Direct Observation of Aryl Gold(I) Carbenes that Undergo Cyclopropanation, C−H Insertion, and Dimerization Reactions

Abstract

Mesityl gold(I) carbenes lacking heteroatom stabilization or shielding ancillary ligands have been generated and spectroscopically characterized from chloro(mesityl)methylgold(I) carbenoids bearing JohnPhos‐type ligands by chloride abstraction with GaCl₃. The aryl carbenes react with PPh₃ and alkenes to give stable phosphonium ylides and cyclopropanes, respectively. Oxidation with pyridine N‐oxide and intermolecular C−H insertion to cyclohexane have also been observed. In the absence of nucleophiles, a bimolecular reaction, similar to that observed for other metal carbenes, leads to a symmetrical alkene.

Gold(I) carbenes have attracted great interest from the outset of the homogeneous gold‐catalysis era1 and have been the center of debate regarding their structures and, in particular, the degree of stabilization provided by the π‐backdonation from gold(I) to the carbon center.2, 3 Indeed, recent studies on well‐characterized gold(I) carbene complexes have shown that these species can be considered anything from metal‐stabilized carbocations to metal carbenes depending on the nature of the ancillary donating ligand(s) on gold(I).3, 4, 5, 6, 7 However, these stabilized complexes require the presence of either heteroatoms4 or highly conjugated systems5 at the carbene moiety and shielding ancillary ligands6 or bidentate phosphines7 at the metal center and, with very few exceptions,8 do not display the reactivity proposed for the intermediate species involved in catalysis.

Metal carbenoids are species in which the metal is bound to an sp³‐carbon center bearing a good leaving group that can generate a metal carbene upon ionization (Scheme 1 a).3a, 9 Based on this relationship, we have recently developed a method for the preparation of chloromethylgold(I) carbenoids, which, after chloride abstraction, display typical reactivities of gold(I) carbenes in solution.10 During the course of our investigation, preliminary results suggested that [JohnPhosAuCHPhCl] (1), after chloride abstraction, generates stilbene (2 a), which undergoes cyclopropanation by an undetected phenyl gold(I) carbene intermediate (Scheme 1 b).9 The observed cyclopropanation closely resembles the reactivity displayed by aryl gold(I) carbenes (5) generated by a gold(I)‐catalyzed retro‐Buchner reaction of cycloheptatrienes (4; Scheme 1 c).11 Although these arylidene complexes (5) have never been observed in solution, such species have been detected in the gas phase.12, 13

Scheme 1.

General concepts and reactivity of [JohnPhosAuCHPhCl] (1) carbenoid. Tf=trifluoromethanesulfonyl, TMS=trimethylsilyl.

Herein, we report the generation and spectroscopic characterization of mesityl gold(I) carbenes from stable carbenoids (1 a–e) bearing JohnPhos‐type ligands. These gold(I) carbenes display the same reactivity towards alkenes as the intermediates of the retro‐Buchner reaction and many other gold(I)‐catalyzed transformations.10 Importantly, the gold(I) carbenes undergo bimolecular homocoupling to form the corresponding symmetrical alkenes by a process reminiscent to that shown by electrophilic and nucleophilic metal carbenes.

Gold(I) carbenoids (1 a–e) were obtained by reaction of the complexes 6 a–e with mesityl diazomethane, and their structures were confirmed by X‐ray diffraction (Scheme 2).14 Remarkably, upon addition of GaCl₃ to 1 a in CD₂Cl₂ at −90 °C, the solution turned deep red, suggesting the formation of the mesityl gold(I) carbene 5 a, which was characterized by NMR techniques (Table 1). Although gold(I) carbenoids bearing JohnPhos and different substitution patterns in the aryl group were tested under the same reaction conditions, the generation of gold(I) carbenes could not be detected by NMR spectroscopy in those cases.15 Although 5 a partially decomposed at −90 °C, the carbenes 5 b–e were stable until −70 °C. These are the first monosubstituted gold(I) carbenes that have been characterized spectroscopically. The complexes 5 a–e present a characteristic signal in ¹H NMR spectroscopy at δ=11.74–12.67 ppm corresponding to H1 (Scheme 3, Table 1). The carbenic carbon centers (C1) resonate at δ=284.6–290.0 ppm as a doublet [² J (¹³C‐³¹P)=96.8–99.8 Hz], within the range of previously characterized gold(I) carbenes (δ=225–321 ppm).4, 5, 6, 7 In addition, clear correlations between the carbenic carbon (C1) and proton (H1) were observed in the ¹H‐¹³C HSQC spectra.16 DFT calculations for 1 b′–c′ and 5 b′–c′ complexes at the B3LYP‐D3/6‐31G(d,p) + SDD(Au) level of theory led to computed ¹H and ¹³C NMR chemical shifts for H1, C1, and ¹ J(¹H1‐¹³C1) constants consistent with the experimental results (Table 1). Furthermore, 5 a–e were detected in the gas phase by ESI‐MS from 1 a–e.

