Catalytic Reduction of Imines with Silylformates: Formation of Silyl Carbamates through CO₂ Insertion

Abstract

Silylformates are emerging surrogates of hydrosilanes, able to reduce carbonyl groups in transfer hydrosilylation reactions, with the concomitant release of CO₂. In this work, a new reactivity is revealed for silylformates, in the presence of imines. Using ruthenium catalysts, and lithium iodide as a co‐catalyst, imines are shown to undergo hydrocarboxysilylation by formal insertion of CO₂ to the N−Si bond of silyl amine to yield silyl carbamates in excellent yields.

A new reactivity of silylformates, an emerging class of surrogates of hydrosilanes, is revealed in the presence of imines. Using ruthenium catalysts, and lithium iodide as a co‐catalyst, imines are shown to undergo hydrocarboxysilylation by formal insertion of CO₂ to the N−Si bond of an intermediate silyl amine to yield silyl carbamates in excellent yields.

Introduction

Mimicking hydrosilylation with surrogates of hydrosilanes is an emerging strategy known as ‘transfer hydrosilylation’. It is a powerful approach to reduce unsaturated substrates without resorting to hydrosilanes, whenever these reductants might be problematic. For instance, silylated cyclohexa‐1,4‐dienes were utilized, independently by Studer[ ¹ , ² ] and Oestreich,[ ³ , ⁴ ] to promote transfer hydrosilylation reactions while circumventing the limitations of the light gaseous and pyrophoric hydrosilanes (e. g., SiH₄, SiMe₃H) (Scheme 1A). More recently, our group introduced the use of silylformates in transfer hydrosilylation chemistry. ^[5] This new class of surrogates, of formula R₃SiOCHO, improves the energy efficiency of hydrosilylation by exploiting the mild reducing power of formic acid compared to true hydrosilane. ^[5] In addition, they generate gaseous CO₂ as the only by‐product.

Scheme 1.

A) Hydrosilane surrogates. B) Application of silyl formates as hydrosilane surrogates.

Silylformates have been successfully employed in transfer hydrosilylation of aldehydes, ^[5] ketones ^[6] and alcohols, ^[7] as well as in the disproportionation of formates ^[8] (Scheme 1B). They are stable species and they require the use of tailored catalysts to exploit their hydrosilylation capacities. Notably, their reactivity differs significantly from that of silylated cyclohexa‐1,4‐dienes, as silylformates cannot produce genuine hydrosilanes intermediates under thermocatalytic activation.

Imines are less reactive than aldehydes and ketones in reduction chemistry, particularly in hydrosilylation, because the C=N center is less electrophilic. ^[9] Additionally, while the formation of a strong Si–O bond drives the (transfer) hydrosilylation of carbonyl groups, the Si–N bond is significantly weaker. Hydrosilylation of imines to silylamines has been previously reported with various transition‐metal‐catalyzed systems.[ ¹⁰ , ¹¹ ] Inspired by these studies, we explored the use of silylformates combined with a suitable catalyst to promote the transfer hydrosilylation of imines. Our results demonstrate that the weak Si–N bond strength, together with the high nucleophilicity of intermediate amine groups, leads to a novel reactivity for silylformates. Specifically, they can facilitate a new hydrocarboxysilylation reaction through the formal insertion of the C=N linkage into the C−H bond of silylformates, without loss of CO₂. This reactivity provides a novel route for the synthesis of silyl carbamates with a high atom economy.

