Insights into the Stability of Siloxy Carbene Intermediates and their

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Insights into the Stability of Siloxy Carbene Intermediates and their Corresponding Oxocarbenium Ions Daniel L. Priebbenow J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01698 • Publication Date (Web): 19 Aug 2019 Downloaded from pubs.acs.org on August 24, 2019

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The Journal of Organic Chemistry

Insights into the Stability of Siloxy Carbene Intermediates and their Corresponding 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Oxocarbenium Ions Daniel L. Priebbenow*a (ORCiD: 0000-0002-7840-0405) a School

of Life and Environmental Sciences, Deakin University, Waurn Ponds, Australia, 3216

[email protected]

Graphical Abstract

Abstract Siloxy carbenes, formed thermally or photochemically from acyl silanes via a 1,2-Brook rearrangement, are intriguing reactive intermediates that partake in a range of chemical reactions. To gain further insight into the properties of this class of carbenes, the thermodynamic stabilities of a series of known siloxy carbenes were explored on the basis of hydrogenation enthalpies. Calculations were conducted at the B3LYP-D3(BJ) level (using dispersion-corrected DFT) on siloxy carbenes (XC-OSiR3, singlet and triplet state), oxocarbenium ions (X-CH-OSiR3+), and their hydrogen addition products (X-CH2-OSiR3). Overall, strong correlation between singlet-triplet gaps and hydrogenation enthalpies was observed. Carbene stabilisation enthalpy (CSE) values were also determined to provide additional insight into the structural features that influence the stability of siloxy carbenes. Introduction Carbenes are neutral, yet highly reactive, intermediates that possess two non-bonding electrons that can be either paired (singlet carbene) or unpaired (triplet carbene).1 Since the attempts of Dumas to isolate and characterize methylidene in the early 19th century, the study of carbenes has intrigued and engaged researchers within the chemical sciences.2 In the 1960s—several decades before carbenes were first isolated—Jack Hine proposed that for a molecular structure to be defined as a carbene, there must exist a stable dimer (either analogous or mixed) or a 4-coordinate derivative produced via formal insertion into a σ-bond (for example H2).3 Such reactivity is an artefact of ambiphilicity at the carbene centre, which for triplet carbenes is a result of two unpaired electrons that can readily form new bonds with other compounds (with the reactivity of triplet carbenes 4 typically paralleling that of radicals).ACS Paragon Plus Environment


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In comparison, singlet carbenes possess the characteristics of both a carbocation and carbanion 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

(i.e. empty p-orbital and a carbon centred lone pair) which gives rise to their ambiphilicity with observed reactivity ranging from electrophilic (including formation of carbene or mixed dimers) to nucleophilic (insertion into a variety of -bonds), thus satisfying Hine’s requirements.5 Substituents that can stabilise a carbocation or carbanion relative to a radical can also stabilise a singlet carbene with the most prevalent of these interactions being conjugation of a heteroatom substituent’s lone pair of electrons to the vacant non-bonding carbene 2p orbital.1a,5 In chemical synthesis, electrophilic singlet carbenes (typically generated from diazoacetates and stabilised by electron-withdrawing groups and/or metal complexes) have been widely exploited as reagents in C-H insertion and cyclopropanation processes.6 Electrophilic singlet carbenes also react with heteroatom nucleophiles to form ylide intermediates that undergo a range of subsequent transformations.7 Since the initial discovery by Arduengo and co-workers in 1990 that singlet nucleophilic carbenes (SNCs)—until that time considered transient—could be synthesised and stored,8 significant progress in the fundamental understanding and application of such carbenes has been realised. SNCs have been widely exploited as ligands to transition metals that catalyse a diverse range of chemical reactions including cross-coupling and metathesis processes.9 SNC derivatives have also been successfully employed in (asymmetric) organocatalysis,10 facilitating the discovery of new modes of chemical reactivity that provide access to important chiral molecules including bioactive natural products or intermediates en route to their production.11 Despite this progress, partially-stabilised singlet carbenes remain underexplored in chemical synthesis yet appear to offer unique chemical reactivity. Existing examples of partially-stabilised singlet carbenes within the literature include alkoxy,12 amino13 and siloxy carbenes.14 To date, the majority of reactions involving partially-stabilised singlet carbenes have involved siloxy carbenes. Siloxy carbenes can be generated photochemically or thermally via the 1,2-Brook rearrangement of acyl silanes.14e Generally, the reactivity patterns of siloxy carbenes corresponds with well-known Lewis base chemistry, with such intermediates possessing the ability to either abstract a proton, undergo 1,2-addition to carbonyl groups or 1,4-addition to electron-deficient alkenes. To this end, siloxy carbenes have been observed to react in the benzoin reaction with aldehydes (Scheme 1A), undergo C-H insertion (Scheme 1B), add to alkynes (Scheme 1C), and participate in electrocyclization processes (Scheme 1D).14b,c,15

