Oxygen Bond-Forming Reactions

A useful assortment of carbon-carbon bond forming reactions such as alkylation of enolates and enamines and carbon-oxygen bond forming reactions such as epoxidation with ylides have been described in this chapter. 

Carbon-Carbon and Carbon-Oxygen Bond-Forming Reactions... 

Carbon - Oxygen Bond Forming Reactions at Room Temperature... 

SCHEME 1.5 Example of a rhodium-catalyzed carbon-oxygen bond-forming reaction [17]. 

Malonic acid ester synthesis is a classic but still one of the most important C—C bond-forming reactions, because it is widely applicable to various types of compounds and the reaction can be performed under mild conditions without special care to remove the trace amount of water and oxygen contained in the solvent. This reaction is especially useful in the synthesis of carboxylic acids. One important class of carboxylic acids is arylpropionates because optically active ones are known to have anti-inflammatory activity and other interesting physiological... 

A variety of double bonds give reactions corresponding to the pattern of the ene reaction. Those that have been studied from a mechanistic and synthetic perspective include alkenes, aldehydes and ketones, imines and iminium ions, triazoline-2,5-diones, nitroso compounds, and singlet oxygen, 10=0. After a mechanistic overview of the reaction, we concentrate on the carbon-carbon bond-forming reactions. The important and well-studied reaction with 10=0 is discussed in Section 12.3.2. 

Arguably the most challenging aspect for the preparation of 1 was construction of the unsymmetrically substituted sec-sec chiral bis(trifluoromethyl)benzylic ether functionality with careful control of the relative and absolute stereochemistry [21], The original chemistry route to ether intermediate 18 involved an unselective etherification of chiral alcohol 10 with racemic imidate 17 and separation of a nearly 1 1 mixture of diastereomers, as shown in Scheme 7.3. Carbon-oxygen single bond forming reactions leading directly to chiral acyclic sec-sec ethers are particularly rare since known reactions are typically nonstereospecific. While notable exceptions have surfaced [22], each method provides ethers with particular substitution patterns which are not broadly applicable. 

Monoanions derived from nitroalkanes are more prone to alkylate on oxygen rather than on carbon in reactions with alkyl halides, as discussed in Section 5.1. Methods to circumvent O-alkylation of nitro compounds are presented in Sections 5.1 and 5.4, in which alkylation of the a.a-dianions of primary nitro compounds and radial reactions are described. Palladium-catalyzed alkylation of nitro compounds offers another useful method for C-alkylation of nitro compounds. Tsuj i and Trost have developed the carbon-carbon bond forming reactions using 7t-allyl Pd complexes. Various nucleophiles such as the anions derived from diethyl malonate or ethyl acetoacetate are employed for this transformation, as shown in Scheme 5.7. This process is now one of the most important tools for synthesis of complex compounds.6811-1 Nitro compounds can participate in palladium-catalyzed alkylation, both as alkylating agents (see Section 7.1.2) and nucleophiles. This section summarizes the C-alkylation of nitro compounds using transition metals. 

This landmark discovery paved the way for the development of transition metal-catalyzed hydroboration. The conversion of an alkene into an organoborane intermediate has made this a valuable synthetic technique, particularly since the development of enantioselective variants.9,10 They serve as synthons for numerous functional groups11 and are often subjected to a consecutive carbon-oxygen, carbon-carbon, boron-carbon, boron-chlorine, or carbon-nitrogen24 bond-forming reaction (Scheme 3). 

Anions derived from malonates are ambident nucleophiles, which can react at the carbon or oxygen atom. Therefore, carbon-carbon bond-forming reactions by alkylation or acylation of enolates have been encountered with difficulties. Side reactions which may cause problems are the above-mentioned competiting O-reaction and dialkylation . 

The copper catalyzed carbon-heteroatom bond forming reactions are also efficient in the introduction of oxygen and phosphorous based substitutents onto the aromatic ring. 3-Iodopyridine was reacted with -butanol in the presence of 10 mol% copper(I) iodide and 20 mol% 1,10-phenantroline... 

The last example focuses not on the functionalization of heterocycles by a transition metal mediated carbon-heteroatom bond forming reaction, but the palladium catalyzed conversion of primary amines, including amino-heterocycles, into urea derivatives. A representative example, shown in 8.38., includes the reaction of an amino-carbazole derivative with morpholine, carbon monoxide and oxygen in the presence of catalytic amounts of palladium(II) iodide. The formation of the urea moiety proceeds with great selectivity and in high yield.49 The reaction works equally well for primary aliphatic and aromatic amines. 

There is keen interest in developing nitrogen-carbon bond-forming reactions akin to oxygen atom transfer and selective oxidations in organic chemistry. 

Oxidative coupling of a terminal alkyne is a particularly easily performed carbon-carbon bond forming reaction, which results in a good yield of the symmetrical diacetylene. A widely used procedure involves the oxidation of the alkyne with air or oxygen in aqueous ammonium chloride in the presence of a copper(i) chloride catalyst (Glaser oxidative coupling). 

The synthesis of substituted tetrahydropyranylidene acetates such as 465 and 466 can be accomplished by TiCU-promoted carbon-carbon bond-forming reactions of ethyl glyoxylate, 3,4-dihydro-2/7-pyran 455, and oxygen or sulfur nucleophiles (Scheme 82). The reaction is an efficient three-component coupling process and the overall outcome of the reaction is dependent upon reaction temperature <1999TL4751>. 

Triethylborane generates Et via the reaction with molecular oxygen under air, and its reacts with RfI to generate Rf and EtI via SH2 reaction pathway. So, Et3B/RfI/electron-rich olefin system can be used for the carbon-carbon bond forming reaction. 

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