Epoxides azide synthesis

Synthesis of Triazoles A number of MCRs that use an epoxide-azide-alkyne Cu(I)-catalyzed cycloaddition sequence to provide substituted p-hydroxy-l,2,3-triazoles 70 (Scheme 3.36) have been recently developed. The azida-tion of an epoxide with sodium azide to give 2-azidoalcohols and subsequent reaction with a terminal alkyne have been carried out under mild conditions in environmentally friendly solvents, such as water, using the catalytic system CuSO sodium ascorbate [65] (see the example depicted in Scheme 3.36) [65a] or a porphyrinatocopper(II) complex... 

A variety of racemic aminodideoxypentopyranoses have been synthesised from 2-methoxy-5,6-dihydro-2H-pyran (85), primarily by manipulating the known products of epoxidation - azide ring opening as exemplified in Scheme 24 for the synthesis of the 2-amino-2.4-dideoxv-DL-threo-Dentoside (86). These amino-sugars... 

Both saturated (50) and unsaturated derivatives (51) are easily accepted by lipases and esterases. Lipase P from Amano resolves azide (52) or naphthyl (53) derivatives with good yields and excellent selectivity. PPL-catalyzed resolution of glycidyl esters (54) is of great synthetic utiUty because it provides an alternative to the Sharpless epoxidation route for the synthesis of P-blockers. The optical purity of glycidyl esters strongly depends on the stmcture of the acyl moiety the hydrolysis of propyl and butyl derivatives of epoxy alcohols results ia esters with ee > 95% (30). 

A novel approach to azabicyclic ring systems, based on an epoxide-initiated electrophilic cyclization of an alkyl azide, has been developed by Baskaran. A new stereo- and enantioselective synthesis of the 5-hydroxymethyl azabicyclic framework 91a, present in (+)- and (-)-indolizidines 167B and 209D, for example, was... 

Treatment of 51 with an excess of sodium benzoate in DMF resulted in substitution and elimination, to yield the cyclohexene derivative (228, 36%). The yield was low, but 228 was later shown to be a useful compound for synthesis of carba-oligosaccharides. <9-Deacylation of228 and successive benzylidenation and acetylation gave the alkene 229, which was oxidized with a peroxy acid to give a single epoxide (230) in 60% yield. Treatment of 230 with sodium azide and ammonium chloride in aqueous 2-methoxyeth-anol gave the azide (231,55%) as the major product this was converted into a hydroxyvalidamine derivative in the usual manner. On the other hand, an elimination reaction of the methanesulfonate of 231 with DBU in toluene gave the protected precursor (232, 87%) of 203. 

By combining several click reactions, click chemistry allows for the rapid synthesis of useful new compounds of high complexity and combinatorial libraries. The 2-type reaction of the azide ion with a variety of epoxides to give azido alcohols has been exploited extensively in click chemistry. First of all, azido alcohols can be converted into amino alcohols upon reduction.70 On the other hand, aliphatic azides are quite stable toward a number of other standard organic synthesis conditions (orthogonality), but readily undergo 1,3-dipolar cycloaddition with alkynes. An example of the sequential reactions of... 

The synthesis of a,a-disubstituted amino acids is a difficult task and continues to attract attention. An efficient route that utilizes the ring-opening of an epoxide with azide has been reported <06TL9268>. Treatment of the sulfoxide substituted epoxide 23 with NaN3 provides intermediate azido aldehyde 24. This aldehyde was not isolated but oxidized to the acid and then the azide reduced to provide the a,a-disubstituted amino acid 25. The regioselectivity of this reaction was impressive with only one product reported. 

Alkyl azides have been involved in the synthesis of indolizidinone derivatives in several ways. One example (Scheme 7) is the intramolecular Schmidt reaction between alkyl azides and ketones which can be used to transform azidoketone 24 into the corresponding indolizidinones 26 through intermediate 25 <2001JOC886> or with epoxides to obtain the indolizidine 27 <2004JOC3093>. 

We did not explore the first of these two approaches too deeply. The synthesis of the epoxide 76, an ideal partner for the alkylation of any trisaccharide amine, was daunting and seemingly difficult but there was available in the literature an excellent route to the enone 77 from tetra-O-benzyl-D-gluconolactone 38 [53]. However, earlier work by Kuzuhara suggested that any reductive amina-tion of the enone 77 would probably proceed in low yield and certainly give a mixture of diastereoisomeric amines [54]. We did prepare the amine 78, via the azide 79, but the amine 78 would not condense with the enone 77 to give the... 

Although we have not yet attempted the alkylation of the amine 81 with the epoxide 125, preliminary experiments with cyclohexylamine and with sodium azide have allowed the synthesis of the model compounds 126 and... 

Reddy, P. G., Baskaran, S. (2004) Epoxide-initiated cationic cyclization of azides a novel method for the stereoselective construction of 5-hydroxymethyl azabicyclic compounds and application in the stereo- and enan-tioselective total synthesis of (+)- and ( —) -indolizidine 167B and 209D. J Org Chem 69, 3093-3101. 

Advantageous use of homochiral cyclohexadiene-cis-l,2-diol, available by means of biocatalytic oxidation of chlorobenzene with toluene dioxygenase, has enabled the synthesis of all four enantiomerically pure C18-sphingosines (Nugent, 1998), which are known inhibitors of protein kinase C and important in cellular response mediation for tumor promoters and growth factors. The four requisite diastere-omers of azido alcohol precursors were accessed by regioselective opening of epoxides with either azide or halide ions. 

---