Pd-Catalyzed Ring-Opening Polymerization of Cyclobutanols through C(sp3)–C(sp3) Bond Cleavage

A new approach to ring-opening polymerization (ROP) based on C(sp3)–C(sp3) bond cleavage is reported. This process is based on the ability of Pd to promote both the β-carbon elimination of a bifunctional cyclobutanol precursor and the C–C coupling process with the resulting Pd-alkyl intermediate. Consequently, novel polyketone materials are obtained. Owing to the modular synthesis of the used cyclobutanol monomers, the present ROP reaction allows the introduction of substitution patterns in the polymeric chain that are not accessible by current polyketone synthesis methodologies. We have explored in detail the initiation, propagation, and termination steps of this new polymerization process.


General remarks
Infrared spectra were recorded on a Jasco FT/IR-4600 spectrophotometer employing the ATR technique.High-resolution ESI mass spectra were recorded on an Agilent 6220 Accurate Mass TOF LC/MS spectrometer.GC/MS spectra were recorded on an Agilent GC/MS/QTOF 7250B spectrometer.Elemental analyses were performed on a LECO CNHS-932 instrument.TGA analyses were performed on a TA Instruments SDT 2960 thermal analyzer.DSC analyses were carried out on a TA Instruments DSC 2920 differential scanning calorimeter.The samples were heated under nitrogen at 10 ºC/min.The given decomposition temperatures for the polymers correspond to a 5 % mass loss.GPC measurements were carried out on a Waters Breeze chromatograph equipped with a Waters 248 UV-Visible detector operating at 254 nm and three Styragel columns (HR3, HR4E, and HR4) stabilized at 32 °C.Measurements were carried out in degassed, HPLC-grade CHCl3, at 1 mL/min flow rate.The system was calibrated with eleven low-polydispersity polystyrene standards.Nuclear Magnetic Resonance (NMR) spectra were recorded on 300 or 400 MHz Bruker NMR spectrometers in CDCl3 or DMSO-d6 at 298 K. 1 H spectra were referenced to TMS, except those measured in DMSO-d6, which were referenced to the residual protonated solvent signal. 13C{ 1 H}-NMR spectra were referenced to solvent signal. 31P{ 1 H}-NMR spectra were referenced to external H3PO4.Abbreviations used: br (broad), vd (virtual doublet).MALDI-TOF mass spectra were obtained in a Bruker Ultraflex MALDI TOF/TOF instrument in the positive reflection mode.DCTB doped with NaI was used as the matrix.In these conditions, (M + Na + ) molecular ions were observed.Toluene and THF were dried with a Pure Solv MD-5 solvent purification system from Innovative Technology and stored under N2 over 4 Å molecular sieves.Other chemicals and solvents were used as received.TLC tests were run on TLC Alugram® Sil G plates and visualized under UV light at 254 nm.
Preparative chromatographic separations were carried out in a Teledyne ISCO CombiFlash Netxgen chromatograph equipped with an UV detector and a silica gel column.A mixture of n-hexane and ethyl acetate was used as eluent.The ethyl acetate proportion usually was increased from 0% to 40%.

Representative cyclobutanol synthesis
All used cyclobutanol derivatives were prepared by a modification of a previously reported procedure. [1]2 M solution of isopropylmagnesium chloride in THF was added dropwise under N2 atmosphere to a solution of the corresponding aryl halide in dry THF at −70 °C.After 20 minutes of stirring, the bath temperature was increased to −30 °C, and the mixture was further stirred for 20 minutes.The resulting solution was added dropwise to a solution of the corresponding ketone in dry THF at 0 °C under N2 atmosphere.The reaction was warmed to RT with continuous stirring (see the characterization data below to check the particular reaction times and quantities).The reaction was quenched with water (0.5 mL), the mixture was filtered and the solid residue was washed with Et2O (2 ´ 5 mL).The filtrate was concentrated to ca. 2 mL, diluted with Et2O (50 mL), and washed with water (30 mL).The aqueous layer was extracted with Et2O (2 ´ 20 mL), and the combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated in vacuum.The product was precipitated with n-pentane, filtered, and dried under reduced pressure or purified by flash column chromatography.
The isolated white solid was a mixture of diastereoisomers in approx.1:0.9 ratio.IR (cm

Representative polymerization procedure
Cyclobutanol 1a (0.5 mmol, 1 equiv.), the catalytic precursor, the ligand, and Cs2CO3 (1.1 equiv) were placed in a Carius tube under N2 atmosphere.Dry toluene (3 mL) was added and the tube was sealed.The mixture was stirred and heated in an oil bath at 100 ºC for 16 hours.The resulting suspension was diluted with dichloromethane (10 mL), filtered over Celite, concentrated in vacuum up to ca. 1 mL and precipitated in methanol (20 mL).The obtained solid was filtered and dried under reduced pressure.

