Chiral auxiliaries anions

The cover picture represents a chiral two-bladed propeller cobalt complex [(Co2(CO)4p,tf, tf -(—H2CC = CCH2—)(-dppm)2][BF4]2 (drawn by H. Amouri). This complex was prepared and resolved by the authors using a chiral auxiliary anion. (Note the carbonyl groups on the cobalt were removed for clarity.)... 

Progress has been made toward enantioselective and highly regioselective Michael type alkylations of 2-cyclohexen-l -one using alkylcuprates with chiral auxiliary ligands, e. g., anions of either enantiomer of N-[2-(dimethylamino)ethyl]ephedrine (E. J. Corey, 1986), of (S)-2-(methoxymethyl)pyrrolidine (from L-proline R. K. EHeter, 1987) or of chiramt (= (R,R)-N-(l-phenylethyl)-7-[(l-phenylethyl)iinino]-l,3,5-cycloheptatrien-l-amine, a chiral aminotro-ponimine G. M. Villacorta, 1988). Enantioselectivities of up to 95% have been reported. 

Chiral oxazolines developed by Albert I. Meyers and coworkers have been employed as activating groups and/or chiral auxiliaries in nucleophilic addition and substitution reactions that lead to the asymmetric construction of carbon-carbon bonds. For example, metalation of chiral oxazoline 1 followed by alkylation and hydrolysis affords enantioenriched carboxylic acid 2. Enantioenriched dihydronaphthalenes are produced via addition of alkyllithium reagents to 1-naphthyloxazoline 3 followed by alkylation of the resulting anion with an alkyl halide to give 4, which is subjected to reductive cleavage of the oxazoline moiety to yield aldehyde 5. Chiral oxazolines have also found numerous applications as ligands in asymmetric catalysis these applications have been recently reviewed, and are not discussed in this chapter. ... 

Only few successful reports utilizing the chiral auxiliary approach for the a-hydroxyalkylation of allyllic anions have been made. 

Aldol addition and related reactions of enolates and enolate equivalents are the subject of the first part of Chapter 2. These reactions provide powerful methods for controlling the stereochemistry in reactions that form hydroxyl- and methyl-substituted structures, such as those found in many antibiotics. We will see how the choice of the nucleophile, the other reagents (such as Lewis acids), and adjustment of reaction conditions can be used to control stereochemistry. We discuss the role of open, cyclic, and chelated transition structures in determining stereochemistry, and will also see how chiral auxiliaries and chiral catalysts can control the enantiose-lectivity of these reactions. Intramolecular aldol reactions, including the Robinson annulation are discussed. Other reactions included in Chapter 2 include Mannich, carbon acylation, and olefination reactions. The reactivity of other carbon nucleophiles including phosphonium ylides, phosphonate carbanions, sulfone anions, sulfonium ylides, and sulfoxonium ylides are also considered. 

The reduction of 2-oxoacids bound to different chiral auxiliaries gave the 2-hydroxyacid derivatives in a 64 to 76% yield and 42 to 86% de depending on solvent, proton donor, supporting electrolyte, temperature, and substituent R in the oxoacid. The results are in accordance with an ECE reduction of the 2-oxoamide to an enolate anion, which subsequently undergoes a face-selective protonation to the hydroxy acid [346, 347]. 

Fig. 1 a Crystal structure of the carboxylate anion portion of the (R)-(+)-l-phenylethyl-amine salt of keto-acid 37a before irradiation, and b after 70% conversion to the corresponding cyclobutanol (ionic chiral auxiliary not shown)... 

If the mesomeric stabilization is provided by a double bond, the lithiated species is a homoenolate synthon, as shown in Scheme 44a. Reaction with an electrophile typically occurs at the y-position, yielding an enamine, which can then be hydrolyzed to a carbonyl compound. An important application of this approach is to incorporate a chiral auxiliary into the nitrogen substituents so as to effect an asymmetric synthesis. 2-AzaaUyl anions (Scheme 44b), which are generated by tin-lithium exchange, can be useful reagents for inter- and intramolecular cycloaddition reactions. ... 

One of the most important factors for successful diastereoselection in chiral amide enolate alkylation reactions is the presence of strongly chelated ionic intermediates1 3. The chelation serves the purpose of locking the chiral auxiliary in a fixed position relative to the enolate. The metal counterion is chelated between the enolate oxygen and an additional polar group, anionic, carbonyl or ether oxygen attached to the chiral auxiliary. 

Kolb and Barth 229) synthesized oc-substituted optically active amines or amino acids (223). Again the authors employed a derivative of naturally occurring (S)-proline, namely (—)-(S)-l-dimethoxymethyl-2-methoxymethyl-pyrrolidine (221) as chiral auxiliary agent. The metalation of the amidines (160) leads to azaallyl anions homologous with (222). After alkylation and hydrolysis, the desired a-substituted amines and amino acids, respectively, are obtained with some stereoselectivity. 

To introduce the chiral auxiliary, a labile anion, unlike the classical BFJ or PF which cannot be exchanged, is required. Preliminary studies showed the triflate to be appropriate. We introduced it during the formation step of the double helix. One equivalent of copper ) triflate was added to the bischelating diphenolic strand in a reductive medium. H NMR showed that the dinuclear copper dou-... 

To obtain the pure topological enantiomers, the chiral auxiliary was easily replaced by the hexafluorophosphate anion. 

An asymmetric synthesis of mevalolactone in over 87% e.e. employs a 1,3-oxathiane as the chiral auxiliary (81TL2859). The reagent (818), easily prepared from (+)-pulegone (81TL2855), was metallated with u-butyllithium and the anion reacted with acetaldehyde. Oxidation of the diastereomeric mixture of alcohols to the ketone (819) and reaction of... 

Principles. How shall we proceed toward catalytic asymmetric induction Scheme 5 illustrates a possible way to achieve enantioselective alkylation by using a small amount of chiral source. Under certain conditions, the presence of a protic chiral auxiliary HX can catalyze the addition of organometallic reagent, R2M, to a prochiral carbonyl substrate by way of RMX. To obtain sufficient chiral efficiency, the anionic ligand X must have a three-dimensional structure that allows differentiation between the diastereomeric transition states of the alkyl transfer step. In addition, unlike in stoichiometric reactions, the rate of... 

Santos I, Paulo A, Correia JDG (2005) Rhenium and Technetium Complexes Anchored by Phosphines and Scorpionates for Radiopharmaceutical Applications. 252 45-84 Scheffer JR, Xia W (2005) Asymmetric Induction in Organic Photochemistry via the Solid-State Ionic Chiral Auxiliary Approach. 254 233-262 Schmidtchen FP (2005) Artificial Host Molecules for the Sensing of Anions. 255 1-29... 

An interesting example of stereoselective coupling of an aromatic radical with a nucleophile is found in the reaction of 1-iodonaphthalene with the imide anion 12, containing a chiral auxiliary. In this reaction the diasteromeric isomers of the substitution compound are formed (Sch. 17) [87]. This reaction is highly dependent on the metal counter ion used. All the ions studied [Li, Na, K, Cs, Ti(IV)] are selective, but the highest stereoselection is reached with Li at low temperature (—78°) and with Ti(IV) (ca. 99% de) [87]. 

As for the induction, type I looks promising, one of the diastereotopic faces of the corresponding anion is shielded by the tiny hydrogen, the other by the much bulkier R1 which can be chosen rather freely. — Type II consists of an optically active ct-methylamino acid which is the chiral auxiliary and contributes C-3 and of a racemic amino add that contributes C-6. 

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