Engaging Alkenyl Halides with Alkylsilicates via Photoredox Dual Catalysis

Article abstract of DOI:10.1021/acs.orglett.6b00024

Single-electron transmetalation via photoredox/nickel dual catalysis provides the opportunity for the construction of C_sp³-C_sp² bonds through the transfer of alkyl radicals under very mild reaction conditions. A general procedure for the cross-coupling of primary and secondary (bis-catecholato)alkylsilicates with alkenyl halides is presented. The developed method allows not only alkenyl bromides and iodides but also previously underexplored alkenyl chlorides to be employed. (Chemical Equation Presented).

Full text of DOI:10.1021/acs.orglett.6b00024

Letter
pubs.acs.org/OrgLett
Engaging Alkenyl Halides with Alkylsilicates via Photoredox Dual
Catalysis
Niki R. Patel,† Christopher B. Kelly,† Matthieu Jouffroy, and Gary A. Molander*
Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia,
Pennsylvania 19104-6323, United States
S
* Supporting Information
ABSTRACT: Single-electron transmetalation via photoredox/
nickel dual catalysis provides the opportunity for the construction
3
2
of Csp −Csp bonds through the transfer of alkyl radicals under very
mild reaction conditions. A general procedure for the cross-
coupling of primary and secondary (bis-catecholato)alkylsilicates
with alkenyl halides is presented. The developed method allows
not only alkenyl bromides and iodides but also previously
underexplored alkenyl chlorides to be employed.
potential of these bench stable and easily prepared solids is yet
unrealized.
ransition-metal-mediated cross-coupling has been instru-
Tmental in facile construction of numerous linkages
including C−N, C−O, and C−C bonds.1 Employment of
cross-coupling strategies to accomplish C−C bond formation
traditionally relies on a three-step catalytic cycle based on two-
electron processes. Although such a reaction manifold is
Recently, the MacMillan group reported that carboxylic acids
bearing an α-heteroatom and alkenyl halides, namely iodides
and bromides, can be effectively cross-coupled via dual
catalysis.12 Although our group has shown that a variety of
alkyltrifluoroborates function as radical precursors in Ni-
photoredox cross-couplings with aryl electrophiles,3a,5−7
integration of these same trifluoroborates with alkenyl halides
has yet to prove fruitful. Therefore, we wondered whether
alkylsilicates would be suitable as nucleophilic partners in
alkenyl dual catalytic cross-coupling (Scheme 1). Indeed, as
recently demonstrated,9,10 organosilicates allow easy access to
primary and secondary alkyl radicals without necessitating the
presence of an α-heteroatom, allowing greater diversity in the
structure of the radical precursor and hence substrate scope. In
addition, the net-neutral fragmentation of the [Si]−C bond
2
2
3
2
effective for Csp −Csp coupling, extension to Csp −Csp bond
formation has proved challenging.2 Very recently, several
groups, including our own, have reported a means of
overcoming this limitation via dual catalysis between a visible-
light activated photoredox catalyst and a classic transition metal
cross-coupling catalyst.3 By exploiting the propensity of
photoredox catalysts to promote single electron transfer
3
(SET) events to generate Csp radicals and the propensity of
these radicals to undergo single-electron transmetalation with
3
2
transition metal catalysts, Csp −Csp cross-coupling can be
accomplished under remarkably mild conditions.3,4 The
simplistic but powerful nature of this paradigm has led to a
series of reports on its application in the context of the cross-
coupling of α-alkoxy,5 α-amino,6 benzylic,3a and secondary
Scheme 1. Proposed Catalytic Cycle for Photoredox-Ni Dual
Catalysis with Alkylsilicates and Alkenyl Halides
alkyl7 Csp radicals typically with aryl electrophiles. These
3
radicals are generated from a variety of radical precursors,
including organotrifluoroborates and carboxylic acids, among
others.3
Although alkyltrifluoroborate salts have been demonstrated
to be exceptional radical precursors,8 they possess several
drawbacks (e.g., release of corrosive BF3, high oxidation
potential requiring use of an expensive Ir-based photocatalyst,
etc.) prompting us to initiate a program to explore alternate
radical precursors. As part of this program, our laboratory has
successfully highlighted a highly efficient class of coupling
partners suitable for a dual catalytic manifold: alkylbis-
(catecholato)silicates.9 Although recent reports by our group
and the groups of Fensterbank and Goddard,10 in addition to
the seminal studies of Nishigaichi,11 have demonstrated the use
of these synthons as radical precursors, the full reactive
Received: January 4, 2016
© XXXX American Chemical Society
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obviates the need for basic additives traditionally required when
using carboxylic acids or organotrifluoroborates as radical
precursors. Furthermore, the oxidation potentials of alkylsili-
cates (E° = +0.75 V vs SCE for primary silicates, on average)13
allow [Ru(bpy)3](PF6)2, an easily accessible photocatalyst, to
be employed.14 Herein, we report the successful integration of
(bis-catecholato)alkylsilicates in photoredox cross-coupling
with alkenyl halides.
