Epoxides with azide ion

Scheme 6.132 Ring-opening of epoxides with azide ions.

P-Aminoalcohols may be generated from (3-azidoalcohols, which are commonly made from the opening of epoxides with azide ion as shown in Scheme 13 (91TL2533). After conversion of the alcohol... 

Opening of epoxides with azide ions represents a very interesting route to azidocarbinols. The large number of examples quoted in the literature proves the broad scope of this technique." " On treatment of nonsymmetrically substituted oxiranes, the products expected from an 5n2 process are usually obtained. In boiling aqueous dioxane, cyclohexene oxide gives rise to 61% of rrans-2-azidocyclohexa-nol. The reported formation of (35 Scheme 46) with styrene oxide is unexpected, particularly if the formation of (36) from the analogous diphenyl precursor is considered. ... 

Cleavage of 5a,6a- and 6a,7a- epoxides with azide ion and subsequent reduction with hydrazine has led to the preparation of 6 -amino-steroids, although similar treatment of 16a,17a-epoxypregnenolone acetate was accompanied by D-homoannulation to give, after reduction, the 16j3-amino-Ha-ketone. Azide displacement (lithium azide in DMF) of 3a,20j8-diacetoxy-... 

Azido-sugars are frequently prepared by reaction of epoxides with azide ion. 3-Azido-3-deoxy-L-threose 68 was synthesized from cu-but-2-ene-l,4-diol 66 via the Sharpless asymmetic epoxidation product 67, and was converted into 6-azido-6-deoxy-L-galocro-heptulose 69 by an enzyme-catalyzed aldol condensation (Scheme 13). 3-Azido-3-deoxy-L-etythrose, and thence 6-azido-6-deoxy-L-g/uco-heptulose were obtained in a similar way via 4-rerf-butyldiphenylsilyoxy-rraiu-but-2-enal. These and two other azido-heptulose isomers made from the enantiomeric 3-azido-3-deoxy-tetroses, were converted to a- and P-l-homonojirimycin and homomannonojirimycin on hydrogenation. Ethyl 3-azido-2,3-dideoxy-D-eryr/iro-pentopyranoside and its 3-C-methyl analogue 71, R=H or Me, were synthesized from crotonaldehyde or 3-methyl-2-... 

DL-Valiolamine (205) was synthesized from the exo-alkene (247) derived from 51 with silver fluoride in pyridine. Compound 247 was treated with a peroxy acid, to give a single spiro epoxide (248, 89%) which was cleaved by way of anchimeric reaction in the presence of acetate ion to give, after acetylation, the tetraacetate 249. The bromo group was directly displaced with azide ion, the product was hydrogenated, and the amine acety-lated, to give the penta-A, 0-acetyl derivative (250,50%). On the other hand. 

Alkyl azides can be prepared by treatment of the appropriate halide with azide ion.939 Phase transfer catalysis940 and ultrasound941 have been used. Other leaving groups have also been used,942 for example, OH,943 OMs, OTs,944 and OAc.945 Epoxides react with NaN3, with HN3 in DMF,94 or with HN3-Et3Al947 to give 3-azido alcohols these are easily converted to aziridines,948 e.g.,... 

Vinyl azides have been prepared by treating epoxides (78) with azide ion to give azido alcohols (79) which are then dehydrated to the vinyl azide.30 This method also complements the iodine azide method since the epoxide route usually gives the isomeric vinyl azide. -Hydroxy azides (81) can also be prepared by the sodium borohydride reduction of a-azidoketones (80). 

Epoxides undergo bimolecular nucleophilic displacement reactions with azide ion to produce azidoalcohols (Table 2). Azide ion preferentially attacks saturated unsymmetrical epoxides at the less substituted carbon atom in accordance with the normal pattern of polar... 

Epoxides which are fused to alicyclic systems undergo ring opening with azide ion in the usual tram diaxial manner This is demonstrated by the formation of the /ran5-2-azidoalcohols (66) and (67) from cyclohexene oxide and cyclopentene oxide respectively . 

The reactions of stable carbocations with water are generally base catalyzed,109,110 and their reactions with hydroxide ion are slower than their reactions with azide ion and sulfhydryl ions. The less favorable reaction of hydroxide ion with carbocations has been attributed to the fact that deprotonation of a water molecule by hydroxide ion is not a thermodynamically favorable reaction, and activation energy to generate a desolvated hydroxide ion is required.110 These factors would also account for the less favorable reaction of hydroxide ion as a nucleophile with 82 to form tetrols instead of as a base to bring about epoxide ring closure. 