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Scheme 1. Siloxy carbenes exhibit diverse reactivity in chemical synthesis

In cooperation with experimental studies, computational analysis has emerged as a useful strategy for gaining insight into the stability and reactivity of carbene derivatives.16 The calculation of singlettriplet gaps can reveal how a singlet carbene is stabilized (or destabilized) relative to the corresponding triplet and determination of the hydrogenation energies of a carbene also affords insight into the carbenic nature of the central carbon atom. Early computational work exploring carbenes was conducted by Arduengo and Dixon who published a series of reports regarding the electronic structure of stable “Arduengo-type” nucleophilic carbenes.17 In the early 2000s, Hadad and co-workers disclosed the outcomes of their experimental and computational investigations into the influence of both solvent and substituent variations on carbene singlet-triplet energy gaps.18 More recently, the team of Gronert, Keeffe and More O’Ferrall reported the development of the Carbene Stabilisation Enthalpy (CSE) scale to provide insight into the properties of carbenes.19 From the results of their DFT analysis (using MP2/6-311+G**), Gronert and co-workers produced Carbene Stabilisation Enthalpy (CSE) scales for both singlet and triplet carbenes which provided a straightforward computational method for the independent assessment of singlet and triplet carbenes and highlighted key structural features that influences the stability of each.19b In 2017, a report from Dixon and co-workers confirmed that computational analysis of the “prototypical” carbene hydrogenation process originally proposed by Hine3 provides useful insight into the stability of carbene derivatives and correlates well with singlet-triplet splitting.20 The outcomes from these previous computational studies infer that the more stable carbenes are those singlet carbenes with large singlet-triplet gaps and the least exothermic hydrogenation energies. In light of my continuing interest in the application of siloxy carbenes in organic synthesis,14b,c,e I set out to employ a computational approach to gain an enhanced understanding of the properties that govern the reactivity of siloxy carbenes. The objective of this study was to gain new insight into the structural features that stabilise siloxy carbenes (including quantifying the influence of the ylide resonance forms in both mono- and di-heteroatom substituted siloxy carbenes) in order to enable these unique singlet carbene intermediates to findPlus greater utility in chemical synthesis. ACS Paragon Environment


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Results and Discussion 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

To gain qualitative insights into the influence of various substituents on siloxy carbene reactivity and stability, geometric optimisation and calculations using dispersion-corrected DFT were completed with Gaussian 16 at a B3LYP-D3(BJ) level employing the 6-311G(2d,p) basis set.21,22 Frequency calculations were conducted with all molecules returning no imaginary frequencies for the optimized structures. Prior to initiating this study, a range of options were considered (weighing up accuracy vs computational cost), however for this project the use of dispersion-corrected B3LYP with a large basis set was considered robust enough to provide valuable qualitative insights.23 Gas-phase enthalpies of reaction were calculated for four processes: singlet-triplet enthalpy gaps of the carbenes (HST); enthalpies for deprotonation of the cations yielding singlet carbenes, (Hacid); hydride ion affinities of the oxocarbenium ions, (HIA); and enthalpies of hydrogenation of the singlet carbenes, (Hhydrog). The general structures and reaction processes examined throughout this study are depicted in Scheme 2. All structures reported herein represent the electronic energy minima. B3LYP-D3(BJ) zero-point corrected energies and enthalpies at 298K (including thermal corrections) for all siloxy carbenes, the conjugate acid carbenium ions and their hydrogenation products in hartrees, are tabulated in the supporting information. Computed energies were used for R–H and R+, but the experimental value for the electronic energy of the hydride ion, 333.1 kcal/mol, was used to obtain the final values. At B3LYP-D3(BJ) the energy of the hydride ion was calculated to be 318.5 kcal/mol.

