A Bench-Stable, Single-Component Precatalyst for Silyl-Heck Reactions

Article abstract of DOI:10.1021/acs.orglett.7b02807

Studies of the silyl-Heck reaction aimed at identifying active palladium complexes have revealed a new species that is formed in situ. This complex has been identified as the palladium iodide dimer, [(JessePhos)PdI₂]₂, which has been

Full text of DOI:10.1021/acs.orglett.7b02807

Letter
pubs.acs.org/OrgLett
A Bench-Stable, Single-Component Precatalyst for Silyl−Heck
Reactions
Sarah B. Krause, Jesse R. McAtee, Glenn P. A. Yap, and Donald A. Watson*
Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, United States
S
* Supporting Information
ABSTRACT: Studies of the silyl-Heck reaction aimed at identifying active palladium complexes have revealed a new species that
is formed in situ. This complex has been identified as the palladium iodide dimer, [(JessePhos)PdI2]2, which has been found to
be a competent single-component precatalyst for the silyl-Heck reaction. This complex is easily prepared and is temperature,
moisture, and air stable. Additionally, this precatalyst provides higher activity and greater reproducibility compared to previous
systems.
the use of commercially available Pd2dba3 as the palladium
precatalyst for the preparation of vinylsilanes from styrenes and
styrene-like alkenes.5
Unfortunately, even with JessePhos, the formation of
allylsilanes required the use of the thermally sensitive
(COD)Pd(CH2SiMe3)2 as the precatalyst to obtain optimal
yields (Scheme 1).4−6 While this latter precatalyst provides a
nsaturated organosilanes, such as allyl- and vinylsilanes,
Uare important intermediates in organic synthesis. These
reagents serve as nucleophiles in a wide range of important
carbon−carbon bond-forming reactions, are employed in cross-
coupling reactions, and act as masking groups for a variety of
heteroatomic functional groups (including alcohols, ketones,
and vinyl fluorides).1
Over the past several years, our group has been investigating
the preparation of both allyl- and vinylsilanes via the palladium-
catalyzed silylation of alkenes using silyl electrophiles (silyl
iodides and triflates).2,3 Using palladium catalysis, we initially
Scheme 1. Previously Optimized Conditions for Allyl- and
Vinylsilane Synthesis Using Silyl−Heck Conditions
a
t
identified commercially available BuPPh2 (L1) as a modestly
effective ligand in these silyl-Heck reactions (Figure 1).
Subsequent studies led to the development of JessePhos
(L2), which was shown to provide superior yields in the
preparation of allylsilanes from terminal alkenes4 and allowed
a
Previous best yields and conditions for α-olefins (ref 4) and styrenes
(ref 5).
workable solution, we considered the thermal sensitivity of
(COD)Pd(CH2SiMe3)2 to be an impediment to the
implementation of this chemistry, and continued to search
for catalysts that would provide a more “bench stable” method.
Simultaneously, we also sought to understand the solvent
dependencies in the reactions involving JessePhos. The
formation of both allyl- and vinylsilanes were optimal in 1,2-
dichloroethane (DCE), which is an unexpected solvent for
what we believe to be a Pd(0)/Pd(II) catalytic cycle.
Received: September 7, 2017
Figure 1. Evolution of Silyl−Heck catalyst systems.
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b02807
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Letter
Herein we report our initial observations into the role of the
chlorinated solvent in the silyl-Heck reaction. We have found
that the previously employed combination of ligand and
palladium precatalyst result in the rapid activation of the solvent
to form a new Pd(II) complex, which in turn can react with
Me3Si−I to form a dimeric Pd(II) complex [(JessePhos)PdI2]2
(1, Figure 1). We have found that 1, which can also be readily
prepared in a single step from commercial materials, is a bench-
stable, single-component precatalyst that is highly effective for
the formation of both allyl- and vinylsilanes from terminal
alkenes. The key to the success of this complex appears to be
due to the sterically enforced ligand to metal ratio of 1:1
imparted by the large iodide ligands. The development of this
catalyst system, as well as direct comparison of its efficacy in
silyl-Heck reactions to previous catalyst systems, is described
below.
