Oxidative Cross-Coupling of Boron and Antimony Nucleophiles via Palladium(I)

Article abstract of DOI:10.1021/acs.orglett.8b01989

The use of an isolatable, monomeric Pd(I) complex as a catalyst for the oxidative cross-coupling of aryl-antimony and aryl-boron nucleophiles is reported. This reaction tolerates a wide variety of substrates, with >20:1 selectivity for cross-coupled products. This strategy offers a new approach to achieving the selective cross-coupling of nucleophiles.

Full text of DOI:10.1021/acs.orglett.8b01989

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Oxidative Cross-Coupling of Boron and Antimony Nucleophiles via
Palladium(I)
Quillon Simpson,† Matthew J. G. Sinclair,‡ David W. Lupton,† Adrian B. Chaplin,*,‡
and Joel F. Hooper*,†
†School of Chemistry, Monash University, Clayton 3800, Victoria, Australia
‡Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, U.K.
S
* Supporting Information
ABSTRACT: The use of an isolatable, monomeric Pd(I)
complex as a catalyst for the oxidative cross-coupling of aryl-
antimony and aryl-boron nucleophiles is reported. This
reaction tolerates a wide variety of substrates, with >20:1
selectivity for cross-coupled products. This strategy offers a
new approach to achieving the selective cross-coupling of
nucleophiles.
Scheme 1. Reactions Promoted by Pd(I) Complexes
ransition-metal-catalyzed cross-coupling reactions are
keystone transformations in contemporary organic chem-
T
istry.1 Selectivity in these reactions has classically been achieved
by exploiting the complementary metal-based reactivity of
electrophilic and nucleophilic substrates. The electrophilic
reagent is first oxidatively added to the metal catalyst, typically
involving insertion into a carbon−halogen bond, before
subsequent transmetalation with the nucleophilic coupling
partner, enabling product formation through bond forming
reductive elimination. While many successful coupling reactions
exploit this sequence of events,2 alternative strategies based on
two nucleophiles or two electrophiles are comparatively
underdeveloped.3 In recent years, coupling approaches involv-
ing single-electron redox events have emerged, with visible-light-
promoted photoredox catalysis a particularly prominent
example.4 Other single-electron transfer mediated processes
proceed through internal redox mechanisms5 or use external
oxidants.6 These alternative coupling approaches are made
viable by transition-metal-based catalysts with accessible M(n)/
M(n + 1) redox couples and, for this reason, have largely been
associated with complexes of first row metals such as Ni,5,7 Cu,8
and Fe.9
Despite widespread use in cross-coupling reactions, the redox
chemistry of palladium catalysts has largely been confined to the
Pd(0)/Pd(II) couple. It has been speculated that Pd(I)
intermediates are involved in radical atom transfer reactions10
and Kumada couplings (Scheme 1, eq 1).10,11 Dimeric Pd(I)
phosphine complexes have shown catalytic application in
trifluoromethylthiolation reactions (Scheme 1, eq 2).12 They
have also proven to be valuable sources of low-coordinate Pd(0),
allowing effective catalysis of carbon−carbon bond forming
reactions via a conventional Pd(0)/Pd(II) cycle.13
Recently, one of us demonstrated the facile one-electron
oxidation of Pd(PtBu3)2 (1) using ferrocenium hexafluorophos-
phate ([Fc][PF6 ]) and subsequent isolation of
[Pd(PtBu3)2][PF6] (2).14 This straightforward method for
generation of monomeric palladium bis(phosphine) metal-
loradicals led us to speculate that the associated Pd(0)/Pd(I)
redox couple could be exploited catalytically in single-electron
transfer reactions. Herein, we report a highly selective oxidative
coupling of organoboron- and organoantimony-based aryl
nucleophiles mediated by commercially available 1 and
[Fc][PF6] or preformed 2 (Scheme 1, eq 3).
While exploring the reactivity of 2, we noted that 2 equiv of
this complex promoted the selective two-electron oxidative
coupling of SbPh3 and aryl trifluoroborate salt 4a to deliver
Received: June 26, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b01989
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
biaryl 5a in 78% yield. We looked to develop a catalytic version
of this coupling by examining the use of 1, with [Fc][PF6] as the
stoichiometric oxidant to generate 2 in situ, with the addition
CsF (Table 1). Pleasingly, this reaction gave extremely high
Replacing catalyst 1 with the preformed Pd(I) salt 2 had little
effect on yield, while the reaction failed in the absence of a
palladium catalyst (Table 1, entries 3 and 4). The electron-rich
Pd(PCy3)2 complex was also a successful catalyst, while
Pd(PPh3)4 and Pd2dba3 gave reduced yields of 44% and 40%.