Scheme 2. Overview of the general processes explored throughout this study where gas-phase enthalpies of reaction were calculated for four processes: singlet-triplet enthalpy gaps of the carbenes (HST); enthalpies for deprotonation of the cations yielding singlet carbenes, (Hacid); hydride ion affinities of the oxocarbenium ions, (HIA); and enthalpies of hydrogenation of the singlet carbenes, (Hhydrog).

The singlet triplet gap for each carbene was determined by evaluating the difference in enthalpy of formation between the singlet carbene and triplet carbene HST). It was observed that across the entire series of siloxy carbenes there was excellent correlation between EST and HST (EST = 0.9537HST – 0.0436, n = 18, r2 = 0.994). As such, for the remainder of the discussion, EST is reported. To further facilitate comparisons, the carbene stabilization enthalpies (CSEs) of each carbene was also calculated which can be defined as the difference in heat of hydrogenation (Hhydrog – see Scheme 2) of a carbene (CR1R2) from the value for the parent methylene as shown in Equation ACS Paragon Plus Environment

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1.19b The CSE values reveals the effects of varying substituents (R1 and R2) on the overall stabilities 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

of carbenes, with the unsubstituted methylidene (singlet or triplet) taken as reference. The calculated values for the singlet-triplet gap and the CSE are discussed in more detail in following section. CSE(R1R2) = Hhydrog(:CR1R2) – Hhydrog(:CH2)

(Eqn. 1)

Determination of chemical hardness is often used to quantify the level of resistance of a chemical species or intermediate to change its electron configuration. In combination with electronegativity, hardness can provide useful insights into chemical reactivity and stability.20,24 In addition to CSE, the hardness (η) and electronegativity (χ) for each siloxy carbene derivative was calculated using Equations 2 and 3 and the values obtained are included in the tables below. The adiabatic ionisation potential (IP) was determined following geometry optimisation and frequency calculations of the carbene and corresponding cation that would result from the loss of one electron (IP = Ecation – Eneutral). η (hardness) = ((HOMO) + (LUMO))/2 + IP

(Eqn. 2)

 (electronegativity) = -((HOMO) + (LUMO))/2

(Eqn. 3)

Alkyl siloxy carbenes have been reported to undergo various transformations including insertion into polar bonds, proton migration and cyclopropanation reactions and were the first carbene class to be investigated during this study (Table 1).25 It has been previously demonstrated that both alkyl groups (through hyperconjugation) and heteroatoms (through -bonding of lone pair electrons with the vacant 2p-orbital at the carbenic carbon) can stabilize singlet carbenes relative to the triplet state. Table 1. Analysis of alkyl substituted siloxy carbenes Carbene CSE EST Entry Hhydrog (singlet) (kcal/mol) Structure

CSE (triplet)

ηb

χc

1

11.80a

-122.18

0.00

0.00

4.56

5.31

2

-27.34

-62.95

59.23

20.83

4.15

3.15

3

-23.00

-67.95

54.23

18.95

3.56

3.14

4

-19.55

-69.22

52.96

18.46

3.50

3.05


The Journal of Organic Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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5

-22.01

-70.10

52.08

18.21

3.19

3.23

6

-19.07

-70.08

52.10

17.95

3.46

2.99

7

-17.96

-74.90

47.28

17.60

3.56

2.86

8

-12.77

-78.83

43.35

18.98

3.39

2.82

9

-10.78

-81.46

40.72

17.92

2.60

3.36

a∆E ST

was calculated at the B3LYP-D3(BJ) level of theory, however a difference of 2.75 kcal/mol between the computed and experimental singlet-triplet gaps for methylidene was observed. b η (hardness), see Equation 2. c  (electronegativity), see Equation 3

