O-C Bond Formation

However, despite success in several tandem reactions, or in epoxidation reactions, there are only a few examples in the literature of simple oxo-Michael reactions with enals. 

In the same year, Maruoka and coworkers developed an alternative for the Michael addition of alcohols [66], Using a biphenyl catalyst derivative, methanol, ethanol, and allylic alcohol react with aliphatic enals, albeit with moderate yields and enantioselectivities. 

Following the development of palladium- and copper-catalyzed C—N bond-forming methodology came the advent of the corresponding C—O bond-forming techniques. Initially, the development of this area progressed slowly in comparison. However, efficient methods using both palladium and copper catalysis are now well established. 

Several research groups have detailed syntheses of benzofurans via similar routes [110,111], including use of on-water chemistry [112] and the use of aldehyde substrates with copper catalysis to yield 2-unsubstituted benzofurans [113]. 

Strategies involving tandem catalytic processes have also found application in benzofuran synthesis. In a process analogous to Barluenga et al. s strategy for indole 

Iron Catalysts Iron-catalyzed C—H oxidation systems such as the Gif [59] and Fenton [60] reactions are well-known examples of C—H functionalization. However, stereospecific sp3 C—H bond oxidation is still a great challenge for the application of iron-catalyzed C—H oxidations. Recently, selective oxidation of non-activated sp3 C—H bonds has been realized (Equation 11.25) [61]. Various complex substrates are converted into the corresponding alcohols with high diastereoselectivity under mild reaction conditions. 

Copper Catalysts When N-hydroxyphthalimide is used as an oxygen source, a range of substrates can be selectively oxygenated using PhI(OAc)2 as an oxidant in the presence of CuCl catalyst (Equation 11.26) [62]. When a radical trap, TEMPO (2,2,6,6-tetramethyl-l-piperidinyloxy), is added to the reaction mixture, a TEMPO-trapped compound can be isolated (21%) along with 23% of the desired product. Therefore, a radical intermediate is most likely involved in this transformation [63]. 

Significantly, unactivated sp3 C—H bond oxidation has been achieved using oxime or pyridine as a directing group and PhI(OAc)2 as a stoichiometric oxidant in the presence of a palladium catalyst (Equation 11.28) [66], y-C- H bonds are selectively oxygenated. The selectivity is dramatically influenced by the steric and electronic properties of the alkane substrates. 

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Tire first C—O bond formation is probably not influenced strongly by the presence of a templating cation. Since it is not crucial for one end of the chain to meet the other rather than reacting with a different molecule, it is not necessary to superimpose either a template or dilution condition on the reaction to prejudice the statistics. In the second step, however, such a prejudicial condition is required. This is available in the form of an... 

In the case of terminal alkynes having oxygenated functions in the linear chain (Scheme 10, route D), Martin, Padron, and coworkers found that homopropargylic alcohols reacted properly, yielding 2-substituted dihydropyrans as sole products, probably via a Prins-type cyclization. This cyclization provides a new approach toward 2-alkyM-halo-5,6-dihydro-2//-pyrans through a concomitant C-C and C-O bond formation (Scheme 21) [35]. 

Muci AR, Buchwald SL (2002) Practical Palladium Catalysts for C-N and C-O Bond Formation. 219 131-209... 

Palladium-catalyzed aromatic C—O bond formation is less developed than palladium-catalyzed aryl amination. Except when the aryl halide is strongly electron deficient,107-110 catalysts ligated by the conventional aryl phosphines such as DPPF and BINAP are ineffective for coupling of... 

Only transformations in the longest linear sequence (LLS) are considered. The term skeleton constructions refers to C-C and C-O bond formations (notwithstanding redox reactions) that directly introduce native structural features of the bryostatins without further modification. The term other functional group manipulations refers to steps that indirectly introduce native structural elements, the interconversion of functional groups (e.g., the introduction and removal of auxiliaries) and miscellaneous transformations that do not involve skeleton construction... 