Optimization of the polymerization reaction
Only the displayed parameters in each

Scope of the polymerization reaction
These reactions were carried out by following the representative procedure with 1 mol% of Pd(OAc)2, 2 mol% of PPh3, 1.1 equiv. of Cs2CO3 and 3 mL of dry toluene as solvent. [a] The reaction was carried out with 0.5 mol% of Pd(OAc)2 and 1 mol% of PPh3.
[b] The reaction was carried out with 7 mol% of Pd(OAc)2 and 14 mol% of PPh3.

Spectroscopic and analytic data
Polymer P1.IR (cm

Polymer P1
The MALDI-TOF mass spectrum of P1 displayed a main polymeric series and several secondary series with much lower relative abundance (Figure S1).All of them showed the expected repeating unit (C17H16O, 236 Da).The mass values of the main series correspond to exact multiples of the repeating unit plus a Na + cation, which agrees with the formation of (C17H16O)n cyclic chains by head to tail cyclization (Scheme S1).However, on increasing n, head to tail cyclization becomes less likely than other chain termination events.Thus, instead of reacting with the terminal cyclobutanol group, the active A second polymeric series with mass values 156 Da higher than those of the main series was observed (Figure S2, blue).These mass values and the observed isotopic distributions suggest that this series is formed by linear (C17H16O)n polymers with bromo and phenyl as end groups.The phenyl group may be incorporated by reductive elimination from an intermediate Pd(II) complex containing both a polymer chain and a phenyl ligand attached to the same metal center (Scheme S3).This suggests that, under the polymerization conditions, Ph-transfer from a PPh3 ligand is possible. [4]In line with this hypothesis, when the polymerization was carried out with P(4-MeOC6H4)3 instead of PPh3 as auxiliary ligand, molecular ions containing 4-MeOC6H4 groups were detected by MALDI in the secondary polymeric series (Figure S3).For n ³ 11, the relative abundances of this series becomes comparable to that of the main series.Finally, a fourth series formed by groups of peaks with very low abundance and a complex isotopic pattern was observed (Figure S2, red).The masses and isotopic distributions of these peak clusters are compatible with an overlap of several isotopic distributions corresponding to linear polymers containing (i) a cyclic group resulting from C-H activation at one end of the chain and Br or Ph at the other chain end and (ii) Ph and unreacted cyclobutanol end groups (Scheme S4).
Scheme S4.Proposed combinations of end groups for the fourth polymeric series.

Polymer P2
This polymer showed the expected series of peaks with a (C22H18O)n composition, corresponding to cyclic chains or to linear chains with protonated and unsaturated end groups (Figure S4).The abundances of the secondary polymeric series were much lower than in the mass spectrum of P1.A detailed analysis of the isotopic distributions of the main series (Figure S5) revealed a complex pattern resulting from an overlap of the expected isotopic distribution for the [(C22H18O)nNa] + ions with two distributions corresponding to ions containing two more or two less H atoms.This suggests that, in addition to the main chaintermination mechanisms (see polymer P1), other mechanisms involving protodepalladation or C-H activation events at both chain ends are competent.In line with this, the 1 H-and

Polymer P3
The MALDI TOF mass spectrum of P3 was similar to that of P1.It shows a main distribution corresponding to Na + adducts of the (C26H24O)n chains (Figure S6).The secondary series show very low abundance.

Polymer P5
The MALDI-TOF mass spectrum of this polymer closely resembles that of its isomer P1.The main series is formed by (C17H16O)n chains (Figure S9).The secondary series are mainly formed by (C17H16O)n chains with (a) Ph and H, (b) MeCOC6H4 and H, (c) MeCOC6H4 and Ph as terminal groups (Figure S10).

Monitoring of the polymerization reaction
A mixture of cyclobutanol 1a (158 mg, 0.50 mmol, 1 equiv.),Pd(OAc)2 (1.12 mg, 5.0 ´ 10 -3 mmol, 1 mol%), PPh3 (2.62 mg, 0.01 mmol, 2 mol%), and Cs2CO3 (179 mg, 0.55 mmol, 1.1 equiv.) in dry toluene (3 mL) under N2 atmosphere was heated in an oil silicon bath at 100 ºC in a Carius tube.0.3 mL aliquots were taken from the reaction mixture at the times specified in the table S7.The samples were evaporated, dissolved in CHCl3, and injected in the GPC chromatograph.After 16 hours, the reaction mixture was processed by following the isolation steps indicated in the general polymerization procedure.
The GPC chromatogram at short reaction time only showed low molecular weight components which were gradually consumed, with a consequent increase on the amount of polymeric material.From 3.5 to 16 h, the increase in the molecular weight of the formed polymer is unsignificant (Figure S12).

