Esters, reaction with azide

Azide is a potent nucleophile and can react with electrophilic substrates other than halides and sulfonate esters. Reaction of azide with the epoxide moiety in carboethoxy oxirane (ethyl glycidate) was followed by catalytic hydrogenation of the azide and hydrolysis of the ester to give isoserine (3-amino-2-hydroxypropanoic acid, 1.23). This synthetic approach to isoserine dates to 1879. 3... 

Once this information had been obtained, a simple asymmetric synthesis of amino acids (130) followed (Scheme 8.30) [67]. Reactions with azide ion were sluggish, and (a-bromoalkyl)boronic esters (126) were preferred. These reactions were carried out... 

The azido group is inert to boronic esters but reacts readily with alkyldichlorobo-ranes [70]. Section 8.4.1 describes the conversion of boronic esters into (alkyldichloro)boranes and their reaction with azides. 

Although there is a number of syntheses of 14 [9] the main problem lies in the differentiability of the two amino functions, preferably in form of p-BOC and a-Fmoc-protection as shown in formula 16. Our synthesis (Fig. 11) proceeds via the P-azido-a-mesyloxycarboxylic acid 17, readily available from 6 by azide opening. Methylation and reduction of the azide function, followed by BOC protection, furnishes 19, which after a second 8 2 displacement reaction with azide gives 20. By ester hydrolysis, azide reduction and Fmoc-protection the desired bis-amino acid 16 is obtained in gram quantities. 

The effect of a substituent may be substantially modified by fast, concurrent, reversible addition of the nucleophile to an electrophilic center in the substituent. Ortho- and para-CS.0 and pam-CN groups have been found by Miller and co-workers to have a much reduced activating effect on the displacement of halogen in 2-nitrohaloben-zenes with methoxide ion [reversible formation of hemiacetal (143) and imido ester anions (144)] than with azide ion (less interaction) or thiocyanate (little, if any, interaction). Formation of 0-acyl derivatives of 0x0 derivatives or of A-oxides, hydrogen bonding to these moieties, and ionization of substituents are other examples of reversible and often relatively complete modifications under reaction conditions. If the interaction is irreversible, such as hydrolysis of a... 

The major application of the Mitsunobu reaction is the conversion of a chiral secondary alcohol 1 into an ester 3 with concomitant inversion of configuration at the secondary carbon center. In a second step the ester can be hydrolyzed to yield the inverted alcohol 4, which is enantiomeric to 1. By using appropriate nucleophiles, alcohols can be converted to other classes of compounds—e.g. azides, amines or ethers. 

The stereoselective total synthesis of (+)-epiquinamide 301 has been achieved starting from the amino acid L-allysine ethylene acetal, which was converted into piperidine 298 by standard protocols. Allylation of 297 via an. V-acyliminium ion gave 298, which underwent RCM to provide 299 and the quinolizidine 300, with the wrong stereochemistry at the C-l stereocenter. This was corrected by mesylation of the alcohol, followed by Sn2 reaction with sodium azide to give 301, which, upon saponification of the methyl ester and decarboxylation through the Barton procedure followed by reduction and N-acylation, gave the desired natural product (Scheme 66) <20050L4005>. 

Figure 5.22 The NHS ester of ANB-NOS reacts with amines to form amide bonds. Subsequent photoactivation of the complex with UV light causes phenyl azide ring expansion and reaction with neighboring amines.

Cyclization of 776 with ortho-esters gave (83JOC1628) [l,2,4]triazolo-[4,3-fc]pyrimido[5,4-< ][ 1,2,4]triazines 777, whereas reaction with sodium nitrite afforded the corresponding tetrazolopyrimidotriazine 778.3-Azido-pyrimido[4,5-e][l, 2,4]triazine 779 exists in a cyclic form as tetrazolo derivative 780, as shown by X-ray analysis (86KGS114). In solution the position of the 779 780 equilibrium depended on temperature and solvent. Higher temperatures favored 779. Azido compound 779 predominated in water, and tetrazolo compound 780 predominated in pyridine. Addition of sodium azide to the aqueous solution shifted the equilibrium toward 780. The... 

Acyl azides show selectivity for acylation at secondary (rather than primary) hydroxyl groups in nucleosides. Thus, on reaction with an excess of N-(benzyIoxycarbonyl)glycyIglycyl azide in 1,4-dioxane-water at 8° and pH 9, adenosine gave the 2 (3 )-0-(aminoacyl) and 2, 3 -di-0-(aminoacyl) derivatives.183 Furthermore, adenosine and uridine were converted into a variety of 2 (3 )-esters of aromatic amino acids by reaction with the appropriate acyl azide.184... 

The importance of reactions with complex, metal hydrides in carbohydrate chemistry is well documented by a vast number of publications that deal mainly with reduction of carbonyl groups, N- and O-acyl functions, lactones, azides, and epoxides, as well as with reactions of sulfonic esters. With rare exceptions, lithium aluminum hydride and lithium, sodium, or potassium borohydride are the... 

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