An improved procedure for the preparation of Ru(bpz)3(PF6)2 via a high-yielding synthesis of 2,2'-bipyrazine

Article abstract of DOI:10.3762/bjoc.11.9

There has been a recent surge of interest in the use of transition metal polypyridyl complexes as visible light-absorbing photocatalysts for synthetic applications. Among the most attractive features of this approach is the availability of many known complexes with well-characterized photophysical and electrochemical properties. In particular, Ru(bpz)₃²⁺ is a powerful photooxidant that has proven to be uniquely suited for oxidatively induced photoredox transformations. We present here a straightforward and highyielding route to Ru(bpz)₃(PF₆)₂ that features an improved Pd-catalyzed synthesis of the 2,2'-bipyrazine ligand that is amenable to gram-scale preparations.

Full text of DOI:10.3762/bjoc.11.9

An improved procedure for the preparation of Ru(bpz)3(PF6)2
via a high-yielding synthesis of 2,2’-bipyrazine
Danielle M. Schultz, James W. Sawicki and Tehshik P. Yoon*
Letter
Open Access
Address:
Beilstein J. Org. Chem. 2015, 11, 61–65.
Department of Chemistry, University of Wisconsin–Madison, 1101
University Avenue, Madison, WI 53706, USA
doi:10.3762/bjoc.11.9
Received: 05 December 2014
Accepted: 07 January 2015
Published: 14 January 2015
Email:
Tehshik P. Yoon* - tyoon@chem.wisc.edu
*
Corresponding author
Associate Editor: I. Marek
Keywords:
© 2015 Schultz et al; licensee Beilstein-Institut.
License and terms: see end of document.
heterocycles; ligand synthesis; palladium; photocatalysis; reductive
coupling
Abstract
There has been a recent surge of interest in the use of transition metal polypyridyl complexes as visible light-absorbing photocata-
lysts for synthetic applications. Among the most attractive features of this approach is the availability of many known complexes
with well-characterized photophysical and electrochemical properties. In particular, Ru(bpz)32+ is a powerful photooxidant that has
proven to be uniquely suited for oxidatively induced photoredox transformations. We present here a straightforward and high-
yielding route to Ru(bpz)3(PF6)2 that features an improved Pd-catalyzed synthesis of the 2,2’-bipyrazine ligand that is amenable to
gram-scale preparations.
Findings
Visible light-photoredox catalysis using transition metal chro- In particular, the homoleptic tris(bipyrazyl) complex 2
mophores is rapidly becoming recognized as an important (Ru(bpz)32+) [10] has emerged as one of the most useful tran-
strategy in organic synthesis [1-5]. This approach towards reac- sition metal photocatalysts for oxidatively induced organic
tion design enables the facile generation and exploitation of transformations (Figure 1). Due to the electron-deficient nature
odd-electron intermediates such as radicals and radical ions of its bipyrazyl ligands, the excited state redox potential of 2 is
under exceptionally mild reaction conditions. A large number of quite positive (+1.45 V vs SCE) [11]. Consequently, it is an
transition metal chromophores with well-characterized photo- effective photocatalyst in oxidatively induced photoredox trans-
physical and electrochemical properties are known, and the formations where less strongly oxidizing complexes (e.g., 1) are
influence of ligand modification on the photoredox properties of not successful. For instance, we have reported that 2 is uniquely
these complexes is well understood [6-8]. As a result, a variety capable of promoting radical cation mediated Diels–Alder
of Ru and Ir based chromophores spanning a range of redox cycloadditions [12], radical thiol–ene couplings [13,14], and
potentials have recently become widely utilized in the design of photooxygenation reactions [15,16]. Similarly, Zheng has
new photocatalytic transformations [9].
reported oxidatively initiated indole synthesis [17] and [3 + 2]
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Beilstein J. Org. Chem. 2015, 11, 61–65.
Figure 1: Influence of ligand structure on photoredox behavior.
cycloaddition [18,19] reactions using photocatalyst 2. Finally, a organometallic and inorganic applications of bpz-supported
variety of transition metal complexes bearing bipyrazyl ligands transition metal complexes.
have been prepared and investigated for a wide range of appli-
cations in inorganic and organometallic chemistry [20-25].
Our optimization studies for the reductive coupling of 2-halo-
pyrazines are summarized in Table 1. Initial exploratory experi-
Unfortunately, the synthesis of 2,2’-bipyrazyl (bpz) is quite ments using 2-chloropyrazine as the substrate gave quite poor
challenging compared to the syntheses of other, structurally yields using either organic or inorganic bases (Table 1, entries 1
similar bidentate bisazene ligands. Various methods for the and 2). Speculating that oxidative addition into the aryl chloride
preparation of bpz have been reported [26-28], the most bond might be problematic in this coupling reaction, we turned
common of which involve transition metal-catalyzed reductive our attention towards the use of more reactive aryl iodides. A
homocouplings of halopyrazine electrophiles [29,30]. However, screen of solvents commonly used in Pd-catalyzed cross-
we found these procedures to be capricious in our hands, and coupling reactions revealed that DMF provided the highest
after a survey of known reductive dimerization protocols, the
highest yields of bpz we were able to obtain resulted from a
Table 1: Optimization of Pd-catalyzed reductive homocoupling of
Pd-catalyzed procedure reported by Plé (Scheme 1) [31]. Using
this protocol, we were able to obtain only 40% yield of the
desired 2,2-bipyrazine ligand on milligram scale, accompanied
by a significant degree of undesired reductive dehalogenation.
Moreover, the yields on larger scales were unreliable, and
work-up and purification of this inefficient coupling reaction
proved difficult.
2-halopyrazines.a
entry
X
solvent
equiv iPrOH
yieldb
1
c
Cl
toluene
toluene
toluene
dioxane
DMF
3
3
3
3
3
2
1
2
2
3%
3%
2
Cl
I
3
4
5
6
7
4%
I
10%
I
85%
I
DMF
87%
I
DMF
83%
8d
I
DMF
44%
Scheme 1: Pd-catalyzed reductive coupling of 2-chloropyrazine.
9e
I
DMF
85% (81%)f
aConditions: Reactions were conducted on a 0.22 mmol scale using
1
1
equiv 2-halopyrazine, 5 mol % Pd(OAc)2, and 1.5 equiv K2CO3 at
00 °C unless otherwise noted. bYields determined by 1H NMR
Thus, in order to accelerate our investigations of complex 2 as a
strongly oxidizing photoredox catalyst, we required a robust,
high-yielding, and scalable synthesis of bpz. An improved syn-
thesis of this ligand would be useful both in the context of the
growing interest in photoredox catalysis as well as other
analysis using an internal standard. cReaction conducted using 1.5
equiv iPr2NEt instead of K2CO3. dReaction conducted at 60 °C.
eReaction conducted for 2 h. fValue in parentheses is the average
isolated yield from two reproduced experiments.
62