Results and Discussion

The study was initiated by subjecting imine 1 a to a reaction with triethylsilyl formate 2 a in the presence of ruthenium pincer catalyst Ru‐1 in THF‐d8, reproducing the conditions employed for the transfer hydrosilylation of ketones. Under these conditions, after 19 h of heating at 100 °C, imine 1 a was recovered quantitatively, whereas silyl formate 2 a was completely consumed (Table 1, entry 1): it underwent a disproportionation reaction (reduction of one silyl formate molecule by another) to form the corresponding methoxysilane (MeOSiEt₃). When ruthenium triphosphine complex Ru‐2 was used as the catalyst, only 7 % of the silylcarabamate and 18 % of methoxysilane were observed (Table 1, entry 2). Notably, this disproportionation was not a competing reaction during the transfer hydrosilylation of aldehydes ^[5] or ketones. ^[6] The [(triphos)Ru(OAc)₂] Ru‐2 catalyst employed for the transfer hydrosilylation of aldehydes (Scheme 1B) was known to be inactive in disproportionating silyl formate, ^[8] while Ru‐1, effective in ketone hydrosilylation, catalyzes this process efficiently to generate methoxysilane. During the transfer hydrosilylation of ketones catalyzed by Ru‐1, disproportionation was not observed probably because ketones are more electrophilic ^[9] than silyl formates, which structure resembles that of an ester. In the case of the less electrophilic imines, Ru‐1 was not able to catalyze the transfer hydrosilylation of imines, and thus only disproportionation occurred. By switching the catalyst to Ru‐3 (ruthenium para‐cymene chloride dimer, Scheme 2), which is known to catalyze the dehydrogenation of formic acid ^[12] (a reaction in which the C−H bond of the formate is cleaved), the silyl formate disproportionation is prevented, and there is 37 % conversion of the imine (Table 1, entry 3). We however observed, most interestingly, that, the imine was not only converted to the expected silyl amine 3 aa in 17 % yield, but also to the silyl carbamate 4 aa in 11 % yield, where the CO₂ is also incorporated in the product. This was confirmed by performing the same reaction with ¹³C‐labeled silyl formate. The characteristic peak of the silyl carbamate (N– C O₂–Si) is observed at δ 155.28 ppm and 156 ppm in the ¹³C NMR (ESI, Figure S1). Assuming that the low conversion of imine is presumably due to the low catalytic activity owing to the difficulty in the cleavage of the strong Ru–Cl bond of Ru‐3, we envisioned that a monomeric version of the catalyst with a more labile acetate ligand would aid in enhancing the conversion of imine. However, in the presence of Ru‐4, the monomeric equivalent of Ru‐3, only 20 % of 2 a were converted, to both silyl amine 3 aa and silyl carbamate 4 aa with only 3 % of the silyl formate disproportionation.

Table 1.

Screening conditions for the hydrocarboxysilylation of imines.^(a)

Entry	Cat (x mol %)	LiI (y mol %)	T (°C)	Time (h)	Silyl formate (equiv.)	Imine conversion (%)(b)	MeOSiEt3 (%)(b)	Silyl amine (%)(b)	Silyl carbamate (%)(b)
1	Ru‐1 (2.5)	0	100	19	2	0	36c	0	0
2	Ru‐2 (2.5)	0	100	19	2	8	18	0	7
3	Ru‐3 (2.5)	0	100	19	2	37	<1	17	11
4	Ru‐4 (2.5)	0	100	19	2	20	3	7	13
5	Ru‐1 (2.5)	25	100	19	2	2	4	0	0
6	Ru‐2 (2.5)	25	100	19	2	13	20	0	8
7	Ru‐3 (2.5)	25	100	19	2	83	<1	0	83
8	Ru‐4 (2.5)	25	100	19	2	65	<1	10	55
9	Ru‐3 (2.5)	25	60	22	2	30	<1	0	30
10	Ru‐3 (2.5)	25	80	22	2	95	<1	0	95
11(d)	Ru‐3 (2.5)	25	120	22	2	51	<1	0	27
12(d)	Ru‐3 (2.5)	25	150	22	2	70	<1	0	27
13	Ru‐3 (0.5)	25	80	19	1.2	70	<1	0	67
14	Ru‐3 (1)	25	80	19	1.2	96	<1	0	95
15	Ru‐3 (0)	25	80	19	1.2	0	<1	0	0
16	Ru‐3 (1)	10	80	19	1.2	60	<1	0	60

General conditions: 1 a (13.3 mg, 0.1 mmol, 1.0 equiv.), 2 a (z equiv.), Ru‐complex (x mol %), lithium iodide (y mol %), mesitylene (5 μL), deuterated THF (0.5 mL), were added into a 2.5 mL J. Young NMR tube in a glovebox. The tube was sealed and heated at (T °C) for (19‐22 h); b) Yields are determined by ¹H NMR with mesitylene as the internal standard, and are reported with a possible error of 5 %; c) The maximum theoretical yield for the formation of methoxysilane via silyl formate disproportionation reaction is 33%, but the observation is still within the margin of error; d) Degradation was observed, indicated by the formation of a black precipitate.