To enable comparison, initially the EST and CSE for both methylidene and methoxy methyl carbene were calculated (Table 1, entries 1 and 2). At the level of theory employed, the EST of methyl carbene was calculated to be 11.80 kcal/mol, whereas experimentally this has been determined to be 9.05 kcal/mol, a difference of 2.75 kcal/mol.4,26 For the acyclic alkyl siloxy carbenes investigated in this study (Table 1, entries 3-6), the calculated EST remained fairly constant (averaging -21 ± 2 kcal/mol), regardless of the structure of the silyl group and alkyl groups present. The EST for the siloxy carbenes was higher (i.e. closer to zero) than that calculated for the analogous methoxy methyl carbene, indicating the methoxy group has a greater capacity to stabilise the singlet carbene than the siloxy group. Interestingly, the cyclic alkyl siloxy carbenes (entries 7 - 9) were determined to have a EST up to 10 units higher than that for the acyclic derivatives (compare entries 3 and 8, table 1). For this series, the hydrogenation enthalpies also varied, averaging about -70 kcal/mol for the acylic variantss and up to -81 kcal/mol for the cyclic siloxy carbenes. For the alkyl carbenes studied, the calculated CSE was consistent across the series of compounds at approximately 53 kcal/mol for the acyclic singlet carbenes, 42 kcal/mol for the cyclic singlet carbenes and 18 kcal/mol for all triplet states. The CSE values for the alkyl-substituted siloxy carbenes reveal that the singlet carbenes are markedly stabilized by the presence of both the siloxy and alkyl groups, whereas the triplet carbenes gain only modest stabilization. The siloxy carbenes returned lower calculated values for hardness and electronegativity when compared to both ACS Paragon Plus Environment

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methylidene and methoxy methyl carbene. To note, the diphenyl oxasilepane carbene derivative 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

(Table 1, entry 9) was calculated to be less hard and more electronegative than all other alkyl variants studied herein. Aryl siloxy carbenes have been successfully employed as reactive intermediates in a range of reaction processes including insertion into C-H bonds, 1,2-addition to carbonyl groups and electrocyclization reactions (see Figure 1).14a,b,15 Phenyl substituents are known to provide greater stabilisation for singlet carbenes than triplet carbenes, so the influence of both an aryl group and siloxy group on carbene stabilisation was next to be explored (Table 2.).4 Table 2. Analysis of aryl substituted siloxy carbene EST Hhydrog Entry Carbene Structure (kcal/mol )

CSE

CSE

(singlet (triplet )

)

ηa

χb

1

-19.67

-60.84

61.34

29.26

3.29 3.68

2

-14.23

-63.54

58.64

32.01

2.75 3.62

3

-16.04

-64.86

57.32

30.84

2.67 3.60

4

-14.00

-66.79

55.39

29.67

2.59 3.66

5

-14.05

-65.02

57.16

30.94

2.65 3.64

6

-19.07

-60.69

61.49

31.39

2.69 3.38

7

-11.11

-65.76

56.42

35.14

2.38 4.43


The Journal of Organic Chemistry a

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b

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η (hardness), see Equation 2.  (electronegativity), see Equation 3

