Silyl Anion Initiated Hydroboration of Aldehydes and Ketones

Abstract Hydroboration is an emerging method for mild and selective reduction of carbonyl compounds. Typically, transition‐metal or reactive main‐group hydride catalysts are used in conjunction with a mild reductant such as pinacolborane. The reactivity of the main‐group catalysts is a consequence of the nucleophilicity of their hydride ligands. Silicon hydrides are significantly less reactive and are therefore not efficient hydroboration catalysts. Here, a readily prepared silyl anion is reported to be an effective initiator for the reduction of aldehydes and ketones requiring mild conditions, low catalyst loadings and with a good substrate scope. The silyl anion it is shown to activate HBpin to generate a reactive borohydride in situ which reacts with aldehydes and ketones to afford the hydroboration product.


General Considerations
All manipulations were carried out under a dry argon or nitrogen atmosphere using standard Schlenk or glovebox techniques. Solvents were obtained from an Inert solvent purification system and stored over 4 Å molecular sieves. C6D6 was dried over potassium then distilled under argon and stored over 4 Å molecular sieves. CDCl3 was used as supplied. 1 H and 13 C NMR spectra were recorded on Bruker AVA 400, 500 or 600 MHz spectrometers. 11 B NMR spectra were recorded on a Bruker PRO 500 spectrometer. 1 H and 13 C spectra were referenced to residual solvent signals. [1] 11 B spectra were referenced to BF3·Et2O as an external standard. Pinacolborane (HBpin) was distilled prior to use to remove traces of BH3, boric acid and B2pin3 which was confirmed by 1 H and 11 B NMR. Acetophenone was stored over 4 Å molecular sieves. All other reagents were used as supplied. Catalysts 1, [2] A [3] and B [4] were prepared according to literature procedures.

Silicon Catalysts
Silicon hydrides with Cp* substituents were investigated as catalysts for the hydroboration of acetophenone. Triethylsilane was also investigated for comparison.
The control reaction (no catalyst) and the reaction using a catalytic amount of triethyl silane only showed trace yields. Silanes A and B gave 8% and trace yields, respectively. Silyl anion 1 gave 2a quantitatively under these conditions.

General Procedure
Pinacolborane was added to a solution of anion 1 or crystalline 1 resulting in a colourless solution. Acetophenone was added and the reaction stirred at room temperature for the specified time. CDCl3 was added in air to quench the reactions. For NMR yields, a solution of 1,3,5-trimethoxybenzene in CDCl3 (0.1 M) was added in air to quench the reactions.

Solvent
A key advantage of pre catalyst 1 over reported inorganic bases is its solubility. The following solvents were screened at 3 mol% catalyst loading. Toluene and THF were also tested at lower catalyst loadings (Table S3)

General Procedure for the Hydroboration of Aldehydes and Ketones
Pinacolborane (91 μL, 0.625 mmol) was added to a solution of anion 1 (1.24 mg, 0.0313 mmol) in toluene (20 μL) at room temperature resulting in a colour change from yellow to colourless. The substrate (0.625 mmol) was added and the reaction stirred for one hour at room temperature. After one hour a solution of trimethoxybenzene in CDCl3 was added to the reaction mixture to quench the reaction. Yields calculated against 1,3,5-trimethoxybenzene as an internal standard.

H NMR Data for Ketone and Aldehyde Hydroboration Products
For 2a, 2e, 2f and 2i analytical data were in accordance with the literature. [5][6][7]  For 2h and 2i analytical data were in accordance with the literature. [8,9]   2k The crude reaction mixture showed a complex mixture of products but a small amount of 2k was identified from characteristic resonances assigned below by comparison with product 2j. NMR data were in accordance with the literature. [10] 2l  12H). [10] The hydroboration of esters was unsuccessful using our procedure.

Stoichiometric Reaction of HBpin and Silyl Anion 1
In a typical reaction anion 1 (14 mg, 0.07 mmol) was dissolved inTHF-d8 or C6D6 (0.6 mL). Pinacolborane (9 μL, 0.07 mmol) was added at room temperature which resulted in the formation of a gel like solid.
In both solvents the 1 H NMR gave broad, intractable signals. In C6D6, a single 11 B resonance was observed which is assigned to silyl boronic ester 3 in accordance with the literature. [11] 6 Attempted Hydroboration of Alkynes Test reactions were carried out in order to determine the activity of silyl anion 1 in the hydroboration of alkynes.
As expected, the hydroboration of phenylacetylene did not occur at room temperature in the presence of 1. However, when the reaction mixture was heated to 60 °C for two hours with 10 mol% catalyst loading, trace yields of the vinyl boronic ester were observed. Heating the reaction mixture to 110 °C gave 74% yield in two hours (entry 4), comparable activity to that reported for aluminum hydrides. [12][13][14] Entry Catalyst Loading (mol%) Initially the silyl anion catalyzed hydroboration of alkynes was tested with a small number of substrates (Scheme S1). The highest yield was found for phenylacetylene but all four substrates showed some conversion. Terminal alkynes were 100% selective for the linear product.
Scheme S1 -Substrates in the silyl anion catalyzed hydrboration of actylenes. The results for the hydroboration using 1 as a catalyst were largely unreliable, with yields varying from 20% to 80% under the same conditions for the same substrate. Furthermore, BH3 was observed in the stoichiometric reaction between HBpin and 1 when it was carried out in THF, as mentioned in the main text. This is likely exacerbated by the high reaction temperatures and long reaction times.
The catalyst free hydroboration of alkynes by HBpin was reported with the initial publication of the preparation of HBpin, [15] presumably due to contamination by the BH3 which was used to synthesize the HBpin. Recently the BH3 catalyzed hydroboration of alkynes has also been reported by some of us. [16] Given the unreliable results and the likelihood that the catalysis is performed by BH3, the hydroboration of alkynes was not further pursued.