Hydrosilation of Carbonyl-Containing Substrates Catalyzed by an Electrophilic η¹-Silane Iridium(III) Complex

Abstract

Hydrosilation of a variety of ketones and aldehydes using the cationic iridium catalyst, (POCOP)Ir(H)(acetone)⁺, 1, (POCOP = 2,6-bis(di-tert-butyl phosphinito)phenyl) is reported. With triethyl silane, all but exceptionally bulky ketones undergo quantitative reactions employing 0.5 mol% catalyst in 20-30 min at 25 °C. Hydrosilation of esters and amides results in over-reduction and cleavage of C-O and C-N bonds, respectively. The diastereoselectivity of hydrosilation of 4-tert-butyl cyclohexanone has been examined using numerous silanes and is highly temperature dependent. Using EtMe₂SiH, analysis of the ratio of cis:trans hydrosilation products as a function of temperature yields values for ΔΔH^‡ (ΔH^‡ (trans) - ΔH^‡ (cis)) and ΔΔS^‡ (ΔS^‡ (trans) - ΔS^‡(cis)) of -2.5 kcal/mol and -6.9 e.u., respectively. Mechanistic studies show that the ketone complex, (POCOP)Ir(H)(ketone)⁺, is the catalyst resting state and is in equilibrium with low concentration of the silane complex, (POCOP)Ir(H)(HSiR₃)⁺. The silane complex transfers R₃Si⁺ to ketone forming the oxocarbenium ion, R₃SiOCR’₂⁺, which is reduced by the resulting neutral dihydride 3, (POCOP)Ir(H)₂, to yield product R₃SiOCHR’₂ and (POCOP)IrH⁺ which closes the catalytic cycle.

Introduction

Hydrosilation of carbonyl functionalities is an extensively explored and widely used synthetic methodology.¹ This process provides an alternative to hydride reductions of ketones and aldehydes as well as a convenient one-step process for converting these substrates directly to protected alcohols which circumvents the normal two step procedure, reduction to alcohol followed by silyl protection. Several different hydrosilation mechanisms have been shown to operate, dependent on the nature of the catalyst. Late metal catalysts typically proceed through a “Chalk-Harrod” pathway in which the key step involves oxidative addition of the silane to a low valent metal center.² Early metal catalysts where oxidative addition is disfavored, proceed via sigma bond metathesis mechanisms.³

Recently, high valent metal oxo complexes have been shown to serve as hydrosilation catalysts. Abu-Omar reported that the Re(O)(hoz)₂⁺ (hoz = 2-(2’-hydroxyphenyl)-2-oxazoline) catalyst operates via a sigma bond metathesis mechanism.^3m-o Through extensive mechanistic studies Toste and Bergman established that hydrosilations catalyzed by (PPh₃)₂Re(O)₂I occur by a unique mechanism which involves addition of the silane across the Re=O bond, insertion of the carbonyl functionality into the resulting Re-H bond and elimination of the hydrosilation product which closes the cycle and regenerates the Re=O bond.3g-j Piers has reported that Ph₃SiH in combination with catalytic amounts of (C₆F₅)₃B achieves hydrosilation of carbonyl compounds.^3b,4a-b Surprisingly, although the carbonyl compounds exhibit much higher binding affinities to (C₆F₅)₃B than Ph₃SiH, the mechanism involves activation of the silane through coordination to (C₆F₅)₃B, transfer of Ph₃Si⁺ to the carbonyl functionality, and reduction of the resulting Ph₃SiOC(R)(R’)⁺ by (C₆F₅)₃BH^- (Scheme 1).

Scheme 1.

We have recently reported reduction of R-X bonds (-X = -Cl, –Br, -I, -OR) using the silane complex 2, a potent R₃Si⁺ donor.⁵ The mechanism was shown to involve transfer of R₃Si⁺ to X to generate R₃Si-X-R⁺ followed by hydride reduction of this species by the iridium dihydride complex, 3 formed upon silyl transfer (See Scheme 2).

Scheme 2.