This process is likely to proceed via a palladacycle intermediate followed by a Pd(ll) to Pd(iv) oxidation. Reductive elimination occurs with C-O bond formation and regeneration of the Pd(ll) catalyst. Evidence for a palladacycle intermediate is supported by the high regioselectivity (8-Me group oxidized) observed for the oxidative functionalization of 5,8-dimethylquinoline, which, in the absence of a possibility of coordination, would otherwise contain two identical methyl groups (Equation (57)). 

C-O Bond Formation through Transition Metal-mediated Etherification... 

Mechanistic studies carried out by the Buchwald group97,98 on the key C-O bond formation step in these reactions have reinforced the importance of the properties of the ligand, and have led to the adoption of a variety of more sterically hindered ligands (e.g., 23, 24, 27, 29, and 30), which have given improved results for the preparation of biaryl ethers (Equation (15)),89 /-butyl aryl ethers,99 and aryl ethers of primary alcohols.100... 

Another approach toward C-O bond formation using alkynes that has been pursued involves the intermediacy of transition metal vinylidenes that can arise from the corresponding y2-alkyne complexes (Scheme 13). Due to the electrophilicity of the cr-carbon directly bound to the metal center, a nucleophilic addition can readily occur to form a vinyl metal species. Subsequent protonation of the resulting metal-carbon cr-bond yields the product with anti-Markovnikov selectivity and regenerates the catalyst. 

Nitrosoimines can undergo thermal reaction, a unimolecular, two-step mechanism has been proposed, as shown in Scheme 3.22 [193]. In this mechanism, a concerted electrocyclization is envisioned to form the strained four-membered ring in 41, followed by a presumably forbidden, but highly exothermic, deazetization to give 41. The electrocyclic ring closure is, at first glance, a 4-electron process, analogous to the cyclization of butadiene [194] or acrolein [194, 195]. This would be expected to involve rotation around the C=N bond coupled with C-O bond formation. 

The Buchwald-Hartwig C—N bond and C—O bond formation reactions 1.7.1 Pd-catalyzed C—N bond formation... 

The Pd-catalyzed intermolecular C—O bond formation has also been achieved [105-108]. Novel electron-rich bulky phosphine ligands utilized by Buchwald et al. greatly facilitated the Pd-catalyzed diaryl ether formation [109], When 2-(di-tert-butylphosphino)biphenyl (95) was used as the ligand, the reaction of triflate 93 and phenol 94 elaborated diaryl ether 96 in the presence of Pd(OAc)2 and K3PO4. The methodology also worked for electron-poor, neutral and electron-rich aryl halides. 

The mechanism for Pd-catalyzed C—O bond formation is similar to that of C—N bond formation. Application of this method to heterocyclic chemistry is yet to be seen, partially because the SnAt displacements of many heteroaryl halides with alkoxides are facile without the aid of palladium. 

Keywords Asymmetric Catalysis a Natural Product Synthesis a Chiral Metal-Based Complexes a Enantioselective C-C Bond Formation a Enantioselective C-O Bond Formation... 

Table 2.12. Demetallation of heteroatom-substituted carbene complexes with simultaneous C-H, C-N, and C-O bond formation.

Direct Pd-catalyzed C-N and C-O bond formation from aryl halides and amines in the presence of stoichiometric amount of base. 

The C-O bond formation reaction follows a similar mechanistic pathway. 

Concerning their structure and reactions, organic radical cations have been the focus of much interest. Among bimolecular reactions, the addition to alkenes and their nucleophilic capture by alcohols, which lead to C—C and C—O bond formation, respectively have been investigated in detail. Unimolecular reactions like geometric isomerization and several other rearrangements have also attracted attention. 

This method was successfully used in a concise catalytic enantioselective total synthesis of (+)-patulolide C by serving as a key asymmetric C—O bond formation step (Scheme 5.33)." ... 

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