Chiral Electrophilic Aminating Reagents

Related Reagents. The synthesis of chiral diazenedicarboxylates as potential chiral electrophilic aminating agents has received little attention. A series of chiral bomyl, isobomyl and menthyl diazenedicarboxylates has been reported and their reaction with achiral enolates of esters and N,N-dimethyl amides afforded a-hydrazino acid derivatives with little or no selectivity. Incorporation of a chiral azodicarboxamide unit into a chiral bridging binaphthyl moiety afforded a-hydrazino acid derivatives with high stereoselectivity in reactions with achiral oxazolidinone anions. ... 

The synthesis of optically active compounds by the diastereoselective reaction of allyltitanium reagents with chiral electrophiles has also been reported. The reaction of allyltitanium reagents with chiral imines proceeds with excellent diastereoselectivity, as shown in Eq. 9.28, thus providing a new method for synthesizing optically active homoallylic amines with or without a P-substituent [51,52],... 

The other development for the direct enantioselective a-chlorination of aldehydes was reported by the present authors, and was seen to differ from the first approach in several ways. For example, the catalysts used for the a-chlorination reaction were the C2-symmetric (2R,5R)-diphenylpyrrolidine 3h and i-proline amide 3i, while the electrophilic chlorinating reagent was N-chlorosuccinimide (NCS) 29 (Scheme 2.34) [26b]. Both chiral amines were effective catalysts for the a-chlorination reaction, and the optically active products 27 were obtained in high yields the use of catalyst 3h provided generally higher enantiomeric excess (81-97% ee) than 3i (70-95% ee). 

Asymmetric deprotonation of a prochiral compound having a sufficiently acidic C-H bond can be performed by a lithium amide generated from an enantio-pure secondary amine or by an organolithium reagent in the presence of a chiral tertiary amine [557, 559]. A chiral mixed aggregate is usually formed [77, 81, 974], and the reaction of this intermediate with electrophiles (including proton sources) can lead to a predominant enantiomer. 

Lewis acid promoted reactions of silicon enolates, /.e., silyl enol ethers and ketene silyl acetals with various electrophiles have yielded a wealth of novel and selective synthetic methods. This combination of reagents has been used in the past to perform such reactions as aldol-condensations with aldehydes and acetals, imine-condensations, conjugate additions to a,P-enones, alkylations, electrophilic aminations, and Diels-Alder/cyclocondensations. Our own interest in this field has involved the use of titanium tetrachloride to promote the reaction of ketene silyl acetals with non-activated imines as an efficient route to P-lactams. This reaction has been applied to the asymmetric synthesis of P-lactams via a chiral imine-titanium tetrachloride template. We have also found that both ketene silyl acetals and vinylketene silyl acetals oxidativelly dimerize or cross-couple, in the presence of titanium tetrachloride to conveniently yield various diesters . Our present study concerns reactions of vinylketene silyl acetals with non-activated imines and vinylimines promoted by titanium and zirconium tetrachlorides. 

Wirth recently demonstrated that an intramolecular reaction could indeed be realized with suitable induction, when a suitable chiral iodine(III) reagent was initially treated with TMS triflate followed by reaction at low temperature (Scheme 15) [54]. Conceptually, this process appears to be different from the usual pathways that originate from electrophilic nitrogen. Instead, the chiral hypervalent Ishihara reagent 70 probably leads to activation of one of the enantiotopic faces of the alkene 69 followed by nucleophilic amination and subsequent reductive de-iodination by oxygenation to arrive at the cyclic aminooxygenation product 71. 

In 2005, Huang et al. reported a tandem asymmetric conjugate reduction-fluorina-tion reaction by an efficient combination of iminium and enamine catalysis using two distinct secondary amine catalysts [16]. This method offered direct access to chiral multifunctionalized aldehydes from P-substituted enals and electrophilic florinated reagents in a biomimetic way (Schane 9.13). The diastereoselectivity of the products varied depending on the catalyst combination (Scheme 9.14). The chemistry presented here demonstrated for the first time the power of the multicatalysis process for control of the product diastereoselectivity based on the cycle-specific catalysis concept. 

Although the diastereoselective addition of nucleophiles to imines offers an attractive route to chiral amine derivatives, most chiral nonracemic imines suffer from low reactivity (electrophilicity), resulting in no reaction or competitive reduction with organometallic reagents. Other problems include enolization of aliphatic imines, poor... 

An aldol reaction in acid solution ensures that the more substituted enol is formed and the aldehyde is by far the most electrophilic of all the carbonyl groups. The Diels-Alder reaction gives the free acid 30 which was resolved with a chiral amine and each enantiomer used for a different part of the B12 molecule. The slightly unusual reagent Cr(VI) was used for the alkene cleavage and acetal formation occurred spontaneously under the acidic conditions. 

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-... 

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