Palladium on Charcoal as a Catalyst for Stoichiometric Chemo- and

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Palladium on Charcoal as a Catalyst for Stoichiometric Chemo- and Stereoselective Hydrosilylations and Hydrogenations with Triethylsilane Sakari Tuokko, and Petri M. Pihko Org. Process Res. Dev., Just Accepted Manuscript • DOI: 10.1021/op5003209 • Publication Date (Web): 27 Oct 2014 Downloaded from http://pubs.acs.org on October 28, 2014

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Organic Process Research & Development

Palladium on Charcoal as a Catalyst for Stoichiometric Chemo- and Stereoselective Hydrosilylations and Hydrogenations with Triethylsilane

Sakari Tuokko and Petri M. Pihko* Department of Chemistry and NanoScience Center, University of Jyväskylä, P.O.B. 35, FI40014 JYU, Jyväskylä, Finland [email protected]

Table of Contents

Abstract Stoichiometric quantities of triethylsilane in the presence of activated Pd/C as the catalyst can be used to effect chemo-, regio- and stereoselective hydrosilylation and transfer hydrogenation reactions. α,β-Unsaturated aldehydes and ketones are selectively hydrosilylated to give the corresponding enol silanes or transfer hydrogenated to give the the saturated carbonyl compounds in the presence of other reducible functional groups.

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Introduction Supported catalyst are widely used in industrial processes. The easy separation, recyclability and applications in flow chemistry make heterogeneous catalysts desirable over homogeneous catalysts. This is especially true in catalytic hydrogenation, where supported Pd, Pt and Rh catalysts, among others, are highly popular.1 A significant problem in heterogenous catalysis is the control of chemo- and regioselectivity, and this problem has attracted the attention of the catalysis community in recent decades.2 In the synthesis of complex molecules, chemo- and regioselective reduction reactions are highly valuable since they allow researchers to differentiate between different functionalities. A problem frequently encountered in chemical synthesis concerns the reduction of C=C bonds in the presence of other reducible functionalities, such as benzyl protective groups or nitro groups, or differentiation between different C=C bonds. In these cases, selectivity is usually achieved with homogenous catalysts, such as Stryker’s reagent,3 via Birch reduction,4 or via organocatalytic reductions.5 Isolated examples of useful selectivities have also been reported with supported catalysts.6,7,8,9 Hydrogen, and other hydrogen sources, are known to affect the catalytic activity of Pd10a-e and other catalytic metals.10f In addition to the classical Langmuir-Hinshelwood –type adsorption and dissociation on the metal surface,11 excess of hydrogen can readily penetrate the Pd lattice.10d,e The resulting subsurface hydrogen atoms are known to dramatically affect the selectivity profile of the Pd catalyst.10d Consequently, in order to maintain a similar catalytic profile throughout the reaction, the amount of hydrogen should be limited. This is practically difficult to do with hydrogen.12 An alternative method is to use


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poisoning additives, such as carbon monoxide, or alternative hydrogen or hydride sources, such as silanes. Indeed, it has been reported that the Et3SiH/Pd-C combination readily reduces a wide variety of functionalities when a tenfold excess of Et3SiH was used.13 Alternatively, with a threefold excess of Et3SiH, chemoselective reductions of S-ethylthioesters with Pd/C (Fukuyama reduction) constitute a well-established protocol in synthetic organic chemistry.14 Interestingly, processes with stoichiometric or near-stoichiometric amounts of silane reductant do not appear to have been explored, in spite of the potential for further increasing the chemo- and regioselectivity of the reduction process. We have earlier described an in situ prepared colloidal Pd as an active catalyst for hydrosilylation of enals and enones.15 However, this process was not fully chemoselective for the hydrosilylation.16 Furthermore, with the previous protocol, the reaction failed to proceed if the nucleation of the catalyst did not initiate properly, and scaling up the protocol turned out to be challenging due to the colloidal nature of the catalyst. Here we report a simple protocol for chemo- and stereoselective hydrosilylation or transfer hydrogenation with near-stoichiometric amounts of Et3SiH and activated commercial Pd/C as the catalyst.

Results and Discussion In our previous work, a crossover experiment with two different silanes demonstrated that silanes such as Et3SiH are likely to fully dissociate on a Pd surface.17 It is therefore not surprising that reductions on a Pd surface using an excess of Et3SiH proceed in analogy to corresponding reactions where H2 is used as a hydrogen source – both Et3SiH and H2 can be sources of H atoms on the Pd surface. However, if stoichiometric amounts of Et3SiH are



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used, chemoselective reactions might be possible. If the silyl groups on the surface will react preferentially with a reactive functional group (e.g. a carbonyl group), it is possible to trap a reduction intermediate such as an enolate with high stereoselectivity.18 Single enol silane stereoisomers are very valuable compounds in a many stereospecific transformations such as Mukaiyama aldol and Mannich reactions or transmetallation.19,20 As revealed in Table 1, our previous catalyst system provided the enol silane in 84% yield with excellent stereoselectivity but only moderate chemoselectivity (entry 1, 84:16 ratio of enol silane to aldehyde). Switching to the commercial Pd/C catalyst, similar results were obtained (entry 4), but a significant improvement was achieved with pre-drying of the Pd/C catalyst before use (entries 5 and 6). Charcoal can adsorb up to 55-60 wt-% of water21 and presumably the residual water promotes the formation of aldehyde. However, adding just a small amount of acid [aq. H2SO4 or aq. HCl (20 μL, both 1M)] into the reaction mixture changed the outcome of the reaction completely (entry 7). Instead of the enol silane, the reduction proceeded to give the corresponding saturated carbonyl compound as a product. Table 1. Chemoselectivity of the Hydrosilylation Reaction with Different Heterogeneous Palladium Catalysts.

Producta Entry

Catalyst

Catalyst loading 2a


3a

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1

PdCl2/PCy3b

1.3 mg/4.2 mg

84 %

16 %

2

Pd-PVP colloidsc

12 mg

29 %

42 %

3

Pd-thioether colloidsd

2 mg

90 %

10 %

4

Pd/C (5 wt-%) (unactivated)

2 mg

83 %

17 %

5

Pd/C (5 wt-%) (vacuum treated)e

2 mg

91 %

9%

6

Pd/C (5 wt-%) (washed)f,g

2 mg

100 %

0%

7

Pd/C (5 wt-%) + Acidi

2 mg

0%

100 %

Reaction conditions: 1a (44 mg, 0.30 mmol), catalyst, triethylsilane (53 mml, 0.33 mmol), THF (1 mL), room temperature, 30 min. [a] Determined by 1H-NMR analysis. [b] Published results.15 [c] All the details are provided in ref. 15. [d] See SI. [e] Pd/C was kept in a vacuum for 10 min. [f] Pd/C was washed 3 times with acetone and dried in vacuum. [g] The chemoselectivity remained unchanged with 5 different batches of Pd/C (5-10 wt-%) from different sources (Sigma-Aldrich, Fluka and other suppliers). [i] aq. H2SO4 or aq. HCl (20 μL, both 1M).

Chemo- and stereoselective hydrosilylation is a practical method for accessing stereochemically well-defined enol silanes. Typically, enol silanes are obtained by direct enolization of ketones in the presence of a silyl halide or pseudohalide (e.g. triflate). However, enolization/silylation sequences with aldehydes are more challenging due to competing self-condensation reactions.22 As an alternative, catalytic hydrosilylation of α,βunsaturated aldehydes and ketones with a range of different homogeneous metal catalysts has also been described, including copper,23 palladium,24 rhodium,25 and other metal complexes as catalysts.26 Typically, the hydrosilylation protocols display a preference for Eenol silanes, and methods to uniformly produce Z-enol silanes are still rare.22,27



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Table 2. Stereoselective Hydrosilylation of α,β-Unsaturated Aldehydes and Ketones

Time

Z/Ea

Yieldb

1

30 min

> 50:1

96 %

2

3h

> 50:1

94 %

3

3h

25:1

85 %

4

30 min

> 50:1

96 %

5

3h

> 50:1

93 %

Entry

Substrate

Product


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6

30 min

> 50:1

92 %

7

3h

> 50:1

N/Ac

8

1h

1:12

76 %

3h

1:5

84 %

3h

1:12

81 %

3h

1:16

71 %

3h

1:10

75 %

O

OSiEt3

H

H O

9

O

1i

2i

10

O

OSiEt3

H

H

O

11

O

OMe 1k

OMe 2k

12



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13

3h

1:8

67 %

14

3h

1:20

63 %

3h

N/A

94 %

16 h

N/A

71 %

O

15 1o

16

a

The stereochemistry of the products was assigned by analogy to previous studies.15 bIsolated yields. cProduct formed as an intermediate

(see SI).