Scheme 2.

Synthesis of the chloro(mesityl)methylgold(I) carbenoids 1 a–e.

Table 1.

Selected measured and calculated NMR data.^[a]

Complex	Method	H1 (ppm)	C1 (ppm)	1 J (1H1‐13C1) [Hz]
5 a	Exp[b]	12.35 (4.92)	290.0 (69.7)[d]	–
	DFT[c]	12.12 (4.22)	280.8 (72.2)	125.2 (144.2)
5 b	Exp[b]	12.67 (4.28)	287.9 (71.8)	129.8 (143.9)
	DFT[c]	12.17 (4.24)	280.2 (71.2)	124.4 (143.4)
5 c	Exp[b]	12.32 (4.17)	290.0 (73.7)	127.8 (144.3)
	DFT[c]	12.09 (4.30	278.9 (75.4)	126.1 (144.6)
5 d	Exp[b]	12.57 (4.24)	289.0 (71.4)[d]	–
	DFT[c]	12.03 (4.69)	274.6 (74.0)	125.6 (144.4)
5 e	Exp[b]	11.74 (3.26)	284.6 (70.7)[d]	–
	DFT[c]	11.06 (−)	272.4 (−)	125.4 (144.4)

[a] Data for the corresponding carbenoid precursor given within parentheses. [b] −90 °C in CD₂Cl₂. [c] Computed at 25 °C in CH₂Cl₂. [d] 25 °C in [D₈]toluene.

Scheme 3.

Generation of the mesityl gold(I) carbenes 5 a–e. ¹H NMR spectrum and selected region of ¹H‐¹³C HSQC spectra of 5 c in CD₂Cl₂ at −90 °C.

The calculated structure 5 c′ shows the mesitylidene fragment parallel to the lower ring of the biaryl ligand plane (Figure 1, top).17 The computed Au‐C1 (2.026 Å) and C1‐C2 (1.401 Å) bond distances for 5 c′ are slightly shorter than those for the precursor 1 c, Au‐C1 (X‐ray: 2.085 Å, computed: 2.095 Å) and C1‐C2 (X‐ray: 1.498 Å, computed: 1.502 Å). The reactivity of electrophilic gold(I) carbenes is dominated by the LUMO orbital, which in the case of 5 c′ is located over the occupied d_xz(Au) orbital at gold and the 2p^π‐system of the carbene ligand (Figure 1, bottom left). An NBO analysis for 5 c′ revealed two main electronic contributions involved in the π‐orbital stabilization of C1. First, a small π‐backdonation from d_xz(Au) to 2p^π(C1) in a donor–acceptor interaction (24.4 kcal mol⁻¹) and 3.7 % contribution of 2p^π(C1) in the corresponding NLMO (Figure 1, bottom right), along with a lone pair at C2 [2p^π(C2)] highly polarized towards C1 [23.5 % on 2p^π(C1)].18 The calculated energy barrier to Au‐C1 (ΔG ^≠=1.3 kcal mol⁻¹) and C1‐C2 (ΔG ^≠=18.6 kcal mol⁻¹) bond rotation supported the low Au‐C1 bond π‐character and a significant C1‐C2 π‐bond. Although for these species the benzyl carbocation structure predominates, back‐donation from gold is expected to be higher for other alkyl‐substituted gold(I) carbenes generated under catalytic conditions.