The most convenient precatalyst was found to be the stable, crystalline, easily isolated acetone complex, 1. Treatment with excess triethylsilane rapidly generates silane complex 2 in situ and one equivalent of Et₃SiOCH(CH₃)₂, the acetone hydrosilation product (eq. 1). These observations suggested

(1)

that 2 should function as a hydrosilation catalyst. We report here synthetic and mechanistic details of the catalytic hydrosilation of a variety of carbonyl-containing compounds employing this system which proves to be exceptionally active and highly efficient.

Results and Discussion

Hydrosilation of Carbonyl-Containing Substrates Catalyzed by 1

Complex 1^5a together with Et₃SiH initiates hydrosilations of ketones, aldehydes, esters, and amides at room temperature. Results of hydrosilation of several carbonyl-containing substrates are summarized in Table 1. Ketones undergo hydrosilation rapidly to attain quantitative conversions in 0.3- 0.5 h at room temperature (200 TOs) (Table 1, entries 1-6). Hydrosilations of ketones bearing exceptionally bulky alkyl substituents, diisopropyl ketone (entry 2) and methyl tert-butyl ketone (entry 3) are rapidly and quantitatively achieved. The exceptional efficiency of the hydrosilation is illustrated by the quantitative hydrosilation of methyl tert-butyl ketone in 30 min using a 0.075 mol% catalyst loading (1330 TOs, entry 4). Hydrosilation of acetophenone yields 94% of the corresponding silyl alkyl ether and 6% of ethylbenzene, which results from further cleavage of the silyl alkyl ether (entry 5). The competitive hydrosilation reaction between acetophenone and 4’-(trifluoromethyl)acetophenone (entry 6) shows that the activity of the more basic acetophenone is ca. 4 times greater than that of 4’-(trifluoromethyl)acetophenone. Hydrosilation of aldehydes with excess silane often results in secondary cleavage of the resultant silyl alkyl ether.^5b However, using just over 1 equiv. of Et₃SiH, benzaldehyde undergoes quantitative hydrosilation in 0.3 h to yield the silyl benzyl ether (entry 7).

Table 1.

Hydrosilation of carbonyl functions by 1^a

Complex 1 catalyzes the hydrosilation of ethyl acetate to afford silyl ethyl ether and diethyl ether in 2:1 ratio (entry 8). This results from formation of the acetal and subsequent cleavage of either of the CO bonds as shown in eq. 2 below.

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In contrast, the hydrosilation of methyl isobutyrate exhibits only cleavage of the C-OMe bond of the acetal to give only isobutyl silyl ether and methyl silyl ether (entry 9). This selectivity can be attributed to a sterically demanding environment around oxygen in the C--OSiEt₃ bond. Introduction of an electron-withdrawing group into the α-position of the ester enables a single hydrosilation even with excess Et₃SiH to selectively form the corresponding acetal (entry 10). The preference for single hydrosilation is likely due to the decreased basicity of the acetal formed via initial hydrosilation and the decreased tendency for ionization of the silated acetal.

N,N-Diethyl acetamide is slowly hydrosilated (42% conversion in 16 h) to give Et₃N together with the disiloxane (entry 11). After 16 h, no further consumption of the amide is observed. The retarded hydrosilation may result from the deactivation of the electrophilic catalytic Ir species by excess Et₃N formed during reaction. The sequence responsible for product formation is shown below (eq. 3) and is similar to that proposed for ester reduction.

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Stereochemistry of Hydrosilation of 4-tert-Butyl Cyclohexanone

Reductions of 4-tert-butyl cyclohexanone by various metal hydrides, especially LiAlH₄ and NaBH₄, have been extensively studied⁶ and found to preferentially give the trans-alcohol via an axial attack of the hydride (eq. 4, path a). Several explanations have been advanced for this diastereoselectivity including the straightforward proposition that there are unfavorable eclipsing interactions between the axial C-H bonds at C2 and C6 and the incoming hydride reagent during equatorial attack (eq. 4, path b).⁷