The present protocol enables the ready access to Z-enol silanes from α-substituted enals as starting materials (Table 2, entries 1-7). With β-substituted enals, the major products are Eenol silanes (Table 2, entries 8-14). The observed stereoisomer of the product appears to correspond to the s-trans conformer of the starting material.27 In the liquid phase, more than 99 % of the acrolein is known to be present as the s-trans conformer at equilibrium.28 Adsorption on the metal surface appears to fix the liquid phase conformation of the substrate, and the hydrosilylation reaction freezes the conformation. The higher stereoselectivity with α-substituted enals (Z/E > 50:1) most likely results from the higher relative stability of the s-trans conformer is more stable in the liquid phase and on the


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surface. The lower selectivity with β-substituted enals can also result from isomerization of the E- to Z-isomer during the reaction. In a control experiment, prolonging the reaction time with substrate 1h from 1 h to 16 h eroded the Z/E selectivity from 1:12 to 1:3.29 The chemoselectivity of the process was very high with α-substituted enals, with only traces of aldehyde detected. In the case of β-substituted enals, the saturated aldehyde products typically constituted 5% of the mass balance. The highest amount of aldehyde (18 %) was detected with β,β-disubstituted enal, citral (Table 2, entry 14). Indicating that β-substituting decreases the barrier for direct C=C bond reduction (3,4-addition) compared to 1,4hydrosilylation. Importantly, the hydrosilylation protocol was also compatible with α,β-unsaturated cyclic ketones (Table 2: entries 15, 16 and Table 3: entry 9), in contrast to previous methods with Pd catalysts.30 The Pd/C protocol is also readily scalable, giving high isolated yields and selectivities with α,β-unsaturated aldehydes and cyclic ketones (Figure 1) in gram-scale experiments.

Figure 1. Gram-Scale Synthesis of Enol Silanes.

In the presence of an acid (approx. 0.1 eq. 1M H2SO4), the reaction readily yields saturated aldehydes, ketones or nitriles, with only 1.0-1.1 eq. of Et3SiH. Reduction of α,β-unsaturated esters or terminal C=C bonds is also feasible (Table 3: entries 11-12), but in these cases 2.2



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equiv of Et3SiH is required. With stoichiometric amounts of Et3SiH, the reactions proceed only to ~ 50 % conversion. Both the hydrosilylation and the transfer hydrogenation protocols were highly selective towards reducing α,β-unsaturated aldehydes and ketones. A variety of functional groups were tolerated, such as non-conjugated (Table 2: entries 5, 14, 16 and Table 3: entries 2, 9) and electron-deficient C=C bonds (Table 2: entry 11), O-benzyl protection (Table 2: entry 10 and Table 3: entry 4), nitro-group (Table 2: entry 7 and Table 3: entry 3) and esters (Table 2: entries 6, 11). Surprisingly, acyclic α,β-unsaturated ketones were viable substrates only in transfer hydrogenation conditions (Table 3: entries 7, 8). Table 3. Chemoselective Transfer Hydrogenation of α,β-Unsaturated Aldehydes and Ketones

Time

Yielda

1

30 min

92 %

2

3h

94 %

Entry

Substrate

Product


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3

16 h

83 %

4

1h

56 %

5

1h

82 %

6

1h

84 %

7

1h

92 %

8

30 min

91 %

9

16 h

75 %



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CN

16 h

67 %b

11c

30 min

88 %

12c

30 min

93 %

10 5

a

Isolated Yields. bDeterminated by 1H NMR (internal standard). c2.2 eq. of Et3SiH was used

We studied the chemoselectivity with more details using mixtures of substrates and potentially reactive additives (robustness screening, Table 4).31 Both hydrosilylation (Table 4: entries 1, 2) and transfer hydrogenation (Table 4: entries 3, 4) were fully compatible with a benzyl ether: benzyloxyacetaldehyde (10). Finally, a mixture of potentially reducible components 1p, 1r, benzyl glycidy ether (11) were subjected to the hydrosilylation protocol (Scheme 1). Only the α,β-unsaturated aldehyde 1a was converted to the enol silane 2a in 100 % conversion and 80 % yield. Table 4. Chemoselectivity Screen

Additive/Product Entry

Substrate

Additive

Conversiona

Producta Ratioa


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1

100 %

50:50

2

100 %

50:50

3

100 %

50:50

4

100 %

50:50

a

Determined by 1H NMR.

Scheme 1. Chemoselectivity Test with Four Components and Five Potentially Reactive Functionalities

The reaction can be used successfully to selectively label the β-position of carbonyl compounds (Scheme 2).32

Scheme 2. Preparation of β-Mono-Deuterated Enol Silanes and Carbonyl Compounds.



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Conclusions In conclusion, we have developed a scalable, easy-to-use protocol for chemo-, regio- and stereoselective hydrosilylation reactions using stoichiometric Et3SiH and activated Pd/C as the catalyst that offers several practical advantages to our previously published protocol. Hydrosilylation or transfer hydrogenation of α,β-unsaturated aldehydes or ketones can be readily conducted in the presence of other reducible functionalities such as benzyl ethers, nitro groups or non-conjugated C=C bonds. The reactivity order appears to be α,βunsaturated aldehydes > α,β-unsaturated ketones > α,β-unsaturated esters. The reduction of α,β-unsaturated esters requires at least 2 equiv of Et3SiH, whereas α,β-unsaturated aldehydes and ketones can be fully reduced with near-stoichiometric quantities of Et3SiH. These results point to a possible change in reaction mechanism. The mechanistic implications of these observations are currently under investigation and will be reported separately.

Experimental Section General Information. All reactions were carried out in screw cap glass vials or septum cap glass flasks under air atmosphere, unless otherwise noted. THF, Et2O, DCM, ACN and toluene were obtained by passing deoxygenated solvents through activated alumina columns (MBraun SPS-800 Series solvent purification system). Other solvents and reagents were used as obtained from supplier, unless otherwise noted. Analytical TLC was performed using Merck silica gel F254 (230-400 mesh) plates and analyzed by UV light or by staining upon heating with vanillin solution (6 g vanillin, 5 mL conc. H2SO4, 3 mL glacial acetic acid, 250 mL EtOH) or KMnO4 solution (1 g KMnO4, 6.7 g K2CO3, 1.7 mL 1M NaOH, 100 mL H2O). For silica gel chromatography, the flash chromatography technique was used, with Merck silica gel 60 (230-400 mesh) and p.a. grade solvents unless otherwise noted.


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Alumina columns were prepared by filling plastic syringes (5-20 mL) with Sigma-Aldrich purum p.a. grade alumina. The 1H NMR and 13C NMR spectra were recorded in CDCl3 on Bruker Advance 500, 400 or 250 spectrometers. The chemical shifts are reported in ppm relative to residual CHCl3 (δ 7.26) for 1H NMR. For the

13

C NMR spectra, the residual CDCl3 (δ 77.16) was used as the internal

standards. GC analysis were performed with Agilent Technologies 7890GC equipped with an Agilent HP-5 capillary column (30 m x 0.320 mm x 0.25 μm). Melting points (mp) were determined in open capillaries using Gallenkamp melting point apparatus. IR spectra were recorded on a Tensor27 FT-IR spectrometer. High resolution mass spectrometric data were prepared using MicroMass LCT Premier Spectrometer. Activating Pd/C. Commercially available Pd/C (5 wt-%, 20 mg) and acetone (1 mL) were mixed in an Eppendorf vial. The resulting suspension was centrifuged for 30 seconds at 5200 rpm and the supernatant was separated with pipette. The washing procedure was repeated 3 times and after the last cycle, the recovered Pd/C was dried in the vacuum line. General Procedure for the Preparation of Enol Silanes. To a solution of the activated Pd/C (5 wt-%, 10 mg) in dry THF (5.0 mL) was added enal (1.50 mmol, 1.0 eq.) and triethylsilane (1.65 mmol, 1.1 eq.) at room temperature. The reaction was followed by TLC (eluent: n-hexane/ethyl acetate 9:1) or by GC. After full conversion (30 min to 16 h), the reaction mixture was filtered through a small pad of alumina (neutral) column and washed with DCM. Filtrate was concentrated in vacuum line to afford the products. (Z)-Triethyl((2-methyl-3-phenylprop-1-en-1-yl)oxy)silane 2a: Prepared according to the general procedure for preparation of enol silanes using Pd/C (5 wt-%, 2 mg), THF (1.0 mL), enal 1a (44 mg, 0.30 mmol, 1.0 eq.) and triethylsilane (35 mg, 48 μL, 0.33 mmol, 1.0 eq.). Reaction time: 10 min. Yield: 76 mg (96 %, colorless oil). Z/E > 50:1. The 1H and

13

C NMR corresponds to previously

published data.15 Data for major isomer 2a; 1H NMR (400 MHz, CDCl3, containing 4 % (SiEt3)2 impurities): δ = 7.29 – 7.20 (m, 5H), 6.23 – 6.19 (m, 1H), 3.44 (s, 2H), 1.46 (d, J = 1.4 Hz, 3H), 1.02 (t, J



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= 7.9 Hz, 9H), 0.71 (q, J = 7.9 Hz, 6H); for minor isomer, the following diagnostic signal was observed: δ = 6.27 – 6.26 (m, 1H); 13C NMR (75 MHz, CDCl3): δ = 141.2, 134.3, 128.9, 128.3, 125.7, 116.0, 35.1, 17.0, 6.7, 4.7. (Z)-Triethyl((2-methyl-3-phenylbut-1-en-1-yl)oxy)silane 2b: Prepared according to the general procedure for preparation of enol silanes using Pd/C (5 wt-%, 10 mg), THF (5.0 mL), enal 1b (240 mg, 1.50 mmol, 1.0 eq.) and triethylsilane (192 mg, 264 μL, 1.65 mmol, 1.1 eq.). Reaction time: 3 h. Yield: 389 mg (94 %, slightly yellow oil). Z/E > 50:1. The 1H and