Scheme 2.

Catalysts studied for the hydrocarboxysilylation of imines.

To explore whether the reactivity of silyl formate could be enhanced by activating the Si–O bond, lithium iodide (LiI) was introduced as a nucleophile to increase the concentration of formate in the reaction medium, as it had proven effective in promoting C−O bond cleavage in related alkyl formates. ^[13] Incorporating 25 mol% of LiI as a co‐catalyst into the reaction mixture significantly minimized the disproportionation of silyl formate in the presence of the catalyst Ru‐1; however, the conversion of the imine was only 2 % (Table 1, entry 5). Notably, when LiI was added to the Ru‐2 catalyzed system, no improvement in catalytic activity was observed (Table 1, entries 2 and 6). In contrast, using LiI as a co‐catalyst with Ru‐3 led to an unexpected outcome: no trace of the anticipated silyl amine 3 aa was detected. Instead, the imine 1 a was converted to a new product, silyl carbamate, in excellent yield of 83 % (Table 1, entry 7). Remarkably, the carbon dioxide (CO₂) generated during the transfer hydrosilylation of the imine to silyl amine was incorporated into the final product, a process that has never been observed in the analogous reactions of aldehydes or alcohols. When both Ru‐4 and LiI were employed, the imine conversion was lower (65 %) and resulted in the formation of both silyl amine 3 aa and silyl carbamate 4 aa, indicating incomplete product selectivity (Table 1, entry 8). Though the silyl amine 3 aa was the expected transfer hydrosilylation product, a complete selectivity towards 3 aa could not be achieved by any of the studied catalytic systems. Nevertheless, silyl carbamate 4 aa, a more interesting product, was selectively obtained employing Ru‐3 as catalyst and LiI as co‐catalyst (Table 1, entry 7), and hence, this catalytic system was chosen for further reaction optimizations. Silyl carbamates, in addition to being a protecting group for amines, have been used as intermediates in various organosilicon and organic syntheses. These compounds, in addition, can be in‐situ converted to organic carbamates on treatment with suitable electrophiles. ^[14]

With such a catalytic system in hand (Ru‐3 in conjunction with LiI), the effect of temperature was studied. Decreasing the heating to 60 °C, only 30 % of silyl carbamate 4 aa was obtained after 22 h (Table 1, entry 9). However, a significant increase in the yield up to 95 % was achieved when heating at 80 °C for 22 h (Table 1, entry 10). At higher temperatures of 120 °C and 150 °C, the yield of silyl carbamate 4 aa was drastically reduced to 27 % (Table 1, entries 11 and 12). At 80 °C, reducing catalyst loading of Ru‐3 to 1 mol% had no effect on the yield of 4 aa (see entries 10 and 14 in Table 1). However, further reducing the catalyst loading to 0.5 mol%, reduced the yield of 4 aa to 67 % (Table 1, entry 13), and there was no reaction in the absence of the catalyst (Table 1, entry 15). When the amount of LiI was reduced to 10 mol% (entry 16), the yield of the silyl carbamate was reduced to 60 %. Hence, the optimized reaction conditions were chosen to be at 80 °C for 19 h with a catalyst (Ru‐3) and co‐catalyst (LiI) loadings of 1 mol% and 25 mol% respectively (Table 1, entry 14).

The effect of solvents was investigated with the optimized conditions, remarkably, the reaction proceeded successfully only in THF, other solvents were found to be inefficient in this catalytic transformation (Table 3 S6 in SI).