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The diastereoselectivity of hydrosilations of cyclohexanones has also received attention. Semmelhack has examined the hydrosilation of 4-tert-butyl cyclohexanone by various di- and trialkylsilanes using classical catalysts (PPh₃)₃RhCl(I) and (PPh₃)₃RuCl₂(II) which operate by the Chalk-Harrod mechanism.^2e Bulky triethyl- and triphenyl silanes provide predominantly the more stable trans silyl ether with up to 95% diastereoselectivity, whereas the less bulky diethyl- and diphenyl silanes give the corresponding silyl ethers with a trans/cis ratio of ca. 50:50. On the other hand, hydrosilation by diphenyl silane using (PPh₃)₄RhH(I) has been reported to give a 84:16 (trans:cis) ratio of diasteromers.^2j A triruthenium carbonyl cluster-catalyzed hydrosilation of 4-tert-butyl cyclohexanone affords predominantly the cis-diastereomer with triethyl silane,^2l which contrasts with the results of the hydrosilation by the mononuclear Rh or Ru complexes. Most recently, Toste, et. al., have obtained silyl ethers with a high trans selectivity (>96%) using the dioxorhenium(V) catalyst (PPh₃)₂Re(O)₂I which operates by the non-Chalk-Harrod mechanism described above.^3j These studies prompted us to examine the diastereoselectivities of hydrosilation of 4-tert-butyl cyclohexanone using catalyst 1 where product ratios depend on axial vs. equatorial attack of iridium dihydride 3 on the silated ketone (see below).

Results of the hydrosilation of 4-tert-butyl cyclohexanone using various silanes and different solvents are shown in Table 2. In chlorobenzene, there is little difference in diastereoselectivity as the bulk of the silane ranges from dimethyl ethyl silane (trans/cis = 69:31) to methyl diethyl silane (74:26) to triethyl silane (68:32) to dimethyl i-propyl silane (76:24). Dimethyl tert-butyl silane and triisopropyl silane are sufficiently unreactive that the reactions must be carried out at 80 °C; however, quantitative conversions can be obtained and result in 87:13 and 51:49 trans/cis product ratios, respectively. In the case of di-tert-butyl silane, selectivity drops to 57:43, but the hydrosilation products are accompanied by a side reaction to form 39% of the silyl enol ether. (Semmelhack et. al., observed the same side product in the hydrosilation using (EtO)₃SiH.^2e)

Table 2.

Hydrosilation of 4-tert-butyl cyclohexanone with various alkylsilanes catalyzed by 1^a

	catalyst			T	t	conversionb	trans/cisb
entry	mol%	silane	solvent	°C	h	%	%
1	1.0	EtMe2SiH	CD2Cl2	22	0.3	quant.	55 : 45
2	1.0	EtMe2SiH	C6D5Cl	22	0.3	quant.	69 : 31
3	1.0	EtMe2SiH	toluene-d6	22	0.3	quant.	75 : 25c
4	1.0	Et2MeSiH	C6D5Cl	22	0.3	quant.	74 : 26
5	1.0	Et3SiH	C6D5Cl	22	0.3	quant.	68 : 32
6	1.0	i-PrMe2SiH	C6D5Cl	22	0.3	quant.	76 : 24
7	1.0	t-BuMe2SiH	C6D5Cl	80	2	quant.	87 : 13
8	1.0	(i-Pr)3SiH	C6D5Cl	80	12	quant.	51 : 49
9	1.0	(t-Bu)2SiH2	C6D5Cl	22	1.5	quant.	57 : 43e
10	1.39	EtMe2SiH	CD2Cl2	-20	0.5	quant.	82 : 18f
11	1.39	Et3SiH	CD2Cl2	-20	0.5	quant.	88 : 12f

^aReaction conditions: 3 equiv. of silane in C₆D₅Cl (0.3 ml).

^bDetermined by NMR spectroscopy.

^c1 is not completely soluble in toluene-d₈.

^e39% of di-tert-butyl silyl enol ether is observed.

^f4 equiv. of silane used.

Solvent effects on diastereoselectivity are also minimal. Hydrosilation with dimethyl ethyl silane in methylene chloride, chlorobenzene and toluene varies from trans/cis = 55:45 to 69:31 to 75:25, respectively. The most dramatic effect on selectivity is seen with variation in reaction temperature. Using dimethyl ethyl silane in methylene chloride, the selectivity increases from 55:45 at 22 °C to 82:18 at -20 °C, while for triethyl silane the selectivity is 68:22 at 22 °C in chlorobenzene and increases to 88:12 at -20 °C in methylene chloride. Temperature effects are examined in more detail in the next section.