Beilstein J. Org. Chem. 2015, 11, 61–65.
yields (Table 1, entries 3–5). We next examined the effect of Ru(bpz)3PF6, showing for the first time that we could effi-
varying equivalents of the terminal reductant, and we observed ciently prepare hundreds of milligrams of this important photo-
that the presence of excess isopropanol had little effect catalyst. Importantly, this protocol has proven to be repro-
(
Table 1, entries 6 and 7). Finally, an evaluation of the reaction ducible in the hands of other researchers as well [38].
temperature revealed that the coupling proceeded sluggishly at
lower temperatures (Table 1, entry 8). Optimal conditions thus
called for 5 mol % Pd(OAc)2, 2 equiv of isopropanol, and 1.5
equiv of K2CO3 in DMF (0.4 M) at 100 °C; under these condi-
tions, the reaction was complete in 2 h and afforded the desired
homocoupling product in 81% isolated yield (Table 1, entry 9).
Although our investigations were motivated by our specific
need to access photocatalyst complex 2, we were pleased to find
that the optimal conditions for the synthesis of 2,2’-bipyrazine
translated smoothly to the reductive coupling of a variety of
pyridyl electrophiles. Table 2 demonstrates the application of
these reaction conditions to the syntheses of a number of elec-
tron-deficient bipyridyl ligands that have been used to prepare
strongly photooxidizing metal–polypyridyl complexes [32-36].
In each case, the requisite aryl iodides are either commercially
available or can be easily synthesized by Finkelstein displace-
ment of the aryl chloride with NaI [37].
Scheme 2: Preparative-scale synthesis of Ru(bpz)3(PF6)2.
Finally, we explored the scalability of the optimized conditions,
and found that they remained applicable on multi-gram scale In conclusion, we have developed an improved, Pd-catalyzed
Scheme 2). Thus, exposure of 4 g of 2-iodopyrazine to the method for the synthesis of 2,2’-bipyrazine, an important ligand
optimized conditions from Table 1 cleanly produced 1.25 g of with growing utility in the context of visible light photocatal-
,2’-bipyrazine in 81% isolated yield. A portion of this material ysis. This method is readily scalable to enable the gram-
(
2
was then carried on to synthesize 689 mg (83% yield) of scale preparation of 2,2’-bipryazine, which facilitates the
Table 2: Pd-Catalyzed synthesis of other ligands used to support electron-deficient Ru(II) chromophores.a
entry
1
iodoarene
product
time
4 h
yieldb
89%
2
3
6 h
5 h
85%
88%
aConditions: 1.0 equiv 2-iodopyrazine, 1.5 equiv K2CO3, 2 equiv isopropanol, 5% Pd(OAc)2, DMF (0.4 M), 100 °C. bIsolated yield (average of two
experiments).
63

Beilstein J. Org. Chem. 2015, 11, 61–65.
1
2
2
2
2
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preparative synthesis of the strongly oxidizing photocatalyst
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