cis-Locked Ru(II)-DMSO Precursors for the Microwave-Assisted Synthesis of Bis-Heteroleptic Polypyridyl Compounds

We describe a synthetic strategy for the preparation of bis-heteroleptic polypyridyl Ru(II) complexes of the type [Ru(L1)2(L2)]2+ (L1 and L2 = diimine ligands) from well-defined Ru(II) precursors. For this purpose, a series of six neutral, anionic, and cationic cis-locked Ru(II)-DMSO complexes (2–7) of the general formula [Y] fac-[RuX(DMSO–S)3(O–O)]n (where O–O is a symmetrical chelating anion: oxalate (ox), malonate (mal), acetylacetonate (acac); X = DMSO–O or Cl–; n = −1/0/+1 depending on the nature and charge of X and O–O; when present, Y = K+ or PF6–) were efficiently prepared from the well-known cis-[RuCl2(DMSO)4] (1). When treated with diimine chelating ligands (L1 = bpy, phen, dpphen), the compounds 2–7 afforded the target [Ru(L1)2(O–O)]0/+ complex together with the undesired (and unexpected) [Ru(L1)3]2+ species. Nevertheless, we found that the formation of [Ru(L1)3]2+can be minimized by carefully adjusting the reaction conditions: in particular, high selectivity toward [Ru(L1)2(O–O)]0/+ and almost complete conversion of the precursor was obtained within minutes, also on a 100–200 mg scale, when the reactions were performed in absolute ethanol at 150 °C in a microwave reactor. Depending on the nature of L1 and concentration, with the oxalate and malonate precursors, the neutral product [Ru(L1)2(O–O)] can precipitate spontaneously from the final mixture, in pure form and acceptable-to-good yields. When spontaneous precipitation of the disubstituted product does not occur, purification from [Ru(L1)3]2+ can be rather easily accomplished by column chromatography or solvent extraction. By comparison, under the same conditions, compound 1 is much less selective, thus demonstrating that locking the geometry of the precursor through the introduction of O–O in the coordination sphere of Ru is a valid strategic approach. By virtue of its proton-sensitive nature, facile and quantitative replacement of O–O in [Ru(L1)2(O–O)]0/+ by L2, selectively affording [Ru(L1)2(L2)]2+, was accomplished in refluxing ethanol in the presence of a slight excess of trifluoroacetic acid or HPF6.

For comparative purposes, the stereoisomer b was selectively prepared by treatment of trans- [RuCl 2 (dmso-S) 4 ] (1t), the stereo and linkage isomer of 1, with phen at room temperature (its NMR spectrum is shown in Figure S1). Complex 1t, in fact, is known to replace selectively two adjacent dmso-S ligands leaving unchanged the geometry of the Ru(II) fragment (Scheme S2). We also found that, consistent with what previously observed for the corresponding bpy complex, S3 compound b is not stable in chloroform solution at room temperature and within 24 hours isomerizes to a mixture of a and of the other symmetrical isomer c. From this solution we managed to get crystals of c suitable for X-ray analysis that afforded the molecular structure of the complex ( Figure S3).

b) Reactions performed in refluxing ethanol.
Complex 1 was treated with one equiv. of phen in refluxing ethanol for 2h, i.e. in the conditions that -with the similar ligand dppz -according to Burke and Keyes afforded selectively the monosubstituted complex cis,cis-[RuCl 2 (dmso-S) 2 (dppz)] in good yield. S4 The orange product that precipitated spontaneously from the cooled solution turned out to be, according to NMR analysis, a ca. 5:1 mixture of cis,cis-[RuCl 2 (dmso-S) 2 (phen)] (a) and cis,trans-[RuCl 2 (dmso-S) 2 (phen)] (c) (see below Figure S4). The mother liquor, beside a and c, contained the disubstituted charged complex cis-[RuCl(dmso-S)(phen) 2 ]Cl (d). The proton NMR spectrum of this species is characterized by two singlets (3H each) for the residual dmso-S and sixteen resolved aromatic resonances for the two inequivalent phen ligands (see below Figure S4). No resonances attributable to unreacted 1 were detected.
Thus, the reactivity of 1 with phen in refluxing ethanol can be summarized as reported in Scheme Very similar results were obtained, under the same conditions, using one equiv. of dppz in the place of phen.
The reaction of 1 with two equiv. of phen in refluxing ethanol (8h) afforded the same three main products a, c, and d as above, even though in different relative ratios. The first fraction was formed by a mixture of a and c ( Figure S4), whereas the second fraction, obtained from the concentrated mother liquor, was almost pure d ( Figure S4). To be noted that one methyl resonance of the dmso-S in d is shifted at very low frequencies. This singlet is attributed to the methyl that falls in the shielding cone of the adjacent phenanthrolines.