Hydrosilation of 4-tert-Butyl Cyclohexanone: Effect of Reaction Temperature on Diastereoselectivity

Although appreciable efforts have been dedicated to the elucidation of factors affecting the diastereoselectivity of metal hydride reductions of 4-tert-butyl cyclohexanone, there have been limited studies of temperature effects on selectivity.⁸ Thus, we have examined the diastereoselectivity of hydrosilation of 4-tert-butyl cyclohexanone with dimethyl ethyl silane over a wide range of temperatures. These data provide information concerning differences of enthalpies and entropies of activation for the two pathways. The trans/cis product ratio for the hydrosilation of 4-tert-butyl cyclohexanone in CD₂Cl₂ at various reaction temperatures is shown in Table 3. A plot of ln[cis]/[trans] versus 1/T made using the data in Table 3 provides a good linear regression with R² = 0.993 as shown in Figure 1. By using the relationship shown in eq. 5 (derived from the Erying equation), ΔΔH^‡ (ΔH^‡ (trans) - ΔH^‡ (cis)) and ΔΔS^‡ (ΔS^‡ (trans) - ΔS^‡(cis)) were calculated to be -2.5 kcal/mol and -6.9 e.u., respectively.

$$\mathbf{ln}\frac{\left[\mathbf{cis}\right]}{\left[\mathbf{trans}\right]}=\frac{\Delta {\mathbf{H}}^{‡}\left(\mathbf{trans}\right)-\Delta {\mathbf{H}}^{‡}\left(\mathbf{cis}\right)}{\mathbf{RT}}+\frac{\Delta {\mathbf{S}}^{‡}\left(\mathbf{cis}\right)-\Delta {\mathbf{S}}^{‡}\left(\mathbf{trans}\right)}{\mathbf{R}}$$ (5)

Table 3.

Hydrosilation of 4-tert-butyl cyclohexanone with EtMe₂SiH at various reaction temperatures^a

	T	t	conversionb	trans/cis ratiob
entry	°C	h	%	%
1	-60	17	quant.	92 : 8
2	-30	3	quant.	86 : 14
3	0	1	quant.	77 : 23
4	17	3	quant.	70 : 30

^aReaction conditions; 4 equiv. of EtMe₂SiH, 1.39 mol% of 1 in CD₂Cl₂ (1 ml).

^bDetermined by ¹H NMR spectroscopy.

Figure 1.

Plot of ln[cis]/[trans] vs. 1/T using the data from Table 3.

The stereo-determining step is attack of 3 on the silated ketone (eq. 6, see below for mechanistic considerations) and thus axial attack is strongly favored enthalpically over equatorial attack but strongly disfavored entropically. Since this is a bimolecular reaction, both activation entropies are no doubt negative, so axial attack must exhibit a more negative entropy of activation relative to equatorial attack. The reasons for these significant differences are not clear.

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It is noteworthy that the iridium-catalyzed hydrosilation of 4-tert-butyl cyclohexanone has considerably larger differences in the activation parameters relative to reductions by LiAlH₄ and NaBH₄ (For LiAlH₄, ΔΔH^‡ = -0.8 kcal/mol and ΔΔS^‡ = 2.0 e.u.).^8d In these cases the temperature dependence of the product ratio is small and ΔΔS^‡ is small and positive in contrast to a large negative value for the hydrosilation.

Hydrosilation of Alkyl-Substituted Cyclohexanone Derivatives Catalyzed by 1

We have examined the hydrosilations of other alkyl-substituted cyclohexanone derivatives to probe the diastereoselectivities in these cases. Results of hydrosilation of 3,3,5-trimethyl cyclohexanone, 2-methyl cyclohexanone, 2-tert-butyl cyclohexanone, and camphor with dimethyl ethyl silane are summarized in Table 4.

Table 4.