13


published data.15 Data for major isomer 2b; 1H NMR (400 MHz, CDCl3, (containing 2 % (SiEt3)2 impurities): δ = 7.27 (d, J = 4.3 Hz, 4H), 7.19 – 7.14 (m, 1H), 6.10 (qd, J = 1.5, 0.6 Hz, 1H), 4.36 (q, J = 7.3 Hz, 1H), 1.35 (d, J = 7.2 Hz, 3H), 1.33 (d, J = 1.5 Hz, 3H), 1.00 (t, J = 7.9 Hz, 9H), 0.68 (q, J = 7.9 Hz, 6H), the minor isomer was not detected by 1H NMR; 13C NMR (101 MHz, CDCl3): δ = 145.6, 133.4, 128.1, 127.5, 125.6, 120.5, 35.7, 16.8, 13.2, 6.8, 4.7. (Z)-triethyl((2-methyl-3-(5-methylfuran-2-yl)but-1-en-1-yl)oxy)silane 2c: Prepared according to the general procedure for preparation of enol silanes using Pd/C (5 wt-%, 10 mg), THF (5.0 mL), enal 1c (246 mg, 1.50 mmol, 1.0 eq.) and triethylsilane (209 mg, 288 μL, 1.80 mmol, 1.2 eq.). Reaction time: 3 h. Yield: 359 mg (85 %, slightly yellow oil). Z/E 25:1. The 1H and 13C NMR corresponds to previously published data.15 Data for major isomer 2c; 1H NMR (400 MHz, CDCl3, containing 12 % (SiEt3)2 impurities): δ = 6.12 – 6.09 (m, 1H), 5.87 – 5.82 (m, 2H), 4.26 (q, J = 7.4 Hz, 1H), 2.24 (s, 3H), 1.37 (d, J = 1.5 Hz, 3H), 1.27 (d, J = 7.2 Hz, 3H), 0.99 (t, J = 7.9 Hz, 9H), 0.67 (q, J = 7.9 Hz, 6H); for minor isomer, the following diagnostic signals were observed: δ = 6.25 – 6.23 (m, 1H), 1.50 (d, J = 1.4 Hz, 3H), 1.30 (d, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ = 157.4, 150.2, 133.9, 118.7, 105.6, 105.0, 30.8, 16.2, 13.7, 13.3, 6.7, 4.6. (Z)-Triethyl((2-methyldec-1-en-1-yl)oxy)silane 2d: Prepared according to the general procedure for preparation of enol silanes using Pd/C (5 wt-%, 5 mg), THF (5.0 mL), enal 1d (251 mg, 1.50 mmol, 1.0 eq.) and triethylsilane (192 mg, 264 μL, 1.65 mmol, 1.1 eq.). Reaction time: 30 min. Yield: 408 mg (96


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%, colorless oil). Z/E > 50:1. Data for major isomer 2d; IR (film, cm-1): 2956, 2922, 1676, 1459, 1174, 1005, 823, 728; 1H NMR (400 MHz, CDCl3, containing 8 % (SiEt3)2 impurities): δ = 6.07 – 6.03 (m, 1H), 2.07 (t, J = 7.4 Hz, 2H), 1.50 (d, J = 1.5 Hz, 3H), 1.38 – 1.21 (m, 15H), 0.97 (t, J = 8.0 Hz, 9H), 0.64 (q, J = 7.9 Hz, 6H), the minor isomer was not detected by 1H NMR; 13C NMR (101 MHz, CDCl3): δ = 133.4, 117.4, 32.1, 29.7, 29.7, 29.5, 28.6, 27.5, 22.9, 17.2, 14.3, 6.7, 4.7; HRMS (ESI+): m/z [M+Na] calcd for [C17H36ONaSi] 307.2428, found 307.2415, Δ = 1.3 mDa. (Z)-Triethyl((2,3,7-trimethylocta-1,6-dien-1-yl)oxy)silane 2e: Prepared according to the general procedure for preparation of enol silanes using Pd/C (5 wt-%, 10 mg), THF (5.0 mL), enal 1e (249 mg, 1.50 mmol, 1.0 eq.) and triethylsilane (192 mg, 264 μL, 1.65 mmol, 1.1 eq.). Reaction time: 3 h. Yield: 393 mg (93 %, colorless oil). Z/E > 50:1. The 1H and 13C NMR corresponds to previously published data.15 Data for major isomer 2e; 1H NMR (400 MHz, CDCl3, containing 5 % (SiEt3)2 impurities): δ = 6.04 (q, J = 1.5 Hz, 1H), 5.14 (tsept, J = 7.2, 1.4 Hz, 1H), 2.91 (dp, J = 8.6, 6.8 Hz, 1H), 1.97 – 1.83 (m, 2H), 1.68 (q, J = 1.2 Hz, 3H), 1.59 (d, J = 1.4 Hz, 3H), 1.40 (d, J = 1.5 Hz, 3H), 1.35 – 1.24 (m, 3H), 0.98 (t, J = 7.9 Hz, 9H), 0.64 (q, J = 7.9 Hz, 6H), the minor isomer was not detected by 1H NMR; 13C NMR (101 MHz, CDCl3): δ = 133.3, 130.9, 125.4, 120.7, 34.9, 30.5, 26.5, 25.9, 18.7, 17.7, 6.8, 4.7. (Z)-1-((Triethylsilyl)oxy)prop-1-en-2-yl acetate 2f: Prepared according to the general procedure for preparation of enol silanes using Pd/C (5 wt-%, 10 mg), THF (5.0 mL), enal 1f (171 mg, 1.50 mmol, 1.0 eq.) and triethylsilane (192 mg, 264 μL, 1.65 mmol, 1.1 eq.). Reaction time: 30 min. Yield: 316 mg (92 %, colorless oil). Z/E > 50:1. Data for major isomer 2f; IR (film, cm-1): 2958, 2879, 1756, 1228, 1164, 729; 1H NMR (400 MHz, CDCl3, containing 5 % (SiEt3)2 impurities): δ = 5.94 (q, J = 1.3 Hz, 1H), 2.14 (s, 3H), 1.75 (d, J = 1.4 Hz, 3H), 0.96 (t, J = 7.9 Hz, 9H), 0.64 (q, J = 7.9 Hz, 6H), the minor isomer was not detected by 1H NMR; 13C NMR (101 MHz, CDCl3): δ = 168.6, 131.2, 127.8, 20.8, 15.4, 4.6; HRMS (ESI+): m/z [M+Na] calcd for [C11H22O3NaSi] 253.1230, found 253.1217, Δ = 1.3 mDa. (Z)-Triethyl((2-methyl-3-(4-nitrophenyl)prop-1-en-1-yl)oxy)silane 2g: Formed as an intermediate in a One-Pot-Reaction. To a solution of pyrrolidine (0.03 mmol, 0.1 eq.) and p-dimethylaminobenzoic



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acid (0.06 mmol, 0.2 eq.) in DCM (1 mL), were added formaldehyde (37 % solution in H2O, 21 μL, 0.28 mmol, 1.0 eq.) and 3-(4-nitrophenyl)propanal (50 mg, 0.28 mmol, 1.0 eq.) at 10 °C.33 After 16 h a full conversion of starting material was observed by TLC. The mixture was added to 7 % NaHCO3 (5 mL) and the resulting mixture was extracted with DCM (3x5 mL). The combined organic extracts were then washed with brine and dried (Na2SO4). THF (2 mL) was added to the mixture and the organic solvents were evaporated to c.a. 2 mL. To the residual mixture of enal 1g in THF (2 mL) was added Pd/C (5 wt-%, 2 mg) and triethylsilane (0.46 mmol, 1.75 eq.) at room temperature. After 30 min a full conversion of starting material was observed by TLC. Yield of the reaction was at this step was not determined as the reaction mixture was used straight to the next step. Crude 1H NMR from the reaction mixture indicated the formation of desired enol silane. Z/E > 50:1. Data for major isomer 2g; 1H NMR (400 MHz, CDCl3, containing (SiEt3)2 and corresponding aldehyde impurities): δ = 8.13 – 8.10 (m, 2H), 7.35 – 7.33 (m, 2H), 6.25 – 6.22 (m, 1H), 3.50 (s, 2H), 1.46 (d, J = 1.5 Hz, 3H), 0.97 (t, J = 7.9 Hz, 9H), 0.68 (q, J = 8.4 Hz, 7.9, 6H), the minor isomer was not detected by 1H NMR. (E)-Triethyl((5-phenylpent-1-en-1-yl)oxy)silane 2h: Prepared according to the general procedure for preparation of enol silanes using Pd/C (5 wt-%, 2 mg), THF (1.0 mL), enal 1h (48 mg, 0.30 mmol, 1.0 eq.) and triethylsilane (38 mg, 53 μL, 0.33 mmol, 1.1 eq.). Reaction time: 1 h. Product was purified by flash chromatography (silica gel, n-hexanes/ethyl acetate 99:1) to afford the product as slightly yellow oil). Yield: 63 mg (76 %). Z/E 1:12. Data for major isomer 2h; IR (film, cm-1): 2957, 2877, 1661, 1171, 908, 730; 1H NMR (400 MHz, CDCl3): δ = 7.32 – 7.25 (m, 2H), 7.22 – 7.15 (m, 3H), 6.26 (dt, J = 11.9, 1.3 Hz, 1H), 5.03 (dt, J = 11.9, 7.4 Hz, 1H), 2.61 (t, J = 7.6 Hz, 2H), 1.94 (qd, J = 7.3, 1.3 Hz, 2H), 1.70 – 1.63 (m, 2H), 0.99 (t, J = 7.9 Hz, 9H), 0.68 (q, J = 8.0 Hz, 6H); for minor isomer, the following diagnostic signals were observed: δ = 6.24 – 6.23 (m, obstructed, 1H), 4.48 (td, J = 7.2, 6.0 Hz, 1H), 2.16 (qd, J = 7.4, 1.4 Hz, 2H); 13C NMR (101 MHz, CDCl3): δ = 142.7, 140.5, 128.6, 128.4, 125.8, 111.2, 35.4, 32.3, 27.1, 6.7, 4.6; HRMS (ESI+): m/z [M+Na] calcd for [C17H28ONaSi] 299.1802, found 299.1784, Δ = 1.8 mDa.


