
OR
OR
BPin
BPin
• (Ar)Pd(OH) → reaction at C-B bond
• (Ar)Pd(X) → reaction at terminal C
Ar1
Ar1
(c) (Non)borylated carbocycles from anion metathsis control in a cascade reaction
X
R
BPin
BPin
Pd cat.
EWG
EWG
R
or
EWG
anion metathesis
control
via (Ar)Pd(OH)
via (Ar)Pd(X)
three olefins
borylated or non-borylated carbocycles
Scheme 1. Anion metathesis of (Ar)Pd(II)(X). (a) Organoboron transꢀ
metalation; (b) Control of anion metathesis using a bifunctional probe; and
(c) utility in a triene cascade annulation.
The essential role of (Ar)Pd(II)(OH) complexes for organoboꢀ
ron transmetallation renders X→OH anion metathesis a critical
mechanistic event, and highlights the different reactivity modes of
(Ar)Pd(II) based on the associated anion. Designed manipulation
of this event may provide a powerful, yet untapped, control vector
in Pd catalysis for the chemoselective manipulation of multiꢀ
reactive systems and control of transmetalation more generally.
In this context, we hypothesized that additional reactivityꢀ
relevant information on this event may be obtained using a chemꢀ
ical probe approach. (Ar)Pd(II)(X) complexes are known interꢀ
mediates for many Pdꢀcatalyzed reactions, including the Mizoroꢀ
kiꢀHeck reaction.1,11 Accordingly, use of an appropriately selecꢀ
tive chemical probe capable of MizorokiꢀHeck via (Ar)Pd(II)(X)
or SuzukiꢀMiyaura via (Ar)Pd(II)(OH) would give a pathway
selectivity response based on the (Ar)Pd(II) species present in
solution and the relative rates of reaction. To this end, vinylBPin
is a competent organoboron nucleophile for SuzukiꢀMiyaura and
is known to undergo MizorokiꢀHeck at the terminal carbon.12
Here we describe the use of a bifunctional chemical probe to inꢀ
terrogate X→OH anion metathesis of (Ar)Pd(II)(X) complexes
(Scheme 1b). We show how this event can be controlled to allow
selection of SuzukiꢀMiyaura or MizorokiꢀHeck crossꢀcoupling
pathways on a bifunctional template leading to development of a
chemoselective triene cascade annulation that provides borylated
or nonꢀborylated carbocycles (Scheme 1c).
To demonstrate its suitability as a chemical probe, we exposed
vinylBPin to stoichiometric (Ph3P)2(Ar)Pd(II)(Br) (1a),
(SPhos)(Ar)Pd(II)(Br) (2a), [(Ph3P)(Ar)Pd(II)(ꢁꢀOH)]2 (1b), and
(SPhos)(Ar)Pd(II)(OH) (2b) (Scheme 2).
The groundbreaking studies by Hartwig,5 Amatore and Jutand,6
and Denmark8 used stoichiometrically prepared Pd(II) complexes
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commonly employed for SuzukiꢀMiyaura, the boronate more
readily distributes to the aqueous phase where protodeboronation
can occur upon heating.15,16 Accordingly, for effective Suzukiꢀ
Miyaura, at least in the mechanistic sense, low [H2O] would apꢀ
pear to be more favorable. (2) The MizorokiꢀHeck of vinylBPin
requires thermal promotion. However, this then requires the sysꢀ
tem to be strictly anhydrous. Adventitious H2O and elevated temꢀ
peratures favor higher [1b] (Chart 1), and based on the stark difꢀ
ference in relative rate (SuzukiꢀMiyaura t1/2 = 2 mins (rt); Mizoroꢀ
kiꢀHeck t1/2 = 50 min (80 °C)), this will favor the SuzukiꢀMiyaura
pathway. Again, from the mechanistic standpoint, anhydrous conꢀ
ditions with organic base favors (Ar)Pd(II)(X), which will proꢀ
mote the MizorokiꢀHeck.
1
2
3
4
5
6
7
8
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Scheme 2. Stoichiometric reactions of Pd(II) complexes with vinylBPin.
Ar = 4ꢀFC6H4. Determined by 19F NMR. 1b includes cis and trans. 2a/2b
include monomer/dimer.
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With a functional understanding of how the metathesis event
can be manipulated, we used vinylBPin to probe the outcome of
control in a catalytic scenario using SPhos to allow subsequent
exploration of electrophile influence (Scheme 4).
