Nucleophiles carbon-centered

A great deal of carbanirms, generated from C-H-active compounds, the Grignard reagents, the cyanide ion, all kinds of organometallic carbon-lithium derivatives, aromatic amines, phenols, pyrroles, indoles, thiophenes, furans, and other organic compounds with electron-rich carbon atoms have been involved in the Sn reactions as C-nucleoplules [1, 2, 10, 11, 114—117]. 

There are plenty of examples for the formation of o -adducts derived from the nucleophilic attack by carbanions of C-H-active compounds at unsubstituted carbon atoms of nitroarenes, azines, azinium salts, and other types of aromatic and heteroaromatic compounds [1, 2, 10-18, 45, 114—117]. As a rule, the formed C-adducts can be identified spectroscopically, and in many cases, these 

Grignard reagents are effective C-nucleophUes for incorporation of alkyl, aryl, and hetaryl substituents into aromatic and heteroaromatic rings. For instance, in the reaction of 4-substituted nitrobenzenes with the alkyl Grignard reagents, the 

Also 6-ferrocenyl-substituted 2,2 -dipyridyl has been obtained by using the Sn methodology, and redox properties on new cobalt(II) and nickel(II) complexes of this ligand have been elucidated [147]. 

5 Carbanions Generated from Nitronyl Nitroxide Radicals 

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This trend is also observed in the reactions with nitrogen- and carbon-centered nucleophiles (2001H425). Thus, the reaction of 109 with sodium indolyl in DMF affords methyl 2-(indol-l-yl)indole-3-carboxylate (188, 77%). In better yield, 2-(indol-l-yl)indole-3-carbaldehyde (189, 95%) is formed in the corresponding reaction (99H1157) of 115a (Scheme 28). Sodium imidazolyl reacts with 109 in DMF at 60°C to afford methyl 2-(imidazol-l-yl)indole-3-carboxylate (190,28%), methyl indole-3-carboxylate (191,11 %), and unreacted 109 (36%). In contrast, under the same conditions, 110 and 115a provide higher yields of methyl 2-(imidazol-... 

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... 

Slightly more exotic carbon-centered nucleophiles can also participate in the ring-optening of epoxides. For example, the vinyl metallate 81, prepared by the treatment of the alkenyl acetal 86 with Schlosser s reagent, attacks mono-substituted epoxides 82 at the C-2 position to give the labile homoallyl alcohols 83 in fair to very good yields <96TET1433>. 

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]. 

As indicated, the reduction of an electron-deficient alkene renders a formally electropositive carbon center nucleophilic. The fields of electrohydrodimerization and electrohydrocyclization are a direct consequence of this realization [1, 2]. The former corresponds to the dimerization of an electron-deficient alkene via a process that couples the electron-deficient -carbons of the substrate. Overall, two electrons and two protons are consumed. Electrohydrocyclization is the intramolecular counterpart of this process. 

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

Propargylic Substitution Reactions with Carbon-Centered Nucleophiles... 

Scheme 7.9 Propargylic substitution reaction with acetone as a carbon-centered nucleophile.

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 1992, Trost and his co-workers investigated desymmetrization of cyclic w j-o-diesters with lithium sulfonyl-methylenenitronate as a nucleophile in the presence of Trost s ligand 118, where the corresponding cyclic compounds are obtained with an excellent enantioselectivity via intramolecular cyclization (Scheme 15),103,103a Asymmetric cyclopropanation and lactone annulation are achieved according to this protocol (Scheme Nitroalkanes can also be employed as carbon-centered nucleophiles in lieu of malonates (Scheme 17). ... 

Trost and his co-workers succeeded in the allylic alkylation of prochiral carbon-centered nucleophiles in the presence of Trost s ligand 118 and obtained the corresponding allylated compounds with an excellent enantioselec-tivity. A variety of prochiral carbon-centered nucleophiles such as / -keto esters, a-substituted ketones, and 3-aryl oxindoles are available for this asymmetric reaction (Scheme jg) Il3,ll3a-ll3g Q jjg recently, highly enantioselective allylation of acyclic ketones such as acetophenone derivatives has been reported by Hou and his co-workers, Trost and and Stoltz and Behenna - (Scheme 18-1). On the other hand, Ito and Kuwano... 

Asymmetric nickel-catalyzed allylic alkylation with soft carbon-centered nucleophiles was reported in 1996 by Mortreux and his co-workers. Use of a catalytic amount of [Ni(cod)2] together with chiral diphosphines 138 promotes the allylic alkylation of a cyclic ester such as 2-cyclohexenyl acetate with dimethyl malonate in the presence of BSA and gives the corresponding alkylated compounds only with a moderate enantioselectivity (40% ee) (Equation (42)). 

Takemoto and his co-workers developed asymmetric allylic alkylation of allylic phosphates with (diphenyl-iminolglycinates as carbon-centered nucleophiles (Equation (56))/" " In this reaction system, use of optically active bidentate phosphites 142 bearing an (ethylthio)ethyl group as chiral ligands promotes the allylic alkylation, and chiral /3-substituted a-amino acids are obtained with an excellent enantioslectivity. 

Several 7] -allylic ruthenium complexes can function as both a nucleophile and an electrophile, as Watanabe and his co-workers observed. Namely, these ruthenium complexes smoothly react with a variety of carbon-centered nucleophiles such as aldehydes, alcohols, and /3-diketones under mild reaction conditions and give the corresponding allylated compounds (Scheme 22). 

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. 

Combinatorial chemistry and solid-phase synthesis have evolved in the last decade to become one of the most important techniques to save time for drug discovery. To reach its full potential, the solid-phase synthesis has to incorporate many versatile organometallic reactions developed over recent several decades. The first example of the Nicholas reaction on solid phase was reported by Kann and his co-workers in 2002, which involves the reaction of polymer-bound cobalt complexes 51 with various carbon-centered nucleophiles in the presence of a Lewis acid to... 

Other kinds of propargylic-substituted products were prepared by this procedure. When Grignard reagents such as allylic and homoallylic magnesium bromides are used in place of lithium enolates as carbon-centered nucleophiles. 

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