Chiral carbanions

With the molecular geometry for a carbanion described as a trigonal pyramid the question is whether or not carbanions can display chirahty. After all, when the activation barrier for inversion of this geometry is too low any attempt at introducing chirality will end in racemization. However, solid evidence exists that carbanions can indeed be chiral, for example, in research carried out with certain organoUthium compounds. 

B Control over solution structure is one of the few nonnegotiable requirements for success at understanding the influence of solvation and a regation on organolithium reactivity  

Classics in Stereoselective Synthesis. Erick M. Carreira and Lisbet Kvaerno Copyright 2009 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 978-3-527-32452-1 (Hardcover) 

Another key advance in the use of chiral carbanions for asymmetric synthesis has stemmed from the use of transition metal catalysts. In this respect, there have been impressive reports of Zr, Pd, and Ni catalysts in asymmetric synthesis. Collectively, these have provided new potential for the functionalization reaction of olefins (Section 13.6) [24, 26-29]. 

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Sulfoxides (R1—SO—R2), which are tricoordinate sulfur compounds, are chiral when R1 and R2 are different, and a-sulfmyl carbanions derived from optically active sulfoxides are known to retain the chirality. Therefore, these chiral carbanions usually give products which are rich in one diastereomer upon treatment with some prochiral reagents. Thus, optically active sulfoxides have been used as versatile reagents for asymmetric syntheses of many naturally occurring products116, since optically active a-sulfinyl carbanions can cause asymmetric induction in the C—C bond formation due to their close vicinity. In the following four subsections various reactions of a-sulfinyl carbanions are described (A) alkylation and acylation, (B) addition to unsaturated bonds such as C=0, C=N or C= N, (C) nucleophilic addition to a, /5-unsaturated sulfoxides, and (D) reactions of allylic sulfoxides. 

As Stated earlier, the combination of an organolithium reagent with sparteine has been widely used to generate chiral carbanions. We will focus here on recent examples where the efficiency of sparteine was compared with other chiral chelating ligands. 

Reaction of the bis-chelate complex 149 and various bis(arylalkyl)barium complexes generates heteroleptic barium complexes with one chelate and one reactive arylalkyl ligand 164. The homoleptic and heteroleptic barium complexes both induce living polymerization of styrene to atactic polystyrene in cyclohexane solution. The fact that no stereocontrol is observed during polymerization despite the presence of the chiral carbanionic ligands is... 

Recently, the use of chiral carbanionic ligands as non-transferable ligands has received attention. Gais and BoBhammer have successfully applied cyclic ct-sulfonimidoyl carbanion 24 in the conjugate addition of alkylcuprates to cycloalkenones (Scheme 14).30... 

The first example of a chiral carbanionic residual ligand has recently been reported [238]. Chiral mixed cuprates generated from alkyllithium reagents and cyclic a-sulfonimidoyl carbanions transfer alkyl ligands [such as n-Bu, Me, (CH2)30CH(Me)0Etj to cyclic enones with excellent enantioselectivities (77-99% ee). 

The aim in the previous sections was to generate chiral carbanions with enantiomeric excess by the interaction of (—)-sparteine (11) during the deprotonation. The addition of... 

The addition of alkyllithium-(—)-sparteine complexes to C=C bonds can lead to chiral carbanions and may be an interesting alternative to deprotonation. 

Reactions of Organocopper Compounds Prepared from Chiral Carbanions 227... 

Stereoselective formation of the C—Sn bond is usually observed in the addition of a trialkylstan-nyl anion to a C-C double bond or carbonyl group. Reactions are also described where a new C—Sn bond is stereoselectively formed via migration of the stannyl group or by stannylation of a chiral carbanion. 

When there is internal return, a deprotonation event escapes detection because exchange does not occur. One experimental test for the occurrence of internal return is racem-ization at chiral carbanionic sites that takes place without exchange. Even racemization cannot be regarded as an absolute measure of the deprotonation rate because, under some conditions, hydrogen-deuterium exchange has been shown to occur with retention of configuration. Owing to these uncertainties about the fate of ion pairs, it is important... 

The simple amino alcohols discussed have been used as catalysts for enantioselective addition of zinc alkyls to carbonyl compounds (Section D. 1.3.1.4.). In most cases, the reactive amino function is used for the formation of derivatives (including hcterocycles. such as dihydrooxa-zoles. which are formed with acids) which are useful as sources of chiral carbanions (see Sections C., D.l.1.1.2., D.l.3.1.4., D.l.6.1.2.1.. D.1.6.1.3., D.1.6.1.5., D.2.1. and D.2.3.I.). 

In the following years, chiral carbanionic reagents of type 4 [4] became valuable reagents in enantioselective synthesis, mainly due to improved access to chiral stannanes of type 1 (Sect. 2.1) and - more importantly - when simple deprotonation procedures became available (Sect. 2.4). 

The covalent character present in many carbanion carbon-metal bonds means that we must use caution in discussing the properties of carbanions based on reactions of organometaUics. One way to study the structures of carbanions is to determine whether chiral carbanions undergo racemization. Studies of noncycHc carbanions indicate that the retention of configuration at a chiral carbanionic center depends on solvent and temperature, with solvents such as diethyl ether decreasing the covalent character of the carbon-metal interaction, and thus facilitating epimerization at the chiral center. 

Although a-nitrile carbanions have been extensively used for carbon-carbon bond formation because of their powerful nucleophilic character due to the small steric demand, extension to an enantioselective version using enantiopure chiral carbanions next to a nitrile group has been considered to be chaUenging because the chirality is immediately lost by the formation of an sp -hybridized keteniminate. 

Sasaki, M., Takegawa, T., Ikemoto, H., Kawahata, M., Yamaguchib, K., and Takeda, K. (2012) Enantioselective trapping of an a-chiral carbanion of acyclic nitrile by a carbon electrophile. Chem. Commun., 2897-2899. 

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