Structural elucidation of a methylenation reagent of esters: synthesis and reactivity of a dinuclear titanium(iii) methylene complex†

Transmetallation of a zinc methylene complex [ZnI(tmeda)]2(μ-CH2) with a titanium(iii) chloride [TiCl3(tmeda)(thf)] produced a titanium methylene complex. The X-ray diffraction study displayed a dinuclear methylene structure [TiCl(tmeda)]2(μ-CH2)(μ-Cl)2. Treatment of an ester with the titanium methylene complex resulted in methylenation of the ester carbonyl to form a vinyl ether. The titanium methylene complex also reacted with a terminal olefin, resulting in olefin-metathesis and olefin-homologation. Cyclopropanation by methylene transfer from the titanium methylene proceeded by use of a 1,3-diene. The mechanistic study of the cyclopropanation reaction by the density functional theory calculations was also reported.


Results and discussion
As in our recent report, 20 the dinuclear zinc methylene complex (1) was prepared by reaction of Zn(0) with CH 2 I 2 in the presence of lead(II) chloride 11 and addition of TMEDA or 2,6-lutidine in THF afforded the corresponding adducts 1a and 1b, respectively. A solid-state structure of the TMEDA adduct 1a (Fig. 1, le) was obtained by X-ray diffraction study of a single crystal grown in THF/hexane. Akin to the recently reported bpy Mes adduct [ZnI(bpy Mes )] 2 (m-CH 2 ) (bpy Mes ¼ 6-Mes-2,2 0 -bipyridyl), 20 the methylene ligand is bridging between two zinc iodido centers (Zn-C: 1.969(7) A, 1.979(7) A; Zn-C-Zn: 109.4(3) ), along with TMEDA in a bidentate coordination mode. The molecular structure of 1a in solid-state revealed a slightly distorted C 2 structure, which gave pseudo-C 2 symmetric NMR spectra in solution.
To gain insight into the transmetallation process between the zinc methylene and titanium chloride, multiple combinations of zinc methylene complexes (1a and 1b) and titanium chlorides ([TiCl 4 (thf) 2 ], [TiCl 4 (tmeda)], [TiCl 3 (thf) 3 ], and 2) with and without additional ligands (PR 3 , pyridine, 4-dimethylaminopyridine, and ethers) were attempted and monitored by NMR spectroscopy. In most cases, 1 H NMR spectra revealed consumption of the zinc methylene species around À1 ppm along with formation of CH 4 and C 2 H 4 as well as some paramagnetic species. Interestingly, the combination of both TMEDA adducts 1a and 2 exclusively resulted in a clean formation of a new diamagnetic titanium methylene species at 9.94 ppm, 21 even though the originally proposed methylidene species should have a single titanium(III) center to be paramagnetic. However, the NMR spectrum still showed a mixture with the remaining zinc methylene species in an approximately 1 : 1 ratio, which was consumed completely by addition of another equivalent of 2 ( Fig. S5, ESI †). 21 Accordingly, treatment of 1a with two equivalents of 2 in benzene (Scheme 2) afforded complex 3 in 69% isolated yield as a reddish brown solid aer removal of a zinc chlorido-iodido TMEDA complex [ZnClI(tmeda)] ( Fig. 1, right), which was structurally characterized by X-ray diffraction. The NMR spectra of the isolated product 3 corroborate the methylene ligand at 1 H: 9.45 ppm and 13 C: 248.2 ppm ( 1 J CH ¼ 114 Hz) along with inequivalent CH 3 and CH 2 resonances of TMEDA. The titanium methylene resonances of 3 are slightly down-eld shied from those of di-or trinuclear m-methylene complexes of titanium ( 1 H: 5.51-8.81 ppm, 13 C: 188.5-253.1 ppm), 22 but much more up-eld shied from those of mononuclear titanium methylidenes ( 1 H: 11.61-12.12 ppm, 13 C: 285.9-295.9 ppm). 23 The methylene complex 3 is stable in solid-state at room temperature for weeks, but the 1 H NMR resonance of the CH 2 ligand at 9.45 ppm gradually diminished in solution at room temperature to form methane CH 4 , which was not deuterated even in THF-d 8 or CD 2 Cl 2 . 