Prochiral electrophiles

Chiral lithiomethyl ethers 101-103 were submitted to the same protocols iudicated iu Scheme 41 in order to study both the euautiomerically pure compouuds (EPC) syuthesis using non-prochiral electrophiles, aud the possible asymmetric iuductiou with prochiral ones. As described for 91, Y = O (Scheme 39), no asymmetric induction was detected . ... 

The use of a chiral starting material (140, R = Me) and a prochiral electrophile, such as pivalaldehyde, gave a ca 1 1 mixture of diastereomers. On the other hand, careful hydrolysis of compounds 142 (aqueous oxalic acid, silica gel) afforded the corresponding functionalized a, -unsaturated cyclohexenones 143 in >95% yield. 

For aU the chiral intermediates above mentioned (253, 257 and 258) the reaction with prochiral electrophiles (aldehydes or differently substituted ketones) gave a c 1 1 mixture of diastereomers so, as occurred in other chiral functionalized organolithium compounds, the asymmetric induction is practically non-existent. 

A useful application of the chemistry shown in Scheme 83 is the synthesis of branched-chain functionalized carbohydrates. For this purpose two epoxides 261 and 262 derived from D-glucose and 263 derived from D-fructose were prepared following reported methodologies, and were submitted to a DTBB-catalyzed lithiation as described above in Scheme 83. The expected intermediates 264-266 and final products 267-269 were prepared in a regio- and stereoselective manner in 15- 95% yield" Also here, the use of a prochiral electrophile gave equimolecular amounts of both diastereomers. 

Other chiral oxetanes used to generate chiral y-oxido functionalized organolithium intermediates are 306-309, which gave the expected enantiopure products by reaction with non-prochiral electrophiles"" °. In all cases, when prochiral electrophilic reagents were used, a mixture of the corresponding diastereomers was obtained in variable proportions depending on the electrophile, which could be easily separated by column chromatography. 

An integration of readily available computational methods and visualization techniques has rendered a simple method to predict nucleophilic asymmetric induction of prochiral electrophiles.303 Taking the examples of ketone and aldehyde reductions, electrostatic potential has been mapped on to the frontier orbital involved. A distinct difference in... 

The sulfoximine group has proved to be an excellent ortho-directing group in lithiation reactions.77 The use of prochiral electrophiles has afforded ortho-functionalized (g) arylsulfoximines in good yields and modest to good diastereoselectivities up to 95%. 

Wilmot, N. Marsella, M. J. Visualization method to predict the nucleophilic asymmetric induction of prochiral electrophiles, Org. Lett. 2006,8, 3109-3112. 

Transition metal (such as Pd, Ir, Mo and W)-catalyzed asymmetric allylic substitutions with various nucleophiles are widely employed in organic synthesis and played an important role in the area of asymmetric C-C bond formation. Trost, Helmchen, Pfaltz and others have focused primarily on the direct allylation of malonates by prochiral electrophiles ... 

To create new chirality we need a prochiral electrophile. Single enantiomers of functionalised allyl silanes 155 are made by kinetic resolution with a lipase.26 Reaction of 155 with an aldehyde and a Lewis acid gives the syn and anti homoallylic alcohols 156 and 157. 

Some stereogenic-chiral DMGs have also been studied oxazolines [112], masked aldehydes [113], amides [114, 115], sulfonamides [116], and sulfoxides [117-119]. Aldehydes, ketones (leading to chiral alcohols), and imines (leading to chiral amines) are standard prochiral electrophiles. With chiral arene sulfoxides, enantiopure aromatic phenyl and naphthyl sulfoxides 17 can be prepared by reaction of (S)-t-butyl t-butanethiosulfinate with aiyllithium derivatives (Scheme 26.4) [120]. The DoM reaction is performed with n-BuLi followed by addition of the lithiated intermediates to W-tosylimines, affording the chiral arene 18. 

The use of palladium(II) 7i-allyl complexes in organic chemistry has a rich history. These complexes were the first examples of a C-M bond to be used as an electrophile [1-3]. At the dawn of the era of asymmetric catalysis, the use of chiral phosphines in palladium-catalyzed allylic alkylation reactions provided key early successes in asymmetric C-C bond formation that were an important validation of the usefulness of the field [4]. No researchers were more important to these innovations than Prof. B.M. Trost and Prof. J. Tsuji [5-10]. While most of the early discoveries in this field provided access to tertiary (3°) stereocenters formed on a prochiral electrophile [Eq. (1)] (Scheme 1), our interest focused on making quaternary (4°) stereocenters on prochiral enolates [Eq. (2)]. Recently, we have described decarboxylative asymmetric allylic alkylation reactions involving prochiral enolates that provide access to enantioenriched ot-quatemary carbonyl compounds [11-13]. We found that a range of substrates (e.g., allyl enol carbonates,... 

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