1a and 2a provided 3a as the only coupling product, while 1b
and 2b delivered only 3b. Use of a monoꢀdeuterio labeled viꢀ
nylBPin ruled out cine substitution, supporting only Suzukiꢀ
Miyaura and MizorokiꢀHeck as the operational pathways (see
Supporting Information). While SuzukiꢀMiyaura was complete in
5 min at rt, the Heck process required heating and extended reacꢀ
tion times for meaningful conversion: t1/2 for vinylBPin with 1a
was ca. 50 min at 353 K, while ca. 2 min at 293 K with 1b,
demonstrating a substantial difference in relative rate.13
To set a foundation for gaining control over crossꢀcoupling
pathways as a function of anion metathesis, we assessed the imꢀ
pact of base, temperature, and [H2O] on the distribution of 1a and
1b in isolation, using reactionꢀlike base:Pd stoichiometry (Scheme
3 and Chart 1).
Scheme 4. Catalytic reactions with vinylBPin with variation of H2O and
base. Ar = 2ꢀnaphthyl. Determined by 1H NMR.
Regardless of the presence of H2O, the stronger bases (KOH,
K3PO4) favored the SuzukiꢀMiyaura pathway. Adventitious H2O
arising from the hygroscopic bases may be a contributing facꢀ
tor.17,18 Alongside the recorded difference in halfꢀlife in the stoiꢀ
chiometric experiments, this suggests a kinetic effect where low
[Pd(OH)] outcompetes the Pd(X)ꢀpromoted Heck pathway. This
was reinforced from the results using Et3N. Under dry conditions,
Heck is operational; however, despite 1a predominating in the
aqueous system (Scheme 3), SuzukiꢀMiyaura increases with inꢀ
creasing [H2O] (9:1 shown in Scheme 4; see SI for full details).
Pd(OAc)2 (4 mol%)
Scheme 3. Effect of base and H2O on (Ar)Pd(II) concentration. Deterꢀ
mined by 31P NMR.
(a) Effect of [H2O] on [Pd] at rt
(b) Effect of temp. on [Pd] (9:1 THF:H2O)
SPhos (8 mol%)
X
BPin
Ar
Ar
BPin
Ar
1,4-dioxane, 80 °C
5-16b
5-16a
base
Suzuki-Miyaura
K3PO4 (3 equiv)
H2O (5 equiv)
Mizoroki-Heck
Et3N (4 equiv)
Me
Br
Br
Br
O
O2N
6a: 68%
Mizoroki-Heck:
Suzuki-Miyaura:
5a: 100%
5b: 98%
7a: 96%
7b: 92%
Br
6b: 96%
Chart 1. Impact of [H2O] (a) and temperature (b) on the relative concenꢀ
trations of 1a and 1b in the presence of KOH. Determined by 31P NMR.
Cl
Br
N
NC
MeO
Under dry conditions, 1a predominated for all bases. However,
when H2O was added, the distribution of 1a and 1b varied as a
function of the base (see SI for the full range of bases). KOH now
favored 1b, K3PO4 provided ca. 2:1 ratio of 1a:1b, while Et3N
continued to favor 1a. Using KOH, lower [H2O] and elevated
temperatures favored 1b (Chart 1), with the former consistent
with Hartwig’s observations.5 Accordingly, the Pd(II) speciation
is profoundly affected by both an aqueous basic medium and temꢀ
perature.
Me
Mizoroki-Heck:
Suzuki-Miyaura:
8a: 84%
8b: 84%
9a: 40%
9b: 87%
10a: 40%
10b: 76%
Cl
OMe
Br
Br
MeO
CbzHN
12a: 75%
O
Mizoroki-Heck:
Suzuki-Miyaura:
11a: 48%
11b: 93%
13a: 90%
13b: 95%
O
12b: 89%
Me
OMe
Br
O
There are two implications of this data: (1) For oxopalladium
transmetalation, hydroxypalladium (e.g., 1b) and a neutral orꢀ
ganoboron are required. From these data, lower [H2O] favors
increased [(Ar)Pd(II)(OH)]. In a landmark study of Suzukiꢀ
Miyaura crossꢀcoupling of potassium organotrifluoroborates,
LloydꢀJones reported that lower [H2O] favors higher concentraꢀ
tions of the boronic acid, with increasing [H2O] favoring the
boronate.14 Moreover, in basic biphasic systems, such as those
N
S
Cl
O
O
Br
Mizoroki-Heck:
Suzuki-Miyaura:
15a: 69%
15b: 91%
16a: 63%
16b: 78%
14a: 44%
14b: 77%
Scheme 5. Generality of speciation control under catalytic conditions.