21 To conclusively establish the connectivity in 3, X-ray diffraction data on a single crystal grown from a concentrated THF solution were collected. As shown in Fig. 2, the solid-state structure of 3 displayed a C 2 symmetric dinuclear titanium structure bridged by a methylene ligand (Ti1-C1: 2.084(6) A; Ti1-C1-Ti1 0 : 78.4(3) ) and chlorides (Ti1-Cl1: 2.409(2) A; Ti1-Cl2: 2.405(2) A, 2.472 (2) A). The crystal structures of the Tebbe complex [Cp 2 Ti(m-CH 2 )(m-Cl)AlMe 2 ] have been reported by Mindiola 24a and more recently by Anwander, 24b and the Ti-CH 2 bond length in complex 3 (2.084(6) A) is comparable to the reported Ti-CH 2 distances (2.095(5) A, 24a 2.058(3) A) 24b of the Tebbe complex. The bridging mode of the methylene ligand, where the hydrogen atoms were located from the difference map and rened isotropically, is oriented to avoid the steric repulsion with the methyl groups of TMEDA (Fig. 2c). The dinuclear methylene complex 3 is almost isostructural to the recently reported dinuclear chromium(III) alkylidene complexes with TMEDA ligands, [CrCl(tmeda)] 2 (m-CHR)(m-Cl) 2 (R ¼ SiMe 3 , GeMe 3 , SnMeCl 2 ), but those dinuclear chromium(III) alkylidene complexes could be enforced to have a C s symmetry due to the bulky substituents on the bridging alkylidenes. 26 In contrast to the reported dinuclear Ti(IV)-Ti(IV) methylene complexes, 22 the molecular structure of the Ti(III)-Ti(III) methylene complex 3 showed a short Ti-Ti distance of 2.634(2) A, which is much shorter than the sum of van der Waals radii. 25 The density functional theory (DFT) calculations of 3 in singlet ( 1 3) revealed a Ti-Ti bonding interaction (2.637 A) at the HOMO (Fig. 2d) along with the Wiberg bond order index 0.96, while the optimized structure in triplet ( 3 3) has a much longer Ti-Ti distance (3.224 A).
Having the methylene complex 3 in hand, we resorted to demonstrating methylenation of esters, 12 which can be achieved by titanium methylidene species such as the Tebbe reagent. 4a As shown in Scheme 3, methylenation of methyl undecanoate with one equivalent of 3 in THF smoothly proceeded in 76% yield to give a mixture of 2-methoxy-1-decene (4) and its hydrolysis product 5, 27 comparable to that with the reagent prepared in situ from 1a and 2 in a 1 : 2 ratio (4: 50%; 5: 25%). In contrast, no methylenation products 4 or 5 were observed without TMEDA, e.g. a mixture of the 2,6-lutidine adduct 1b and [TiCl 3 (thf) 3 ], 20 implying the necessity of TMEDA to generate the reactive species for methylenation of esters. In addition, methylenation of cyclic esters with 3 could proceed to afford cyclic vinyl ethers, but some ring-opening and oligomerization products were also formed. 21 The titanocene methylidene generated from the Tebbe or Petasis reagents reacts with olens to form titanacyclobutanes reversibly (Scheme 4), 1,28 resulting in olen-metathesis. 6,7 Tebbe and Parshall also found that titanacyclobutanes can undergo b-H elimination and formation of olen-homologation products. 1 In contrast to other metallacyclobutanes, 29 Grubbs and coworkers pointed out the difficulty in promoting reductive elimination of cyclopropane from the mononuclear titanium(IV) metallacyclobutane due to formation of a thermodynamically unfavored titanium(II) product, 30,31 unless assisted by oxidation with I 2 32 or formation of metal-metal interacting Scheme 3 Methylenation of methyl undecanoate by isolated 3 and in situ preparation of 3. Scheme 4 Reversible [2+2]-cycloaddition of olefin to titanium methylidene 1,28 and olefin-metathesis, 6,7 olefin-homologation, 1 and formation of cyclopropane from titanacyclobutanes. 32,33 Scheme 5 Olefin-metathesis and homologation of terminal olefin by 3 and the proposed mechanism (Ti ¼ TiCl(tmeda)).
Takeda and co-workers reported a successful example of cyclopropanation by a combination of titanocene allylidenes and terminal olens (Scheme 6a), 35 while olen-homologation of terminal olens was observed by use of titanocene alkylidenes without a-vinyl groups. 36 Inspired by Takeda's work on the vinylcyclopropanation system, we employed a 1,3-diene for the cyclopropanation reaction by methylene transfer from complex 3. Treatment of a 1,3-diene, (E)-6-phenyl-1,3hexadiene, with 3 at room temperature in CH 2 Cl 2 resulted in selective formation of an (E)-vinyl cyclopropane (11) in 49% yield (Scheme 6b). More conversion of the 1,3-diene to cyclopropane 11 (80% yield) was achieved by further addition of 3 (2 equiv.) and gentle heating at 40 C. However, various olenmetathesis products from the 1,3-diene as well as a small amount of the Z-isomer of 11 were formed by performing the reaction at 80 C (Fig. S12, ESI †).
