Tetrahedral chirality centers, reactions that

Reactions That Generate Tetrahedral Chirality Centers 471... 

REACTIONS THAT GENERATE TETRAHEDRAL CHIRALITY CENTERS... 

Any reaction that creates a new bond to an achiral carbon has the potential to create a new chiral center if that carbon has a tetrahedral geometry in the product. Examples in which the starting carbon was also tetrahedral include free-radical halogenation (replace H- with X-) and a-alkylation of an enolate... 

Next, Evans et al. [15] reported that Cu-based catalysts were superior in the Diels-Alder reaction of the oxazolidinone 9 with cyclopentadiene 8. ITie (5,5)-bis(oxazo-line)-Cu(II) and -Zn(II) complexes were very effective catalysts of the reaction. The optimum tert-butyl ligand 13-Cu(II) complex afforded (2S)-endo-ll with > 98 % ee. In contrast, the optimum catalyst system for the phenyl-substituted ligand 12-Zn complex afforded the enantiomeric (R) product, (2R)-endo-ll, with 92 % ee. The different direction of asymmetric induction was explained in terms of the geometry of cata-lyst-dienophile complexes at the corresponding metal centers. The bis(oxazoline)-Zn(II) complex-catalyzed reaction proceeded via the tetrahedral chiral Zn-dienophile complex VIII, in a manner similar to the bis(oxazoline)-Mg catalyst reported by Corey [13], whereas the reaction catalyzed by the cationic bis(oxazoline)-Cu complex proceeded via the square-planar Cu(II)-dienophile intermediate VII, so the diene preferred to approach from the opposite si face of the bound dienophile with s-cis configuration, avoiding steric repulsion by one of the tert-butyl substituents on the oxazoline rings. 

While copper and iron Lewis acids are the most prominent late transition metal Diels-Alder catalysts, there are reports on the use of other chiral complexes derived from ruthenium [97,98],rhodium [99],andzinc [100] in enantioselective cycloaddition reactions, with variable levels of success. As a comparison study, the reactions of a zinc(II)-bis(oxazoline) catalyst 41 and zinc(II)-pyridylbis(ox-azoline) catalyst 42 were evaluated side-by-side with their copper(II) counterparts (Scheme 34) [101]. The study concluded that zinc(II) Lewis acids catalyzed a few cycloadditions selectively, but, in contrast to the [Cu(f-Bubox)](SbFg)2 complex 31b (Sect. 3.2.1), enantioselectivity was not maintained over a range of temperatures or substitution patterns on the dienophile. An X-ray crystal structure of [Zn(Ph-box)] (01)2 revealed a tetrahedral metal center the absolute stereochemistry of the adduct was consistent with the reaction from that geometry and opposite that obtained with Cu(II) complex 31. 

Since nucleophilic addition to a carbonyl causes an sp -hybridized carbon to become tetrahedral, such reactions can form new chiral centers. For ordinary aldehydes and ketones in an achiral environment, addition of nucleophiles to the enantiotopic faces of the carbonyl results in the usual racemic mixture of alcohols. For carbonyls that already contain chiral centers, however, it is often possible to predict which of the possible diastereomeric products will be preferred by considering the stabilities of the competing diastereomeric transition states. 

Asymmetric synthesis represents a robust field of research, with entire journals and books devoted to the topic. The current literature is full of examples of new and improved chiral reagents, catalysts, and auxiliaries that can be used for enantioselective syntheses. In every case, a chiral environment is produced that favors reaction with one prochiral face of a planar center, or one prochiral group of a tetrahedral center. The ongoing research seeks to not only develop... 

Subsequent investigations revealed that the corresponding hexafluoroanti-monate complex 166 generally possessed higher reactivity and resulted in improved stereoselectivity in such cycloadditions [89]. In all cases, the observed induction could be explained in terms of a catalyst-substrate model complex as depicted for 163 with a distorted tetrahedral geometry around the copper(II) center. The tert-butyl substituents on the C2-symmetric chiral ligand efficiently shield one of the r-faces of the chelated dienophiles [90, 91]. A variety of substrates readily participate in enantioselective Diels-Alder reactions with copper complex 166. An intramolecular variant of such cycloadditions furnished 167 (96% ee, dr >99 1) and constituted a key step in the synthesis of the marine natural product (-)-isopulo upone... 

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