Carbenes phenol reactions

Structural analogues of the /]4-vinylketene E were isolated by Wulff, Rudler and Moser [15]. The enaminoketene complex 11 was obtained from an intramolecular reaction of the chromium pentacarbonyl carbene complex 10. The silyl vinylketene 13 was isolated from the reaction of the methoxy(phenyl)-carbene chromium complex 1 and a silyl-substituted phenylacetylene 12, and -in contrast to alkene carbene complex 7 - gave the benzannulation product 14 after heating to 165 °C in acetonitrile (Scheme 6). The last step of the benzannulation reaction is the tautomerisation of the /]4-cyclohexadienone F to afford the phenol product G. The existence of such an intermediate and its capacity to undergo a subsequent step was validated by Wulff, who synthesised an... 

Wulff et al. examined the necessary reaction conditions for a,fi-unsaturated aminocarbene complexes to react in a benzannulation reaction [23]. The reaction of dimethylamino(alkenyl)carbene complexes 18 with terminal alkynes in non-coordinating and non-polar solvents afforded phenol products in acceptable yields (Scheme 12). 

The convergent approach comprises, among other reaction steps, a regio-specific intermolecular benzannulation reaction between the alkyne 88 and the chromium carbene complex 89 for AB ring construction (Scheme 43). It is noteworthy that the regioselectivity of this reaction is attributed to the bulky TBDMS ether in the alkyne a-substituent, that dictates the incorporation of the large substituent ortho to the phenol. Another curiosity is the fact that the reaction failed to provide 90 in the absence of acetic anhydride. 

A plausible pathway is that the aromatisation of the cyclohexadienone 92 by a proton shift is accelerated in the presence of Ac20 under formation of acetate 93. The simultaneously generated acetic acid then cleaves the acetate to form the free phenol 94 (Scheme 44). This effect was observed for the first time during studies towards the total synthesis of the lipid-alternating and anti-atherosclerotic furochromone khellin 99 [64].The furanyl carbene chromium complex 96 was supposed to react with alkoxyalkyne 95 in a benzannulation reaction to give the densely substituted benzofuran derivative 97 (Scheme 45). Upon warming the reaction mixture in tetrahydrofuran to 65 °C the reaction was completed in 4 h, but only a dimerisation product could be isolated. This... 

Generally phenol formation is the major reaction path however, relatively minor modifications to the structure of the carbene complex, the alkyne, or the reaction conditions can dramatically alter the outcome of the reaction [7]. Depending on reaction conditions and starting reactants roughly a dozen different products have been so far isolated, in addition to phenol derivatives [7-12], In particular, there is an important difference between the products of alkyne insertion into amino or alkoxycarbene complexes. The electron richer aminocarbene complexes give indanones 8 as the major product due to failure to incorporate a carbon monoxide ligand from the metal, while the latter tend to favor phenol products 7 (see Figure 2). 

Arene(alkoxy)carbene chromium complexes react with aryl-, alkyl-, terminal, or internal alkynes in ethers or acetonitrile to yield 4-alkoxy-1-naphthols, with the sterically more demanding substituent of the alkyne (Rl Figure 2.24) ortho to the hydroxy group. Acceptor-substituted alkynes can also be used in this reaction (Entry 4, Table 2.17) [331]. Donor-substituted alkynes can however lead to the formation of other products [191,192]. Also (diarylcarbene)pentacarbonyl chromium complexes can react with alkynes to yield phenols [332]. 

Depending on the types of substituents and the precise reaction conditions (l,3-butadien-l-yl)carbene complexes can undergo direct cyclization to yield cyclo-pentadienes [337,350]. As mentioned in Section 2.2.5.1, cyclopentadiene formation occurs particularly easily with aminocarbene complexes [351]. Alternatively, in particular at higher reaction temperatures, CO-insertion can lead to the formation of a vinylketene complex, which, again depending on the electronic properties of the substituents and the reaction conditions, can cyclize to yield cyclobutenones, furans [91,352], cyclopentenones, furanones [91], or phenols (Dotz benzannulation) [207,251,353]. 