The similar reactivity of our titanium methylene 3 with titanocene alkylidenes raised the question of whether our dinuclear Ti(III)-Ti(III) system remains in the dinuclear structure during the reaction 37 or generates a mononuclear titanium methylidene. Unfortunately, experimental observation of the dinuclear or mononuclear titanium methylidene species in the reaction system has not been achieved and we decided to carry out the mechanistic study by quantum chemical calculations based on DFT. The vinylcyclopropanation reaction system by complex 3 and a 1,3-diene was employed to gain insight into the reaction selectivity of cyclopropanation. We rst examined whether the 1,3-diene forms a new C-C bond via insertion to the Ti-C bond in the dinuclear complex 3 (Fig. 3) or via [2+2]cycloaddition with a mononuclear titanium methylidene species [Ti]CH 2 ] (A) (Fig. 4). Despite the dinuclear structure of 3 being 2.8 kcal mol À1 lower in relative free energy than  generation of A and [TiCl 2 (tmeda)](m-Cl) 2 (12) (Fig. S14, ESI †), the dinuclear 1,3-diene adduct B, in which the [TiCH 2 Ti] unit is better described as a semi-bridging titanium methylidene (Ti-CH 2 : 1.886 A, 2.546 A), could be located at 37.3 kcal mol À1 (Fig. 3). 38 The transition state of the insertion step (B-TS) was also found with a very high reaction barrier of 45.4 kcal mol À1 leading to dimetallacycle species C and D. In contrast, the mononuclear 1,3-diene adduct E was located at 21.4 kcal mol À1 from A. Upon [2+2]-cycloaddition as illustrated in Fig. 4, the TMEDA ligand changes its coordination mode into a k 1 -fashion (F) to traverse the transition state F-TS. The resulted titanacyclobutane intermediate G undergoes hapticity change of a vinyl group on the a-position to transform into an h 3 -allyl species H. To afford the corresponding cyclopropane 11, reductive elimination from the mononuclear titanium(III) metallacyclobutane should take place, requiring formation of a thermodynamically unfavored titanium(I) species. The p-allylic interaction in H allows reductive ring-closing elimination in H-TS to maintain the titanium(III) character (Fig. 5). As a result, this back-bonding interaction lowers the reaction barrier of the reductive elimination process to give the cyclopropanation product selectively rather than undergoing metathesis or b-H elimination process as in the reaction of terminal olens. 39 Note that a positional isomer of G, b-vinyl titanacyclobutane (G 0 ) given by [2+2]cycloaddition in the other fashion, is also a conceivable intermediate but cannot form a similar p-allyl conguration due to its strained structure for coordination to the titanium center. 40 The mononuclear complex I may bind [TiCl 3 (tmeda)] to form a dinuclear chloride (J) and then eliminate cyclopropane 11 and a titanium(II) chloride dimer (13) rather than formation of unlikely "TiCl(tmeda)". Although a mononuclear titanium(II) chloride [TiCl 2 (tmeda) 2 ] is kinetically stable, 30 the titanium(II) chloride dimer [TiCl(tmeda)] 2 (m-Cl) 2 (13) can readily undergo disproportionation to titanium(III) chloride and some low-valent byproducts. 30a,31 In fact, a dinuclear mixed-valent Ti(II)-Ti(III) chloride [TiCl(tmeda)] 2 (m-Cl) 3 (Fig. S15, ESI †), which has been reported by Gambarotta from thermal decomposition of [TiCl 2 (tmeda) 2 ], 30a was reproducibly observed in our cyclopropanation reaction system.

Conclusions
We have shown a transmetallation pathway between a zinc methylene complex [ZnI(tmeda)] 2 (m-CH 2 ) and titanium(III) chloride, resulting in formation of a dinuclear titanium methylene [TiCl(tmeda)] 2 (m-CH 2 )(m-Cl) 2 . The solid-state structure showed the rst example of a dinuclear Ti(III)-Ti(III) methylene complex. Methylene transfer reactions to ester, terminal olen and 1,3-diene have been demonstrated. The powerful methylenation reactivity and mechanistic study both propose generation of a titanium(III) methylidene species.

Conflicts of interest
There are no conicts to declare.