Chiral-auxiliary

Chiral-auxiliary control in radical addition reactions is presented in a general format in Eqs. (3), (4) and (5). In these equations, a or d represents a resident group which has a stereogenic center that controls the configuration of the new center formed in the transformation. In Eq. (3), the resident stereogenic center resides on the radical. In Eq. (4), the resident center is attached to the radical trap at the site of unsaturation undergoing reaction, while in Eq. (5), the center resides on the unsaturated radical trap at a site remote from the unsaturated center undergo- 

The addition of carbon radicals to carbon-carbon double bonds is, perhaps, the single most important radical transformation [3]. This reaction is discussed elsewhere in this volume, but, because of the importance of addition reactions in the development of the use of chiral auxiliaries, a few background comments are made here. Typical carbon radicals are nucleophilic and undergo reaction more readily with electron-deficient than with electron-rich compounds. For alkene addition reactions, therefore, substitution of electron-withdrawing groups on the alkene increases the rate of radical addition relative to the unsubstituted parent compound. 

Activation of an alkene to enable addition of carbon radicals may be achieved by complexation of the alkene undergoing addition to an electron-deficient species such as a Lewis acid. This strategy has been used extensively in the activation of dienophiles towards cycloadditions, and the reasons for its efficacy in both cycloaddition and radical addition have the same roots. In a Diels-Alder reaction [4] with normal electron demand, the dominant frontier orbital interaction is between the HOMO of the diene and the LUMO of the dienophile. Complexation of a Lewis acid to the dienophile lowers its LUMO and magnifies the important frontier MO interaction. 

For addition of nucleophilic radicals to an alkene, the dominant interaction is between the SOMO of the radical and the LUMO of the olefin. Complexation of a Lewis acid to the alkene lowers its LUMO and magnifies the SOMO-LUMO interaction [3a]. Thus, one expects that the rate of addition of carbon radicals to alkenes should be dependent on the presence of Lewis acid if that alkene is capable of complexation to Lewis acid. The important processes for such a reaction are shown in Eqs. (7)-(9). 

In the reactions described in Eqs. (7)-(9), the unactivated alkene adds the radical with some rate constant, Atq, while the alkene complexed to a Lewis acid, adds the radical with some rate constant k. For a maximum effect of Lewis acid on the reaction, kc should be much greater than ko and the equilibrium constant K should be 

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Asymmetric DieJs-Alder Reactions - Chiral Auxiliaries... 

Clearly, there is a need for techniques which provide access to enantiomerically pure compounds. There are a number of methods by which this goal can be achieved . One can start from naturally occurring enantiomerically pure compounds (the chiral pool). Alternatively, racemic mixtures can be separated via kinetic resolutions or via conversion into diastereomers which can be separated by crystallisation. Finally, enantiomerically pure compounds can be obtained through asymmetric synthesis. One possibility is the use of chiral auxiliaries derived from the chiral pool. The most elegant metliod, however, is enantioselective catalysis. In this method only a catalytic quantity of enantiomerically pure material suffices to convert achiral starting materials into, ideally, enantiomerically pure products. This approach has found application in a large number of organic... 

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. 

The first practical method for asymmetric epoxidation of primary and secondary allylic alcohols was developed by K.B. Sharpless in 1980 (T. Katsuki, 1980 K.B. Sharpless, 1983 A, B, 1986 see also D. Hoppe, 1982). Tartaric esters, e.g., DET and DIPT" ( = diethyl and diisopropyl ( + )- or (— )-tartrates), are applied as chiral auxiliaries, titanium tetrakis(2-pro-panolate) as a catalyst and tert-butyl hydroperoxide (= TBHP, Bu OOH) as the oxidant. If the reaction mixture is kept absolutely dry, catalytic amounts of the dialkyl tartrate-titanium(IV) complex are suflicient, which largely facilitates work-up procedures (Y. Gao, 1987). Depending on the tartrate enantiomer used, either one of the 2,3-epoxy alcohols may be obtained with high enantioselectivity. The titanium probably binds to the diol grouping of one tartrate molecule and to the hydroxy groups of the bulky hydroperoxide and of the allylic alcohol... 

Efficient acetalization of alkenes bearing various EWG with an optically active 1.3-diol 72 proceeds smoothly utilizing PdCN, CuCI. and O2 in DME to give the 1,3-dioxane 73[113], Methacrylamide bearing 4-t-butyloxazolidin-2-one 74 as a chiral auxiliary reacts with MeOH in the presence of PdCE catalyst... 

Chips, semiconductor Chiral additives Chiral-AGP Chiral auxiliaries Chiral crown ethers Chiral hydrogenation Chirality... 

Enantioselective aldoi condensation by means of a chiral auxiliary and boron enolates... 

Chiral Controller. (Synonymous with Chiral Auxiliary). A chiral structural unit which when attached to a substrate enhances stereoselectivity in the formation of new stereocenter(s). 

The most valuable characteristic of the Patemo-Buchi reaction is the ability to set multiple stereocenters in one reaction and the development of diastereocontrolled reactions has been a major theme of research concerning this reaction. Stereocontrol can be envisioned to spring from either the carbonyl or the alkene and be controlled by either the substrate directly or by a chiral auxiliary. Little success has been achieved in substrate-induced selection by the carbonyl the most successful results were produced by... 

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. ... 

Cleavage of the chiral auxiliary is effected in a three-step procedure commencing with quatemization of the nitrogen with methyl fluorosulfonate, methyl trlfluoromethanesulfonate, or trimethyloxonium tetrafluoroborate. Reduction of the corresponding iminium salt 19 with NaBH4 and acidic hydrolysis of the resulting product affords substituted aldehyde 5 without epimerization of either stereocenter. 

Zincke-type salts derived from other aromatic nitrogen heterocycles also undergo Zincke reactions. The isoquinolinium salt 6 (Scheme 8.4.16) permitted incorporation of a phenyl ethylamine chiral auxiliary, providing salt 48. In this context and others (vide infra), Marazano and co-workers found that refluxing -butanol was a superior solvent system for the Zincke process. Additionally, the stereochemical integrity of the or-chiral amino fragment was reliably maintained. 

A -sulfinyl chiral auxiliaries have been used to prepare enantiopure tetrahydro-P-carbolines and tetrahydroisoquinolines in good yields under mild reaction conditions. Both enantiomers of V-p-toluenesulfinyltryptamine 46 could be readily prepared from the commercially available Andersen reagents.Compound 46 reacted with various aliphatic aldehydes in the presence of camphorsulfonic acid at -78 °C to give the A-sulfinyl tetrahydro-P-carbolines 47 in good yields. The major diastereomers were obtained after a single crystallization. Removal of the sulfinyl auxiliaries under mildly acidic conditions produced the tetrahydro-P-carbolines 48 as single enantiomers. 

Asymmetric reactions using nonnatural chiral auxiliaries with participation and formation of heterocycles 98YGK386. 

Nonlinear dependence between ee values of chiral auxiliary compound or ligand and product of reaction with participation or formation of heterocycle 98AG(E)2922. 

Asymmetric syntheses of heterocycles using carbohydrates as chiral auxiliaries 97T14823. 

Syntheses and use of vicinal diamines with one or two N atoms included in heterocycle as chiral auxiliaries 98AG(E)2580. 

Novel chiral auxiliary, 2 -isopropyl-5 -methylbenzoxazine-spiro-[2.1 ]cyclo-hexan-4-one, and its application to the synthesis of carbapenem antibiotics 97YGK858. 

Disubstituted 2-oxazolidines as chiral auxiliaries synthesis from 2-oxazolones 97YZ339. 

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