desired product 2 in only 73% assay yield with the mass balance
being mainly unreacted starting material. This is significantly
less efficient than the previously optimized conditions for this
same reaction using the combination of 2 mol % (COD)Pd-
(CH2SiMe3)2 and 3 mol % L2.4 Our prior studies strongly
suggest that the active catalyst in silyl-Heck reactions are
monoligated complexes supported by a single phosphine ligand,
and that the reactions are highly sensitive to the ligand/Pd
ratio. Optimal ligand/Pd ratios typically range between 1:1 to
1.5:1 ligand to metal, with significant decreases in catalytic
efficiency observed when the ligand/Pd ratio is increased to 2:1
or higher. In this context, we attribute the relatively poor
catalytic efficiency of complex 5 to the fact that it is a bis-ligated
compound.
Our investigation began by studying the reaction of the
precatalyst components previously used in allylsilane synthesis.
As is expected from prior literature reports,7 combining
(COD)Pd(CH2SiMe3)2 and JessePhos (L2) in an inert solvent,
such as toluene, led to clean formation of the Pd(0) complex
(L2)2Pd (4, Scheme 2). This air-sensitive complex was isolated
Next, to understand the catalytic relevance of complex 5
better, we sought to elucidate how this complex might be
involved in the catalytic cycle. Those studies led us to examine
the stoichiometric reaction of complex 5 with Me3SiI in DCE
(Scheme 3, left). Following the reaction by 31P NMR revealed
Scheme 2. Role of Solvent in Catalyst Formation
Scheme 3. Identification of Complex 1
the rapid formation of a new palladium complex, along with
traces of free ligand L2. 29Si NMR also revealed the formation
of Me3SiCl. Isolation and characterization by X-ray diffraction
revealed the complex to be the μ-iodo-Pd(II) dimer 1 (Scheme
3, right).9 Presumably driven by the Si−Cl bond strength,10
complex 5 undergoes halide metathesis with Me3SiI to provide
the Pd(II)I2 complex and Me3SiCl. Critically, because of the
size of the iodo ligand, the complex sheds an extra phosphine
ligand and is stabilized by the bridging halide centers.
Recognizing that complex 1 contains a ligand to metal ratio
of 1:1, a ratio we found to be critical for highly reactive
catalysts, we investigated its use in silyl-Heck reactions. Using
the same model system as before, we found that at catalyst
loadings of 1−2 mol %, complex 1 is highly efficient as a
catalyst for the silyl-Heck reaction (Table 1, entries 2 and 3). At
higher catalyst loadings isomerization of the starting alkene
became competitive, and at lower catalyst loadings incomplete
conversion was observed (entries 1 and 4). This is the first time
that a highly efficient, single component precatalyst has been
identified for the silyl-Heck reaction, which both eases reaction
setup and leads to more reproducible results, as the ligand to
metal ratio is dictated by the catalyst structure.
in 59% yield and was characterized by single-crystal X-ray
diffraction (Scheme 2, bottom left). In contrast, the same
reaction run in DCE provided the Pd(II) complex
(JessePhos)2PdCl2 (5) in 35% isolated yield. X-ray analysis of
5 established this as a monomeric chloride complex with two
ligands per palladium atom (Scheme 2, bottom right).8 It is
evident from this result, and in accord with our expectations,
that the initially formed palladium complex 4 is able abstract
two chloride atoms from the solvent.
Complex 5 can also be prepared from (MeCN)2PdCl2 and
L2 in high yield (eq 1). On the basis of our earlier report that
complex 5 is an effective precatalyst in boryl−Heck reactions,8
we decided to investigate its use in silyl-Heck reactions.