Electron-rich carbyne complexes can react at the carbyne carbon atom with electrophiles to yield carbene complexes. Numerous examples of such reactions, mostly protonations, have been reported [519]. Depending on the nucleophilicity of the carbyne complex, such reactions will occur more or less readily. The protonation of weakly nucleophilic carbyne complexes requires the use of strong acids, such as triflic [533], tetrafluoroboric [534] or hydrochloric acid [535,536]. More electron-rich carbyne complexes can, however, even react with phenols [537,538], water [393,539], amines [418,540,541], alkyl halides, or intramolecularly with arenes (cyclometallation, [542]) to yield the corresponding carbene complexes. A selection of illustrative examples is shown in Figure 3.25. 

Density functional calculations on the Dotz reaction leading from chromium carbene (75) with acetylene to give the phenol (78) suggested a new mechanism involving the formation of a chromahexatriene complex (77) from the initially formed vinylallyl-idene complex (76). " Complex (77) then collapses to the phenol complex (78). 

Cannizzaro reaction, 2, 3 Carbanion, electrophilic amination, 72, 1 Carbenes, 13, 2 26, 2 28, 1 Carbene complexes in phenol and quinone synthesis, 70, 2... 

However, difluoromethylation occurs when nucleophiles intercept difluoro-carbene generated under basic conditions, providing a route to difluoromethyl-ethers of phenols [33] and thiophenols [34]. The reaction with phosphite anion leads to the corresponding difluoromethyl phosphonate (see Sect. 2.3.2) while nucleophilic carbanions such as alkynes [35] also undergo formal alkylation, as do malonates [36,37]. An -difluoromethylaziridine was reported in a reaction with a glycine imine [38]. The scope of the established chemistry is summarised in Fig. 1. Bromodifluoromethylation occurs with a similar range of nucleophiles [39,40], and also with carbonyl-stabilised carbanions such as malonates [41,42]. 

At the beginning of the new millennium, Hashmi et al. presented a broad research study on both intramolecular and intermolecular nucleophilic addition to alkynes and olefins [18]. One of the areas covered by these authors was the isomerization of co-alkynylfuran to phenols [19]. After that, Echavarren and coworkers identified the involvement of gold-carbene species in this type of process, thus opening a new branch in gold chemistry [20]. And subsequently, Yang and He demonstrated the initial activation of aryl —H bonds in the intermolecular reaction of electron-rich arenes with O-nucleophiles [21, 22]. 

Fig. 10. Multiple derivatization of purines including palladium-catalyzed reaction at the poorly reactive C2 position, (a) NaBH(OAc)3, 1% HOAc, THF (b) 59 (0.5 equiv.), 2,6-dichloropurine (1 equiv.), DIEA (1.5 equiv.), BuOH 80° (c) R2OH, PPh3, DiAD (1.5 2 1.3) in excess, THF, RT (d) boronic acids (5 equiv.), 7% Pd2(dba)3, 14% carbene ligand, Cs2C03 (6 equiv.), 1,4-dioxane, 90°, 12 h (e) anilines (5 equiv.), 7% Pd2(dba)3, 14% carbene ligand, KO Bu (6 equiv.), 1,4-dioxane, 90°, 12 h (f) phenols (5 equiv.), 7% Pd2(dba)3, 28% phosphine ligand, K3P04 (7 equiv.), toluene, 90°, 12 h (g) primary or secondary amines (5 equiv.), 90°, 12 h.

Well-established is the formation of hydroquinone and phenol derivatives 273 from alkynes. This reaction is called the Dotz reaction [78,79]. The reaction of carbene complex 271 to give 273 can be expressed by the general scheme 272. 

Generally, octatriene formation is favored by higher temperatures, higher phosphine and/or butadiene concentrations and, importantly, by an increase in steric bulk of either the ligand or the nucleophile. Indeed, Harkal et al. showed a selectivity switch from telomerization products to 1,3,7-octatriene formation by altering the steric demand of the /V-heterocyclic carbene ligand in the reaction of butadiene with isopropanol under further identical reaction conditions [48]. For the more basic nucleophiles, such as the alcohols, the telomer products are stable under experimental conditions, i.e. product formation is irreversible, but for more acidic substrates such as phenol, product formation is reversible and more 1,3,7-octatriene will be formed after the substrate has been depleted. 

The preparation of different (NHC) - Pd°(dvds) complexes allowed the authors to make a systematic comparison of structure/activity for the telomerization reaction [228]. This study showed that electron-withdrawing substituents on the carbene backbone destabilizes the catalyst and therefore enhance its reactivity. These catalysts are applicable to primary and secondary alcohol as well as phenols and represent the first industrially viable catalyst system for palladium-catalyzed telomerization of butadiene with alcohol. 

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