Hydrosilations of alkyl-substituted cyclohexanone derivatives catalyzed by 1^a

			T	t	conversionb	trans/cis ratiob
entry	ketone	silane	°C	h	%	%
1	3,3,5-trimethylcyclohexanone	EtMe2SiH	22	0.3	quant.	86 : 14
2	2-methylcyclohexanone	EtMe2SiH	22	0.5	quant.	29 : 71
3	2-tert-butylcyclohexanone	EtMe2SiH	22	0.5	quant.	24 : 76
4	camphor	EtMe2SiH	0	2	quant.	21 : 79c

^aReaction conditions; 0.5 mol% of 1 and 3 equiv. of silane in C₆D₅Cl.

^bDetermined by NMR spectroscopy.

^cexo/endo ratio.

3,3,5-Trimethyl cyclohexanone undergoes quantitative hydrosilation with dimethyl ethyl silane in 0.3 h to give the silyl alkyl ether with 86% of trans diastereoselectivity (entry 1). The preference for trans stereochemistry can be attributed to blocking of the axial approach of the bulky iridium dihydride by the axial methyl group at C3. (Trans selectivity ranging from 52% to 83% is seen in hydride reductions of 3,3,5-trimethyl cyclohexanone).6h,i,n,p 2-Alkylcyclohexanone derivatives possessing large equatorial alkyl substituents are reported to inhibit axial attack of metal hydrides.6a,e,l,m For example, reduction of 2-methyl cyclohexanone by LiAlH₄ affords alcohols with a trans : cis selectivity of ca. 73:27. However, when the steric bulk of the C2 substituent is increased to tert-butyl, axial approach is somewhat inhibited to yield product alcohols with slight cis selectivity (50%-64%). The hydrosilation of 2-methyl cyclohexanone by 1 at 22 °C proceeds rapidly to give the silyl alkyl ether with 71% of cis selectivity (entry 2). The use of 2-tert-butyl cyclohexanone in the hydrosilation leads to a slight increase in the cis selectivity to 76% (entry 3). The steric impact of 2-substituents is significantly greater in these cases compared to the metal reductions. The hydrosilation of camphor at 0 °C yields the exo and endo isomers in 21:79 ratio, respectively (entry 4). In the (Ph₃P)₄RhH-catalyzed hydrosilation of camphor with diphenyl silane the opposite selectivity is observed with an exo:endo product ratio of 64:36 reported.^2j

Mechanistic Investigation of the Hydrosilation of Ketones

Based on earlier mechanistic investigations of silane reductions of alkyl halides and alkyl ethers using iridium complex 1, our working hypothesis concerning the catalytic mechanism of hydrosilation of ketones is shown in Scheme 3 and illustrated with acetone. Binding triethyl silane to the electrophilic iridium center in 2 renders this complex a potent Et₃Si⁺ donor which can transfer Et₃Si⁺ to acetone forming the oxocarbenium ion, 4, and iridium dihydride, 3. The dihydride, earlier established as a good hydride donor,^5b reacts with 4 to produce hydrosilated product, 5, and the cationic hydride, 6, which then reenters the catalytic cycle.

Scheme 3.

Proposed catalytic cycle for the iridium-catalyzed hydrosilation of acetone with triethyl silane

Low temperature reactions were carried out to probe the details of this cycle. ¹³C labeled acetone, (CH₃) ¹³₂CO) was employed to allow monitoring by ¹³C as well as ¹H and ³¹P NMR spectroscopy. Initially, the equilibrium between 1 and 2 was probed, as shown in Scheme 4. Reaction of 1 (containing unlabeled bound acetone) with triethyl silane (4 equiv.) in CD₂Cl₂ at 25 °C rapidly produced 1 equiv. of Et₃SiOCHMe₂ (¹H NMR) and silane complex 2 (21%), CD₂Cl₂ complex, 6 (48%), and cationic trihydride, 7 (31%) (Scheme 4A). The complexes were identified by ³¹P NMR shifts. The trihydride results from reaction of 2 with traces of water.⁹ This solution was cooled to -70 °C and (CH₃)₂*CO (2 equiv) was added. Acetone immediately displaces silane from 2 and CD₂Cl₂ from 6 to give a solution containing acetone complex 1* (ca. 64%) and trihydride 7 (ca. 34%) and traces of solvent complex, 6 (Scheme 4B). ¹H NMR spectroscopy was used to determine the ratio of free acetone (δ2.13, doublet, J_13C-H = 5 Hz) to bound acetone (δ2.57, doublet, J_13C-H = 5 Hz) as 64 : 36. No silane complex can be easily detected (< 0.5%) and no hydrosilation product is formed. The hydrosilation product of (CH₃)₂*CO, Et₃SiO*CHMe₂ can be distinguished from Et₃SiOCHMe₂ since the CH resonance at δ3.99 is split into a doublet with J_13C-H = 138.5 Hz. These results imply that the equilibrium between 1 and 2, not surprisingly, lies strongly to the left and that equilibrium is established rapidly relative to product formation.

