Diastereoisomeric enrichment of 1,4–enediols and H 2 –splitting inhibition on Pd–supported catalysts

Pd-supported catalysts are fundamental tools in organic reactions involving H2 splitting. Here we show that 1,4-enediols enriched in one diastereoisomer are produced from the classical Pd-catalyzed semi-hydrogenation reaction with H2, starting from the corresponding, widely available 1,4-diacetylenic diols. The semi-hydrogenation reaction proceeds concomitantly with the desymmetrization of the meso/racemic form of the enediol. We also show that these products, if added in advance to H2, completely inactivate the Pd catalyst (only when added before H2). These results provide a simple way not only to produce 1,4-enediols enriched in one diastereoisomer by a classical catalytic method but also to stop H2 dissociation on Pd nanoparticles.

Glassware was dried in an oven at 175 ºC before use.Reagents and solvents were obtained from commercial sources and were used without further purification otherwise indicated.
Products were characterized by gas chromatography-mass spectrometry and 1 H, 13 C and DEPT liquid nuclear magnetic resonance, and the resulting spectra compared with the given literature.The metal content of the samples was determined by inductively coupled plasma-atomic emission spectroscopy (ICP-AES).Solids were disaggregated in aqua regia and later diluted before analysis.
Gas chromatography-mass spectrometry.Gas chromatographic analyses were performed in an instrument equipped with a 25 cm capillary column of 5% phenylmethylsilicone.
N-dodecane was used as an external standard.Gas chromatography-mass spectrometry analyses were performed on a spectrometer equipped with the same column as the GC and operated under the same conditions.
Nuclear magnetic resonance. 1H, 13 C and distortionless enhancement by polarization transfer (DEPT) liquid nuclear magnetic resonance (NMR) measurements, and also 2Dnuclear Overhauser enhancement spectroscopy (NOESY), were recorded on a 400 MHz Bruker Avance instrument at room temperature, using deuterated chloroform as a solvent, which contains TMS as internal standard.
Raman spectroscopy.The Raman spectra of the Lindlar and Pd/C catalysts with or without 2a/3a were obtained with an excitation wavelength of 514 nm in a Renishaw inVia spectrometer, under a stream of H2.H2 / D2.A fixed-bed reactor was loaded with 2-5 mg of catalyst.After maintaining an argon flow rate of 18 ml/min for 20 min, 1 ml/min H2 and 1 ml/min D2 were added to the argon stream (total flow rate of 20 ml/min).This mixture of Ar, H2 and D2 was flowed for 15 min through the reactor bypass to calibrate the signal and then approximately 15 min through the fixed bed to obtain the measurement.The pressure was kept constant at 1 bar, and the temperature was maintained at 30 °C throughout the experiment.The compounds at the reactor exit (H2, D2, H-D) were quantified by on-line mass spectroscopy (m/z = 2, 4 and 3, respectively).
Synthesis of trans-2,4,7,9-tetrametyl-5-decen-4,7-diol (4a).500 mg (2.2 mmol) of 1a were dissolved in 15 mL of anhydrous THF and the mixture was stirred and cooled to 0 °C in an ice bath.Then, 4 equivalents of LiAlH4 in a 2 M solution in THF were introduced 1e 1g dropwise (4.4 mL).The progress of the reaction was constantly measured by taking reaction aliquots, neutralizing them in water, extracting them in THF and monitoring the GC conversion.The reaction reached full conversion after 90 minutes, and was at that point neutralized in 15 mL of water.The mixture was extracted with CH2Cl2, dried over MgSO4.Final yield of 95% for 4a (trans).
Semi-hydrogenation reactions.All the hydrogenation reactions were performed in a 6-mL round bottom vial with a stirring magnet, in 0.5 mL of ethanol or toluene, and 0.3 mmol of starting material, otherwise stated.The reactions were conducted at 30-65 ºC and stirred at 450 rpm, in a H2 pressurized atmosphere of 3 bars.At the start of the reaction, the alkyne: H2 molar ratio was roughly 1-2.5, and enough H2 was always present to fully hydrogenate the alkyne to the corresponding alkane.The catalytic Pd amount was adjusted for each catalyst in order to precisely measure the initial rate for any substrate, i.e.Pd-(CaCO3)n (0.003 mol%), c-Pd/TiS catalyst (0.015 mol% Pd), Pd/C catalyst (0.04 mol%) and the Lindlar catalyst (0.15 mol%) for TMDD 1a.Yields were obtained by combined gas chromatography, gas chromatography-mass spectrometry and nuclear magnetic resonance, and the latter were used to identify the products.
Reuses.Reactions were performed and analyzed following the above procedure; conditions: 3 bar H2, 0.6 M 1a and 65 ºC.After reaction, the solid catalyst was recovered by either gravity filtration or centrifugation (3000 rpm), washed with ethanol and centrifugated again, and weighed for the next use.H2O( 18 O) isotopic exchange.The reaction was performed in a 6-mL round bottom vial with a stirring magnet, in 0.1 mL of H2O or H2 18 O, with 70 mg (0.3 mmol) of TMDD 1a or 72 mg (0.3 mmol) of alkenediols 2a/3a, and Lindlar catalyst (2 mg), in the presence or not of and H2 (pressurized atmosphere of 3 bars).The reactions were conducted at 65 ºC, stirred at 450 rpm, and monitored by gas chromatography-mass spectrometry.
Typical poisoning experiment.The hydrogenation reaction was performed in a 6-mL round bottom vial with a stirring magnet, in 0.5 mL of ethanol or toluene, and 70 mg (0.3 mmol) of TMDD 1a.Previously, the Lindlar cat.(2 mg) and alkenediols 2a/3a (60 mg, 0.25 mmol) were mixed.The reactions were conducted at 60 ºC and stirred at 450 rpm, in a H2 pressurized atmosphere of 3 bars, during 90 min.The reaction mas monitored by gas chromatography.

