Transfers azide

Azidation.1 Arylsulfonyl azides generally react with enolates to effect net diazo transfer, but this hindered and electron-rich azide can effect azide transfer at the expense of diazo transfer. The nature of the enolate counterion also plays a role, with K being more effective than Na. In addition, acetic acid (or KOAc) is required as the quench for decomposition of the triazine intermediate to the azide with elimination of the arylsulfinic acid, ArS(0)0H. By use of these conditions, chiral N-acyloxazolidones such as 2 undergo diastereoselective azidation to give the azides 3 in 75-90% yield and in high optical purity (>91 9). These... 

The utilization of a-amino acids and their derived 6-araino alcohols in asymmetric synthesis has been extensive. A number of procedures have been reported for the reduction of a variety of amino acid derivatives however, the direct reduction of a-am1no acids with borane has proven to be exceptionally convenient for laboratory-scale reactions. These reductions characteristically proceed in high yield with no perceptible racemization. The resulting p-amino alcohols can, in turn, be transformed into oxazolidinones, which have proven to be versatile chiral auxiliaries. Besides the highly diastereoselective aldol addition reactions, enolates of N-acyl oxazolidinones have been used in conjunction with asymmetric alkylations, halogenations, hydroxylations, acylations, and azide transfer processes, all of which proceed with excellent levels of stereoselectivity. 

B. Ganem, Electrophilic azide transfer to chiral enolates, a general approach to the asymmetric synthesis of x-amino-aeids, Chemtracts Org. Chem. 1, 145 (1988). 

See also Refs 1 2 and others in CA Refs l)F.L.Scott et al, "Azide Transfer-... 

A mechanistic rationale for the observations is presented, although it is not really known why it is the potassium enolate, the trisyl azide and the acetic acid quench that lead to the high yield in the stereoselective azide transfer reactions2. The diastereomeric //-configurated carbox-imides were prepared via a bromination/azide substitution sequence, not detailed here2. 

In summary, the stereoselective formation of the a-azido carboximides (S)-7 by means of electrophilic azide transfer to the JV-acyloxazolidinones 5 leads to a new class of very versatile protected amino acids which can be easily tranformed into free amino acids (or peptides). This methodology, in contrast to the preparation of a-amino acids by means of alkylation of chiral glycine enolates9, also provides access to arylglycines and hindered amino acid derivatives such as tcrt-alkylglycines. 

The best results are obtained with trisyl azide, which again leads to high yields of the azide transfer product 2, especially if the enolate 1 is added to trisyl azide (see entries 1 and 2). Interestingly, the best chemoselectivity and, in addition, identical yields of azide (73%) result from the reaction of the lithium enolate with trisyl azide (entry 3). The reaction of the ester enolate 1 with trisyl azide is less sensitive to the nature of the enolate metal than is the corresponding imide enolate reaction (see Section 7.1.1.). Acetic acid quench, on the other hand, again proved to be useful. Unfortunately, bis-azidation to 3 and diazo transfer to 4 are also observed. 

The application of these observations to a stereoselective azide transfer is shown in the following example. Reaction of the dilithiuni compound 6, prepared from the racemic 3-hy-droxybutyrate 5 with trisyl azide and acetic acid quench, leads to the (3-hydroxy-a-azido ester 7 in 77% yield and a diastereoselection d.r. [(2R, >R )/(2R, 3S )] of 82 18 (determined by H NMR). 

From this reaction and the reaction of 6 to give 7 (see Section 7.1.1.1.), it can be concluded that the steric requirements for azide transfer are modest, in fact even smaller than in analogous enolate methylation reactions2. It is worth comparing the low levels of internal asymmetric induction observed in the case of a cyclic amide enolate3 (see 2->-3->-4 in Section 7.1.1.). 

The successful azide transfer with triisopropylbenzenesulfonyl azide (trisyl azide)2 (see Section 7.1.1.) is also the method of choice for the preparation of optically active a-aminophospho-nic acids from chiral, phosphorus-stabilized carbanions12. 

Wait 5-30 min, then stop the reaction by adding phosphate buffer containing 0.1% azide. Transfer the iodination reaction to a Sephadex G-50 column and wash the reaction vial with 5% BSA-phosphate buffer, transfering the washes to the column. Start the column flow after all the washes and transfers have been completed. Collect 0.4-ml fractions in each of 20 tubes. 

Hakimelahi, G.H., and Just, G., Two simple methods for the synthesis of trialkyl a-aminophospho-noacetates. Trifluoromethanesulfonyl azide as an azide-transfer agent, Synth. Commun., 10, 429, 1980. 

Azidation of N-hydroxy fl-lactams. Reaction of 1 with the N-hydroxy /3-lactam 2 docs not provide the expected a-diazo-/3-kcto ester but compound 3, formed by azide transfer to C3 with cleavage of the N-hydroxy bond. Similar results obtain in reaction... 

Azide transfer to 3-deoxyglycak. This explosive-prone reagent is prepared in situ... 

A. Kirschning, S. Domann, G. Drager, and L. Rose, Iodine(III)-promoted azide transfer, Synlett (1995) 767-769. 

Kappe and co-workers employed an isomunchnone generation-trapping sequence to access conformationally restricted dihydropyrimidine derivatives as novel calcium channel modulators. The stable isomunchnone 481 was prepared from dihydropyrimidone 479 by the standard A -malonylacylation and azide transfer to give 480, and then treatment of the latter with rhodium acetate (Scheme 4.19). Isomunchnone 481, which is stable in the open air for months, reacts with N-methylmaleimide and methyl vinyl ketone to give adducts 482 and 483, respectively, the latter arising by rearrangement of the primary adduct. 

In a study on the electrophilic azide transfer to chiral enolates, Evans found that the use of potassium bis(trimethylsilyl)amide was crucial for this process. The KN(TMS)2 played a dual role in the reaction as a base, it was used for the stereoselective generation of the (Z)-enolate (1). Reaction of this enolate with trisyl azide gave an intermediate triazene species (2) (eq 4). The potassium counterion from the KN(TMS)2 used for enolate formation was important for the decomposition of the triazene to the desired azide. Use of other hindered bases such as Lithium Hexamethyldisilazide allowed preparation of the intermediate triazene however, the lithium ion did not catalyze the decomposition of the triazene to the azide.This methodology has been utilized in the synthesis of cyclic tripeptides. 

Benzenesulfonyl azide transfers its azido function to Grignard reagents (164). The soft reagents do not attack the hard sulfonyl group. 

General Considerations. The reactions of arylsulfonyl azides with enolates have been reported to give a range of products, depending on the fragmentation of the initial adduct. This may differ according to the nature of the enolate, the particular sulfonyl azide, and the quenching procedure. Net diazo transfer is usually observed for stabilized enolates, while azide transfer is more common with more reactive enolates. 

The azide transfer methodology may also be applied to a variety of esters and is compatible with a number of other functional groups (eqs 13-15). It may also be used with... 

Azide Transfer to Enolates. Evans chiral oxazolidinone auxiliaries continue to be widely used in the azide transfer to enolates because high stereoselectivity can be achieved (eqs 21, 22, and 233 ). 

Under similar azide transfer to enolate conditions, the unexpected primary amide that arose from the hydrolysis of the Evans chiral auxiliary was also isolated (eq 25). Double enolization of the bisamide followed by trapping of the dianion with trisyl azide provided the diazido diastereoisomers in 4 1 ratio (eq 26). ... 

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