For the phenyl substituted siloxy carbenes (Table 2, entries 2-5), the EST remained fairly constant across the series (-15 ± 1 kcal/mol) regardless of the structure of the silyl group present and again was slightly higher than that of the analogous methoxy carbene (MeOCPh, Table 2, entry 1).12a,b The hydrogenation enthalpies of the aryl series averaged about -65 kcal/mol, with the para-methoxy phenyl derivative (entry 6), more stabilised than the siloxy carbenes studied with a value of -60 kcal/mol. For this series of siloxy carbenes, the CSE remained fairly consistent at approximately 57 kcal/mol for the singlet and 30 kcal/mol for the triplet state, again indicating the preference for the singlet carbene due to the ability of the siloxy group to stabilise the vacant 2p-orbital at the carbene centre. The CSE values for the aryl-substituted siloxy carbenes infer that singlets are somewhat more stabilized by the aryl than the alkyl substituents (Table 1). The triplets gain modest stabilization, with the aryl group able to stabilise the triplet state more so than for the alkyl siloxy carbenes (Table 1). Overall, the aryl siloxy carbenes were calculated to be less hard and more electronegative than the alkyl derivatives. When investigating variation in the substituent at the para-position on the phenyl ring (the position most likely to influence the electronic nature of the carbene centre), the effects were quite pronounced with the electron donating methoxy group producing a more stabilised singlet carbene (Table 2, entry 6), and the electron withdrawing nitro group (entry 7) affording a less stabilised singlet carbene when compared to the parent compound (entry 2).27 Overall the calculated EST differed by almost 8 kcal/mol between these two substrates (Table 2, entries 6 & 7). This effect was also apparent from the CSE values, with the electron-donating methoxy group increasing the singlet CSE by 3 kcal/mol (when compared to the unsubstituted phenyl compound, entry 2, with little variation in the triplet CSE) and the electron-withdrawing nitro group increasing the triplet CSE by 3 kcal/mol (with a minor decrease in the singlet CSE). Amino siloxy carbenes are another class of reactive carbene intermediates that are formed via the 1,2-Brook rearrangement of carbamoyl silanes. These carbene intermediates react with imines and carbonyl groups and partake in transition-metal mediated cross-coupling reactions (Scheme 1).28 The ability of two heteroatoms to stabilise carbenes is well known and has been widely exploited in organic and inorganic chemistry in the form of N-heterocyclic (NHC) carbene derived ligands and organocatalysts. The enhanced stability of NHCs is a result of -donation to the carbenic carbon by two heteroatom substituents which gives rise to highly stabilised singlet carbenes due to a stabilizing contribution from the ylide resonance form. Gronert and co-workers observed the significant influence on CSE of two heteroatom substituents, with methoxy carbene (H3CO-C-H) returning a CSE(singlet) of 47.9 kcal/mol, a value which increased to 77.0 kcal/mol for dimethoxycarbene (H3CO-C-OCH3).19b In an effort to better understand the impact of a second heteroatom substituent on the properties of siloxy carbenes, a series ACS Paragon Plus Environment

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of known amino-substituted siloxy carbenes were subjected to computational analysis using the 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

methods previously described (Table 3).

Table 3. Analysis of amino siloxy carbenes Entr EST Carbene Structure Hhydrog y (kcal/mol)

a b

CSE

CSE

(singlet)

(triplet)

ηa

χb

1

-50.36

-34.30

87.88

23.54

4.04

2.74

2

-50.28

-34.18

88.00

24.10

3.95

2.75

3

-48.25

-38.52

83.66

21.71

3.98

2.76

η (hardness), see Equation 2. Electron not bound so ε(LUMO) = 0 was used for these substrates.  (electronegativity), see Equation 3. Electron not bound so ε(LUMO) = 0 was used for these substrates.

For the amino siloxy carbenes studied, regardless of variations within both the silyl and amino groups present the EST averaged -50 kcal/mol. The hydrogenation enthalpies are much lower than for the alkyl and aryl siloxy carbenes, averaging -35 kcal/mol. For these substrates the CSE(singlet) was calculated to be 84-88 kcal/mol, which is more than 60 kcal/mol greater than the CSE(triplet). As expected, the presence of a secondary heteroatom adjacent to the carbene centre stabilises significantly the singlet siloxy carbene when compared to the aryl and alkyl siloxy carbenes discussed earlier. The triplet carbene is also moderately stabilised by the second heteroatom substituent. When compared to the alkyl and aryl derivatives the amino siloxy carbenes were calculated to be the least electronegative and the hardest carbenes of the siloxy carbenes studied herein. In their report, Gronert and co-workers concluded that for any carbene with a CSE greater than ~65-75 kcal/mol, the resonance form containing a formal -bond to the carbene centre can be considered a more accurate representation.19b However, in their original report on SNCs, Dixon and Arduengo concluded that for the imidazolium carbene derivatives, although a formal ylide resonance form could be considered, the calculated bond distances and charge distribution implied true carbene character and depiction of such structures as charge-separated ylide species was not an accurate representation.17a Thus, for amino siloxy carbenes, while there also appears to be a considerable influence on stability and reactivity from the ylide resonance form (which explains their ease of ACS Paragon Plus Environment


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formation and enhanced reactivity when compared to alkyl and aryl siloxy carbenes), these 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

intermediates remain more accurately represented as the carbene.