Baseꢀmediated hydrolysis of vinyl BPin could potentially exꢀ
plain some of the discrepancies observed. However, analysis of
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styrenyl BPin with a series of bases at 80 °C revealed no hydrolyꢀ
ology used in natural product synthesis,22 we designed a threeꢀ
component annulation reaction via crossꢀcoupling of a vinylhalꢀ
ide/pseudohalide with a vinylBPin reagent to generate a diene
intermediate. This diene would then engage a third olefin in a
DielsꢀAlder reaction to produce the expected carbocyclic prodꢀ
ucts. Importantly, this would be a divergent platform: control of
Pd(II) using the knowledge garnered above would allow selective
MizorokiꢀHeck or SuzukiꢀMiyaura in the initial step, delivering
borylated or nonꢀborylated diene intermediates, and therefore
borylated or nonꢀborylated carbocycles (Scheme 6). In the event,
the orthogonal series of products were generated in good yield via
either pathway using a standard catalyst system (Pd(OAc)2,
SPhos) with K3PO4 driving SuzukiꢀMiyaura and Et3N driving
MizorokiꢀHeck selectivity as expected. Use of AgOAc was found
to improve the efficiency of the MizorokiꢀHeck process with these
olefinic electrophiles; this did not affect the selectivity profiles but
bolstered reactivity, consistent with previous observations.10
sis: the vinyl BPin remained intact with some small levels of proꢀ
1
2
3
4
5
6
7
8
todeboronation observed for KOH (see SI).19
As shown above, a change in reaction medium is sufficient to
induce significant changes to the product distribution, favoring
SuzukiꢀMiyaura with inorganic bases (e.g., K3PO4) and Mizorokiꢀ
Heck with Et3N. Accordingly, we assessed the generality of this
baseꢀinduced transmetalation switch across a range of aryl halides
(I, Br, Cl) using the Pd(OAc)2/SPhos system (Scheme 5). The
switch took place with complete fidelity, delivering the orthogoꢀ
nal products exclusively and in generally good yield. Some diminꢀ
ished Heck efficiency was noted with substrates containing Lewis
basic functionality, consistent with previous observations.11 Interꢀ
estingly, MizorokiꢀHeck using Buchwaldꢀtype ligands is rare but
was found to be effective under these conditions.20,21
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With control at Pd(II) established under catalyticallyꢀrelevant
conditions, we sought to demonstrate the utility of the transmetalꢀ
lation switch in a synthetic context. Inspired by cascade methodꢀ
Pd(OAc)2 (4 mol%)
X
R
PinB
R
BPin
SPhos (8 mol%)
1,4-dioxane
BPin
Diels-Alder
EWG
EWG
EWG
R
or
R
or
conditions
EWG
R
via Pd(OH)
K3PO4, H2O
80 °C
via Pd(X)
Et3N, AgOAc
16a-l
17a-l
borylated or non-borylated carbocycles
40 °C
Pd(OH) pathway
non-borylated products
Pd(X) pathway
borylated products
O
PinB
PinB
O
O
H
H
H
H
PinB
O
CO2Et
Me
Me
CO2Et
NMe
NPh
Me
N
Bn
CO2Et
HO
Ph
CO2Et
N
O
O
F
Me
17a
17b
17c
18a
90%
18b
54%
18c
71%
65%a
93%a
78%
PinB
O
MeO
H
PinB
O
PinB
O
O
O
O
CN
NPh
Me
OMe
Me
Me
Me
H
O
N
O
F
Cl
Me
17d
17e
17f
93%b
18d
63%
18e
68%
PinB
18f
81%
Me
80%b
85%b
O
O
Ph
PinB
PinB
O
O
H
H
Me
H
H
CO2Et
CN
H
NPh
NPh
H
CO2Et
N
Me
H
O
O
Me
Me
O
17g
17h
17i
85%b
18g
63%
18h
42%
18i
58%
PinB
94%b
75%
O
PinB
PinB
O
O
O
H
H
H
H
OTBDMS
OEt
CO2Et
CO2Et
H
H
NPh
H
NPh
H
H
NPh
O
H
H
O
O
O
MeO
O
MeO
MeO
O
MeO
MeO
17j
17k
17l
89%
18j
18k
42%
18l
69%
81%b
66%
36%
H
TsOH
PhMe, 80 °C
O
H
O
MeO
19
64%
Scheme 6. Cascade crossꢀcoupling/DielsꢀAlder annulation: borylated or nonꢀborylated carbocycles based on Pd(II) species. a As a mixture of two regioisoꢀ
mers. b As a mixture of two diastereomers arising from enolization.
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(3) Lennox, A. J. J.; LloydꢀJones, G. C. Angew. Chem. Int. Ed.
