Alkyl carbon centers, nucleophilic substitution

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... 

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. 

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>. 

Nucleophilic substitution reactions of aniline are also studied at tertiary alkyl carbon centers in MeCN66. The reactions with 2-cyano-2-propyl, 5, and 1-cyanooctyl, 6, arenesulfonates are reported in MeCN at 50.0 °C. 

In the first systematic study on nucleophilic substitutions of chiral halides by Group IV metal anions, Jensen and Davis showed that (S )-2-bromobutane is converted to the (R)-2-triphenylmetal product with predominant inversion at the carbon center (Table 5)37. Replacement of the phenyl substituents by alkyl groups was possible through sequential brominolysis and reaction of the derived stannyl bromides with a Grignard reagent (equation 16). Subsequently, Pereyre and coworkers employed the foregoing Grignard sequence to prepare several trialkyl(s-butyl)stannanes (equation 17)38. They also developed an alternative synthesis of more hindered trialkyl derivatives (equation 18). 

Enantioselective catalytic alkylation is a versatile method for construction of stereo-genic carbon centers. Typically, phase-transfer catalysts are used and form a chiral ion pair of type 4 as an key intermediate. In a first step, an anion, 2, is formed via deprotonation with an achiral base this is followed by extraction in the organic phase via formation of a salt complex of type 4 with the phase-transfer organocata-lyst, 3. Subsequently, a nucleophilic substitution reaction furnishes the optically active alkylated products of type 6, with recovery of the catalyst 3. An overview of this reaction concept is given in Scheme 3.1 [1],... 

The Friedel-Crafts alkylation and acylation are of very little, if any, synthetic interest when applied to heterocyclic aromatic bases the substitution of protonated heterocycles by nucleophilic carbon-centered radicals is instead successful. This reaction, because of the dominant polar effect which is mainly related to the charge-transfer character of the transition state (Scheme 1), reproduces most of the aspects of the Friedel-Crafts aromatic substitution, but reactivity and selectivity are the opposite. 

Two major mechanisms have to be taken into consideration for the alkylation of Co -corrins. The classical mechanism of a bimolecular nucleophilic substitution reaction at carbon (the Co -corrin acts as a nucleophile) leads to /3-aUcylated Co -corrins with high diastereoselectivity. Secondly, an electron transfer-induced radical process (where the Co -corrin acts as a one-electron reducing agent) may also lead to cobalt alkylation. The observed formation of incomplete a-aUcylated Co -corrins under kinetically controlled conditions has been proposed to occur via this path. The high nucleophilic reactivity of Co -corrins and their diastereoselective nucleophilic reaction on the ( upper ) /3-face are not increased by the nucleotide function on the ( lower ) a-face rather they appear to be an inherent reactivity of the corrin-bound tetracoordinate Co -center. Among the organometallic B12 derivatives prepared to date, neopentylcobalamin, benzylcobalamin, and... 

The mechanism of the foregoing copper-catalyzed substitution at the sp carbon center is proposed as follows [Eq. (36) 88]. Formation of an intermediate alkylcopper RCu should play an important role, with the nucleophilic displacement of alkyl halides with this copper species being the rate-limiting step. 

Irradiation of methyl-substituted phenylcyclopropanes gave rise to the formation of products 11 in which the nucleophile was attached to a carbon carrying a methyl group. Since the course of these reactions is stereospecific and the products show an inversion of configuration at the electrophilic center, an St 2-type reaction has to be assumed. In 1,1-diphenylcyclo-propanes with alkyl substituents at the other carbon atoms the nucleophilic substitution occurs at the most sterically hindered carbon. ... 

Despite their overall electtical neutrality, carbon-centered radicals can show pronounced electrophilic or nucleophilic character, depending on the substituents present. " This electrophilic or nucleophilic character is reflected in rates of reaction with nonradical species, for example, in additions to substituted alkenes. Alkyl radicals and a-alkoxyalkyl radicals are distinctly nucleophilic in character and react most rapidly with alkenes having EWG substituents. Even methyl radicals with a single EWG, such as t-butoxycarbonyl or cyano are weakly nucleophilic. Radicals having two EWGs, such as those derived from malonate esters, react preferentially with double bonds having ERG substituents. Perfluoro radicals are electiophilic and are about 10 more reactive than alkyl radicals. ... 

Thioethers and selenoethers can be displaced with various nucleophiles after methylation by MeOTf. This has been used extensively in the carbohydrate synthesis field (see the section on glycosylation). A phenylselenide moiety was substituted stere-ospecifically by an alkyl stannane following MeOTf activation in the construction of a C—C bond between two quaternary carbon centers (eq 20). ... 

Also the prediction has proved correct of a molecular configuration, in which intramolecular alkyl shifts are realized, i.e., an intramolecular nucleophilic substitution at the tetrahedral carbon atom. It has been found [6] that a fast (10 s at 25°C) bond-switching process associated with the rupture-formation of the C—S bonds of the anchored center does occur in the degenerate rearrangement of the l,8-fcis-(arylthio)-anthracene-9-carbinyl cation XIV in solution ... 

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