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(E)-Triethyl((5-(5-methylfuran-2-yl)hex-1-en-1-yl)oxy)silane 2i: Prepared according to the general procedure for preparation of enol silanes using Pd/C (5 wt-%, 10 mg), THF (5.0 mL), enal 1i (267 mg, 1.50 mmol, 1.0 eq.) and triethylsilane (209 mg, 288 μL, 1.80 mmol, 1.1 eq.). Reaction time: 3 h. Product was purified by flash chromatography (silica gel, n-hexanes/ethyl acetate 99:1) to afford the product as slightly yellow oil). Yield: 373 mg (84 %). Z/E 1:5. Data for major isomer 2i; IR (film, cm-1): 2956, 2877, 1662, 1157, 1016, 777, 730; 1H NMR (400 MHz, CDCl3): δ = 6.23 (dt, J = 11.9, 1.3 Hz, 1H), 5.90 – 5.76 (m, 2H), 4.98 (dt, J = 11.9, 7.4 Hz, 1H), 2.75 (dt, J = 13.9, 6.9 Hz, 1H), 2.25 (d, J = 1.0 Hz, 3H), 1.88 (qd, J = 7.6, 1.3 Hz, 2H), 1.75 – 1.63 (m, 1H), 1.47 (dtd, J = 13.3, 7.9, 6.9 Hz, 1H), 1.20 (d, J = 7.0 Hz, 3H), 0.98 (t, J = 7.9 Hz, 9H), 0.66 (q, J = 7.8 Hz, 6H); for minor isomer, the following diagnostic signals were observed: δ = δ =6.19 (dt, J = 5.9, 1.5 Hz, 1H), 4.43 (td, J = 7.2, 5.9 Hz, 1H), 2.15 – 2.04 (m, 2H), 1.22 (d, J = 6.9 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ = 159.3, 159.0, 150.1, 150.0, 140.3, 138.7, 111.3, 110.5, 105.7, 104.1, 104.0, 35.8, 32.8, 32.5, 25.2, 21.5, 19.3, 19.0; HRMS (ESI+): m/z [M+Na] calcd for [C17H30O2NaSi] 317.1907, found 317.1891, Δ = 1.6 mDa. (E)-((4-(Benzyloxy)but-1-en-1-yl)oxy)triethylsilane 2j: Prepared according to the general procedure for preparation of enol silanes using Pd/C (5 wt-%, 2 mg), THF (1.0 mL), enal 1j (53 mg, 0.30 mmol, 1.0 eq.) and triethylsilane (38 mg, 53 μL, 0.33 mmol, 1.1 eq.). Reaction time: 3 h. Product was purified by flash chromatography (silica gel, n-hexanes/ethyl acetate 99:1) to afford the product as colorless oil). Yield: 71 mg (81 %). Z/E > 1:12. Data for major isomer 2j; IR (film, cm-1): 2955, 2876, 1664, 1163, 1098, 730, 696; 1H NMR (400 MHz, CDCl3): δ = 7.35 – 7.27 (m, 5H), 6.31 (dt, J = 12.0, 1.3 Hz, 1H), 5.01 (dt, J = 12.0, 7.5 Hz, 1H), 4.51 (s, 2H), 3.44 (t, J = 6.9 Hz, 2H), 2.21 (qd, J = 7.0, 1.3 Hz, 2H), 0.98 (t, J = 7.9 Hz, 9H), 0.66 (q, J = 7.9 Hz, 6H); for minor isomer, the following diagnostic signal was observed: δ = 6.26 (dt, J = 5.8, 1.4 Hz, 1H); 13C NMR (101 MHz, CDCl3): δ = 141.7, 138.8, 128.5, 127.8, 127.6, 107.6, 73.1, 71.2, 28.2 6.7, 4.6; HRMS (ESI+): m/z [M+Na] calcd for [C12H18O2NaSi] 315.1751, found 315.1757, Δ = -0.6 mDa.



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(2E,8E)-Methyl-9-((triethylsilyl)oxy)nona-2,8-dienoate 2k: Prepared according to the general procedure for preparation of enol silanes using Pd/C (5 wt-%, 10 mg), THF (5.0 mL), enal 1k (261 mg, 1.43 mmol, 1.0 eq.) and triethylsilane (192 mg, 264 μL, 1.65 mmol, 1.15 eq.). Reaction time: 3 h. Product was purified by flash chromatography (silica gel, n-hexanes/ethyl acetate 99:1) to afford the product as colorless oil). Yield: 302 mg (71 %). Z/E > 1:16. The 1H and

13

C NMR corresponds to

previously published data.15 Data for major isomer 2k; 1H NMR (400 MHz, CDCl3): δ = 6.95 (dt, J = 15.6, 7.0 Hz, 1H), 6.23 (dt, J = 11.9, 1.3 Hz, 1H), 5.80 (dt, J = 15.6, 1.6 Hz, 1H), 4.96 (dt, J = 11.9, 7.5 Hz, 1H), 3.72 (s, 3H), 2.18 (qd, J = 7.1, 1.6 Hz, 2H), 1.88 (qd, J = 7.2, 1.3 Hz, 2H), 1.49 – 1.41 (m, 2H), 1.34 (dtd, J = 7.4, 6.9, 1.3 Hz, 2H), 0.97 (t, J = 7.9 Hz, 9H), 0.65 (q, J = 7.9 Hz, 6H); for minor isomer, the following diagnostic signal was observed: δ = 6.20 – 6.18 (m, 1H); 13C NMR (101 MHz, CDCl3): δ = 167.3, 149.8, 140.3, 121.0, 111.1, 51.5, 32.2, 30.0, 27.5, 27.2, 6.7, 4.6. (E)-((2-Cyclohexylvinyl)oxy)triethylsilane 2l: Prepared according to the general procedure for preparation of enol silanes using Pd/C (5 wt-%, 10 mg), THF (5.0 mL), enal 1l (186 mg, 1.50 mmol, 1.0 eq.) and triethylsilane (174 mg, 240 μL, 1.50 mmol, 1.0 eq.). Reaction time: 3 h. Product was purified by flash chromatography (silica gel, n-hexanes/ethyl acetate 99:1) to afford the product as colorless oil). Yield: 271 mg (75 %). Z/E > 1:10. The 1H and

13

C NMR corresponds to previously published

data.15 Data for major isomer 2l; 1H NMR (400 MHz, CDCl3): δ = 6.23 (dd, J = 12.0, 1.0 Hz, 1H), 4.97 (dd, J = 12.0, 8.0 Hz, 1H), 1.93 – 1.78 (m, 1H), 1.70 – 1.62 (m, 5H), 1.56 – 1.50 (m, 1H), 1.31 – 1.18 (m, 4H), 0.97 (t, J = 7.9 Hz, 9H), 0.65 (q, J = 7.4 Hz, 6H); for minor isomer, the following diagnostic signals were observed: δ = 6.10 (dd, J = 5.9, 1.1 Hz, 1H), 4.31 (dd, J = 8.8, 5.9 Hz, 1H), ; 13C NMR (101 MHz, CDCl3): δ = 138.7, 118.4, 36.9, 34.3, 26.3, 6.7, 4.6. (E)-((3-Cyclohexylprop-1-en-1-yl)oxy)triethylsilane 2m: Prepared according to the general procedure for preparation of enol silanes using Pd/C (5 wt-%, 10 mg), THF (5.0 mL), enal 1m (207 mg, 1.50 mmol, 1.0 eq.) and triethylsilane (174 mg, 240 μL, 1.50 mmol, 1.0 eq.). Reaction time: 3 h. Product was purified by flash chromatography (silica gel, n-hexanes/ethyl acetate 99:1) to afford the product