2013, 52, 7362–7370.
Variation of the three olefinic components was broadly applicable
allowing the preparation of functionalized monoꢀ (17a-g;
18b,e,f,h), biꢀ(17h; 18a,c,d,g), triꢀ (17i,j; 18k), and tetracyclic
(17k,l; 18i,j,l) products. Of particular note was the access to sterꢀ
oidꢀlike scaffolds bearing a BPin functional group (18i,j,l), allowꢀ
ing straightforward functionalization of the boronꢀbearing carbon
and allylic position via established methods (Scheme 7).23 For
example, Brown oxidation (20), conversion of BPin to BF3K to
allow established crossꢀcoupling methods at either position (22),24
and nucleophilic allylation with carbonyl groups to deliver the
VaultierꢀHoffmannꢀtype product 21.25
1
2
3
4
5
6
7
8
(4) Matos, K.; Soderquist, J. A. J. Org. Chem., 1998, 63, 461–470.
(5) Carrow, B. P.; Hartwig, J. F. J. Am. Chem. Soc. 2011, 133,
2116–2119.
(6) (a) Amatore, C.; Jutand, A.; Le Duc, G. Chem. Eur. J. 2011, 17,
2492–2503. (b) Amatore, C.; Jutand, A.; Le Duc, G. Chem. Eur. J.
2012, 18, 6616–6625.
(7) Schmidt, A. F.; Kurokhtina, A. A.; Larina, E. V. Russ. J. Gen.
Chem. 2011, 81, 1573–1574.
(8) (a) Thomas, A. A; Wang, H.; Zahrt, A. F.; Denmark. S. E. J.
Am. Chem. Soc. 2017, 139, 3805–3821. (b) Thomas, A. A; Denmark,
S. E. Science 2016, 352, 329–332.
9
PinB
O
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
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H
(9) For a recent example of “cationic” transmetalation, see: Chen,
L.; Sanchez, D. R.; Zhang, B.; Carrow, B. P. J. Am. Chem. Soc. 2017,
139, 12418–12421.
(10) For previous studies of L2Pd(Ar)(OH) monomer and dimer
equilibria, see: Grushin, V. V.; Alper, H. Organometallics 1996, 15,
5242–5245.
18g
NPh
Me
H
O
H2O2,
KOH
ArCHO,
PhMe
KHF2,
MeOH
(11) For general information, see: The Mizoroki-Heck reaction;
Oestreich, M. (Ed.); Wiley, Chichester, UK, 2009.
KF3B
HO
O
O
O
H
H
H
H
H
Br
N
(12) For selected examples, see: Hunt, A. R.; Stewart, S. K.; Whitꢀ
ing, A. Tetrahedron Lett. 1993, 34, 3599–3602. (b) Itami, K.; Toꢀ
nogaki, K.; Nokami, T.; Ohashi, Y.; Yoshida, J. Angew. Chem. Int.
Ed. 2006, 45, 2404–2409. (c) Batsanov, A. S.; Knowles, J. P.; Whitꢀ
ing, A. J. Org. Chem. 2007, 72, 2525–2532.
NPh
NPh
NPh
Me
Me
Me
H
O
O
O
HO
20
93%
21
90%
22
quant.
(13) Control experiments to establish the presence of [Pd(Ar)X2]–
complexes were inconclusive (see SI). For an example of [Pd(Ar)X2]–
in the Heck reaction, see: Carrow, B. P.; Hartwig, J. F. J. Am. Chem.
Soc. 2010, 132, 79–81.
Scheme 7. Derivitization of BPin products.
In summary, using vinylBPin as a bifunctional chemical probe,
we have demonstrated that X→OH anion metathesis of (Ar)Pd(II)
complexes can be controlled. In stoichiometric experiments,
crossꢀcouplingꢀrelevant bases, coꢀsolvent medium (solvent:H2O
composition), and temperature can be used to control the relative
concentration of (Ar)Pd(II)(X) or (Ar)Pd(II)(OH) complexes. This
allows control of crossꢀcoupling pathways via promotion or inhiꢀ
bition of organoboron transmetalation, leading to either Suzukiꢀ
Miyaura or MizorokiꢀHeck products on a bifunctional template.
Finally, we show how this transmetalation switch can be used in a
cascade crossꢀcoupling/DielsꢀAlder annulation reaction, deliverꢀ
ing (non)borylated carbocycles.
(14) Butters, M.; Harvey, J. N.; Jover, J.; Lennox, A. J. J.; Lloydꢀ
Jones, G. C.; Murray, P. M. Angew. Chem. Int. Ed. 2010, 49, 5156–
5160.