Scheme 3. Amino siloxy carbenes are more stabilised than alkyl or aryl siloxy carbenes due to influences from zwitterionic ylide resonance forms Comparison of singlet and triplet carbene hydrogenation enthalpies In line with previous studies,19b the data obtained from this study also infers that the stabilisation of singlet carbenes is much more sensitive to substituent variation (Figure 1A) than the triplet carbene, with an almost constant value of -86   kcal/mol for the Hhydrog(triplet), regardless of aryl, alkyl or amino substituents present on the siloxy carbene (Figure 1B).

(A)

Hhydrog(singlet)

(B)

Hhydrog(triplet)

0.00 -100.00

-50.00

0.00

-10.00

0.00 -100.00

-50.00

-10.00

-20.00

-20.00

-30.00

-30.00

-40.00

-40.00

-50.00

-50.00

-60.00

-60.00

0.00

Figure 1. Plots of HST (Y-axis) against (A) Hhydrog(singlet) and (B) Hhydrog(triplet) for the complete series of carbenes studied herein (values in kcal/mol).

Hacid and HIA In 1991, Arduengo and co-workers reported the proton affinity of the Arduengo type carbenes to to be approximately 250 kcal/mol.17a Since that time, the study and exploitation of the Brønsted basicity of carbenes has gained increasing interest in chemical synthesis. More recently, the groups of Arduengo, Lee and Smith have disclosed the outcomes of their investigations into the influence carbene Brønsted basicity has on the outcomes of NHC catalysed synthetic transformations.29 To this end, I set out to gain an enhanced understanding of the Bronsted basicity of siloxy carbene derivatives. To achieve this, computational analysis of both the carbene and protonated carbene derivative was conducted. Protonation at the central carbon of the siloxy carbene yields a secondary intermediate in the form of an oxocarbenium ion (or oxonium ion – see Scheme 2). In this case, the oxocarbenium resonance form is preferred over the carbocation-based carbenium ion due to all atoms satisfying the octet rule. The ease at which the reverse process takes place, that is abstraction of the proton from the oxonium ion, corresponds to the alpha-acidity of the carbenium ion (somewhat similar to beta-acidity whereby the loss a proton an alkene).30 ACSof Paragon Plusgenerates Environment

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To explore this acidity, Hacid was calculated for a series of alkyl, aryl and amino siloxy carbenes 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

(refer to Tables S4-6 in supporting information). The Hacid value provides insight into the basicity of carbenes by determining the energy required to remove the proton from the corresponding protonated carbene. Compared to methylidene (Hacid = 208 kcal/mol), the siloxycarbenes returned much higher values ranging from 259-270 kcal/mol for the alkyl siloxy carbenes, 260-275 kcal/mol for the aryl siloxy carbenes and an average of 265 kcal/mol for the amino siloxy carbenes. To note, protonated alkoxy carbenes that have been determined to have similar Hacid values have been estimated to have pKa values in the range of 13-23.30a,c The hydride ion affinity (HIA) of the oxocarbenium ions was also calculated which provides insight into the role the heteroatom plays in stabilising the oxocarbenium ion relative to the carbene (refer to Tables S4-6 in supporting information). Addition of a hydride ion to the oxonium ion generates the alkyl, benzyl or methylamino silyl ether (Scheme 2). From this analysis, compared to the methylidene carbenium ion (A = -313 kcal/mol), the siloxycarbenes returned much higher values ranging from -201 to -213 kcal/mol for the alkyl siloxy carbenes, -183 to -205 kcal/mol for the aryl siloxy carbenes and -167 to -172 kcal/mol for the amino siloxy carbenes. This infers that the same interactions from the heteroatom substituent that partially-stabilises the siloxy carbene also stabilises the oxocarbenium ion, with the di-heterosubstituted amino siloxy carbenes possessing the most stable carbenium ion. Atomic Orbital Occupancy A closer look at the effect of the siloxy groups on carbene and oxocarbenium ion stability was facilitated by examining the atomic orbital occupancies. Table 4 lists the calculated natural atomic orbital occupancies (NAOO) in the formally unoccupied valence 2p orbital of the central carbon of selected siloxy carbenes and their corresponding oxocarbenium ions. Table 4. Natural Atomic Orbital Occupancies (NAOO) and Population Analysis of Siloxy Carbenes Entry