Scheme 4.

To quantitatively assess K_eq, 16 equiv. of Et₃SiH were added to this solution (Scheme 4C). Even under these conditions no silane complex, 2, could be detected by ³¹P NMR spectroscopy. Upon warming this solution in the NMR probe to -50 °C, catalytic hydrosilation begins as shown by the appearance in the ¹H NMR spectrum of Et₃SiO*CHMe₂. As acetone is consumed and the ratio of Et₃SiH to free acetone further increases, a point is reached where finally a sufficient quantity of silane complex is formed that the equilibrium constant can be measured. After 10 min at -50 °C, the ratio of free acetone to Et₃SiH is 1:18.9 (¹H NMR) and the ratio of acetone complex, 1, to silane complex, 2, is 37.5:1 (³¹P NMR) which yields an equilibrium constant of 1.4 × 10^-3 at -50 °C (eq. 7)¹⁰:

$$K_{\mathrm{eq}}=\frac{[{\left({\mathrm{CH}}_3\right)}_2\mathrm{C}=\mathrm{O}]}{\left[{\mathrm{Et}}_3\mathrm{SiH}\right]}\cdot \frac{\left[2\right]}{\left[1\right]}=0.053\cdot 0.027=1.4\times {10}^{\text{-}3},\text{-}50°\mathrm{C}$$ (7)

While these experiments establish a rapid equilibrium between 1 and 2 during catalysis with the ketone complex as the nearly exclusive resting state, they do not provide a decision as to whether step I, silation of acetone, or step II, reduction of 4 by iridium dihydride, 3, is turnover-limiting (Scheme 5). Either scenario predicts that the turnover frequency is zero-order in ketone and first-order in Et₃SiH. Indeed that has been confirmed for reduction of 4-tert-butyl cyclohexanone at -60 °C under typical catalytic conditions. Figure 2 (left) shows a typical plot of the initial rate of disappearance of 4-tert-butyl cyclohexanone (1.06 M) using Et₃SiH (0.639 M) and complex 1 (6.4 mM) in CD₂Cl₂. Figure 2 (right) shows a plot of the initial rates of disappearance of 4-tert-butyl cyclohexanone at various concentrations of 4-tert-butyl cyclohexanone using 1.87 M Et₃SiH and 6.4 mM 1 in CD₂Cl₂ at -60 °C. This plot establishes that the turnover frequency is zero-order in ketone. Figure 3 shows a plot of the initial rates of disappearance 4-tert-butyl cyclohexanone (0.32-1.06 M) at various concentrations of Et₃SiH using complex 1 (6.4 mM) in CD₂Cl₂ (-60 °C). This plot shows clearly that the turnover frequency is first-order in silane.

Scheme 5.

Free energy diagram for the iridium-catalyzed hydrosilation of acetone with triethyl silane

Figure 2.

(Left) Plot of concentration of 4-tert-butyl cyclohexanones [ketone] vs. time for the hydrosilation of 4-tert-butyl cyclohexanone catalyzed by 1 at -60 °C. (Right) Plot of the initial rate, V_i of 4-tert-butyl cyclohexanone vs. 4-tert-butyl cyclohexanone concentration at -60 °C.

Figure 3.