Figure 1.

Top: Optimized geometry for 5 c′. Bottom left: plot for the LUMO orbital for 5 c′. Bottom right: plot for the NLMO associated to Au‐to‐C1 π‐backdonation for complex 5 c′. Cutoff: 0.05.

Gold(I) carbenes (5 b–c) were trapped by PPh₃ at −90 °C, affording the phosphonium‐ylide complexes 7 a,b, whose structures were confirmed by X‐ray diffraction (Scheme 4 a). 7 a,b resemble the phosphonium‐ylide gold adducts previously used to detect aryl gold(I) carbenes in the gas phase.11a–11c, 12 In our reactivity studies, small amounts of 2,4,6‐trimethylbenzaldehyde (8) were detected, corresponding to the oxidation of gold(I) carbenes with oxygen.19 Indeed, we observed instantaneous formation of 8 as the only organic product when oxygen was bubbled through solutions of 5 a–d at −90 °C.20 Clean oxygen‐atom transfer also took place by treatment of 5 a–d with pyridine N‐oxide at −90 °C (Scheme 4 b). Similar reactivity has been observed for other gold(I) carbenes.5

Scheme 4.

a) Synthesis of the phosphonium‐ylide complexes 7 a,b. b) Oxygen transfer from pyrine N‐oxide. Yields determined by ¹H NMR spectroscopy using Ph₂CH₂ as an internal standard. Mes=2,4,6‐trimethylphenyl.

To date, none of the isolated gold(I) carbenes have been shown to undergo C−H insertion into alkanes. In contrast, 5 a–e, generated at −30 °C from the corresponding 1 a–e in the presence of cyclohexane, undergo clean C−H insertion to give 9 in 39–69 % yield (Scheme 5).

Scheme 5.

Gold(I)‐promoted C−H insertion. Yields determined by ¹H NMR spectroscopy using Ph₂CH₂ as an internal standard. Mes=2,4,6‐trimethylphenyl.

In the reactions of 5 a–d with pyridine N‐oxide or cyclohexane, traces of (E)‐1,2‐dimesitylethene [(E)‐2 b] were also detected (Schemes 4 b and 5). (E)‐2 b was cleanly formed, together with the corresponding chloride‐bridged digold(I) complexes (10 a–e),21 when solutions of 5 a–e in CD₂Cl₂ were warmed up from −90 °C to either −30 or 0 °C (Table 2). Significant amounts of the cyclopropane 3 b were also obtained in some cases (Table 1, entries 1,3, and 5). Analysis of the reactivity of 5 c 22 shows that (E)‐2 b was initially formed between −70 and −40 °C. Then, around −40 °C, 3 b and small amounts of (Z)‐2 b were also detected. The formation of (E)‐2 b follows a second‐order dependence on the concentration of 5 b.20 Related bimolecular couplings to form symmetrical alkenes have been observed as common decomposition pathways for rhenium methylidenes23, 24 and ruthenium carbenes,25, 26 as well as typical Fischer27 and Schrock carbenes.28

Table 2.

Alkene and cyclopropane formation.^[a]

Entry	Complex	T [°C]	2 b Yield [%]	E/Z	3 b Yield [%]
1	5 a	−10	25	12:1	36
2	5 b	−20	68	>60:1	<1
3	5 c	−10	27	9:1	39
4	5 d	−30	62	>60:1	<1
5	5 e	0	7	>60:1	83

[a] Yields were determined by ¹H NMR spectroscopy using 1,3,5‐tris(trifluoromethyl)benzene as the internal standard. Mes=2,4,6‐trimethylphenyl.

As suggested by the competitive cyclopropanation observed in the formal dimerization of the carbene fragments leading to 2 b (Table 2), the substituted alkenes 2 c–e readily react at −90 °C with 5 a–e to form the corresponding cyclopropanes 3 c–e (Table 3, entries 1–5).29 Importantly, the gold(I)‐catalyzed retro‐Buchner reaction10, 30 of the aryl cycloheptatriene 4 a in the presence of 2 c,d also leads to cyclopropanes (3 c–e; entry 6), and strongly suggests that 5 a is also generated under catalytic conditions. The lower yields of 3 c–e obtained under catalytic conditions can be explained by the steric hindrance introduced by the mesityl group in the rate‐determining cleavage of the cyclopropane bond of the norcaradiene in tautomeric equilibrium with the cycloheptatriene.