S26
diastereoisomers.We attribute this feature to a possible association of two molecules through hydrogen bond interaction in CDCl3 solution.This splitting only affected to this carbon and was also observed in the 13 C{ 1 H}-NMR spectrum of complex 8 in CDCl3.For complex 8, the splitting disappeared when the 13 C{ 1 H}-NMR was recorded in DMSO-d6.[Pd(dba)2] (318 mg, 0.553 mmol), 2,2'-bipyridyl (89 mg, 0.570 mmol) and a magnetic stirrer.
The tube was set under a nitrogen atmosphere, placed in an ice/salt-bath, and dry CH2Cl2 was added (15 mL).The tube was sealed, and the mixture was stirred at -15 ºC for 30 min and then allowed to warm to room temperature, while stirring for another 4 h.Decomposition to metallic palladium was observed.The mixture was filtered through a Celite plug.The filtrate was concentrated to ca. 0.5 mL, and Et2O (15 mL) was added.The suspension was filtered, and the pink solid was washed with Et2O (2 ´ 3 mL) and air-dried to give complex 8 as a mixture of diastereoisomers (ca.1:1 ratio by 1 H-NMR).Yield: 75 mg, 0.12 mmol, 22 %.

Crystal structure of complex 8
The crystal structure of 8•CH2Cl2 was solved by X-ray diffraction studies (Figure S13).The

Figure S1 .
Figure S1.MALDI-TOF MS of P1.The m/z values of the most abundant peaks of the main polymeric series have been calculated according to the molecular formula [(C17H16O)nNa] + .

Figure S2 .
Figure S2.Detail of the MALDI-TOF MS of polymer P1 showing the proposed composition for the main and secondary polymeric series.All observed m/z values correspond to the Na + adducts of the indicated molecules.

Figure S3 .
Figure S3.Detail of the MALDI-TOF MS of polymer P1 obtained by using P(4-MeOC6H4)3 instead of PPh3.The inset shows a representative mass distribution of a molecular ion containing a 4-MeOC6H4 group.
Scheme S3.Proposed structures and chain termination reactions for the second and third polymer series.

13 C{ 1
H}-NMR spectra of this polymer show additional signals with lower intensity near the main set of signals.

Figure S4 .Figure S5 .
Figure S4.MALDI-TOF MS of P2.The m/z values of the most abundant peaks of the main polymeric series have been calculated according to the molecular formula [(C22H18O)nNa] + .

Figure S6 .
Figure S6.MALDI-TOF MS of P3.The m/z values of the most abundant peaks of the main polymeric series have been calculated according to the molecular formula [(C26H24O)nNa] + .

Figure S7 .
Figure S7.MALDI-TOF MS of polymer P4.The m/z values of the most abundant peaks of the main polymeric series have been calculated according to the molecular formula [(C23H20O)nNa] + .

Figure S9 .Figure S10 .
Figure S9.MALDI-TOF MS of polymer P5.The m/z values of the most abundant peaks of the main polymeric series have been calculated according to the molecular formula [(C17H16O)nNa] + .
TOF mass spectrum of this polymer shows two main series of ions corresponding to linear oligomers with either (a) two H atoms or (b) a H atom and a Ph group as terminal groups.(FigureS11).

Figure S11 .
Figure S11.MALDI-TOF MS of polymer P6.The m/z values corresponding to the marked peak of each observed isotopic distribution have been calculated with the displayed formulae.
palladium atom was in a square-planar environment, with a mean deviation of the Pd(II)coordination plane of 0.016 Å.The N(1)−Pd(1)−N(2) angle was 79.03(15)°, quite smaller than the standard value of 90° for an ideal square-planar complex, due to the steric constraints imposed by the bite angle of the bipyridine ligand.The Pd(1)−N(1) bond length (2.130 Å; trans to C1) was significantly longer than the Pd(1)−N(2) bond length (2.087 Å; trans to I1), reflecting the greater trans influence of the C-donor ligand.The aryl ring (C1-C6) bonded to palladium formed an angle of 83.1º with respect to the Pd(II)-coordination plane, avoiding steric hindrance.The discrete molecules 8•CH2Cl2 are associated through hydrogen bonds, giving double chains along the (110) direction.

Figure S44 .
Figure S43.DSC traces of the polymers.Exothermic peaks point upward.

Table S1 .
Influence of the catalytic precursor and the amount of added precursor.

Table S2 .
Influence of the ligand.

Table S3 .
Influence of the base.

Table S4 .
Influence of the solvent.

Table S6 .
Scope of the polymerization reaction.

Table S7 .
Change of the average molecular weight of the polymer with the polymerization time.