Plot of the initial rate, V_i of disappearance of 4-tert-butyl cyclohexanone vs. Et₃SiH concentration at -60 °C.

Jian et al., has reported the Ir-catalyzed reduction of alkyl halides by Et₃SiH, and proposed a quite similar catalytic cycle to Scheme 3 based on the kinetic data, although, as here, they were not able to distinguish whether the silation of alkyl halides, RX, or the transfer of hydride to Et₃SiXR⁺ was the turnover limiting step.^5a

Conclusions

Iridium complex 1 is a highly active, long-lived catalyst for hydrosilation of a variety of ketones and aldehydes with trialkyl silanes to afford the corresponding silyl alkyl ethers in excellent yields. Highly hindered ketones such as diisopropyl ketone are effective substrates. The majority of the cases studied here have used Et₃SiH as the silane, but several other silanes including the bulky (i-Pr)₃SiH have been shown to be effective with cyclohexanone. Hydrosilation of esters leads to “over reduction” and cleavage of C-O bonds. Similarly, diethyl acetamide reacts to yield triethyl amine. The diastereoselectivity of the hydrosilation of 4-tert-butyl cyclohexanone with 1 and EtMe₂SiH shows unprecedented temperature dependence. Analysis of product ratios as a function of temperature yields values for ΔΔH^‡ (ΔH^‡ (trans) - ΔH^‡ (cis)) and ΔΔS^‡ (ΔS^‡ (trans) - ΔS^‡(cis)) of -2.5 kcal/mol and -6.9 e.u., respectively.

A mechanistic study of the reaction showed that the ketone and silane complexes are in rapid equilibrium relative to the rate of catalytic hydrosilation and that ketone complex is strongly favored and can be viewed as the resting state. Catalysis ensues by silation of ketone by the cationic silane complex followed by reduction of this species by the resultant iridium dihydride. Low temperature mechanistic studies revealed that the ketone complex is the dominant resting state in rapid equilibrium with silane complex, 2. The turnover-limiting step in this catalytic cycle is either silation of ketone by 2, or the reduction of resultant oxocarbenium ion via a hydride transfer from iridium dihydride, 3. The turnover frequency is first-order in silane and zero-order in ketone in accord with this proposal. This mechanism is similar to that proposed by Piers for hydrosilation of ketones using (C₆F₅)₃B/Ph₃SiH where the silane is activated by (C₆F₅)₃B and transfers Ph₃Si⁺ to ketone.^4a

Experimental Section

General Procedures

All manipulations were carried out using standard Schlenk, high-vacuum and glovebox techniques. Argon and nitrogen were purified by passing through columns of BASF R3-11 catalyst (Chemalog) and 4 Å molecular sieves. THF was distilled under a nitrogen atmosphere from sodium benzophenone ketyl prior to use. Pentane, methylene chloride and toluene were passed through columns of activated alumina¹¹ and degassed by either freeze-pump-thaw methods or by purging with argon. Benzene and acetone were dried with 4 Å molecular sieves and degassed by freeze-pump-thaw methods. Silanes were dried with LiAlH₄ or 4 Å molecular sieves and vacuum transferred into a sealed flask. All of the other substrates purchased from Sigma-Aldrich were dried with either K₂CO₃ or 4 Å molecular sieves and vacuum transferred into a sealed flask for the substrate with boiling point less than ca. 110 °C, except that 4-tert-butyl cyclohexanone was purified by sublimation at ca. 40 °C. Deuterated solvents (CD₂Cl₂, C₆D₅CD₃, C₆D₅Cl) for NMR were dried with CaH₂ or 4 Å molecular sieves and vacuum transferred into a sealed flask. NMR spectra were recorded on Bruker spectrometers (DRX-400, AVANCE-400, AMX-300 and DRX-500). ¹H and ¹³C NMR spectra were referenced to solvent peaks. Ph₃C[B(C₆F₅)₄],¹² (POCOP)Ir(H)₂,¹³ and [(POCOP)Ir(H)(acetone)]⁺[B(C₆F₅)₄]^-, 1⁵ were prepared according to published procedures.