As least as important to the fact that 1 is a single component
catalyst is that it is also completely bench stable. We have
stored samples of the complex under air at room temperature,
without special precautions, for over 30 months without
Using the reaction of 1-decene and Me3SiI as a model
system, 5 mol % of complex 5 proved to be only a modestly
effective catalyst for the silyl-Heck reaction, providing the
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that this catalyst system may in fact provide better reactivity
than the previous conditions.
Further supporting the superior activity of the single
component catalyst 1, larger silyl iodides are now competent
substrates for the silyl-Heck reaction using α-olefins (Scheme
5). Previously, silyl iodides larger than Me3SiI led to substantial
Table 1. Exploration of Complex 1 as a Precatalyst for the
Silyl−Heck Reaction
a
entry
1 (mol %)
yield 2 (%)
Scheme 5. Performance of Single-Component Catalyst 1
with Larger Silyl Iodides
1
2
3
4
0.5
1.0
2.0
2.5
83
99
98
83
a
a
1
Yield determined by H NMR against an internal standard.
detectable decomposition. Moreover, we have found that the
complex can be prepared in a single step from commercially
available JessePhos and PdI2 in near-quantitative yield (eq 3).11
This synthesis makes this complex highly accessible and easy to
use in silyl-Heck reactions.
a
b
Isolated yields. 72 h.
alkene isomerization with alkenes bearing allylic hydrogen
atoms.12 With catalyst 1, both aromatic- (12, 13) and benzyl-
substituted (14) silyl iodides led to allylsilanes in good yield
without significant isomerization of the starting material. These
are important substrates, as silanes bearing aromatic and
benzylic groups are often superior to trimethylsilanes in a
variety of downstream reactions, including oxidation and cross-
coupling.1f,13 Likewise, for the first time, we have been able to
observe appreciable yield of the much more sterically
demanding triethylsilane (15) using α-olefins.
To compare efficiency of the single component catalyst 1
directly, to our earlier catalytic systems, we invested the silyl-
Heck reaction of a variety of α-olefin substrates (Scheme 4). In
Scheme 4. Performance of Single-Component Catalyst 1
Compared to Previously Optimized Catalytic Conditions
a,b
with α-Olefins
Finally, we also investigated the use of complex 1 in the
silylation of styrenes. Although the conditions reported in 2015
do not require a thermally sensitive precatalyst to obtain good
yields in these transformations, a unified set of single-
component conditions for both α-olefins and styrenes would
simplify the utilization of the silyl-Heck reaction by others.
Toward this end, we have found that the same conditions used
for α-olefin silylation apply directly to the silylation of styrenes
(Scheme 6). As shown above, using the single-component
Scheme 6. Performance of Single-Component Catalyst 1
Compared to Previously Optimized Catalytic Conditions
a,
b
with Styenes
a
b
Isolated yields. Parenthetical yields are for the same substrate and
product using the conditions reported in ref 4 using 2−6 mol % L2
c
and 2−4 mol % (COD)Pd(CH2SiMe3)2 as catalyst. 2.8 g scale; 0.5
d
mol % 1. Contains 5% of homoallylsilane, which is similar to the prior
results.
cases where we have reported the transformation under prior
conditions, the previous yield is given in parentheses. For
simple terminal alkenes (2, 6, 7) as well as allyl aromatic
compounds (8−10), comparable (and in some cases higher)
yields of allylsilane were observed. Notably, on a multigram
scale, only 0.5 mol % precatalyst was required (see 2). In all
cases, the observed E/Z ratio of the allylsilane was nearly
identical to previous conditions. Further, α-olefins bearing
heterocycles (such as 3-methylindole) are also tolerated (11). It
is notable that under the previously optimized conditions some
of the examples required up to 10 mol % of Pd to obtain the
reported yield. With the present system, 1 mol % of catalyst (2
mol % Pd) is effective for a wide range of substrates, suggesting
a
b
Isolated yields. Parenthetical yields are for the same substrate and
product using the conditions reported in ref 5 using 5 mol % of L2 and
2.5 mol % of Pd2(dba)3 as catalyst.
catalyst, we directly compared performance of several substrates
to the previously best conditions. In all cases, similar yields of
the product were observed, but all the reactions required less
than half of the catalyst loading compared to the prior
conditions. In some cases, less silyl iodide was also required.