Scheme 3. Scope of Alkenyl Halides in Ni/Photoredox
Cross-Coupling
Based on MacMillan’s success with carboxylic acids,12 we
posited that an alkyl−Ni(I) complex produced during photo-
redox cross-coupling involving silicates would be capable of
oxidative addition into the alkenyl halide’s C−X bond (Scheme
2a). Alternatively, oxidative addition into this same C−X bond
Scheme 2. Potential Pathways for the Oxidative Addition of
Alkenyl Halides onto Ni
could occur prior to ligation of the alkyl radical by in situ
generation of Ni(0) (Scheme 2b).4 Because of the rapid rate of
oxidative addition of alkenyl halides to d10 transition metals
(e.g., Ni and Pd) compared to aryl halides,15 it may mean that
the latter sequence is operative in alkenyl photoredox cross-
coupling. Ultimately, both pathways presumably furnish the
same reactive Ni(III) intermediate. Following reductive
elimination, the resulting Ni(I)−X intermediate is postulated
to be reduced by the ground-state Ru(I) photocatalyst,
regenerating the Ni(0) and the Ru(II) photocatalyst.4
Our initial studies probing the amenability of silicates to this
type of cross-coupling proved very fruitful. Thus, our previously
established conditions developed for aryl cross-coupling of
ammonium alkylsilicates with aryl bromides9 {2 mol %
[Ru(bpy)3](PF6)2, 5 mol % [NiCl2(dme)], 5 mol % dtbbpy
in DMF (0.1 M)} could be applied to the coupling with alkenyl
halides without need for modification (dme: dimethoxyethane;
dtbbpy: 4,4′-di-tert-butyl-2,2′-dipyridyl; bpy: 2,2′-dipyridyl).
Control experiments confirmed that light,16 a Ru photocatalyst,
a Ni catalyst, and the bipyridyl ligand are all necessary to
achieve cross-coupling; without any of these components, only
trace cross-coupled product was observed (see Supporting
Information). This rules out a strictly photoredox-based
coupling via a radical addition−elimination mechanism, as
reported by Fensterbank with vinyl sulfones and halides.10
Using these conditions, we set out to examine the scope of
this reaction within the context of various alkenyl halides
(Scheme 3). Using the alkylsilicate 1a and alkenyl iodide 2a,
the resulting cross-coupled product 3a was obtained in 58%
isolated yield after 24 h. However, the reaction is not limited to
alkenyl iodides, as alkenyl bromides could also be employed.