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as colorless oil). Yield: 257 mg (67 %). Z/E 1:8. Data for major isomer 2m; IR (film, cm-1): 2920, 1661, 1448, 1161, 1005, 728; 1H NMR (400 MHz, CDCl3, containing 8 % (SiEt3)2 impurities): δ = 6.19 (dt, J = 11.9, 1.3 Hz, 1H), 4.98 (dt, J = 11.9, 7.8 Hz, 1H), 1.76 (ddd, J = 7.9, 6.6, 1.3 Hz, 2H), 1.72 – 1.65 (m, 5H), 1.26 – 1.15 (m, 4H), 0.98 (t, J = 7.9 Hz, 9H), 0.66 (q, J = 7.9 Hz, 6H); for minor isomer, the following diagnostic signals were observed: δ = 6.22 (dt, J = 5.9, 1.5 Hz, 1H), 4.44 (td, J = 7.4, 6.0 Hz, 1H); 13C NMR (101 MHz, CDCl3): δ = 140.5, 110.1, 38.7, 35.3, 33.2, 26.8, 26.5, 6.9, 4.6; HRMS (ESI+): m/z [M+Na] calcd for [C15H30ONaSi] 277.1958, found 277.1936, Δ = 2.2 mDa. (E)-((3,7-Dimethylocta-1,6-dien-1-yl)oxy)triethylsilane 2n: Prepared according to the general procedure for preparation of enol silanes using Pd/C (5 wt-%, 10 mg), THF (5.0 mL), enal 1n (228 mg, 1.50 mmol, 1.0 eq.) and triethylsilane (228 mg, 252 μL, 1.58 mmol, 1.05 eq.). Reaction time: 3 h. Product was purified by flash chromatography (silica gel, n-hexanes/ethyl acetate 99:1) to afford the product as colorless oil). Yield: 253 mg (63 %). Z/E 1:20. The 1H and

13

C NMR corresponds to

previously published data.15 Data for major isomer 2n; 1H NMR (300 MHz, CDCl3): δ = 6.21 (dd, J = 12.0, 0.8 Hz, 1H), 5.09 (thept, J = 7.1, 1.1 Hz, 1H), 4.85 (dd, J = 12.0, 8.9 Hz, 1H), 2.08 – 1.83 (m, 3H), 1.70 – 1.66 (m, 3H), 1.61 – 1.58 (m, 3H), 1.37 – 1.16 (m, 3H), 0.98 (t, J = 8.3 Hz, 9H), 1.00 – 0.94 (m, obstructed, 2H), 0.67 (q, J = 7.8 Hz, 6H); for minor isomer, the following diagnostic signals were observed: δ = 6.16 (dd, J = 5.9, 1.0 Hz, 1H), 4.23 (dd, J = 9.3, 6.0 Hz, 1H); 13C NMR (75 MHz, CDCl3): δ = 139.2, 131.3, 125.0, 118.0, 38.0, 32.4, 26.1, 25.9, 22.1, 17.8, 6.7, 4.7. (Cyclohex-1-en-1-yloxy)triethylsilane 2o: Prepared according to the general procedure for preparation of enol silanes using Pd/C (5 wt-%, 2 mg), THF (1.0 mL), enol 1o (29 mg, 0.30 mmol, 1.0 eq.) and triethylsilane (38 mg, 53 μL, 0.33 mmol, 1.1 eq.). Reaction time: 1 h. Yield: 59 mg (93 %, colorless oil). The 1H and 13C NMR corresponds to previously published data.30 2o; 1H NMR (400 MHz, CDCl3, containing 11 % (SiEt3)2 impurities): δ = 4.91 – 4.83 (m, 1H), 2.06 – 1.96 (m, 4H), 1.70 – 1.62 (m, 2H), 1.55 – 1.46 (m, 2H), 0.97 (t, J = 7.9 Hz, 9H), 0.65 (q, J = 7.9 Hz, 6H); 13C NMR (101 MHz, CDCl3): δ = 150.6, 104.1, 30.0, 24.0, 23.4, 22.5, 6.9, 5.2.



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(R)-Triethyl((2-methyl-5-(prop-1-en-2-yl)cyclohex-1-en-1-yl)oxy)silane 2p: Prepared according to the general procedure for preparation of enol silanes using Pd/C (5 wt-%, 2 mg), THF (1.0 mL), enol 1p (45 mg, 47 μL, 0.30 mmol, 1.1 eq.) and triethylsilane (31 mg, 43 μL, 0.27 mmol, 1.0 eq.). Reaction time: 16 h. Product was purified by flash chromatography (silica gel, n-hexanes/ethyl acetate 95:5) to afford the product as colorless oil). Yield: 51 mg (71 %). 2p; IR (film, cm-1): 2955, 2876, 1690, 1178, 1017, 928, 887, 804, 723; 1H NMR (400 MHz, CDCl3): δ = 4.72 (dt, J = 4.2, 1.3 Hz, 2H), 2.28 – 2.18 (m, 1H), 2.12 – 1.92 (m, 4H), 1.76 – 1.71 (m, obstructed, 1H), 1.74 (s, 3H), 1.59 (s, 3H), 1.44 – 1.32 (m, 1H), 0.99 (t, J = 7.9 Hz, 9H), 0.66 (q, J = 7.8 Hz, 6H), contains traces of other products (We prepared a separate sample containing more of the side products to ease the characterisation. See 2D COSY); 13

C NMR (101 MHz, CDCl3): δ = 149.6, 142.6, 111.1, 108.8, 42.7, 35.7, 30.4, 28.1, 20.9, 16.1, 7.0, 5.8;

HRMS (ESI+): m/z [M+H] calcd for [C16H31OSi] 267.2139, found 267.2158, Δ = -1.9 mDa. General Procedure for the Preparation of Saturated Aldehydes and Ketones. To a solution of the activated Pd/C (5 wt-%, 10 mg) in dry THF (5.0 mL), was added enal or enol (1.50 mmol, 1.0 eq.), H2SO4 (100 μL, 1M) and triethylsilane (1.65 mmol, 1.1 eq.) at room temperature. The reaction was followed by TLC (eluent: n-hexanes/ethyl acetate 9:1) or by GC. After full conversion (30 min to 16 h), the reaction mixture was filtered through a small pad of alumina (neutral) column and washed with DCM. The DCM was evaporated and the residue was purified from traces of silane/silanols by flash chromatography (silica gel, n-hexanes/ethyl acetate or pentane/Et2O 99:1) to afford the pure products. 2-Methyl-3-phenylpropanal 3a: Prepared according to the general procedure for preparation of saturated aldehydes and ketones using Pd/C (5 wt-%, 10 mg), THF (5.0 mL), enal 1a (219 mg, 1.50 mmol, 1.0 eq.), H2SO4 (100 μL, 1M) and triethylsilane (192 mg, 264 μL, 1.65 mmol, 1.1 eq.). Yield: 205 mg (92 %, colorless oil). Reaction time: 30 min. The 1H and

13


published data.34 3a; 1H NMR (300 MHz, CDCl3): δ = 9.73 (d, J = 1.4 Hz, 1H), 7.33 – 7.15 (m, 5H), 3.16


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– 3.03 (m, 1H), 2.74 – 2.57 (m, 2H), 1.10 (d, J = 6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ = 204.4, 139.0, 129.2, 128.7, 126.6, 48.2, 36.8, 13.4. 2,3,7-Trimethyloct-6-enal 3e: Prepared according to the general procedure for preparation of saturated aldehydes and ketones using Pd/C (5 wt-%, 10 mg), THF (5.0 mL), enal 1e (248 mg, 1.50 mmol, 1.0 eq.), H2SO4 (100 μL, 1M) and triethylsilane (192 mg, 264 μL, 1.65 mmol, 1.1 eq.). Yield: 236 mg (94 %, mixture of diastereomers (dr 3:1), colorless oil). Reaction time: 3 h. The 1H and 13C NMR corresponds to previously published data.35 Data for major diastereomer 3e; 1H NMR (300 MHz, CDCl3): δ = 9.68 (d, J = 1.9 Hz, 1H), 5.14 – 5.04 (m, 1H), 2.40 – 2.24 (m, 1H), 2.10 – 1.85 (m, 3H), 1.68 (s, 3H), 1.60 (s, 3H), 1.45 – 1.14 (m, 2H), 1.05 (d, J = 7.0 Hz, 3H), 0.99 (d, J = 6.9 Hz, 3H); for minor diastereomer, the following diagnostic signals were observed: δ = 9.65 (d, J = 1.5 Hz, 1H), 1.00 (d, J = 7.0 Hz, 3H), 0.84 (d, J = 6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ = 205.9, 205.8, 132.0, 124.2, 124.2, 51.7, 50.7, 34.9, 33.6, 33.6, 32.4, 25.9, 25.8, 25.8, 17.8, 17.5, 15.5, 10.1, 8.3. 2-Methyl-3-(4-nitrophenyl)propanal 3g: Prepared in a One-Pot-Reaction. To a solution of pyrrolidine (0.03 mmol, 0.1 eq.) and p-dimethylaminobenzoic acid (0.06 mmol, 0.2 eq.) in DCM (1 mL), were added formaldehyde (37 % solution in H2O, 21 μL, 0.28 mmol, 1.0 eq.) and 3-(4-nitrophenyl)propanal (50 mg, 0.28 mmol, 1.0 eq.) at 10 °C.33 After 16 h a full conversion of starting material was observed by TLC. The mixture was added to 7 % NaHCO3 (5 mL) and the resulting mixture was extracted with DCM (3x5 mL). The combined organic extracts were then washed with brine and dried (Na2SO4). THF (2 mL) was added to the mixture and the organic solvents were evaporated to c.a. 2 mL . To the residual mixture of enal 1g in THF (2 mL) was added Pd/C (5 wt-%, 2 mg) and triethylsilane (0.46 mmol, 1.75 eq.) at room temperature. After 30 min a full conversion of starting material was observed by TLC. To the reaction mixture was added trifluoroacetic acid (1 mL). After 16 h a full conversion of enol silane 2g was observed by TLC. The mixture was added to H2O (5 mL) and the resulting mixture was extracted with DCM (3x5 mL). The combined organic extracts were then washed with brine, dried (Na2SO4) and concentrated in vacuum line to give the product as slightly



