O-quinone methide complex

Lev, D. A. Grotjahn, D. B. Amouri, H. Reversal of reactivity in diene-complexed o-quinone methide complexes insights and explanations from ab initio density functional theory calculations. Organometallics 2005, 24, 4232 -240. 

Amouri, H. Besace, Y. Bras, J. L. Vaissermann, J. General synthesis, first crystal structure, and reactivity of stable o-quinone methide complexes of Cp Ir. J. Am. Chem. Soc. 1998, 120, 6171-6172. 

Amouri and coworkers also demonstrated that the nucleophilic reactivity of the exocyclic carbon of Cp Ir(T 4-QM) complex 24 could be utilized to form carbon -carbon bonds with electron-poor alkenes and alkynes serving as electrophiles or cycloaddition partners (Scheme 3.17).29 For example, when complex 24 was treated with the electron-poor methyl propynoate, a new o-quinone methide complex 28 was formed. The authors suggest that the reaction could be initiated by nucleophilic attack of the terminal carbon of the exocyclic methylene group on the terminal carbon of the alkyne, generating a zwitterionic oxo-dienyl intermediate, followed by proton transfer... 

In a similar approach, double deprotonation of r 6-coordinated ortho- and para-cresols, 30 and 31, with t-BuOK led to formation of stable r 4-coordinated p- and o-quinone methide complexes of manganese, 32 and 33 (Scheme 3.19).37... 

The synthesized complex does not react with air, carbon monoxide, or trimethylpho-sphine. It is noted [183a] that the rhodium center is very strongly bound to the quinonoid ligand. Recently, Vaissermann et al. have synthesized and fully characterized (even by x-ray diffraction) the first o-quinone methide complex, with Ir as the metal center [183b]. This complex is highly stable at room temperature, a notable difference when it is compared with the simplest known o-quinone methide that is unstable above — 100°C [183c],... 

Phenol complexes of [Os] display pronounced reactivity toward Michael acceptors under very mild conditions. The reactivity is due, in part, to the acidity of the hydroxyl proton, which can be easily removed to generate an extended enolate. Reactions of [Os]-phenol complexes are therefore typically catalyzed using amine bases rather than Lewis acids. The regio-chemistry of addition to C4-substituted phenol complexes is dependent upon the reaction conditions. Reactions that proceed under kinetic control typically lead to addition of the electrophile at C4. In reactions that are under thermodynamic control, the electrophile is added at C2. These C2-selective reactions have, in some cases, allowed the isolation of o-quinone methide complexes. As with other [Os] systems, electrophilic additions to phenol complexes occur anti to the face involved in metal coordination. 

Fig. 7. Formation of an j/2-o-quinone methide complex from an aldol condensation of crotonaldehyde and the j/2-phenol complex 85.

Another example of C2 alkylation is the generation of o-quinone methide complexes from [Os]-phenol and crotonaldehyde. When these reagents are combined in the presence of BF3-OEt2, addition occurs at C4 (Table 14). In the absence of a catalyst, an aldol condensation occurs at C2 to generate the o-quinone methide complex 97 in 85 % yield (Figure 7) [29]. This reaction appears to be general for aldehydes and r/2-phenol complexes, even when the phenol is not substituted at C4. 

W(Tp)(NO)(PMe3)(r]2-benzene)] reacted with an excess of phenol to yield the two steroisomers of [W(Tp)(NO)(PMe3)(r]2-2H-phenol)] (Fig. 2.44), which in the presence of base and electrophilic species such as benzaldehyde, alkyl iodides, and Michael acceptors, is able to form new C-C bonds. Methyl and ethyl iodide react at C2 to form 2-alkyl-2H-phenol complexes, whereas the Michael acceptors react at C4 to give 4-alkyl-4H-phenol complexes. The crystal and molecular structures of the 2-ethyl-2H-phenol and of the phenyl o-quinone methide complexes have been reported.190... 

Another interesting example of ort/zo-addition to phenol complexes is its reaction with aldehydes. In the presence of a weak base, the aldehyde undergoes an aldol condensation at C2 to give a rare example of a stable o-quinone methide complex. In Fig. 9 citronellal (34) is combined with phenol complex 20 to generate the quinone methide 35. Upon oxidative decomplexation a hetero-Diels-Al-der reaction occurs to form the benzochromene core 37 in 52% yield [48]. 

Fig. 9 Formation of an o-quinone methide complex, decomplexation, and subsequent cycloaddition of the free quinone methide...

An additional notable mode of the reactivity of these quinone methide complexes is formation of metal stabilized p- and o-xylylenes.10... 

These reactions clearly indicate that the exocyclic carbon of the complexed QM in these systems is nucleophilic in character, in contrast to its electrophilic nature in free o-quinone methides. The Cp Ir metal center stabilizes the mesomeric form in which the exocyclic carbon experiences high electron density (Scheme 3.18).29... 

