Allylic Substrates with Chiral Leaving Groups

Allylic Substrates with Chiral Leaving Groups 

Most asymmetric induction processes with chiral auxiliaries involve a stereo-differentiating reaction that affords one diastereomer as the primary product To obtain the desired enantiomer, the chiral auxiliary must be removed Highly diaster eos elective reactions between organocopper reagents and aEylic substrates with 

The first attempts to develop reactions offering control over the absolute stereochemistry of a chiral center created by y-sdective substitution of an achiral allylic alcohol-derived substrate, involved the use of chiral auxiliaries incorporated in the nudeofuge. The types of stereodirecting groups utilized vary, and have induded sulfoximines [IS], carbamates [16], and chiral heterocydic sulfides [17-19]. 

Optimization of the reaction conditions was undertaken in order to find the best Sn27Sn2 ratio and the best substrate conversion. Initial formation of a lithium carbamate salt of 1 on treatment with Me Li, followed by treatment with a stoichiometric amount of MeCu in Et O at 0 C, produced dean 3 2 selectivity and isolation of the desired alkene in 75% yield. A variety of chiral carbamates 1 were investigated, the substrate with R = 1-naphthyl and X = OMe being chosen as the candidate for further studies. It is noteworthy that substrates in which X = H gave 

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. 

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Allylic Substrates with Chiral Leaving Groups... 

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-... 

It may be concluded from the different examples shown here that the enantioselective copper-catalyzed allylic substitution reaction needs further improvement. High enantioselectivities can be obtained if chirality is present in the leaving group of the substrate, but with external chiral ligands, enantioselectivities in excess of 90% ee have only been obtained in one system, limited to the introduction of the sterically hindered neopentyl group. 

Scheme 2.1.4.1 Mechanistic scheme for the Pd(0)-catalyzed reaction of symmetrical racemic allylic substrates (X = leaving group) with nucleophiles (Nu) in the presence of a chiral C2-symmetric ligand L. ...

An ingenious extension of the Tsuji-Trost reaction was the cornerstone of Oppolzer s enantioselective synthesis of a heteroyohimbine alkaloid, (-t-j-B-isorauniticine (267) [117]. Substrate 263 was prepared from a commercially available glycinate equivalent by Malkylation, installation of the sultam chiral auxiliary followed by a sultam-directed C-alkylation. As illustrated in Scheme 48, the crucial double cyclization was accomplished by the treatment of 263 with Pd(dba), Bu,P, in the presence of carbon monoxide (1 atm) in acetic acid to give enone 264 and two other stereoisomers in a 67 22 11 ratio. In this case, an allyl carbonate, rather than an allyl acetate, was used as the allyl precursor. Since carbonate is an irreversible leaving group, formation of the n-allylpalladium complex occurs readily. In the presence of Pd(0), the allylic carbonate is converted into a n-allylpalladium complex with concurrent release of CO, and... 

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