Inversion azide displacement

Bruce, G. W. J. Fleet, A. CJirdhar, M. Haraldsson, J. M. Peach, and D. I. Watkin, Retention and apparent inversion during azide displacement of avtriflates of 1,5-lactones, Tetrahedron 46 19 (1990). 

Oppolzer s camphor sultam, a well known chiral auxiliary, has been applied to the asymmetric synthesis of chial fluorine-containing amino acids <07OL2513>. Photoinduced addition of perfluoroalkyl iodides 189 to /V-acyloylcamphorsultam 188 in the presence of an aqueous solution of sodium sulfite provides alkyl iodides 190 with moderate to good stereoselectivities. Azide displacement with the major diastereomer of 190 proceeds with inversion of configuration. Subsequent removal of the sultam auxiliary and hydrogenation of the azide afford the chiral fluorine-containing amino acid 192. 

Benzyl 2,3,4-triacetamido-2,3,4,6-tetradeoxy-a-D-galacto-pyranoside has been synthesized from the corresponding 3,4,6-tri-O-mesyl-allopyranoside by selective reduction at C-6 (NaBH j-DMSO), followed by azide-displacement of the sulphonates at 3 and 4 with Inversion mass spectral fragmentation of its derived alditol acetate was also recorded. 

The only complete synthesis of cephalosporin C provides a classic example of the synthetic art of the late R. B. Woodward, and formed the subject of his Nobel Prize winning lecture of 1965. The synthesis, published in 1966, starts from L(+)-cysteine (189) 164, 165). Protection of the nitrogen, sulphur and acid functional groups provided the cyclic intermediate (191) ideally suited for the introduction of the amino function which was to become the nitrogen atom of the crucial -lactam intermediate (195). This was achieved in a completely stereocontrolled manner by a novel substitution method. Thermal introduction of the hydrazo-substituent to form (192) was followed by oxidation and conversion to the tran -hydroxy ester (193). Inversion by displacement of the mesylate with azide and subsequent reduction gave the cw-amino ester (194) which afforded the (i-lactam (195) on cyclisation. 

Neopentyl (2,2-dimethylpropyl) systems are resistant to nucleo diilic substitution reactions. They are primary and do not form caibocation intermediates, but the /-butyl substituent efiTectively hinders back-side attack. The rate of reaction of neopent>i bromide with iodide ion is 470 times slower than that of n-butyl bromide. Usually, tiie ner rentyl system reacts with rearrangement to the /-pentyl system, aldiough use of good nucleophiles in polar aprotic solvents permits direct displacement to occur. Entry 2 shows that such a reaction with azide ion as the nucleophile proceeds with complete inversion of configuration. The primary beiuyl system in entry 3 exhibits high, but not complete, inversiotL This is attributed to racemization of the reactant by ionization and internal return. 

Displacement of the /Moluenesul Innate leaving group by sodium azide in an SN2 process and proceeds with inversion of configuration. 

The nitrogen heterocycles, aziridines, can be made by displacement of an alcohol by an amine after activation. In their synthesis of the antitumour and antibiotic compound 30, whose active region is the aziridine, J. P. Michael and group opened the cyclic sulfite 28 with azide ion. Reaction occurred at the allylic position and with inversion. Activation of the alcohol as a mesylate gave 29 and reduction of the azide to an amine was followed by base-catalysed cyclisation, again with inversion.4... 

Several different nucleophilic displacement reactions of ring substituents were utilized in the synthesis of 3-azido-oxetane-2-carboxylates (Scheme 12) <2001TL4247>. The triflate ester 66, prepared from the corresponding trans-/3-hydroxy ester and triflic anhydride, was displaced by reaction with sodium azide, and inversion of configuration, to... 

The 1,2-diols formed by the asymmetric oxidation can be used as substrates in a wide variety of transformations. Conversion of the hydroxy groups to p-toluenesulfonates then allows nucleophilic displacement by azide at both centers with inversion of configuration (Scheme 9.22).161... 

Displacement of a halide at the a-position with tetramethyl-guanidinium azide (TMGA) introduces nitrogen functionality with inversion of the original halide configuration and <1% epimerization (eq 30). ... 

The general procedures previously outlined in this section for the formation of the carbon to azide bond have been widely employed in the steroid field, particularly as a stage in the stereospecific synthesis of aminosteroids. Bimolecular nucleophilic displacement reactions of sterols substituted with j -toluenesulphonyl, methanesulphonyl or halogeno groups etc. with azide ion proceeds with Walden Inversion and enables the stereospecific introduction of the azido group, which may then be reduced to an amino group. 

Displacement of secondary sulphonates usually proceeds with inversion and significant exceptions are stereochemically informative. When the reaction of 107 with azide ion in dimethylformamide was carried out over 24 hours at 85°, the triazide (109) was isolated. Substitution at C(4j proceeds with the expected Walden inversion, but at C(3) the azido function is introduced with retention of configuration. This result has been rationalized in terms of neighbouring group... 

Since direct displacement with azide ion competes favourably with anchimeric reactions, less direct routes such as the double inversion procedure illustrated for conversion of 119 into the triazide 122 in equation (62), must often be used to achieve substitution with overall retention of configuration . 

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