Solid state excitation of electron donor-acceptor complexes of various diaryl-acetylenes and dichlorobenzoquinone in either the acceptor or the 1 2 complex absorption bands induces [2+2] cycloaddition and produces identical mixtures of the quinone methides. Evidence is presented for the participation of an ion-radical pair as the reactive intermediate in both cases. Irradiation of an appropriately substituted o-hydroxybenzyl alcohol precursor generates the corresponding o-quinone methide which is reported to undergo an efficient [4+2] cycloaddition to form the hexahydrocannabinol system. Time-resolved studies confirm the intermediacy of the o-quinone methide and show its lifetime to be > 2 ms. Laser photolysis of 1,2-bis(phenoxymethyl)benzene, l,2-bis[(phenylthio)-methyl]benzene, and l,2-bis[(phenylseleno)methyl]benzene occurs by a two-photon process to produce o-quinodimethane which will cycloadd to various dienophiles including maleic anhydride, dimethyl maleate, dimethyl fumarate, fumaronitrile and dimethyl acetylenedicarboxylate. ... 

With the exception of the abundant o-quinone methide Uterature (62), there is only a single example of a diene exocycUc to a ring [59]. The use of the very reactive o-quinone methide diene, for intramolecular cycloaddition, was introduced by Oppolzer in 1971 (64). Initially, these were prepared by thermolysis of a preformed benzocyclobutene [60, 61]. Later, Vollhardt demonstrated that 1,5 diacetylenes could serve as precursors to benzocyclo-butenes and thus, to o-quinone methides [62]. Since that time, several other methods for the generation of o-quinone methides have been developed [63-68], some of which allow generation of the o-quinone methide under very mild reaction conditions. These methods also allow the incorporation of more complex functionality in the ring system. 

Release and Reactivity of tf-o-QMs Although the r 2-o-QM Os complexes 11 are stable when exposed to air or dissolved in water, the quinone methide moiety can be released upon oxidation (Scheme 3.8).16 For example, reaction of the Os-based o-QM 12 with 1.5 equivalents of CAN (ceric ammonium nitrate) in the presence of an excess of 3,4-dihydropyran led to elimination of free o-QM and its immediate trapping as the Diels-Alder product tetrahydropyranochromene, 14. Notably, in the absence of the oxidizing agent, complex 12 is completely unreactive with both electron-rich (dihydropyran) and electron-deficient (A-methylmaleimide) dienes. 

An alternative route for stabilization of quinone methides by metal coordination involves deprotonation of a ri5-coordinated oxo-dienyl ligand. This approach was introduced by Amouri and coworkers, who showed that treatment of the [Cp Ir(oxo-ri5-dienyl)]+ B1, 22 with a base (i-BuOK was the most effective) resulted in formation of stable Cp Ir(r 4-o-QM) complexes 23 (Scheme 3.14).25 Using the same approach, a series of r 4-o-QM complexes of rhodium was prepared (Scheme 3.14)26 Structural data of these complexes and a comparison of their reactivity indicated that the o-QM ligand is more stabilized by iridium than by rhodium. 

Rabin, O. Vigalok, A. Milstein, D. A novel approach towards intermolecular stabilization of para-quinone methides. First complexation of the elusive, simplest quinone methide, 4-methylene-2,5-cyclohexadien-l-one. Chem. Eur. J. 2000, 6, 454-462. 

FIGURE 6.16 ortho-Quinone methide 3 stabilization of the zwitterionic rotamer in a complex with /V-methyImorpholine /V-oxide (17). The zwitterionic, aromatic precursor 3a affords the common quinoid form of the o-QM 3 by in-plane rotation of the exocyclic methylene group. 

The geometry of the zwitterions with its exocylic out-of-plane methylene group was quasi-preserved in the recently reported dibenzodioxocine derivative (18) that was formed in rather small amounts by rapidly degrading the NMMO complex at elevated temperatures.45 Strictly speaking, dibenzodioxocine dimer 18 is actually not a dimer of ortho-quinone methide 3, but of its zwitterionic precursor or rotamer 3a (Fig. 6.17). As soon as the out-of-plane methylene group in this intermediate rotates into the ring plane, the o-QM 3 is formed irreversibly and the spiro dimer 9 results... 

FIGURE 6.17 Oxidation of a-tocopherol (1) conventionally leads to its spiro dimer (9) via ortho-quinone methide 3 (path A). The zwitterionic o-QM precursor 3a is stabilized by NMMO in complex 17, which upon rapid heating produces small amounts of new dioxocine dimer 18 (path B). Acid treatment of 18 causes quantitative conversion into spiro dimer 9, via o-QM 3 (path C). 

It was shown that complexes 19 of the zwitterionic precursors of ortho-quinone methides and a bis(sulfonium ylide) derived from 2,5-di hydroxyl 1,4 benzoquinone46 were even more stable than those with amine N-oxides. The bis(sulfonium ylide) complexes were formed in a strict 2 1 ratio (o-QM/ylide) and were unaltered at —78 °C for 10 h and stable at room temperature under inert conditions for as long as 15—30 min (Fig. 6.18).47 The o-QM precursor was produced from a-tocopherol (1), its truncated model compound (la), or a respective ortho-methylphenol in general by Ag20 oxidation in a solution containing 0.50-0.55 equivalents of bis(sulfonium ylide) at —78 °C. Although the species interacting with the ylide was actually the zwitterionic oxidation intermediate 3a and not the o-QM itself, the term stabilized o-QM was introduced for the complexes, since these reacted similar to the o-QMs themselves but in a well defined way without dimerization reactions. 

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