Tables.
Table S1.Semi-hydrogenation reaction of TMDD 1a performed with different solvents (1 M, 0.3 mL solvent, 65 ºC, 10 bar H2, 1 mg Lindlar cat., 12 h; see  1 in the main text, entry 1), the inset magnifies the diasteroisomer area.Top: 1 H NMR spectrum of the isolated products from the reaction of 1a with LiAlH4.approximately 60% of the mixture is the alkene, and that all of the alkene contains both hydroxyl groups (3.19 ppm signal).

Figure S5 .
Figure S5.Results for the semi-hydrogenation reaction of TMDD 1a catalyzed by the Lindlar catalyst in ethanol, under the indicated reaction conditions, before and after recovering the solid catalyst by simple filtration and washings with ethanol.* Denotes a second experiment with more Pd catalyst and reaction time.

Figure S6 .
Figure S6.Kinetic results for the semi-hydrogenation reaction of TMDD 1a (60%) mixed with the alkene products 2a/3a (40%) catalyzed by the Lindlar catalyst in ethanol (left) or toluene solvent (right), under the indicated reaction conditions in Table1of the main text.

Figure S7 .
Figure S7.Kinetics for the semi-hydrogenation reaction of TMDD 1a catalyzed by the Lindlar catalyst in toluene instead than in ethanol solvent, under the indicated reaction conditions in Figure 3 of the main text.

Figure S9 .
Figure S9.Raman spectra of a commercial sample of Pd/C under a flow of H2, previously treated (gray) or not (orange) with the 1,4 enediols 2a/3a.It can be seen how the signals assigned to the Pd-H bonds formed after H2 splitting on the Pd sites, at 455 and 583 cm - 1 , are much smaller in the treated material, and do not appear in the baseline spectra (blue), measured with the same catalyst under argon.

Figure S10 .Figure S11 .
Figure S10.Fourier-transformed infrared (FT-IR) spectra of the Lindlar catalyst before and after adding the 1,4 enediols 2a/3a.For the sake of comparison, the spectrum of neat 1,4 enediols 2a/3a is also shown.The arrows indicate the change in the carbonate band.

Figure S12 .
Figure S12.Modelling of alkenes 2a (cis, top) and 4a (trans, bottom) on a Pd (111) slab, with either one (left) or the two OH groups bound to Pd (right).Color code: Pd blue spheres, C grey spheres, H white spheres and O red spheres.

Table S2 .
Table 1 in the main text).The mass balance is completed with dihydroxylation products.Semi-hydrogenation reaction of TMDD 1a performed with different catalysts (0.6 M, 0.5 mL EtOH, 65 ºC, 3 bar H2, 3 h; see Table 1 in the main text).

Table S4 .
Results for the reaction of alkyne 1a and alkenes 2a/3a with H2O( 18 O) (15 equivalents) in the presence of the Lindlar catalyst (0.15 mol%), followed by GC-MS.Isotopic incorporation is not observed in any case without the Lindlar catalyst.Gas chromatogram for the semi-hydrogenation reaction of TMDD 1a (Table1in the main text, entry 1).
1H NMR spectrum of the isolated products from the semihydrogenation reaction of TMDD 1a (Table