Electrophilic with chiral azodicarboxylates

Under a different manner of cinchona alkaloid activation, azodicarboxylates were utilized as substrates for enantioselective aUylic aminations. The electrophilic addition of nucleophiles to electron-withdrawing aUyUc C-H bonds (21) was feasible via activation by a chiral Bronsted base, DHQ(2PYR) (Scheme 13.6) [15]. This discovery, from Jorgensen s group, highUghts the first enantioselective, metal-free allylic amination using alkyUdene cyanoacetates with dialkyl azodicarboxylates. 

The chemistry of chiral 1,3-dithiane 1-oxides, in particular their use as chiral auxiliaries, has been reviewed <19980PP145>. Some further developments in this field are the stereoselective a-alkylation with alkyl halides <1997T13149> or a-hydrazination with di-fert-butyl azodicarboxylate (DBAD) <2000T9683>. The carbonyl group of 2-acyl-l,3-dithiane 1-oxides was also used as an electrophile (Scheme 82). Interestingly, acyclic enolates react with these substrates to give a 95 5 mixture of anti- and ry -adduct, whereas cyclic enolates produce a mixture of anti- and ry -adduct in 8 92 ratio <2000JOC6027>. 

The preparation of chiral dialkylazodicarboxylates and their use as electrophilic enolate animation reagents, were first reported in 1995 by Vederas and co-workers [51]. A series of chiral dialkyl (menthyl 97a, bomyl 97b, isobomyl 97c) azodicarboxylates were prepared by conversion of the corresponding alcohols into chloro-formates, condensation with hydrazine and oxidation with IV-bromosuccinimide and pyridine. Compounds 97 were obtained in 35-50% yield (Scheme 45). 

Electrophilic Amination of Chiral Enolates with Di-ferf-butyl Azodicarboxylate... 

Azodicarboxylate esters are the reagents of choice for electrophilic N-amino amination leading to hydrazine derivatives. Besides Grignard reagents and alkyl or aryl lithium compounds,enolates and silyl enol ethersderived from ketones have been aminated by this method. In particular, di-r-butyl azodicarboxylate has been reacted with a variety of chiral enolates (Scheme I9)i03->o and chiral silyl ketene acetds (Schemes 20 and to afford a-hydrazino acid derivatives with high dia-... 

In the Mitsunobu reaction, a chiral 2° alcohol and a carboxylic acid are converted to an ester with clean inversion at the electrophilic C. The reaction requires PI13P and Et02CN=NC02Et (diethyl azodicarboxylate, DEAD). It is usually carried out by adding DEAD slowly to a mixture of the alcohol, PI13P, and the nucleophile in its protonated form. 

FIGURE 11.1. Chiral secondary amine catalysts used for the enamine mediated electrophilic a-amination of carhonyl compounds with azodicarboxylate esters. 

Ma has developed a three-component allene carboamination reaction for the stereoselective synthesis of 2,5-as-disubstituted pyrrolidine derivatives [54]. A representative transformation involving allene 58, 4-iodoanisole, and imine 59 that generates 60 in 90% yield is shown below (Eq. (1.28)). The reaction is believed to proceed through the intermediate Jt-allylpalladium complex 62, which is formed by carbopalladation of the alkene to give 61 followed by addition of the malonate anion to the activated imine. Intramolecular capture of the allylpalladium moiety by the pendant nitrogen nucleophile affords the pyrrolidine product. A related asymmetric synthesis of pyrazolidines that employs azodicarboxylates as one of the electrophilic components has also been reported [55]. The pyrazolidine products are obtained with up to 84% ee when chiral bis oxazolines are employed as ligands. 

In another context, excellent enantioselective nickel-catalysed a-ami-nations of N-Boc-oxindoles with azodicarboxylates have been achieved by using chiral Schiff base nickel catalysts. BINAP ligands have also encountered success in asymmetric nickel-catalysed electrophilic a-aminations and also in combination with other metals such as palladium. On the other hand, the use of other sources of electrophilic nitrogen, such as nitroso compounds and iodinanes, in reactions catalysed by nickel has so far not been described. 

In related procedures that are based on lithium enolates of Evans Af-acyl oxazohdinones, azodicarboxylates 477 are used as electrophiles [228]. Excellent diastereoselectivity and high chemical yields in the formation of hydrazines 478 are reached with Af-acyl oxazohdinones 468 (R = CHjPh) and di-t-butyl azodicarboxylate (Scheme 4.101) [228a]. For the cleavage of the chiral auxihary from the substrate, saponification (LiOH in THF/water) and transesterification methods (A4eA4gBr in methanol or LiOCH2Ph in THF) were developed and occurred without significant racemization in the esters or acids 479, except for... 

Only few procedures for enantioselective animation of enoiates have been developed [256]. The stoichiometric use of several chiral electrophilic animation reagents was plagued by low enantioselectivity [257]. Evans and Johnson developed a first efficient catalytic approach that is based on the reaction of sihcon enoiates with azodicarboxylate derivatives [258]. Thus, silyl enol ethers 526 were reacted with azoimide 527 under catalysis of the copper f-butyl-PHOX complex 216a. The presence of 1 equiv. of trifluoroethanol was crucial for high conversion. 

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