The addition of excess Hg(0) to the reaction mixture did not
affect the yield, suggesting that the reaction is not catalyzed by
heterogeneous palladium. Moreover, monitoring the conversion
of the reaction over time did not show any evidence of an
induction period (see Supporting Information (SI)).
Table 1. Oxidative Coupling of Aryl Nucleophiles
The reaction did not proceed in the absence of the oxidant,
while O2 as the oxidant gave only a trace amount of product
(Table 1, entries 5, 6). A screen of alternative oxidants (see SI)
identified AgBF4 and Selectfluor as viable reagents, consistent
with a pathway involving single-electron oxidation of palladium
(Table 1, entries 7, 8).15a,b Low conversion was observed in the
absence of CsF, along with the formation of a THF-derived
polymer.
We also examined the use of nonantimony-based aryl transfer
reagents, to determine if this oxidative coupling strategy could
be applied more generally to other pairs of nucleophiles.
Coupling of 4a with triphenylborane gave a 2:1 mixture of the
cross-coupled product 5a and the dimer 6 along with biphenyl.
Tetraphenyltin gave predominantly 6, while tetraphenyllead and
triphenylbismuth showed useful selectivity toward the cross-
coupled biaryl (Table 1, entries 10−13). Gratifyingly, of the five
coupling partners tested, four were viable, highlighting the
orthogonal reactivity enabled by this approach.
With the optimized reaction conditions established, we next
set about applying this coupling to a number of aryl-borate and
antimony compounds (Figure 1). All triaryl-antimony reagents
were synthesized in one step from commercially available SbCl3
and were bench stable. While triarylantimony reagents have seen
limited use as nucleophiles in organic synthesis,15c they offer
improved stability compared with organometallic reagents based
on Mg or Zn, and when all three aryl groups are utilized, better
atom economy than most B- or Sn-based reagents. Care should
a
ratio Ph/4a/
yield 5a, %
(ratio 5a:6)
b
entry MPhx t, °C
oxidant
variation
1
2
3
4
5
6
7
8
SbPh3
SbPh3
SbPh3
SbPh3
SbPh3
SbPh3
SbPh3
SbPh3
rt
3:1:2
1:2:3
1:2:3
1:2:3
1:2:0
−
−
67 (>20:1)
86 (>20:1)
84 (>20:1)
60
60
60
60
60
60
60
2 as cat.
no Pd cat.
no oxidant
O2 oxidant
AgBF4 oxidant
Selectfluor
oxidant
<5
<5
<5
54
70
c
1:2:1
1:2:3
1:2:3
d
9
SbPh3
BPh3
SnPh4
PbPh4
BiPh3
60
rt
rt
rt
rt
1:2:3
3:1:2
4:1:2
4:1:2
no CsF
8
10
11
12
13
−
−
−
−
31 (2:1)
e
nd (1:4.5)
44 (11:1)
54 (4:1)
3:1:2
a
b
1
Isolated yield. Determined by H NMR analysis of crude mixture.
Performed under 1 atm of O2. Significant polymerization of solvent
c
d
e
observed. Not determined.
selectivity for the cross-coupling, delivering biaryl 5a in 67%
yield (Table 1, entry 1). Using 0.33 equiv of the antimony
reagent (1 equiv with respect to the phenyl group), all three aryl
groups could be transferred at 60 °C, using a 2:3 ratio of 4a/
[Fc][PF6] to give an 86% yield of 5a (entry 2).
Figure 1. Scope of the boron/antimony coupling.
B
DOI: 10.1021/acs.orglett.8b01989
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
be taken, however, due to the potential toxicity of antimony-
based reagents.
leading to formation of new Sb−F bonds, lending support to the
latter conjecture.22
Using SbPh3, electron-rich and -poor fluoroborate salts were
well tolerated, giving the biaryls in good yields (Figure 1, 5a−g).