Electron-rich, electron-neutral, and electron-deficient β-bro-
mostyrenes as well as a 2-bromoindene (2b−e) were
competent alkenyl cross-coupling partners. In addition to
giving good yields of their respective cross-coupled products
and being amendable to scale-up (e.g., both 2d and 2e could be
performed on a gram scale), the geometry of the double bond
was virtually unaffected throughout the reaction. This latter fact
a
Reaction run on gram scale using white or blue LEDs; all yields are
isolated yields after purification.
again discriminates this process from an addition−elimination
mechanism.10 On a small scale, 2d produced the cross-coupled
product in a 15:1 ratio of cis/trans isomers. Upon scale-up, the
pure cis isomer was obtained in 76% yield. This is important
given the typical degradation of stereoselectivity that occurs for
styryl halides irradiated in the presence of Ir-based photo-
catalysts.12,17 Additionally, nonstyryl or styryl-like bromides
were similarly well-tolerated toward cross-coupling. An acryl
bromide 2f as well as more substituted cyclic 2g, exo-cyclic 2h,
and acyclic 2i alkenyl bromides underwent facile cross-
coupling. Additionally, 2g′ served equally well under the
reaction conditions and gave a comparable yield of the cross-
coupled product, indicating the interchangeability of iodides
and bromides in this reaction manifold. Although the free
hydroxyl group in 2j was not tolerated, its TBS-protected
B
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analogue 2k was cross-coupled with ease and in excellent yield.
As with the styryl systems (2b−d), the geometry of the double
bond was conserved during cross-coupling.
Scheme 5. Alkenyl Bromide Scope with Primary and
Secondary Alkyl Bis(catecholato)alkylsilicates
We next explored the scope of the reaction within the
context of various alkylsilicates (Scheme 4).18 We found that
Scheme 4. Scope of Alkyl Bis(catecholato)Silicates in Ni/
a
Photoredox Cross-Coupling
a
1
Inseparable bibenzyl impurity in H NMR; R′ = R″ = Et or R′ = H,
R″ = i−Pr; all yields are isolated yields after purification
aryl bromides,9 they proved to be rather recalcitrant when
coupling with alkenyl bromides (3ab, 3ag, and 3al). Although
the failure to generate 3ag is somewhat expected given the
instability of such systems, the low yield or failure of other
systems cannot be readily explained.
a
R′ = R″ = Et or R′ = H, R″ = i-Pr; all yields are isolated yields after
purification.
Finally, to demonstrate the robust nature of the developed
cross-coupling protocol, the viability of alkenyl chlorides as
cross-coupling partners was assessed. Remarkably, under the
same conditions utilized for alkenyl bromides and iodides, near-
identical reactivity was observed (Scheme 6). The cross-
coupled product of 2l with 1a was obtained in 50% yield. In
addition, a representative β-chlorostyryl derivative 2m reacted
with ease with 1j. Similarly, cross-coupling of 2n with
benzylsilicate 1e was accomplished successfully and in
comparable yield to its bromide congener (90% vs 80%,
respectively).
In summary, ammonium organobis(catecholato)silicates,
which serve as powerful radical precursors, and alkenyl halides
can be readily cross-coupled via dual photoredox/Ni catalysis.
By exploiting the relatively low oxidation potential of primary
and secondary (bis-catecholato)alkylsilicates, a variety of
primary and secondary radicals can be accessed using a
practical ruthenium photocatalyst. Subsequently, these radicals
are amenable to nickel-mediated cross-coupling with a diverse
array of alkenyl halides, including yet unexplored alkenyl
moderate to excellent yields were obtained for the cross-
coupling of a range of primary and secondary alkylsilicates with
2a. Secondary alkylsilicates (1b−d) performed well, with the
exception of a bicyclic species, 1d. Primary systems faired
equally well. Benzyl (1e) and allylic (1f) silicates, which
produce stabilized radicals, underwent cross-coupling success-
fully. Additionally, isobutyl, alkene-containing, and hexylsili-
cates were also amendable to cross-coupling (1g−i). Various
functional groups that were tolerated include ether, amide,
pyridyl, and amine substituents (1j−m).