S-6
Experimental section
The final deep-orange solution was evaporated to an oil that, upon addition of acetone (5 mL), afforded a yellow solid that was removed by filtration, washed with acetone and diethyl ether, and dried under vacuum. According to its 1 H NMR spectrum this precipitate is a ca. 1:1 mixture of the stereoisomers a and b plus unreacted 1. Upon dropwise addition of diethyl ether to the concentrated mother liquor (ca. 2 mL) a pale yellow -creamy precipitate was obtained that, according to the 1 H NMR spectrum in CDCl 3 , was mainly composed by unreacted 1. The estimated yield in the a + b mixture was lower than 50%.

trans-[RuCl 2 (dmso-S) 4 ] (1t) + phen in methanol.
A 50.0 mg amount of trans-[RuCl 2 (dmso-S) 4 ] (1t) (0.10 mmol) was dissolved in 5 mL of methanol together with one equiv. of phen (18.7 mg). The orange solution became progressively red and afforded a deep-orange precipitate formed. This was collected by filtration, washed with diethyl ether and dried under vacuum. According to its 1 H NMR spectrum this precipitate was pure cis,trans-[RuCl 2 (dmso-S) 2 (phen)] (b). Upon dropwise addition of diethyl ether to the concentrated mother liquor (ca. 2 mL) a second fraction of the same product was obtained. Total yield of b: 41.9 mg (80%).

cis-[RuCl 2 (dmso) 4 ] (1) + 1 equiv of phen in refluxing ethanol.
A 50.0 mg amount of cis-[RuCl 2 (dmso) 4 ] (1) (0.10 mmol) was dissolved in 10 mL of ethanol together with one equiv. of phen (18.7 mg) and heated to reflux for 2h. The final red-orange solution slowly afforded (72 h) at room temperature an orange precipitate, that was collected by filtration, washed with cold ethanol and diethyl ether, and dried under vacuum. According to its 1 H NMR spectrum this precipitate is a ca. 6:1 mixture of the stereoisomers a and c. Yield 25.3 mg (48%). Upon dropwise addition of diethyl ether to the concentrated mother liquor (ca. 4 mL) a second orange precipitate was obtained that, according to the 1 H NMR spectrum in CDCl 3 , contained comparable amounts of a, c, and cis-[RuCl(dmso-S)(phen) 2 ]Cl (d).

cis-[RuCl 2 (dmso) 4 ] (1) + 2 equiv of phen in refluxing ethanol.
A 101.6 mg amount of cis-[RuCl 2 (dmso) 4 ] (1) (0.21 mmol) was dissolved in 15 mL of ethanol together with two equiv. of phen (74.8 mg) and heated to reflux for 8h. The final deep-red solution was concentrated to ca. half volume. Dropwise addition of diethyl ether until cloudiness afforded an orange precipitate, that was collected by filtration, washed with cold ethanol and diethyl ether, S-7 and dried under vacuum. According to its 1 H NMR spectrum this precipitate was a ca. 5:1 mixture of the stereoisomers a and c. Yield 62.45 mg (59%). A small amount of a second fraction precipitated spontaneously from the mother liquor (containing also the diethyl ether from the washing). According to its 1 H NMR spectrum it was almost pure cis- [RuCl(dmso-S)
S-25        Figure S39 for the labeling scheme.