Sb(4-C6H4OCH3)3 was also effectively coupled, employing aryl
and heteroaryl fluoroborate salts including benzofuran (5k) and
thiophene boronic acid (5l). Sb(4-C6H4F)3 was coupled with a
variety of aryl and heteroaryl fluoroborates in good yields (5n−
r).16 Heteroaryl antimony reagents were also incorporated, with
the benzothiophene and furan derived reagents coupling in 45−
92% yields (5t−x). Alkyl and alkenyl fluoroborate reagents were
also examined, but did not deliver the desired products.
Tris(phenylethynyl)stibane was also synthesized, but proved
to be unstable under the reaction conditions.
While we attribute the role of [Fc][PF6] to the previously
established,14 one-electron oxidation of Pd(0) during catalysis,
we sought to preclude the possible formation of aryl radicals17 or
Sb(V) species by oxidation of the coupling partners. The cyclic
voltammograms of SbPh3 and 4a in THF/[nBu4N][PF6] show
irreversible oxidation waves, but only at potentials >0.9 V higher
than Fc/[Fc]+ (see SI).18 Consistent with this observation,
treatment of SbPh3 or 4a with [Fc][PF6] in the presence of
TEMPO gave no detectable biaryl formation or TEMPO
adduct. Likewise their catalytic coupling is unaffected in the
presence of the known radical trap 1,1-diphenylethylene. Finally,
treatment of SbPh3 with [Fc][PF6] at 60 °C in THF returned
the starting material in quantitative yield after 16 h.19
In an attempt to provide experimental support for our
proposal, reactions of isolated Pd(I) salts with Sb(2-
C6H4OCH3)3 (3w) in THF were studied using 31P NMR
spectroscopy: although, under the catalytic coupling conditions
3w performed poorly (Table 2, 5w), the large steric profile is
attractive from a practical perspective. Stoichiometric reaction of
3w with [Pd(PtBu3)2][PF6] (2) under catalytically relevant
conditions (60 °C, 16 h) resulted in complete consumption of
the metalloradical and formation of a complex reaction mixture
containing [HPtBu3]+ (δ 52.4) and a new compound that was
subsequently characterized as [Pd2(PtBu3)2(μ-C6H4OCH3)(μ-
SbC6H4OCH3)]+ (7, two geometric isomers in a 1:1 ratio; δ
87.4, 86.6; Figure 2). The conversion to 7 is only moderate
Informed by the reactivity of conceptually related dimeric
Pd(I) pincer complexes,20 we propose the mechanism depicted
in Scheme 2 for the cross-coupling. The critical step involves
Figure 2. Solid-state structure of one of the isomers of 7. Thermal
ellipsoids for selected atoms at the 30% probability level; minor
disordered component (Pd2Sb core), tBu hydrogen atoms, and
Scheme 2. Proposed Mechanism and Preparation of 7
[BArF ]− anion omitted for clarity. Selected bond lengths (Å) and
4
angles (deg): Pd1−Pd2, 2.7918(6); Pd1−Sb3, 2.4723(5); Pd2−Sb3,
2.5026(5); Pd1−P4, 2.299(15); Pd2−P5, 2.3223(14); Pd1−C6,
2.135(6); Pd2−C6, 2.137(5); Pd2−Pd1−P4, 161.04(5); Pd1−Pd2−
P5, 153.70(4); Pd1−Sb3−Pd2, 68.274(15); Pd1−C6−Pd2,
81.62(18).
under these conditions (ca. 20%), but increased when carried
out at room temperature (ca. 45%). Using 0.5 equiv of Sb(2-
C6H4OCH3)3 and employment of the weakly coordinating
[BArF ]− anion (ArF = 3,5-(CF3)2C6H3)23 resulted in a slower
4
reaction but gave enhanced production of 7 (ca. 50%). Isolation
proved difficult, but was realized in low yield by manual
separation of single crystals and successive recrystallization.
The structure of 7 contains an unusual combination of
bridging aryl and stibinidene ligands and a significant Pd−Pd
bond (2.7918(6) Å).24 We assign formal Pd(II) and Sb(III)
oxidation states, with the latter consistent with pronounced
pyramidalization at the metalloid (∑angles@Sb3 = 265.7°).
