Carbon-centered nucleophiles, additions

The first example of asymmetric catalytic ring-opening of epoxides with sp2-hybridized carbon-centered nucleophiles was reported by Oguni, who demonstrated that phenyllithium and a chiral Schiff base ligand undergo reaction to form a stable system that can be used to catalyze the enantioselective addition of phenyllithium to meso-epoxides (Scheme 7.24) [48]. Oguni proposed that phenyllithium... 

Zhang et al. developed the enantioselective chiral phosphine-catalyzed addition of 2,3-allenoates with carbon-centered nucleophiles and electron-deficient olefins leading to efficient enantioselective C-C bond formation [248, 249]. 

Besides the classical additions of carbon-centered nucleophiles to the electrophilic sites of the cumulenic chain, transition-metal allenyhdenes are able to promote... 

Transition metal-catalyzed allylic alkylation is generally considered to involve mechanistically four fundamental steps as shown in Scheme 1 coordination, oxidative addition, ligand exchange, and reductive elimination. A key step of the catalytic cycle is an initial formation of a (7r-allyl)metal complex and its reactivity. The soft carbon-centered nucleophiles, defined as those derived from conjugate acids whose pAj, < 25, usually attack the allyl ligand from the opposite side... 

A formal asymmetric nucleophilic addition to carbonyl compounds is achieved by Trost and his co-workers in the allylic alkylation of acylals of alkenals. An excellent enantioselectivity is observed in this alkylation. The starting acylals are easily prepared by the Lewis-acid catalyzed addition of acid anhydrides to aldehydes, by use of Trost s ligand 118 (Scheme 13), where various carbon-centered nucleophiles are available (Scheme l4),101,101a-10lc Asymmetric synthesis of some natural products is achieved according to this procedure. 

In 2002, Trost and his co-workers reported a stereospecific ruthenium-catalyzed allylic alkylation reaction (Equation (58)). Treatment of an optically active allylic carbonate with carbon-centered nucleophiles in the presence of a ruthenium complex gives the corresponding allylic alkylated compounds with enantiomeric purity being completely maintained. Additionally, the regioselectivity is revealed not to be highly dependent on the nature of the starting carbonates. 

Carbon-centered nucleophiles can also be used to advantage in the reaction with epoxides. For example, the lithium enolate of cyclohexanone 96 engages in nucleophilic attack of cyclohexene oxide 90 in the presence of boron trifluoride etherate to give the ketol 97 in 76% yield with predominant syn stereochemistry about the newly formed carbon-carbon bond <03JOC3049>. In addition, a novel trimethylaluminum / trialkylsilyl triflate system has been reported for the one-pot alkylation and silylation of epoxides, as exemplified by the conversion of alkenyl epoxide 98 to the homologous silyl ether 99. The methyl group is delivered via backside attack on the less substituted terminus of the epoxide <03OL3265>. 

Indeed, a variety of heterocyclic compounds, such as thiophenes, dithiophenes, pyrroles, indoles, or carbazoles can be involved as carbon-centered nucleophiles in these reactions to modify the pyrimidine ring (Scheme 31) [120-122]. For instance, it has been shown that 5-bromopyrimidine reacts with dithiophene into the corresponding 5-substituted pyrimidine due to palladium-catalyzed aryl-aryl C-C cross-coupling reaction. On the other hand, 5-bromo-4-dithiophenyl-substituted pyrimidine was prepared from the same starting material through the SH (addition-oxidation) reaction catalyzed by a Lewis acid in the presence of potassium... 

BB catalysts provided that the presence of the basic unit has been demonstrated to be crucial for successful catalytic activity. The use of this type of catalysts has been very successful in many organocatalyzed conjugate additions involving carbon-centered nucleophiles. However, few effective enantioselective approaches are known for the aza-Michael reaction employing BB catalysis. All the examples described employ cinchone-based catalysts which may or may not include hydrogen-bond donors. One example is the enantioselective Michael addition... 

A very important relationship between stereochemistry and reactivity arises in the case of reaction at an 5 carbon adjacent to a chiral center. Using nucleophilic addition to the carbonyl group as an example, it can be seen that two diastereomeric products are possible. The stereoselectivity and predictability of such reactions are important in controlling stereochemistry in synthesis. 

The reaction starts with the nucleophilic addition of a tertiary amine 4 to the alkene 2 bearing an electron-withdrawing group. The zwitterionic intermediate 5 thus formed, has an activated carbon center a to the carbonyl group, as represented by the resonance structure 5a. The activated a-carbon acts as a nucleophilic center in a reaction with the electrophilic carbonyl carbon of the aldehyde or ketone 1 ... 

The reaction is induced by nucleophilic addition of the hydroxide anion to one of the two carbonyl groups. Then the respective substituent R migrates with the bonding electrons to the adjacent carbon atom (a 1,2-shift). Electron excess at that center is avoided by release of a pair of r-electrons from the carbonyl group to the oxygen ... 

Naphthol 1 is initially protonated at a carbon center of high electron density (C-2 or C-4). The cationic species 3 thus formed is stabilized by resonance it can add a bisulfite anion at C-3. The addition product can tautomerize to give the more stable tetralone sulfonate 4 the tetralone carbonyl group is then attacked by a nucleophilic amine (e.g. ammonia). Subsequent dehydration leads to the cation... 

In an initial step the carbenium ion species 2 has to be generated, for example by protonation of an alcohol 1 at the hydroxyl oxygen under acidic conditions and subsequent loss of water. The carbenium ion 2 can further react in various ways to give a more stable product—e.g. by addition of a nucleophile, or by loss of a proton from an adjacent carbon center the latter pathway results in the formation of an alkene 3. 

The initial step of olefin formation is a nucleophilic addition of the negatively polarized ylide carbon center (see the resonance structure 1 above) to the carbonyl carbon center of an aldehyde or ketone. A betain 8 is thus formed, which can cyclize to give the oxaphosphetane 9 as an intermediate. The latter decomposes to yield a trisubstituted phosphine oxide 4—e.g. triphenylphosphine oxide (with R = Ph) and an alkene 3. The driving force for that reaction is the formation of the strong double bond between phosphorus and oxygen ... 

Silicon centered radicals can be generated by transfer to silanes and by photolysis of polysilanes. Rate constants for addition to monomer are several orders of magnitude higher than similar carbon centered radicals.453,43 The radicals have nucleophilic character. 

The dithioacid family of ligands includes dithiocarbamates (R2N CS2 ), xanthates (RO-CS2 ), thioxanthates (RS CS2 ) and dithiocarboxylates (R CS2 ), which have been described in CCC(1987, Section 47.8.10).1 The ligands are prepared by addition of a suitable nucleophile to the carbon center in CS2, usually in the presence of a base. It has been established for some decades that they bind to Co almost exclusively as bidentate chelates, including S-donors acting as bridging ligands in dinuclear systems. 

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