(15) Molloy, J. J.; Clohessy, T. A.; Irving, C.; Anderson, N. A.;
LloydꢀJones, G. C.; Watson, A. J. B. Chem. Sci. 2017, 8, 1551–1559.
(16) For recent studies, see: (a) Cox, P. A.; Leach, A. G.; Campꢀ
bell, A. D.; LloydꢀJones, G. C. J. Am. Chem. Soc. 2016, 138, 9145–
9157. (b) Cox, P. A.; Reid, M.; Leach, A. G.; Campbell, A. D.; King,
E. J.; LloydꢀJones, G. C. J. Am. Chem. Soc. 2017, 139, 13156–13165.
(17) Fyfe, J. W. B.; Valverde, E.; Seath, C. P.; Kennedy, A. R.;
Redmond, J. M.; Anderson, N. A.; Watson, A. J. B. Chem. Eur. J.
2015, 24, 8951–8964.
(18) K3PO4 as a desiccant in crossꢀcoupling: (a) Fyfe, J. W. B.;
Seath, C. P.; Watson, A. J. B. Angew. Chem. Int. Ed., 2014, 53,
12077–12080. (b) Muir, C. W.; Vantourout, J. C.; IsidroꢀLlobet, A.;
Macdonald, S. J. F.; Watson, A. J. B. Org. Lett. 2015, 17, 6030–6033.
(c) Seath, C. P.; Fyfe, J. W. B.; Molloy, J. J.; Watson, A. J. B. Angew.
Chem. Int. Ed. 2015, 54, 9976–9979. (d) Fyfe, J. W. B.; Fazakerley,
N. J.; Watson, A. J. B. Angew. Chem. Int. Ed. 2017, 56, 1249–1253.
(19) It should be noted that the boronic acid/ester equilibrium typiꢀ
cally favors the ester under higher pH conditions. For example, see:
Springsteen, G.; Wang, B. Tetrahedron 2002, 58, 5291–5300.
(20) For previous examples see: (a) McMullen, J. P.; Stone, M. T.;
Buchwald, S. L.; Jensen, K. F. Angew. Chem. Int. Ed. 2010, 49,
7076–7080. (b) BorrajoꢀCalleja, G. M.; Bizet, V.; Besnard, C.; Mazet,
C. Organometallics 2017, 36, 3553–3563.
(21) The use of βꢀsubstituted vinylBPin reagents gave poor effiꢀ
ciency as well as mixture of olefin diastereomers (see SI).
(22) For examples, see: Nicolaou, K. C.; Bulger, P. G.; Sarlah, D.
Angew. Chem. Int. Ed. 2005, 44, 4442–4489.
(23) For examples, see: Boronic acids: preparation and applica-
tions in organic synthesis, medicine and materials (vols 1 and 2),
2nd ed.; Hall, D. (Ed.); Wiley VCH, Weinheim, Germany, 2011.
(24) For examples, see: (a) Lee, J. C. H.; McDonald, R.; Hall, D.
G. Nature Chem. 2011, 3, 894–899. (b) Wang, C.ꢀY.; Derosaa, J.;
Biscoe, M. R. Chem. Sci. 2015,6, 5105–5113. (c) Tellis, J. C.; Kelly,
C. B.; Primer, D. N.; Jouffroy, M.; Patel, N. R.; Molander, G. A. Acc.
Chem. Res., 2016, 49, 1429–1439.
ASSOCIATED CONTENT
Supporting Information. Experimental procedures, characterizaꢀ
tion data, NMR spectra, crystallographic data. The Supporting
Information is available free of charge on the ACS Publications
website.
AUTHOR INFORMATION
Corresponding Author
*allan.watson.100@strath.ac.uk
Funding Sources
No competing financial interests have been declared.
ACKNOWLEDGMENT
J.J.M thanks GlaxoSmithKline for a PhD studentship. C.P.S.
thanks the Carnegie Trust for the Universities of Scotland for a
PhD studentship. We thank the EPSRC UK National Mass Specꢀ
trometry Facility at Swansea University for analyses.
REFERENCES
(1) Metal-catalyzed cross-coupling reactions; de Meijere, A.;
Bräse, S.; Oestreich, M. (Eds.); Wiley VCH, Weinheim, 2014.
(2) (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–2483.
(b) Lennox, A. J. J.; LloydꢀJones, G. C. Chem. Soc. Rev. 2014, 43,
412–443.
(25) Vaultier, M.; Truchet, F.; Carboni, B.; Hoffmann, R. W.;
Denne, I. Tetrahedron Lett. 1987, 28, 4169−4172.
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