Overall, we believe that these results support the superiority of
C
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Ed.; Thieme: Stuttgart, 2001; Vol. 4, p 837. (i) Denmark, S. E.; Fu, J.
Chem. Rev. 2003, 103, 2763−2794. (j) Denmark, S. E.; Liu, J. H. C.
Angew. Chem., Int. Ed. 2010, 49, 2978−2986. (k) Nakao, Y.; Hiyama,
T. Chem. Soc. Rev. 2011, 40, 4893−4901.
(2) (a) McAtee, J. R.; Martin, S. E. S.; Ahneman, D. T.; Johnson, K.
A.; Watson, D. A. Angew. Chem., Int. Ed. 2012, 51, 3663−3667.
(b) Martin, S. E. S.; Watson, D. A. J. Am. Chem. Soc. 2013, 135,
13330−13333. (c) Martin, S. E. S.; Watson, D. A. Synlett 2013, 24,
2177−2182. (d) McAtee, J. R.; Martin, S. E. S.; Cinderella, A. P.; Reid,
W. B.; Johnson, K. A.; Watson, D. A. Tetrahedron 2014, 70, 4250−
4256. (e) Cinderella, A. P.; Vulovic, B.; Watson, D. A. J. Am. Chem.
Soc. 2017, 139, 7741−7744. (f) Vulovic, B.; Watson, D. A. Eur. J. Org.
Chem. 2017, 2017, 4996−5009.
catalyst 1 compared to all previously reported catalysts for the
silyl-Heck reaction.
In conclusion, through study of the fate of the catalytic
additives under previously optimized conditions, we have
discovered a new, single-component catalyst 1 that is both
bench stable and highly effective in silyl-Heck reactions. The
key to this finding was the discovery that complex 5 forms as a
stable μ-bridged Pd(II)I2 dimer with a 1:1 ligand to metal ratio
using the large JessePhos ligand (L2). This new precatalyst
appears to be the most effective system developed to date for
the silyl-Heck reaction. It requires only low catalyst loading
(0.5−1 mol %) and provides a unified set of conditions that are
applicable to both α-olefin and styrene substrates. Further
studies are underway to understand better the details of how
this complex is reduced in situ to Pd(0), which will be reported
in due course. However, in the meantime, catalyst 1 provides a
very significant practical advantage that should greatly facilitate
the implementation of silyl-Heck transformations in the
preparation of unsaturated silanes.
(3) For early studies in the area, see: (a) Yamashita, H.; Hayashi, T.;
Kobayashi, T.; Tanaka, M.; Goto, M. J. Am. Chem. Soc. 1988, 110,
4417−4418. (b) Yamashita, H.; Kobayashi, T.; Hayashi, T.; Tanaka,
M. Chem. Lett. 1991, 20, 761−762. (c) Yamashita, H.; Tanaka, M.;
Goto, M. Organometallics 1997, 16, 4696−4704.
(4) McAtee, J. R.; Yap, G. P. A.; Watson, D. A. J. Am. Chem. Soc.
2014, 136, 10166−10172.
(5) McAtee, J. R.; Krause, S. B.; Watson, D. A. Adv. Synth. Catal.
2015, 357, 2317−2321.
(6) Pan, Y.; Young, G. B. J. Organomet. Chem. 1999, 577, 257−264.
(7) Lee, H. G.; Milner, P. J.; Colvin, M. T.; Andreas, L.; Buchwald, S.
L. Inorg. Chim. Acta 2014, 422, 188−192.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.7b02807.
(8) Reid, W. B.; Spillane, J. J.; Krause, S. B.; Watson, D. A. J. Am.