Carbene Structure

NAOO, electron

Calculated C-O Bond Length

NPA charge, q

Carbene

Oxonium ion

Carbene O

Carbene C

Oxonium ion O

Oxonium ion C

Carbene

Oxonium ion

1

0.00

0.02a

N/A

-0.11

N/A

0.38

N/A

N/A

2

0.35

0.55

-0.50

0.30

-0.37

0.58

1.30

1.25

3

0.35

0.56

-0.83

0.24

-0.62

0.57

1.32

1.24

4

0.41

0.69

-0.51

0.19

-0.41

0.46

1.31

1.28



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5

0.40

0.67

-0.83

0.20

-0.68

0.47

1.32

1.27

6

0.48

0.69

-0.83

0.31

-0.63

0.59

1.31

1.24

0.57

1.35 (CO) 1.33 (CN)

1.28 (CO) 1.30 (CN)

7 aCalculated

0.54

0.76

-0.89

0.27

-0.74

for the carbenium ion

Where the NAOO of the vacant 2p-orbital at the carbenic carbon is greater than 0.50, Gronert and Keeffe again proposed that the zwitterionic resonance form containing a formal -bond between the heteroatom and central carbene can provide a more accurate structural descriptor.19a As seen in Table 4, when compared to methylidene (Table 4, entry 1) the alkyl and aryl siloxy (and methoxy) carbenes have a reasonable level of occupancy in their vacant 2p-orbital (entries 2-6, NAOO = 0.35-0.48). For the amino siloxy carbene examined (entry 7, NAOO = 0.54 in the vacant 2p-orbital), this intermediate is stabilised by a larger contribution from the ylide resonance form, yet still displays the reactivity expected of carbenes as originally proposed by Hine.3 The result obtained for the cyclic siloxy carbene (Table 4, entry 6) remains intriguing as the calculated CSE(singlet) of this substrate was considerably less than that for acyclic derivatives indicating a less-stabilised singlet carbene, yet the calculated orbital occupancy of the 2p-orbital is significantly greater than that of the acyclic derivatives. For all relevant substrates in Table 4, the NAOO of the vacant 2p-orbital at the central carbon atom of the oxocarbenium ion was calculated to be greater than 0.50, indicating that the oxonium resonance form is preferred over the carbocation resonance form, which is expected as the octet rule is also satisfied for this form. The other point of interest from this analysis was the increase in charge on the oxygen atom (increase of approximately 0.30 units) for the siloxy group when compared to the methoxy group for both the carbene and oxocarbenium ions. Carbene Bond Angles and Ring Strain Effects It is known that variations in geometric angle at the central carbene, X-C-Y, can influence the relative stability (and thus reactivity) of carbene intermediates. Singlet carbenes typically have carbenic angles close to 105 while for triplets this angle can exceed 130. By increasing the bulk of the carbene substituents, it is possible to force open the carbene angle which favours the triplet state carbene.1 For the acyclic siloxy carbenes reported herein, the bond angle at the central carbon of the singlet carbene was determined to be 110° ±ACS 1. Paragon For the Plus cyclic siloxy carbenes studied in Table 1, geometry Environment

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optimisation revealed that the angle at the carbene is forced open to 116° for the dimethyl oxasilepane 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

(Figure 2A) whereas for the diphenyl oxasilepane singlet carbene derivative (Figure 2B) the carbenic angle was 107°. Across the series of carbenes studied, the calculated angle for the triplet siloxy carbene varied slightly between substrates averaging 124° for the alkyl siloxy carbenes, 128° for the aryl siloxy carbenes and 122° for the amino siloxy carbenes. (A)

(C)

(B)

(D)

Figure 2. Geometry optimised models of (A) dimethyloxasilepane carbene (singlet carbene bond angle = 116.1°); (B) diphenyloxasilepane carbene (singlet carbene bond angle = 107.1°); (C) isopropyl trimethylsiloxy carbene (singlet carbene bond angle = 109.2°); and (D) 4-methoxyphenyl trimethylsiloxy carbene (singlet carbene bond angle = 110.3°).