With the optimized catalytic system, the influence of the silyl formate on the formation of silylcarbamates was studied, by the reaction between the imine 1 a and different silyl formates 2 a‐e, (Scheme 3). The reaction worked efficiently with triethyl‐ (Et₃SiOCHO), phenyl dimethyl‐ (PhMe₂SiOCHO), and diphenyl methyl (Ph₂MeSiOCHO) silyl formates (2 a‐c) with yields of 95 % of the corresponding silyl carbamates (4 aa, 4 ab and 4 ac). Especially, the excellent yield obtained in 4 ac indicated that the steric hindrance around the silicon core hardly affected the reactivity. However, the reaction with other bulky substituents like triisopropyl silyl formate 2 d afforded only 43 % of the corresponding silyl carbamate (4 ad), though the dimethyl tert‐butyl (4 ae) gave a decent yield of 70 %. The scope of silyl formates was also tested with ketimine 1 s (shown in Scheme 3), in which case, the phenyl dimethyl silyl formate (2 b) worked slightly better. Further experiments were thus performed using silyl formate 2 b.

Scheme 3.

Scope of silyl formates in the hydrocarboxysilylation of imines. 0.1 mmol scale. Yields are determined by ¹H NMR with mesitylene as the internal standard.

The optimized reaction conditions for the catalytic conversion of imines to silyl carbamates are shown in Scheme 4, together with the scope of silyl carbamates that were obtained from different aldimines and ketimines. First, a number of aryl N‐ethyl aldimines were converted to their respective silyl carbamates (4 ab‐4 kb), in very good to excellent yields (89 to 98 %), after heating at 80 °C for 19 h. Electron‐donating and withdrawing substituents on the aryl group had little influence, with the exceptions of para‐nitro (4 ib) and para‐cyano (4 jb) derivatives, for which a prolonged heating (40 h) was necessary to reach yields of 97 % and 59 % respectively, while notably remaining intact after the reaction. Interestingly, the reaction showed compatibility with various groups known to be easily reduced, such as nitro 4 ib, cyano 4 jb, (amido group 4 hb was not even silylated), and halides (4 eb‐4 gb). To further evaluate the functional group tolerance, the reaction was performed in the presence of different functional group‐containing additives, including iodobenzene, benzamide, methyl benzoate, benzoic acid, and 4‐octyne. Using imine 1 b in the presence of silyl carbamate 2 b, the reaction proceeded efficiently when iodobenzene, benzamide, methyl benzoate, and 4‐octyne were used as additives, yielding the silyl carbamate product 4 bb in 97 %, 86 %, 96 %, and 88 %, respectively, vs. 98 % without additives. However, in the presence of benzoic acid as an additive, the imine was converted into a mixture of silyl amine (43 %) and silyl carbamate (48 %). (shown in Table 7, S10 in SI).To check the effect of steric hindrance on the reaction, an ortho‐substituted electron‐donating imine 1 k was chosen to carry out the reaction: it was interesting to find that the more crowded ortho‐substituted silyl carbamate 4 kb was obtained in excellent yield (97 %) after 19 h.

Scheme 4.

Scope of aldimines and ketimines in the hydrocarboxysilylation reaction employing silyl formates.^[a] Reaction conditions: In a J. Young NMR tube, imine 1 a‐t (0.1 mmol), silyl formate 2 b (0.12 mmol) mesitylene (Internal standard, 5 μL) were added to a solution of Ru‐3 (1 mol%) and LiI (25 mol%) in deuterated THF (0.5 mL). The tube was sealed, brought out of the glove box and the solution heated for 19 h. The reaction progress was monitored by ¹H NMR spectroscopy. Yields were determined by ¹H NMR integration versus mesitylene as an internal standard.^[b] 40 h reaction time^[c] 21 % of silylamine 3 ob were formed.^[d] 2 equiv. of 2 b ^[e] 2 mmol scale^[f] reaction performed under 1 atm of CO₂.