The substrate-diversity of the reaction was next assessed via
the coupling of various alkenyl bromides with a range of
alkylsilicates (Scheme 5). Both activated and nonactivated
alkylsilicates performed well with several sterically and
electronically disparate alkenyl bromides. Again, the geometry
of the double bond was unaffected during cross-coupling (e.g.,
compounds 3ac−3ag). Interestingly, although primary amine-
containing silicates were previously shown to couple well with
C
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M. N.; Glorius, F. J. Am. Chem. Soc. 2013, 135, 5505. (h) Shu, X. Z.;
Zhang, M.; He, Y.; Frei, H.; Toste, F. D. J. Am. Chem. Soc. 2014, 136,
5844. (h) Tasker, S. Z.; Jamison, T. F. J. Am. Chem. Soc. 2015, 137,
9531.
Scheme 6. Ni/Photoredox-Catalyzed Cross-Coupling
Alkenyl Chlorides with Alkyl Bis(catecholato)silicates
a
(4) Gutierrez, O.; Tellis, J. C.; Primer, D. N.; Molander, G. A.;
Kozlowski, M. C. J. Am. Chem. Soc. 2015, 137, 4896.
(5) Karakaya, I.; Primer, D. N.; Molander, G. A. Org. Lett. 2015, 17,
3294.
(6) El Khatib, M.; Serafim, R. A. M.; Molander, G. A. Angew. Chem.,
Int. Ed. 2016, 55, 254.
(7) Primer, D. N.; Karakaya, I.; Tellis, J. C.; Molander, G. A. J. Am.
Chem. Soc. 2015, 137, 2195.
(8) Molander, G. A. J. Org. Chem. 2015, 80, 7837.
(9) Jouffroy, M.; Primer, D. N.; Molander, G. A. J. Am. Chem. Soc.
2016, 138, 475.
(10) Corce, V.; Chamoreau, L.-M.; Derat, E.; Goddard, J.-P.; Ollivier,
C.; Fensterbank, L. Angew. Chem., Int. Ed. 2015, 54, 11414.
(11) (a) Matsuoka, D.; Nishigaichi, Y. Chem. Lett. 2014, 43, 559.
(b) Matsuoka, D.; Nishigaichi, Y. Chem. Lett. 2015, 44, 163.
(12) Noble, A.; McCarver, S. J.; MacMillan, D. W. C. J. Am. Chem.
Soc. 2015, 137, 624.
a
R′ = R″ = Et or R′ = H, R″ = i-Pr; all yields are isolated yields after
purification.
(13) Nishigaichi, Y.; Suzuki, A.; Takuwa, A. Tetrahedron Lett. 2007,
48, 211.
(14) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Chem. Rev.
2013, 113, 5322.
chlorides. The developed method complements existing
protocols for alkenyl cross-coupling via dual catalysis and
enables access to several previously inaccessible fragments.
Additionally, the mild reaction conditions allow functional
group tolerance, and complete stereochemical fidelity is
exhibited.
(15) (a) Jutand, A.; Negri, S. Organometallics 2003, 22, 4229.
(b) Fahey, D. R.; Mahan, J. E. J. Am. Chem. Soc. 1977, 99, 2501.
(16) Note that the source of the irradiation (CFL, white or blue
LEDs) had no effect on the overall outcome of the reaction.
(17) For examples, see: (a) Noble, A.; MacMillan, D. W. C. J. Am.
Chem. Soc. 2014, 136, 11602. (b) Singh, K.; Staig, S. J.; Weaver, J. D. J.
Am. Chem. Soc. 2014, 136, 5275.
ASSOCIATED CONTENT
(18) Note that both diisopropylammonium and triethylammonium
counterions show no discernible difference in reactivity or yield.
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.6b00024.
Experimental details and spectral data (PDF)
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: gmolandr@sas.upenn.edu.
Author Contributions
†N.R.P. and C.B.K. contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank Kingson Lin (University of Pennsylvania) for the
preparation of alkylsilicates. We thank NIGMS (RO1
GM113878) for financial support of this research.
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■
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