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yellow oil). Yield: 45 mg (83 %, over 3 steps). 3g; IR (film, cm-1): 2933, 1721, 1598, 1514, 1342, 1109, 857, 700, 647; 1H NMR (300 MHz, CDCl3): δ = 9.71 (d, J = 1.1 Hz, 1H), 8.18 – 8.14 (m, 2H), 7.37 – 7.32 (m, 2H), 3.25 – 3.15 (m, 1H), 2.77 – 2.66 (m, 2H), 1.14 (d, J = 6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ = 203.0, 147.0, 130.0, 123.9, 47.8, 36.3, 13.5; HRMS (ESI+): m/z [M+Na+MeOH] calcd for [C11H15O4NNa] 248.0893, found 248.0869, Δ = 2.4 mDa. 3-(Benzyloxy)-2-methylpropanal 3q: Prepared according to the general procedure for preparation of saturated aldehydes and ketones using Pd/C (5 wt-%, 2 mg), THF (1.0 mL), enal 1q (53 mg, 0.30 mmol, 1.0 eq.), H2SO4 (20 μL, 1M) and triethylsilane (38 mg, 53 μL, 0.33 mmol, 1.1 eq.). Yield: 30 mg (56 %, colorless oil). Reaction time: 1 h. 3q; IR (film, cm-1): 2859, 1721, 1454, 1094, 1028, 736, 697; 1

H NMR (300 MHz, CDCl3): δ = 9.73 (d, J = 1.6 Hz, 1H), 7.39 – 7.28 (m, 6H), 4.53 (s, 2H), 3.69 (dd, J =

9.5, 6.6 Hz, 2H), 3.63 (dd, J = 9.5, 5.3 Hz, 1H), 2.67 (pdd, J = 7.0, 5.3, 1.6 Hz, 1H), 1.14 (d, J = 7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ = 203.9, 138.1, 128.6, 127.9, 127.7, 73.5, 70.3, 47.0, 10.9; HRMS (ESI+): m/z [M+Na] calcd for [C11H14O2Na] 201.0886, found 201.0873, Δ = -1.3 mDa. 5-(5-Methylfuran-2-yl)hexanal 3i: Prepared according to the general procedure for preparation of saturated aldehydes and ketones using Pd/C (5 wt-%, 2 mg), THF (1.0 mL), enal 1i (53 mg, 0.30 mmol, 1.0 eq.), H2SO4 (20 μL, 1M) and triethylsilane (38 mg, 53 μL, 0.33 mmol, 1.1 eq.). Yield: 45 mg (82 %, colorless oil). Reaction time: 1 h. 3i; IR (film, cm-1): 2926, 1723, 1614, 1220, 1019, 780, 733; 1H NMR (300 MHz, CDCl3): δ = 9.74 (t, J = 1.8 Hz, 1H), 5.83 (s, 2H), 2.76 (p, J = 6.8 Hz, 1H), 2.44 – 2.35 (m, 2H), 2.24 (s, 3H), 1.71 – 1.51 (m, 4H), 1.22 (d, J = 7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ = 205.9, 205.8, 132.0, 124.2, 124.2, 51.7, 50.7, 34.9, 33.6, 33.5 32.4, 25.9, 25.8, 25.8, 17.8, 17.5, 15.5, 10.1, 8.3; HRMS (ESI+): m/z [M+Na] calcd for [C12H20O3Na] 235.1305, found 235.1276, Δ = 2.9 mDa. 5-Phenylpentanal 3h: Prepared according to the general procedure for preparation of saturated aldehydes and ketones using Pd/C (5 wt-%, 10 mg), THF (5.0 mL), enal 1h (240 mg, 1.50 mmol, 1.0 eq.), H2SO4 (100 μL, 1M) and triethylsilane (192 mg, 264 μL, 1.65 mmol, 1.1 eq.). Yield: 204 mg (84 %, colorless oil). Reaction time: 1 h. 3h; IR (film, cm-1): 2933, 1721, 1453, 747, 698; 1H NMR (400 MHz,


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CDCl3): δ = 9.76 (t, J = 1.8 Hz, 1H), 7.31 – 7.16 (m, 5H), 2.68 – 2.61 (m, 2H), 2.49 – 2.41 (m, 2H), 1.72 – 1.64 (m, 4H); 13C NMR (101 MHz, CDCl3): δ = 202.5, 142.1, 128.5, 128.5, 126.0, 43.9, 35.8, 31.0, 21.8; HRMS (ESI+): m/z [M+Na] calcd for [C12H18O2Na] 217.1199, found 217.1200, Δ = -0.1 mDa. 6-Phenylhexan-2-one 3r: Prepared according to the general procedure for preparation of saturated aldehydes and ketones using Pd/C (5 wt-%, 2 mg), THF (1.0 mL), enol 1r (52 mg, 0.30 mmol, 1.0 eq.), H2SO4 (20 μL, 1M) and triethylsilane (38 mg, 53 μL, 0.33 mmol, 1.1 eq.). Yield: 49 mg (92 %, colorless oil). Reaction time: 1 h. 3r; IR (film, cm-1): 2936, 1713, 1357, 1159, 748, 732; 1H NMR (400 MHz, CDCl3): δ = 7.31 – 7.25 (m, 2H), 7.21 – 7.15 (m, 3H), 2.65 – 2.59 (m, 2H), 2.47 – 2.42 (m, 2H), 2.12 (s, 3H), 1.65 – 1.60 (m, 4H); 13C NMR (101 MHz, CDCl3): δ = 209.1, 142.3, 128.5, 128.4, 125.9, 43.7, 35.9, 31.1, 30.0, 23.6; HRMS (ESI+): m/z [M+Na] calcd for [C12H16ONa] 199.1093, found 199.1081, Δ = 1.2 mDa. Nonan-2-one 3s: Prepared according to the general procedure for preparation of saturated aldehydes and ketones using Pd/C (5 wt-%, 10 mg), THF (5.0 mL), enol 1s (210 mg, 1.50 mmol, 1.0 eq.), H2SO4 (100 μL, 1M) and triethylsilane (192 mg, 264 μL, 1.65 mmol, 1.1 eq.). Yield: 194 mg (91 %, colorless oil). Reaction time: 30 min. The product is commercially available. 3s; 1H NMR (400 MHz, CDCl3): δ = 2.41 (t, J = 7.5 Hz, 2H), 2.13 (s, 3H), 1.57 (q, J = 7.4 Hz, 2H), 1.33 – 1.21 (m, 9H), 0.87 (t, J = 6.9 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ = 209.5, 44.0, 31.8, 30.0, 29.3, 29.2, 24.0, 22.8, 14.2. (5R)-2-Methyl-5-(prop-1-en-2-yl)cyclohexanone 3p: Prepared according to the general procedure for preparation of saturated aldehydes and ketones using Pd/C (5 wt-%, 2 mg), THF (1.0 mL), enol 1p (45 mg, 47 μL, 0.30 mmol, 1.0 eq.), H2SO4 (20 μL, 1M) and triethylsilane (35 mg, 48 μL, 0.30 mmol, 1.0 eq.). Yield: 35 mg (75 %, mixture of diastereomers (dr 30:1), colorless oil). Reaction time: 16 h. The product is commercially available. Data for major diastereomer: 3p; 1H NMR (300 MHz, CDCl3): δ = 4.84 – 4.67 (m, 2H), 2.48 – 2.22 (m, 4H), 2.12 (ddt, J = 12.6, 5.9, 3.3 Hz, 1H), 1.99 – 1.89 (m, 1H), 1.76 – 1.72 (m, 3H), 1.72 – 1.57 (m, 1H), 1.37 (qd, J = 13.0, 3.5 Hz, 1H), 1.03 (d, J = 6.5 Hz, 3H); for minor diastereomer, following diagnostic signal was observed: δ = 1.09 (d, J = 6.8 Hz, 3H), also containing 6