Scheme 2 reconciles how 7 could be formed, with the transient
presence of a reactive three-coordinate Pd(II)-aryl cation
evidenced through isolation of the aryl phosphonium salt
[PtBu3(2-C6H4OMe)][BArF ].25 Although presumably an off-
4
cycle species, in the context of the proposed mechanism the
formation of 7 directly evidences Sb−C bond cleavage and
single-electron oxidation events at palladium. Only partial
decomposition (ca. 10%) to 1 was observed on reaction of 7
with excess K[F3BC6H4F] and CsF in THF (60 °C, 16 h).
In summary, we have presented the first synthetic application
of a well-defined monomeric Pd(I) species, facilitating the
oxidative cross-coupling of aryl-boron and aryl-antimony
radical oxidative addition of an aryl-antimony bond across two
Pd(I) centers giving a Pd(II)-aryl and Pd(II)-stibide.21 The
Pd(II)-aryl species could mediate the formation of the biaryl
product via a conventional metalation/reductive elimination
sequence, while the Pd(II)-stibide could react with fluoride to
regenerate the common zerovalent palladium species. There is
literature precedent for reaction of M−Sb moieties with fluoride
C
DOI: 10.1021/acs.orglett.8b01989
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(10) Liu, Q.; Dong, X.; Li, J.; Xiao, J.; Dong, Y.; Liu, H. ACS Catal.
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be harnessed for new catalytic organic transformations.
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ASSOCIATED CONTENT
* Supporting Information
■
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2012, 134, 606−612. (b) Sperger, T.; Stirner, C. K.; Schoenebeck, F.
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The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.8b01989.
Full experimental data, including synthetic procedures,
characterization data, and NMR spectra (PDF)
(14) Troadec, T.; Tan, S.-y.; Wedge, C. J.; Rourke, J. P.; Unwin, P. R.;
Chaplin, A. B. Angew. Chem., Int. Ed. 2016, 55, 3754−3757.
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Accession Codes
CCDC 1839868 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_
request@ccdc.cam.ac.uk, or by contacting The Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, UK; fax: +44 1223 336033.
(16) These yields compare favourably with related oxidative cross-
coupling methods for biaryl synthesis. For example, see 97% yield of 5n,
compared with 70% in ref 3c.
AUTHOR INFORMATION
Corresponding Authors
■
(17) As deduced in a recent copper catalyzed oxidative coupling
reaction. See ref 8.
(18) Radicals derived from single-electron oxidation of triaryl-stibanes
have been isolated using a more potent chemical oxidant: Li, T.; Wei,
H.; Fang, Y.; Wang, L.; Chen, S.; Zhang, Z.; Zhao, Y.; Tan, G.; Wang, X.
Angew. Chem. Int. Ed. 2017, 56, 632−636.
*E-mail: a.b.chaplin@warwick.ac.uk.
*E-mail: joel.hooper@monash.edu.
ORCID
(19) Formation of Sb(V) reagents, a potential electrophilic aryl source
is unlikely Qin, W.; Yasuike, S.; Kakusawa, N.; Sugawara, Y.; Kawahata,
M.; Yamaguchi, K.; Kurita, J. J. Organomet. Chem. 2008, 693, 109−116.
Nevertheless, to double-check this possibility, Ph3SbF2 was synthesized
and subjected to coupling conditions in the absence of further oxidant.
The associated biaryl product was not formed (see SI).
(20) Fafard, C. M.; Adhikari, D.; Foxman, B. M.; Mindiola, D. J.;
Ozerov, O. V. J. Am. Chem. Soc. 2007, 129, 10318−10319.
(21) For examples of metal-stibides, see: (a) Jones, C.; Junk, P. C.;
Steed, J. W.; Thomas, R. C.; Williams, T. C. J. Chem. Soc., Dalton Trans.
David W. Lupton: 0000-0002-0958-4298
Adrian B. Chaplin: 0000-0003-4286-8791
Joel F. Hooper: 0000-0002-9941-2034
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We acknowledge financial support from the Australian Research
Council, through a DECRA award (J.F.H.) and Discovery
Programs (D.W.L.), the EPSRC (M.J.G.S.; DTP studentship),
and the Royal Society (A.B.C.; UF100592, UF150675).
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DOI: 10.1021/acs.orglett.8b01989
Org. Lett. XXXX, XXX, XXX−XXX