General Procedure for the Hydrosilation of Substrates with Et₃ SiH in C₆D₅Cl

Et₃SiH (0.48 ml, 3.00 mmol, 3 equiv.) was added to a solution of 1 (6.7 mg, 0.005 mmol, 0.5 mol%) in C₆D₅Cl (0.3 ml) in a medium-walled J. Young NMR tube and the contents were well shaken. The substrate (1.00 mmol, 1 equiv.) was then added and the reaction was allowed to stand at room temperature. The progress was followed by NMR spectroscopy. With the exception of diethyl acetamide (entry 11, Table 1) conversions are quantitative and no starting material remains at the end of the reaction. NMR data for the hydrosilated products in Table 1 are available in Supporting Information.

General Procedure for the Hydrosilation of 4-tert-Butyl Cyclohexanone with Various Silanes in C₆D₅Cl

Silane (3.00 mmol, 3 equiv.) was added to a solution of 1 (6.7 mg, 0.005 mmol, 0.5 mol%) in C₆D₅Cl (0.3 ml) in a medium-walled J. Young NMR tube and the contents were well shaken. 4-tert-Butylcyclohexanone (154 mg, 1.00 mmol, 1 equiv.) was then added and the reaction was allowed to stand at room temperature for the specified time. The reaction mixture was then analyzed by NMR spectroscopy. NMR data for the hydrosilated products in Table 2 are available in Supporting Information.

General Procedure for the Hydrosilation of Alkyl-Substituted Cyclohexanone Derivatives with EtMe₂SiH in C₆D₅Cl

Silane (0.40 ml, 3.00 mmol, 3 equiv.) was added to a solution of 1 (6.7 mg, 0.005 mmol, 0.5 mol%) in C₆D₅Cl (0.3 ml) in a medium-walled J. Young NMR tube and the contents were well shaken. Alkyl-substituted cyclohexanone derivatives (1.00 mmol, 1 equiv.) were then added and the reaction mixtures were allowed to stand at room temperature or 0 °C for a specific time. The reaction mixtures were then analyzed by NMR spectroscopy. NMR data for the hydrosilated products in Table 4 are available in Supporting Information.

General Procedure for Kineic Studies (CD₂Cl₂

Et₃SiH was added to a solution of 1 (6.7 mg, 0.005 mmol) in CD₂Cl₂ in a medium-walled J. Young NMR tube and the solution was well shaken. The NMR tube was placed in a bath at -100 °C to freeze the solution, and then 4-tert-butyl cyclohexanone in CD₂Cl₂ (0.32-0.98 M) was added on the top of the frozen solution at -100 °C. After briefly shaking, the NMR tube was quickly placed in the NMR probe pre-cooled to -70 °C. The reaction was allowed to warm -60 °C and the ratio of 4-tert-butyl cyclohexanone to the silyl ether product was monitored with respect to time by ¹H NMR. The data were analyzed using the method of initial rates and the initial reduction rates were obtained from the linear portion of the concentration vs. time curve in the early stage of the reaction (Figure 2, 3).

Low Temperature Reaction of 1, Et₃SiH, and acetone-2-¹³C, -70°C to -50 °C

To the solution of 1 (10.05 mg, 0.0075 mmol) in CD₂Cl₂ in a medium-walled J. Young NMR tube was added 4 equiv. of Et₃SiH (4.8 μl, 0.03 mmol), and the solution was stirred at 22 °C for 30 min. The solution was cooled to -70 °C and 1 equiv. of acetone-2-¹³C was added from a stock solution of acetone-2-¹³C in CD₂Cl₂. After briefly shaking, the NMR tube was quickly placed in the NMR probe pre-cooled to -80 °C. The reaction was allowed to warm to -70 °C and monitored by NMR spectroscopy. After NMR experiments at -70 °C, 16 equiv. of Et₃SiH was additionally added to the solution while keeping temperature at -70 °C, followed by warming the solution up to -50 °C. The hydrosilation of acetone-2-¹³C with Et₃SiH began at -50 °C and the concentration of all species were monitored by NMR spectroscopy to determine the equilibrium constant between 1 and 2 (Scheme 6).5a,b

Scheme 6.

Equilibrium between 1 and 2 at -50 °C