The influence of substitution at the N‐atom of the imine was then studied, employing various N‐alkyl substituted aldimines. Replacing N–Et aldimine by N–Me group had no major effect and 4 lb was obtained in 91 % yield. N–allyl and N–isopropyl bulky substitutions of the aldimines (1 m and 1 n) could still be converted to the respective carbamates 4 mb and 4 nb, albeit in lower yields (70 and 69 %, respectively). The N‐cyclohexyl imine 1 o, under the optimized reaction conditions, was not converted to silyl carbamate 4 ob but to the corresponding silyl amine in 21 % yield. Further heating of the reaction at 120 °C for 17 h increased the conversion of imine to 80 %, but only 55 % silyl amine was obtained. It is likely that the steric hindrance due to the presence of cyclohexyl ring on the N‐atom prevented the insertion of CO₂ into the N−Si bond (to form a silyl carbamate) of the silyl amine formed. Similarly, the boc‐protected aldimine 4 p failed to undergo hydrocarboxysilylation. In the presence of 1.2 equiv. of silyl formate 2 b, the boc‐protected aldimine 4 p, interestingly, underwent N‐formylation reaction to obtain 52 % of 4 pb. With the addition of excess 2 b (2 equiv.), 4 p was formylated in 79 % yield.

The reaction was also tested with different ketimines. The N–Me ketimine of acetophenone (1 q) reacted with silyl formate 2 b to obtain the silyl carbamate 4 qb in 91 % yield. However, the yield was lower (60 %) for the N–Et derivative (4 rb). A ketimine bearing an electron‐withdrawing substituent (para‐nitro) was tested and silyl carbamate 4 sb was obtained in 73 % yield, although it required prolonged heating (40 h). The oxidising nitro functionality was unaffected. However, the presence of significant steric bulk prevented reactivity: the reaction of N‐benzyl‐1,1‐diphenylmethanimine 1 t with 2 b yielded only 13 % of the corresponding silyl carbamate (4 tb).

To evaluate the influence of CO₂ concentration on the formation of silyl carbamate from imine, the hydrocarboxysilylation reactions of some low‐yielding substrates were conducted under a CO₂ atmosphere. Notably, the reaction with N‐cyclohexyl imine (1 o) afforded the silyl carbamate 4 ob in an excellent 95 % yield after heating at 80 °C for 19 h under CO₂, whereas no silyl carbamate was formed in its absence. Similarly, the cyano‐substituted imine (1 j) delivered the silyl carbamate 4 jb in 98 % yield when CO₂ was present. In contrast, adding an atmosphere of CO₂ to the reaction of N‐benzyl imine of benzophenone (1 t) failed to improve the yield of silyl carbamate, and only 8 % of 4 tb was obtained, under identical conditions, highlighting substrate‐specific limitations of the method (results shown in Table 6, S9 in SI).

To probe their usability in further studies, the stability of silyl carbamates was investigated in terms of both air exposure and thermal conditions. When silyl carbamate 4 aa was exposed to air for 3 days, only 36 % of it underwent decomposition to form the corresponding amine. Subjecting silyl carbamate 4 aa to a temperature of 150 °C for 22 hours resulted in the decomposition of 68 % of the starting material, to yield the corresponding silyl amine 3 aa. All the silyl carbamates prepared are novel; however, their moderate stability prevented us from fully isolating each compound. Nevertheless, some silyl carbamates have been stable enough to be reported in the literature. ^[15] As a proof of concept, the stable silyl carbamate (4 ld) prepared from N‐methyl aldimine 1 l and triisopropylsilyl formate 2 d was prepared on a larger scale (from 239 mg, 2 mmol of 1 l) and isolated by column chromatography in 89 % yield. The ¹H and ¹³C NMR peaks (shown in SI) were consistent with the literature data. ^[15]

Finally, some investigations on the catalytic systems were made to understand the catalytic/mechanistic roles of each reaction partner. First, we evaluated the importance of the presence of the co‐catalyst LiI on the reactivity. Several salts were tested instead of LiI (Table 2): when NaI is used, almost all the catalytic activity is lost (entry 2). However, switching the iodide for other halides such as Cl and Br, most of the activity was retrained: 84 % and 77 % of silyl carbamate 4 aa were obtained, with good selectivity, to compare to 95 % with LiI in the same reaction conditions (entries 3 and 4). This suggests that the lithium ion is necessary for the formation of silyl carbamate, but that the halide may be replaced. This is in contrast to the previous system described for the transfer hydroalkylation of imines using alkyl formates, in which case both lithium and iodide ions play a crucial role and are necessary. ^[13]

Table 2.

Control experiments for co‐catalysts.