Conclusion This computational analysis provided valuable insight into the role that aryl, alkyl and amino groups play in stabilising siloxy carbene intermediates.31 For all cases, the singlet carbene state was strongly favoured over the triplet carbene, predominantly due to the ability of the lone pair of electrons from the siloxy substituent to conjugate with the vacant 2p-orbital at the carbenic centre. In certain cases (for example amino siloxy carbenes generated thermally from carbamoyl silanes) the ylide resonance form can be considered to play a more significant role in the stability and reactivity of such carbenes. Interestingly, the structure of the silicon group does not appear to influence the electronic properties of the carbenes, however steric factors (for example when using bulkier silicon ACS Paragon Plus Environment


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groups) have been reported to impact both carbene reactivity and the efficiency of the initial 1,21 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Brook rearrangement required to generate the carbene intermediate from acylsilanes.14c

Experimental The geometries were optimized and molecular orbital theory calculations conducted to predict the heats of hydrogenation in the gas phase and the singlet–triplet gap using dispersion-corrected DFT at a B3LYP-D3(BJ) level22 employing the 6-311G(2d,p) basis set. Calculations were done with the Gaussian 16 program.21 The use of dispersion-corrected B3LYP with a large basis set was was chosen as it represents a good compromise between computational cost and accuracy and was considered robust enough to provide useful qualitative insights.23 Zero-point energy corrections were applied to all calculations and harmonic vibrational frequencies were calculated for all optimized structures, verifying they were a minimum. To note, less than 0.5 kcal/mol difference was typically observed between the zero-point energies of singlet and triplet carbenes. Supporting Information Available Tables containing B3LYP energies, enthalpies and free energies for all computed structures in addition to Cartesian coordinates for the computed structure sets and the ΔEST, ΔHST and ΔHhydrog values for carbenes and HIA and ΔHacid values for oxocarbenium ions. HOMO and LUMO values, Ionisation Potentials and calculated hardness and electronegativity values are also reported. Acknowledgements The author acknowledges Dr Lars Goerigk (School of Chemistry, University of Melbourne, Australia) for helpful discussions regarding dispersion-corrected DFT. References 1 (a) Bourissou, D.; Guerret, O.; Gabbaï, F. P.; Bertrand, G. Stable Carbenes. Chem. Rev. 2000, 100, 39-92; (b) Moss, R. A.; Doyle, M. P. Contemporary Carbene Chemistry, Vol. 7, Wiley, Hoboken, New Jersey, 2013. 2 Dumas, J. B.; Péligot, E. Mémoire sur l’Esprit-de-Bois et les Divers Composés Éthéres qui en Proviennent. Ann. Chim. Phys. 1835, 58, 5-74. 3 Hine, J. S. Divalent Carbon, Ronald Press, New York, 1964. 4 Hirai, K.; Itoh, T.; Tomioka, H. Persistent Triplet Carbenes. Chem. Rev. 2009, 109, 32753332. 5 Vignolle, J.; Cattöen, X.; Bourissou, D. Stable Noncyclic Singlet Carbenes. Chem. Rev. 2009, 109, 3333-3384 6 (a) Lebel, H.; Marcoux, J.-F.; Molinaro, C.; Charette, A. B. Stereoselective Cyclopropanation Reactions. Chem. Rev. 2003, 103, 977-1050; (b) Aggarwal, V. K.; Alonso, E.; Fang, G.; Ferrara, M.; Hynd, G.; Porcelloni, M. Application of Chiral Sulfides to Catalytic Asymmetric Aziridination and Cyclopropanation with In Situ Generation of the Diazo Compound. Angew. Chem., Int. Ed. 2001, 40, 1433-1436; (c) Davies, H. M. L.; Beckwith, R. E. J. Catalytic Enantioselective C-H Activation by Means of Metal-Carbenoid-Induced C-H Insertion. Chem. Rev. 2003, 103, 2861-2903. 7 (a) Priebbenow, D. L.; Bolm, C. The Rhodium-Catalysed Synthesis of PyrrolidinoneSubstituted (Trialkylsilyloxy)acrylic Esters. RSC Adv. 2013, 3, 10318-10322; (b) Xia, Y.; ACS Paragon Plus Environment

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