Azide-alcohols, cyclization

The pentacychc skeleton of 3 was constructed around a central organizing piperidine ring 9. This was prepared from the known (and commercial) enantiomericaUy-pure lactone 4. The akylated stereogenic center of 9 was assembled by diastereoselective hydroxy methyla-tion of the acyl oxazohdinone 5 with j-trioxane, followed by protection. Reduction of the hnide to the alcohol led to the mesylate 7, which on reduction of the azide spontaneously cyclized to give, after protection, the piperidine 8. Selective desilylation of the primary alcohol then enabled the preparation of 9. 

In another approach, 2-(alkylamino)alcohol is employed as starting material for aziridine syntheses with the aid of dihalogenophosphoranes (70BCJ1185). Intramolecular transformation of 3-azidopropyloxirane 73 results in a simultaneous formation of a condensed aziridino[l,2-a]pyrrol-idine system (Scheme 39). The azide group is first transformed into imino-phosphorane 74, the nucleophilic N atom cleaves the oxirane to form betaine 75 [as in the Mitsunobu reaction (81S1)], and the phosphorus is shifted from N to O and then eliminated as phosphane oxide under simultaneous cyclization to bicyclic 76 (89JA7500). 

Cyclization of haloamines 0-46 Cyclization of amino alcohols 0-61 Cyclization of p-azido alcohols 5-31 From 3-iodo azides... 

The alcohol 177 was converted to starting substrates oxazolidinone 178 by acylation followed by reduction of the azide function along with cyclization. Oxazolidinone 178 was protected with f-butylpyrocarbonate-4-(dimethylamino) pyridine (DMAP) and triethylamine, which was further subjected to reductive cleavage of the benzyl ester unit to afford carboxylic acid 179. The treatment of 179 with solution of l-chloro-/V./V,2-trimethyl-1-propenv I airline resulted in the easy formation of the corresponding acid chloride which on reaction with imine in the presence of triethylamine provided the stereoselective formation of spiro-p-lactam 180. 

Cyclization of the furanose derivative 340 was mediated by the action of sodium hydride to afford 341 (R = Ts) in 90% yield. The amine 340 had been obtained from the azide 342 and it was later found that thermolysis of this 1,3-azido alcohol under Staudinger reaction conditions (triphenylphosphine in f-xylene) gave the azetidine 341 (R = H) directly in 99% yield <2003TL5267>. 

The alkene pseudohalogen adducts (15) of Scheme 8 are also useful intermediates for aziridine synthesis. These adducts are discussed later in Sections 3.5.6.2-4. The iodine azide " and bromine azide ° adducts may be reduced to aziridines with many reagents recent references report use of lithium aluminum hydride and dimethylamineborane. TTie iodine isocyanate aziridination continues to prove useful, as in Scheme 10. Since the recent reviews, - the mechanism of the triphenylphosphine-based cyclization of azido alcohols has appeared (Scheme 11) there are clear steric consequences. Alkenes can be chlorinated in acetonitrile to give intermediates which can be worked up to yield aziridines (Scheme 12). ... 

In the presence of a palladium catalyst, allyl epoxides (113) react with nitrogen nucleophiles at the al-kenic carbon atom remote from the oxirane ring to give 1,4-adducts (114)." In the absence of a palladium catalyst, azide ion attacks the oxirane ring affording 1,2-adducts (115 Scheme 52 and Table 2)." Vinyl epoxide (116) gave 1,2- and 1,4-azido alcohol in a ratio of 1 1.5 irrespective of the reaction system. " Intramolecular cyclization of vinyl epoxide (117) in the presence of a palladium catalyst afforded isoquinuclidine (118 Scheme 52). ... 

The enantioselective total synthesis of the complex bioactive indole alkaloid enf-WIN 64821 was accomplished by L.E. Overman and co-workers." This natural product is a representative member of the family of the C2-symmetric bispyrrolidinoindoline diketopiperazine alkaloids. The stereospecific incorporation of two C-N bonds was achieved using the Mitsunobu reaction to convert two secondary alcohol functionalities to the corresponding alkyl azides with inversion of configuration. The azides subsequently were reduced to the primary amines and cyclized to the desired ib/s-amidine functionality. 

A further use of Barton esters has been described as a path to enol ether radicals. The reaction involves the photochemical decomposition at 355 nm of the derivative (85). As part of an approach to the synthesis of a series of Kopsia alkaloids, the reductive decarboxylation of the derivative (86) was carried out. This involved irradiation of the Barton ester (86a) in the presence of t-BuSH. This affords the product (86b). The photochemical decomposition of the Barton ester (87) provides a path to the silyl derivatives (88). The nature of the trapping agent X is dependent on the conditions under which the reaction is carried out. Thus a variety of derivatives can be obtained using alcohols to afford ethers, or using ethanesulfonyl azide to give azides. The Barton esters (89) undergo the usual photochemical decarboxylation to afford ethenoyloxy radicals. Cyclization within these, in the presence of tributylstannane yields the lactones (90). ... 

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