Chem. Soc. 2016, 138, 5539−5542.
(9) Only a few complexes bearing an L2Pd(II)2I4 core have been
previously reported. See: (a) Alcock, N. W.; Wilson, W. L.; Nelson, J.
H. Inorg. Chem. 1993, 32, 3193−3195. (b) Ryabov, A. D.; Kuz’mina, L.
G.; Polyakov, V. A.; Kazankov, G. M.; Ryabova, E. S.; Pfeffer, M.; van
Eldik, R. J. Chem. Soc., Dalton Trans. 1995, 999−1006. (c) Wing-Sze
Hui, J.; Wong, W.-T. J. Chem. Soc., Dalton Trans. 1997, 2445−2450.
(d) Smith, D. C., Jr.; Lake, C. H.; Gray, G. M. Dalton Trans. 2003,
2950−2955. (e) Mednikov, E. G.; Dahl, L. F. Inorg. Chim. Acta 2005,
358, 1557−1570. (f) Xu, C.; Wang, Z.-Q.; Zhang, Y.-P.; Liang, T.; Xu,
Y. Z. Kristallogr. - New Cryst. Struct. 2010, 225, 273.
Crystallographic data for compound 1 (CIF)
Crystallographic data for compound 4 (CIF)
Experimental procedures and spectral data (PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: dawatson@udel.edu.
ORCID
(10) The bond strength for the Si−Cl bond is appoximately 113
kcal/mol vs 77 kcal/mol for the Si−I bond. See: Walsh, R. Acc. Chem.
Res. 1981, 14, 246−252.
(11) Aspira Chemical (Oakland, CA), Product No. 300685.
(12) Larger silyl iodides have been previously used to prepare vinyl
silanes using silyl-Heck conditions; see ref 5.
Donald A. Watson: 0000-0003-4864-297X
Notes
The authors declare no competing financial interest.
(13) (a) Trost, B. M.; Machacek, M. R.; Ball, Z. T. Org. Lett. 2003, 5,
1895−1898. (b) Denmark, S. E.; Tymonko, S. A. J. Am. Chem. Soc.
2005, 127, 8004−8005. (c) Yamane, M.; Uera, K.; Narasaka, K. Bull.
Chem. Soc. Jpn. 2005, 78, 477−486.
ACKNOWLEDGMENTS
■
The University of Delaware, the National Science Foundation
(CAREER CHE-1254360), the Delaware Economic Develop-
ment Office (Grant 16A00384), Gelest, Inc. (Topper Grant
Program), and the Research Corp. Cottrell Scholars Program
are gratefully acknowledged for support. S.B.K. thanks the NSF
for a Graduate Research Fellowship (1247394). Data was
acquired at UD on instruments obtained with the assistance of
NSF and NIH funding (NSF CHE0421224, CHE0840401,
CHE1229234, CHE1048367; NIH S10OD016267,
S10RR026962, P20GM104316, P30GM110758).
REFERENCES
■
(1) (a) Brook, M. A. Silicon in Organic, Organometallic, and Polymer
Chemistry; Wiley: Chichester, 2000. (b) Fleming, I. Organic Silicon
Chemistry. In Comprehensive Organic Chemistry; Barton, D. H. R.,
Ollis, W. D., Eds.; Pergamon: Oxford, 1979; Vol. 3, p 539. (c) Hosomi,
A. Acc. Chem. Res. 1988, 21, 200−206. (d) Fleming, I. Allylsilanes,
Allylstannanes, and Related Systems. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991;
Vol. 2, p 563. (e) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207−
2293. (f) Jones, G. R.; Landais, Y. Tetrahedron 1996, 52, 7599−7662.
(g) Fleming, I.; Barbero, A.; Walter, D. Chem. Rev. 1997, 97, 2063−
2192. (h) Sarkar, T. K. Allylsilanes. In Science of Synthesis; Fleming, I.,
D
DOI: 10.1021/acs.orglett.7b02807
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