Entry	Co‐catalyst (25 mol%)	Imine conversion (%)a	Yield of 4aa (%)a
1	LiI	96	95
2	NaI	7	0
3	LiCl	91	84
4	LiBr	80	77

a) Yields are determined by ¹H NMR with mesitylene as the internal standard.

The formation of silyl carbamate by the reaction between imine and silyl formate can be formally called as a hydrocarboxysilylation reaction and not a transfer hydrosilylation reaction. This is, to the best of our knowledge, the first time where a CO₂ insertion happens during the employment of silyl formate as a transfer reagent. Silyl carbamates can be prepared by a simple heating of silyl amine in the presence of supercritical CO₂. ^[15] The transition metal catalyzed reaction of secondary amines with hydrosilanes in the presence of CO₂ is also known to produce silyl carbamates. ^[16]

Next, we wished to determine whether the silyl carbamate is formed directly or is the result of the insertion of the in‐situ formed gaseous CO₂ to the N−Si bond of silyl amine. We carried out the transfer hydrosilylation of imine 1 q in the presence of Ru‐3 and LiI as co‐catalyst under static vacuum employing silyl formate 2 a (Scheme 5). After 17 h of heating at 80 °C under static vacuum, a mixture of silyl amine 3 qa and silyl carbamate 4 qa was obtained, in 59 and 39 % yield. Putting the reaction mixture under an atmosphere of CO₂ at room temperature resulted in the immediate conversion of some silyl amine to silyl carbamate, yielding 85 % of the latter. Heating the same reaction mixture at 80 °C for 1 h resulted in the full conversion of silyl amine 3 qa to yield exclusively silyl carbamate 4 qa (95 % yield). From this experiment, we suppose that the mechanism starts with a hydrosilylation of the imine, which is then converted to the corresponding silyl carbamate through the exothermic insertion of CO₂ into the N−Si bond. ^[17]

Scheme 5.

Mechanism of CO₂ insertion: experiments under static vacuum and with CO₂

From these observations and the previously reported mechanisms for transfer hydrosilylation^,[5][6] and transfer hydroalkylation ^[13] reactions, we propose a mechanism for the hydrocarboxysilylation (Scheme 6). First, silyl formate 2 (HCOOSiR₃) is preactivated by LiI (co‐catalyst) to generate a stronger electrophile (SiR₃I) and lithium formate (HCOOLi) (See ESI for details). Lithium formate reacts with the pre‐catalyst ([Ru]–Cl) to form ruthenium complex A, which is the active catalyst. The formate ligand on A is able to undergo decarboxylation via a beta‐elimination, thus forming the hydride complex B and CO₂. The presence of ruthenium hydride species B was confirmed by ¹H NMR analysis (A hydride peak was observed at –13.2 ppm during catalysis after heating the reaction mixture at 80 °C). Hydride complex B is a potent reductant, able to reduce the incoming imine 1 to form amido complex C. The latter can react with R₃SiI to form silyl amine 3 (not observed in ¹H NMR) and ruthenium iodide complex D. CO₂, generated by the formate decarboxylation, can insert into the N−Si bond of the silyl amine to obtain the desired silyl carbamate 4. Further transmetallation between ruthenium iodide D and HCOOLi regenerates the active catalyst A and co‐catalyst (LiI), thereby completing the catalytic cycle.

Scheme 6.

Proposed mechanism for the hydrocarboxysilylation of imines to silyl carbamates.

Conclusions

In this work, the applicability of silyl formates in the transfer hydrosilylation of imines is studied. In the presence of [Ru(p‐cymene)Cl₂]₂ and lithium iodide as co‐catalyst, imines can react with silyl formates to form silyl carbamates, the hydrocarboxysilylated product. Both electron donating and electron withdrawing imines were hydrocarboxysilylated to their corresponding silyl carbamates in excellent yields.

Conflict of Interests

The authors declare no conflict of interest.

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Supporting Information

Thyagarajan N., Buhaibeh R., Nicolas E., Cantat T., Chem. Eur. J. 2025, 31, e202403907. 10.1002/chem.202403907

Data Availability Statement

The data that support the findings of this study are available in the supplementary material of this article.