For benzo[a]pyrene benzylic carbocations (82 and 83)88,89 and 4-methoxyphenyl-stabilized carbocations (52a, 54b, 66b, 68b and 127),59,63,70,108 values of kaz/ks are in the range 25-600 M-1. It is reasonable to assume that these carbocations also react with azide ion at the diffusional limit of 1010M-1s-1. The rate constants for reaction of these carbocations with water (ks) are estimated to be (8 x 106) to (2 x 108)s, which correspond to energies of activation of 6.5-8.0kcalmol-1. Benzo[a]pyrene 7,8-diol 9,10-epoxides (80 and 81) and tetrahydronaphthalene epoxide each has two optimized conformations similar to structures 132 and 134, which are shown in Scheme 42. The carbocation formed from reaction of each of these... 

The conversion of epoxides to aziridines by nucleophilic ring-opening with azide ion or amines followed by cyclization was covered in Section 1.01.9.3. The conversion of azirines to aziridines by nucleophilic addition and the conversion of aziridines to azirines by elimination were covered in Sections 1.01.6 and 1.01.7, respectively. 

Now the epoxide 41 was opened regioselectively and stereospecifically with azide ion to give the trans di-axial product 42 that was reduced to the amine 43. The synthesis of fortamine 44 was completed by the removal of the protecting carbamate.4... 

These may seem strange molecules to have a place in the new chiral pool but they were made on a vast scale by Merck in the synthesis of their HIV protease inhibitor crixivan (Indinavir). They both come from Jacobsen epoxidation of indene 283 (chapter 25) the anti-compound 285 by opening the epoxide 284 at the benzylic centre with azide ion.51... 

The 2,5-anhydro-3,4-diamino-pentose diethyl acetal 72 was synthesized from L-xylose by sequential reaction of epoxide and triflate intermediates with azide ion. After reduction to a 3,4-diamino-2,5-anhydroalditol, oxoruthenium(V) complexes of it and related 2,3-diamino-nucleosides (see Chapter 17) were prepared and evaluated as ribonuclease inhibitors. A number of routes were investigated for the preparation of the 2-amino-3-azido-2,3-dideoxy-D-glucoside 73, a precursor for a mimetic of the cyclopdepsipeptide didemnin B, from 2-acetamido-2-deoxy-D-glucose. Because A -deacetylation was much easier in the presence of a free 3-hydroxy-group, the best route involved preparation of a 2-deoxy-2-trifluoroacetamido-D-allopyranoside, and displacement of a mesylate group from C-3 by azide ion with inversion. ... 

The 2a-benzoylamido derivative of docetaxel, A3.3.3, has been prepared from 10-deacetylbaccatin III (523). The synthesis proceeded through a ring-opening of the epoxide A3.3.1 with azide ion to give the ce-azide A3.3.2, followed by standard conversions to the final product A3.3.3. The a-amide A3.3.3 was 16-20 times less cytotoxic than taxol in A-549 and KB cell lines, but had comparable cytotoxicity to taxol in... 

From Achiral Non-carbohydrates. — 3-Deoxy-3-guanidino-D-threose 48 equilibrates with 49. a transition state inhibitor for galactosidase. It was synthesized as shown in Scheme 12 from epoxide 47, which was obtained by porcine pancreatic lipase catalysed enantioselective esterification of the racemic epoxy-alcohol precursor. 6-Deoxy-L-talonolactone 50 was synthesized by an asymmetric aldol condensation - dihydroxylation sequence (Vol.24, p.lS2) in improved diastereoselectivity and was converted into 2-acetamido-2,6-dideoxy-L-fucose (shown as its furanose isomer 51 in Scheme 13), 3-acetamido-3,6Hlideoxy-L-idose and 5-acetamido-S,6-dideoxy-D-allose by S 2 displacements of triflate with azide ion. 4-Amino-4-deoxy-DL-erthrose 53 was obtained from the hetero-Diels-Alder adduct 52 by a sequence of reactions including cis-dihydroxylation (OSO4, NMNO) of the alkene moiety (Scheme 14). The synthesis of a racemic branched-chain lactam is covered in Chapter 16. 

Direct introduction of HN3, or its equivalents, onto olefins constitutes an efficient and straightforward approach. Unfortunately, the most efficient reactions are multi-step sequences, such as epoxidation followed by opening with azide ions or hydroboration followed by iodination and snbstitution. Several one-step methods, such as halo-azidation, diazidation, seleno-azidation, nitrato-azidation, ° formation of a-azido ketones," and carboazidation, have also been reported, bnt the conceptually simplest reaction, the hydroazidation reaction, has been much less developed (Figure 4.1). 

---