Chiral Leaving Groups

The main disadvantage of this reaction is that it is necessary to use stoichiometric amounts, or more, of the organocopper reagent, together with stoichiometric amounts of the chiral auxiliary. The leaving group chiral auxiliary, however, can be recovered and recycled after the reaction. 

More recently, RajanBabu has reported that in the presence of appropriate chiral Ni-based catalysts, enantioselective addition of Grignard reagents to acyclic allylic ethers maybe effected (Scheme 12) [31]. Within this context, a systematic study of the effect of reaction solvent, leaving groups, chiral Hgands and nucleophiles was undertaken. As shown in Scheme 12, treatment of allylic ether 32 with EtMgBr in the presence of 5 mol % of (S,S)-chiraphos-Ni complex [formed upon treatment of Ni(cod)2 with (S,S)-chiraphos 33] results in the formation of (R)-34 in 79% ee and 78% yield. 

Stereospecific effects on both nonleaving group (1,2-diaminocyclohexane) and leaving group (chiral sulfoxide) have been shown for both biological activity and DNA binding. 

Not stereospecific racemization ac companies inversion when leaving group IS located at a chirality cen ter (Section 8 10) Stereospecific 100% inversion of configuration at reaction site Nu cleophile attacks carbon from side opposite bond to leaving group (Section 8 4)... 

Hie use of chiral catalysts as an approach to enantiomer icaliy enriched products by means of coppet-mediated substitution reactions is covered in this chapter. Reactions in which a chiral auxiliary resides in the leaving group of the substrate w ill also he dealt with, since these reactions provide direct and efBcient routes to single enantiomers of the desired products. Most studies so far have been concerned with allylic substrates, with a new chiral center being produced in the course of a selec-... 

A result equivalent to an allylic substitution reaction with a chiral leaving group can also be achieved by a two-step procedure involving a conjugate addition reaction and a subsequent elimination reaction, as demonstrated by Tamura et al., wbo studied the reaction shown in Scheme 8.15 [27]. 

A chiral sulfoxide can be used as a leaving group for the asymmetric inducdon via addidon-eliminadonprocess. 5-Lactam enolates are converted into the corresponding nitroalkenes subsdnited with lactams fEq. 4.101. ... 

The use of chiral transition-metal complexes as catalysts for stereoselective C-C bond forming reactions has developed into a topic of fimdamental importance. The allyhc alkylation is one of the best known of this type of reaction. It allows the Pd-catalyzed substitution of a suitable leaving group in the allylic position by a soft nucleophile. 

Answer The required disconnection is (13a) which clearly needs optically active epoxide (15). This must be made from (14) without inverting the chiral centre so reduction of the COgEt group and conversion to a leaving group are needed. 

Replacement of a Chiral Leaving Group by an Achiral Nucleophile. . 74... 

Substitution of a Good Leaving Group with a Chiral Reagent.79... 

A second method is the replacement of a chiral leaving group of an (optically unstable) organotin compound (a triorganotin menthoxide for instance) by a more nucleophilic reagent (a Grignard reagent or lithium aluminum hydride for instance). 

Another asymmetric synthesis is the substitution of a good achiral leaving group by reaction with a chiral reagent. 

Other chiral leaving groups have been used (see Table 4), for instance (—)-methyl-S-thioglycolate 42), or the conjugate base of cinchonine 92), which seems to give rather good results yielding for instance benzylmethylphenyl-t-butyltin with [a] 6 = —22.6. 

Table 4. Synthesis of optically active organotin compounds RR R"SnL from an optically unstable compound bearing a chiral leaving group Y RR R"Sn—Y RR R"Sn-L ... 

They have developed direct asymmetric synthesis of quaternary carbon centers via addition-elimination process. The reactions of chiral nitroenamines with zinc enolates of a-substituted-8-lactones afford a,a-disubstituted-6-lactones with a high ee through addition-elimination process, in which (5)-(+)-2-(methoxy methy l)pyrrolidine (SMP) is used as a chiral leaving group (Eq. 4.96).119 Application of this method to other substrates such as a-substituted ketones, esters, and amides has failed to yield high ee. 

---