Chiral auxilliary

The use of chiral auxilliaries in the Staudinger reaction has been explored extensively. Chiral imines derived from (15)-(-t-)-camphor 10-sulfonic acid <96TA2733>,... 

The new heterocyclic derivative 130 has been shown to be an efficient chiral auxilliary for asymmetric desymmetrization of cyclic meso-l,2-diols via diastereoselective acetal cleavage . 

Of course, with the drastic simplification inherent in the use of aldehyde 8 as the "real world" equivalent of the hypothetical threose 2, came the postponement of the goal of the synthesis of the natural enantiomer of NeuSAc. The only way to strive for enantiospecificity would involve replacing 7 with another diene equipped with a chiral auxilliary (111. At this exploratory stage, we preferred to accept a downscaling of goals, confident that lessons learned in the synthesis of racemic NeuSAc could be applied to the preparation of enantiomer 1 (synthesis of (-) NeuSAc has been accomplished DeNinno, M. P., Yale University, unpublished data). 

The oxazoline ring acts as an electron-withdrawing group for a substituent at the 2-position. Thus, the ot-protons of a 2-alkyloxazoline exhibit some acidity and can be abstracted by a base. A 2-alkenyloxazoline can be viewed as a masked acrylic acid derivative and is capable of undergoing Michael addition and Diels-Alder reactions. These reactions can often be carried out stereoselectively using a chiral oxazoline. Other types of chiral auxilliaries, most notably oxazolidinones, are also very effective for these types of applications. However, they are outside the scope of this chapter. The discussion in this section will focus on the new developments with oxazolines. 

In an effort to demonstrate the interesting concept of a catalytic chiral auxilliary, Williams and co-workers showed that the oxazoline-substituted acrylate ester 526... 

Catalysis of D-A reactions by Lewis acids makes it possible to conduct the cycloadditions under mild conditions, which promotes higher levels of diastereoselection and enantioselection in comparison to the thermally induced reactions. Control over the formation of single diastereomers or enantiomers in D-A reactions may be achieved using chiral promoters functioning either as chiral auxilliaries substrate control) or chiral catalysts reagent control). 

Camphor-derived scaffolds can function as chiral auxilliaries in Lewis acid—promoted D-A reactions to direct the cycloaddition in a predictable manner with nearly complete asymmetric induction. ... 

Chiral auxilliaries have been employed to direct stereochemistry in 2,3-rearrangements of ester enolates. The (-)-8-phenylmenthyl a-allyloxyacetates (208) rearrange via their lithium enolates to the syn... 

A recent synthesis of (+)-sedridine (167) was reported in which a key step was the asymmetric cycloaddition of the nitrone 2,3,4,5-tetrahydropyridine A-oxide with an asymmetric crotonic acid derivative containing a chiral auxilliary [439], Sedridine has recently been isolated from the bark of Punica granatum [440],... 

Aziridine-2-carboxylic acid derivatives 133 may be prepared in a stereochemically predictable method by using the Oppolzer camphor sultarn as achiral auxilliary. The standard protocol of amine addition onto an a/pha-bromoacrylate is imbued with stereodifferentiation by the face-selective a/pfia-protonation of enolate 131, a step which the chiral auxilliary dictates to occur in a -fashion [94TL1653]. 

Another approach to this enantioselective cyclization involves the formation of imines from N-)S-(3-indolyl)ethyl amino acid esters and a variety of aryl aldehydes. These imines give tetrahydro-)S-carbolines with diastereomer ratios of up to 98.5 1.5 (Scheme 27) <94T11865>. The chiral auxilliary group can be removed after cyclisation. The iminophosphorane (103), derived from a dehydrotryptophan, reacts thermally with aldehydes to give the /J-carbolines (104) (Equation (28)) <92TL289i>. In contrast, the dehydrotryptophan (105) itself interacts with aldehydes to form compounds (106) with the clavicipitic acid skeleton (Scheme 28) <86TL4757>. 

The use of dianhydro sugars derived from o-glucose as novel chiral auxilliaries is covered in Chapter 24. 

Thus, from the beginning of the eighties, polymers containing chiral aminoalcohols and their derivatives were used as chiral auxilliaries for LAH [49], BH3 [50] [51] or NaBH4 [52]. 

Several examples of other glycosylated inositols are noted in Chapters 3 and 4. The syntheses of carba-disaccharides related to salbostatin and fortimycins are metioned in Chapter 19, and the syntheses of 6-membered carbocyclic nucleosides and the use of cyclitols as chiral auxilliaries in Diels-Alder reactions are covered in Chapters 20 and 24, respectively. 

Friestad etal. had reported the synthesis of chiral homoallylic amines and their derivatives through the diastereofacial selective addition of tetraallylsilane to chiral N-acylhydrazones [72]. These chiral N-acylhydrazones are essentially imines linked to a chiral auxilliary that could be removed to liberate the homoallylic amine moieties after allylation. The success of this novel strategy lies in the activation of the allyl nucleophile through the use of tetrabutylammonium triphenyldifluo-rosilicate (TBAT), and the activation and formation of cyclic rigid complexes of the N-acylhydrazones through the use of ln(OTf)3 (Figure 8.39). 

Free radical chemistry continues to be of importance in the field and a survey has been published on polar and enthalpic effects in free radical reactions. A further short review dealt with free radicals, carbenes and nitrenes at the anomeric centre of carbohydrates. A useful survey has appeared of the application of carbohydrate based chiral auxilliaries in stereoselective syntheses which covers a range of reactions, for example cycloaddition processes, reductions and Strecker reactions. ... 

All the models already discussed for the diastereofacial seledivity in the case of carbonyl compounds are still valid for the imines. However, due to the substitution on the nitrogen atom, imines can possess an additional chiral auxilliary capable of influencing the diastereoseledivity. Carbohydrates, for instance, were used as chiral templates, for the synthesis of N-glycosyl-N-homoallylamines and /3-ami-noacids [256]. As a consequence, the introdudion of chiral centers both on the carbonyl and the amine moieties of the substrate may cause matching or mismatching effeds [257]. 

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