Table 3.

Cyclopropanation by 5 a–e from 1 a–e (left) or through decarbenation of 4 a (right).^[a]

Entry	Precursor	Yield [%][b]
		3 c	3 d	3 e
1	1 a	99	80	99 (2.3:1)
2	1 b	87	90	99 (3:1)
3	1 c	99	99	99 (1:1.2)
4	1 d	99 (1:1.5)31	99	72 (1:2.1)
5	1 e	99	90	99 (3.5:1)
6	4 a	32	38	17 (1:7.5)

[a] Yields determined by ¹H NMR spectroscopy using Ph₂CH₂ as the internal standard. [b] Diastereomeric ratio given within parenthesis. DCE=1,2‐dichloroethane.

To get a deeper insight into the mechanism of this rate‐limiting bimolecular coupling, we performed DFT calculations with 5 b′ (Scheme 6). Our calculations suggest that the association complex IntI, which is stabilized by face‐to‐face π–π interactions between the two mesitylidenes fragments and shows a relatively short C1‐C1 distance (3.13 Å), is preferentially formed (ΔG=−3.3 kcal mol⁻¹) and can evolve through TS_{IntI‐IntIII} (ΔG ^≠=12.1 kcal mol⁻¹) to form a (η ²‐Z‐5 a)gold(I) complex (IntIII) in a highly exothermic process (ΔG=−48.2 kcal mol⁻¹). Alternatively, the less stable association complex IntII (ΔG=1.9 kcal mol⁻¹), with the optimal orientation of the mesitylidenes for trans C1–C1 bond formation, can evolve via TS_IntII‐IV (ΔG ^≠=6.2 kcal mol⁻¹) to form (E)‐2 b. At −35 °C, the calculated (E/Z)‐2 b ratio (ΔΔG ^≠=0.6 kcal mol⁻¹, 3:1 E/Z) is in close agreement with the experimental results (2.4:1 E/Z). Related mechanisms have been proposed for the formation of alkenes from rhenium21 and ruthenium23 carbenes.

Scheme 6.

Calculated reaction profile for the bimolecular coupling of 5 b′. L=MeJohnPhos. DFT calculations were carried out at the B3LYP‐D3/6‐31G(d,p) + SDD on Au and Ga. CH₂Cl₂ was represented with the PCM. Free energies in kcal mol⁻¹.

We also examined theoretically the reaction pathways for the cyclopropanation of (Z)‐2 b and (E)‐2 b by 5 b′.32 As we have found before for intermolecular cyclopropanations of intermediate gold(I) carbenes,33 these reactions proceed by an asynchronous concerted mechanism with an activation barrier for (E)‐2 b (ΔG ^≠=12.7 kcal mol⁻¹), 8.5 kcal mol⁻¹ lower than that for (Z)‐2 b (ΔG ^≠=21.2 kcal mol⁻¹).29

In summary, we have generated and characterized spectroscopically monosubstituted gold(I) carbenes for the first time in solution, and they undergo representative transformations, such as cyclopropanation, oxidation, and C−H insertion reactions, of intermediate gold(I) carbenes formed under catalytic conditions. These aryl gold(I) carbenes correspond to the intermediates generated in the gold(I)‐catalyzed decarbenation of cycloheptatrienes (retro‐Buchner reaction). In the absence of other reagents, we observed dimerization to form preferentially the E‐configured alkene by a process similar to that followed by other well‐known metal carbenes, and places these highly electrophilic species among the metal carbene family, despite the weak back donation from gold(I) to the carbenic carbon center.

Conflict of interest

The authors declare no conflict of interest.

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Supplementary

C. García-Morales, X.-L. Pei, J. M. Sarria Toro, A. M. Echavarren, Angew. Chem. Int. Ed. 2019, 58, 3957.