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% of fully saturated product (diagnostic isopropyl signal: 0.89 (dd, J = 6.5, 3.1 Hz, 6H)); 13C NMR (101 MHz, CDCl3): δ = 212.8, 147.8, 109.7, 47.2, 47.0, 44.9, 35.1, 30.9, 20.6, 14.5. Butyronitrile 5: Prepared according to the general procedure for preparation of saturated aldehydes and ketones using Pd/C (5 wt-%, 10 mg), diethyl ether (5.0 mL), unsaturated nitrile 6 (100 mg, 1.50 mmol, 1.0 eq.), H2SO4 (100 μL, 1M) and triethylsilane (192 mg, 264 μL, 1.65 mmol, 1.1 eq.). After full conversion of starting material dibenzylether (74 mg, 71 μL, 0.38 mmol, 0.25 eq.) was added to the mixture. Yield (67 %) was determined by 1 H NMR. Reaction time: 16 h. The product is commercially available. 5; 1H NMR (300 MHz, CDCl3): δ = 2.32 (t, J = 7.0 Hz, 2H), 1.70 (h, J = 7.4 Hz, 2H), 1.08 (t, J = 7.4 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ = 53.5, 19.3, 19.2, 13.4. General Procedure for the Hydrogenation of C=C bonds. To a solution of the activated Pd/C (5 wt-%, 2 mg) in dry THF (1.0 mL) was added ester or olefin (0.30 mmol, 1.0 eq.), H2SO4 (20 μL, 1M) and triethylsilane (0.66 mmol, 2.2 eq.) at room temperature. The reaction was followed by TLC (eluent: n-hexanes/ethyl acetate 9:1). After full conversion (30 min to 6 h), the reaction mixture was filtered through a small pad of alumina (neutral) column and washed with DCM. The DCM was evaporated and the residue was purified from traces of silane/silanols by flash chromatography (silica gel, nhexanes/ethyl acetate or pentane/Et2O 99:1) to afford the pure products. Benzyl butyrate 7: Prepared according to the general procedure for hydrogenation of C=C bonds using Pd/C (5 wt-%, 2 mg), THF (1.0 mL), ester 6 (53 mg, 0.30 mmol, 1.0 eq.), H2SO4 (20 μL, 1M) and triethylsilane (76.7 mg, 105 μL, 0.66 mmol, 2.2 eq.). Yield: 47 mg (88 %, colorless oil). Reaction time: 30 min. The 1H and

13

C NMR corresponds to previously published data.36 7; 1H NMR (300 MHz,

CDCl3): δ = 7.41 – 7.30 (m, 5H), 5.12 (s, 2H), 2.34 (t, J=7.4, 2H), 1.68 (h, J=7.4, 2H), 0.95 (t, J=7.4, 3H); 13

C NMR (75 MHz, CDCl3): δ = 173.6, 136.3, 128.7, 128.3, 66.2, 36.4, 18.6, 13.8.

2-Methoxy-4-propylphenol 9: Prepared according to the general procedure for hydrogenation of C=C bonds using Pd/C (5 wt-%, 2 mg), THF (1.0 mL), eugenol 10 (49 mg, 0.30 mmol, 1.0 eq.), H2SO4 (20 μL,


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1M) and triethylsilane (76.7 mg, 105 μL, 0.66 mmol, 2.2 eq.). Yield: 46 mg (93 %, colorless oil). Reaction time: 30 min. The product is commercially available. 9; 1H NMR (300 MHz, CDCl3): δ = 6.87 – 6.79 (m, 1H), 6.70 – 6.65 (m, 2H), 5.46 (s, 1H), 3.88 (s, 3H), 2.52 (t, J=7.5, 2H), 1.63 (h, J=7.4, 2H), 0.94 (t, J=7.3, 3H); 13C NMR (75 MHz, CDCl3): δ = 146.4, 143.7, 134.8, 121.1, 114.2, 111.2, 56.0, 37.9, 25.0, 13.9. Preparation of Enol Silanes in a Gram Scale (Z)-Triethyl((2-methyl-3-phenylprop-1-en-1-yl)oxy)silane 2a: Prepared according to the general procedure for preparation of enol silanes using Pd/C (5 wt-%, 100 mg), THF (10.0 mL), enal 1a (2.0 g, 13.7 mmol, 1.0 eq.) and triethylsilane (1.9 g, 2.6 mL, 16.4 mmol, 1.2 eq.). Reaction time: 16 h. Product 2a was purified by flash chromatography (silica gel, n-hexanes/ethyl acetate 95:5) to afford the pure products as colorless oil). Z/E > 50:1. Yield: 3.3 g (92 %). The 1H and

13

C NMR data

corresponds to those prepared in small scale experiments. (Cyclohex-1-en-1-yloxy)triethylsilane 2o: Prepared according to the general procedure for preparation of enol silanes using Pd/C (5 wt-%, 20 mg), THF (10.0 mL), enol 1o (2.00 g, 2.01 mL, 20.81 mmol, 1.0 eq.) and triethylsilane (2.66 g, 3.66 mL, 22.89 mmol, 1.1 eq.). Reaction time: 2d. Product 2o was purified by flash chromatography (silica gel, n-hexanes/ethyl acetate 99:2) to afford the pure products as colorless oil). Yield: 3.62 g (82 %). The 1H and 13C NMR data corresponds to those prepared in small scale experiments. Preparation of β-Mono-deuterated Enol Silanes and Carbonyl Compounds β-Mono-deuterated-(Z)-triethyl((2-methyl-3-phenylprop-1-en-1-yl)oxy)silane

2a-dβ:

Prepared

according to the general procedure for preparation of enol silanes and ketones using Pd/C (5 wt-%, 2 mg), THF (1.0 mL), enal 1a (52 mg, 0.30 mmol, 1.0 eq.) and triethylsilane-d (39 mg, 53 μL, 0.33 mmol, 1.1 eq.). Yield: 74 mg (94 %, colorless oil). Reaction time: 30 min. H/D ratio 6:94 was determined by 1

H NMR. 2a-dβ; IR (film, cm-1): 2956, 2877, 1669, 1178, 1134, 727, 698; 1H NMR (300 MHz, CDCl3): δ =



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7.30 – 7.12 (m, 7H), 6.21 – 6.16 (m, 1H), 3.42 (s, 2H), 1.46 – 1.40 (m, 2.06H), 1.00 (t, J = 7.7 Hz, 9H), 0.68 (q, J = 7.9 Hz, 6H); 13C NMR (75 MHz, CDCl3): δ = 141.2, 134.3, 128.9, 128.3, 125.7, 115.9, 35.1, 16.8 (t, J = 19.3 Hz), 6.8, 4.7; HRMS (ESI+): m/z [M+Na] calcd for [C16H25ONaSi] 286.1707, found 286.1701, Δ = 0.6 mDa. β-Mono-deuterated-2-methyl-3-phenylpropanal from β-mono-deuterated-(Z)-triethyl((2-methyl-3phenylprop-1-en-1-yl)oxy)silane 3a-dβ: To the solution of enol silane 2a-dβ (H/D 6:94) (50 mg, 0.19 mmol) in THF (1.0 mL) was added H2SO4 (20 μL, 1M). After full conversion the reaction mixture was filtered through small pad of alumina (neutral) column and washed with DCM. The DCM was evaporated and the residue was purified from traces of silane/silanols by flash chromatography (silica gel, n-hexanes/ethyl acetate 99:1) to afford the pure product as colorless oil). Yield: 8 mg (29 %). Reaction time: 4 h. H/D ratio for α-position > 50:1 and for β-position 9:91 were determined by 1H NMR. H/D ratio 6:94 for the product was determined by MS-experiment. 3a-dβ; IR (film, cm-1): 2933, 1703, 1176, 733, 698; 1H NMR (300 MHz, CDCl3): δ = 9.73 (d, J = 1.4 Hz, 1H), 7.41 – 7.09 (m, 5H), 3.14 – 3.03 (m, 1H), 2.73 – 2.55 (m, 2H), 1.09 (dd, J = 4.8, 2.8 Hz, 1.03H), 1.06 (dd, J = 3.9, 1.9 Hz, 1.03H); 13

C NMR (75 MHz, CDCl3): δ = 204.5, 139.0, 129.2, 128.7, 126.6, 48.1, 36.8, 13.1 (t, J = 19.7 Hz); HRMS

(ESI-): m/z [M-H] calcd for [C10H10OD] 148.0877, found 148.0874, Δ = -0.3 mDa. β-Mono-deuterated-2-methyl-3-phenylpropanal

from

2-benzylacrylaldehyde

3a-dβ:

Prepared

according to the general procedure for preparation of saturated aldehydes and ketones using Pd/C (5 wt-%, 2 mg), THF (1.0 mL), enal 1a (44 mg, 0.30 mmol, 1.0 eq.), H2SO4 (20 μL, 1M) and triethylsilane-d (39 mg, 53 μL, 0.33 mmol, 1.1 eq.). Yield: 38 mg (85 %, colorless oil). Reaction time: 30 min. H/D ratio for α-position > 50:1 and for β-position 14:86 were determined by 1H NMR. H/D ratio 12:88 for the product was determined by MS-experiment. 3a-dβ; The characterization data corresponds to the compound produced from compound 2a-dβ. α,β-dideuterated-2-methyl-3-phenylpropanal

from

β-mono-deuterated-(Z)-triethyl((2-methyl-3-

phenylprop-1-en-1-yl)oxy)silane 3a-dα,β: To the solution of enol silane 2a-dβ (25 mg, 0.08 mmol) in


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THF (1.0 mL) was added D2SO4 (20 μL, 1M). After full conversion the reaction mixture was filtered through a small pad of alumina (neutral) column and washed with DCM. The DCM was evaporated and the residue was purified from traces of silane/silanols by flash chromatography (silica gel, nhexanes/ethyl acetate 99:1) to afford the product. Yield: 9 mg (64 %, slightly yellow oil). Reaction time: 4 h. H/D ratio for α-position 7:93 and for β-position 4:96 were determined by 1H NMR. 3a-dα,β; IR (film, cm-1): 2926, 1724, 1496, 1454, 739, 698; 1H NMR (300 MHz, CDCl3): δ = 9.73 (s, 1H), 7.43 – 7.07 (m, 6H), 3.08 (d, J = 13.9 Hz, 1H), 2.60 (d, J = 13.9 Hz, 1H), 1.11 – 1.02 (m, 2.06H), also containing (SiEt3)2 impurities 0.95 – 1.00 (m), 0.56 – 0.64 (m) and grease 1.26 (s); 13C NMR (75 MHz, CDCl3): δ = 204.6, 139.0, 129.2, 128.7, 126.6, 36.7, 29.9, 13.0 (t, J = 20.0 Hz). α,β-dideuterated-2-methyl-3-phenylpropanal

from

2-benzylacrylaldehyde

3a-dα,β:

Prepared

according to the general procedure for preparation of saturated aldehydes and ketones using Pd/C (5 wt-%, 2 mg), THF (1.0 mL), enal 1a (44 mg, 0.30 mmol, 1.0 eq.), D2SO4 (20 μL, 1M) and triethylsilane-d (39 mg, 53 μL, 0.33 mmol, 1.1 eq.). Yield: 44 mg (98 %, colorless oil). Reaction time: 30 min. H/D ratio for α-position 19:81 and for β-position 8:92 were determined by 1H NMR. 3a-dα,β; The characterization data corresponds to the compound produced from compound 2a-dβ. Chemoselectivity Tests (Z)-Triethyl((2-methyl-3-phenylprop-1-en-1-yl)oxy)silane 2a: Prepared according to the general procedure for preparation of enol silanes using Pd/C (5 wt-%, 2 mg), DCM (1.0 mL), enal 1a (44 mg, 0.30 mmol, 1.0 eq.), 2-(benzyloxy)acetaldehyde 10 (45 mg, 42 μL, 0.30 mmol, 1.0 eq.) and triethylsilane (54 mg, 74 μL, 0.47 mmol, 1.55 eq.). Reaction time: 4 h. 1H NMR and 13C NMR indicated 100 % chemoselectivity towards hydrosilylation. The data corresponds to previously prepared compound 2a and commercially available 10. (Cyclohex-1-en-1-yloxy)triethylsilane 2o: Prepared according to the general procedure for preparation of enol silanes using Pd/C (5 wt-%, 2 mg), DCM (1.0 mL), enol 1o (29 mg, 29 μL, 0.30



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mmol, 1.0 eq.), 2-(benzyloxy)acetaldehyde 10 (45 mg, 42 μL, 0.30 mmol, 1.0 eq.) and triethylsilane (37 mg, 50 μL, 0.32 mmol, 1.05 eq.). Reaction time: 1h. 1H NMR and

13

C NMR indicated 100 %

chemoselectivity towards hydrosilylation. The data corresponds to previously prepared compound 2o and commercially available 10. 2-Methyl-3-phenylpropanal 3a: Prepared according to the general procedure for preparation of saturated aldehydes and ketones using Pd/C (5 wt-%, 2 mg), DCM (1.0 mL), enal 1a (44 mg, 0.30 mmol, 1.0 eq.), 2-(benzyloxy)acetaldehyde 10 (45 mg, 42 μL, 0.30 mmol, 1.0 eq.), H2SO4 (20 μL, 1M) and triethylsilane (37 mg, 50 μL, 0.32 mmol, 1.05 eq.). Reaction time: 1 h. 1H NMR and 13C NMR indicated 100 % chemoselectivity towards hydrogenation. The data corresponds to previously prepared compound 3a and commercially available 10. Nonan-2-one.Compound 3s: Prepared according to the general procedure for preparation of saturated aldehydes and ketones using Pd/C (5 wt-%, 2 mg), DCM (1.0 mL), enol 1s (42 mg, 50 μL, 0.30 mmol, 1.0 eq.), 2-(benzyloxy)acetaldehyde 10 (45 mg, 42 μL, 0.30 mmol, 1.0 eq.), H2SO4 (20 μL, 1M) and triethylsilane (37 mg, 50 μL, 0.32 mmol, 1.05 eq.). Reaction time: 30 min. 1H NMR and 13C NMR indicated 100 % chemoselectivity towards hydrogenation. The data corresponds to previously prepared compound 3s and commercially available 10. (Z)-Triethyl((2-methyl-3-phenylprop-1-en-1-yl)oxy)silane 2a: Prepared according to the general procedure for preparation of enolsilanes using Pd/C (5 wt-%, 2 mg), THF (1.0 mL), enal 1a (44 mg, 0.30 mmol, 1.0 eq.), 1p (45 mg, 47 μL, 0.30 mmol, 1.0 eq.), 11 (49 mg, 47 μL, 0.30 mmol, 1. eq.), 1r (52 mg, 53 μL, 0.30 mmol, 1.0 eq), H2SO4 (20 μL, 1M) and triethylsilane (35 mg, 48 μL, 0.30 mmol, 1.0 eq.). Reaction time: 4 h. 1H NMR and 13C NMR indicated 100 % conversion of 1a with 80 % of 2a and 11 % of 3a. No conversion of 1p, 1r and 11 were observed. The data corresponds to previously prepared compounds 2a and 3a; to 1r37 and commercially available 1p and 11.

Associated Content


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Supporting Information Additional notes to experimental procedures, screening experiments and copies of NMR spectra are available free of charge via the Internet at http://pubs.acs.org. Acknowledgements We thank Dr. Elina Kalenius for assistance with mass spectrometry and Mr. Esa Haapaniemi for assistance with NMR spectroscopy. This work was supported by the University of Jyväskylä, Department of Chemistry and Tekes. References

(1) (a) Augustine, R. L. In: Heterogeneous Catalysis for the Synthetic Chemistry, Marcel Dekker, New York, 1996. (b) Smith, G. V.; Notheisz, F. In: Heterogeneous Catalysis in Organic Chemistry, Academic Press, 1999. (c) Bartók, M.; Czombos, J.; Felfoldi, K.; Gera, L.; Gondos, G.; Molnar, A.; Notheisz, F.; Palinko, I.; Wittman, G.;Zsigmond, A. G. Stereochemistry of Heterogeneous Metal Catalysis, Wiley, New York, 1985. (2) (a) Guisnet, M.; Barrault, J.; Bouchoule, C.; Duprez, D.; Montassier, C.; Pérot, G, Eds. Heterogeneous Catalysis and Fine Chemicals, Elsevier, 1988. (b) Guisnet, M.; Barrault, J.; Bouchoule, C.; Duprez, D.; Pérot, G; Maurel, R.; Montassier, C. Eds. Heterogeneous Catalysis and Fine Chemicals II, Elsevier, 1991. (c) Guisnet, M.; Barbier, J.; Barrault, J.; Bouchoule, C.; Duprez, D.; Pérot, G; Montassier, C. Eds. Heterogeneous Catalysis and Fine Chemicals III, Elsevier, 1993. (d) Blaser, H. U.; Baiker, A., Prins, R. Eds. Heterogeneous Catalysis and Fine Chemicals IV, Elsevier, 1997. (e) Somorjai, G. A.; Kliewer, C. J. React. Kinet. Catal. Lett. 2009, 96, 191-208. (f) Blaser, H.-U.; Malan, C.; Pugin, B.; Spindler, F.; Steiner, H.; Studer, M. Adv. Synth. Catal. 2003, 345, 103-151.



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T.; Chen, L.; Minato, T.; Ishikawa, Y.; Chen, M.; Asao, Na; Yamamoto, Y.; Jin, T. Chem. Commun. 2014, 50, 3344-3346. (31) Collins K. D.; Glorius, F. Nature Chemistry 2013, 5, 597-601. (32) For a recent application of the protocol in kinetic isotope effect studies, see: Leskinen, M. V.; Madarász, Á.; Yip, K.-T.; Vuorinen, A.; Pápai, I.; Neuvonen, A. J.; Pihko, P. M. J. Am. Chem. Soc. 2014, 136, 6453-6462. (33) (a) Erkkilä, A.; Pihko, P. M. Eur. J. Org. Chem. 2007, 4205-4216. (b) Benohoud, M.; Erkkilä, A.; Pihko, P. M. Org. Synth. 2010, 87, 201-208. (34) Maruoka, K.; Itoh, T.; Sakurai, M.; Nonoshita, K.; Yamamoto, H. J. Am. Chem. Soc. 1988, 110, 3588-3597. (35) Savoia, D.; Tagliavini, E.; Trombini, C.; Umani-Ronchi, A. J. Org. Chem. 1981, 46, 53445348. (36) Dev, D.; Palakurthy, N. B.; Thalluri, K.; Chandra, J.; Mandal, B. J. Org. Chem., 2014, 79, 5420-5431. (37) Leung, P. S.-W.; Teng, Y.; Toy, P. H. Synlett. 2010, 13, 1997-2001.


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