Bicyclic derivatives, synthesis

Phosphorinane, 4-t-butyl-1 -phenyl-synthesis, 1, 500 Phosphorinane, I-chloro-synthesis, 1, 500 Phosphorinane, 1-hydrocarbyl-I-sulfide synthesis, 1, 500 Phosphorinane, 1-phenyl-synthesis, 1, 499 Phosphorinanes, 1, 497-506 bicyclic bridged derivatives synthesis, 1, 501 conformation, 1, 503-504 NMR, 1, 497 oxidation, 1, 498 reactions, 1, 497 structure, 1, 497, 503-504 sulfuration, 1, 499 synthesis, 1, 499... 

With respect to five-membered lactones fused to hexopyranose units, some approaches have been reported so far and the exploitation of their synthetic potential has led to the access of new carbohydrate derivatives. Bicyclic derivatives of this type are key intermediates in the synthesis of the epimer at C-3 of the sugar moiety contained in miharamycins [212, 213]. The latter are antibiotics known to inhibit strongly Pyricularia oryzae, which produces the rice blast disease. These compounds are also considered to be a potential bioterrorism agent (Scheme 42). Hence, the 3,3-spiroepoxide 176 was converted into the 3-C-cyanomethyl derivative 177, the hydrolysis of which led to spontaneous cyclization in the presence of... 

Fluorination of bicyclic derivatives, which has been used in prostaglandin synthesis from nor-bornadicne, gives a 1 1 mixture of two isomeric ot-fluoro esters, e.g. 3.18 The reaction is performed in tetrahydrofuran at — 78 °C, while a violent explosion occurs if the reaction is performed at — 40 C (upon quenching the reaction with water). 

Stragies and Blechert [89] have described the synthesis of [ .3.0]bicyclic derivatives with different ring sizes and functional groups in a single domino process. With an excess of allyltrimethylsilane, a bicyclic product was obtained in high yield (Eq. 53). 

A type 2 intramolecular /V-acylnitroso Diels-Alder reaction of hydroxamic acid 177 followed by catalytic hydrogenation of the double bond was employed for the synthesis of substituted bridged bicyclic derivative 178, as a single diastereomer (Scheme 75 <2002OL2637>). Cleavage of the N-O bond was performed by reduction with Na(Hg) amalgam and provided m-3,7-disubstituted azocane 9, as a single isomer in 80% yield. 

This method seems to be the one of choice from a preparative standpoint, since the yields are usually high (40-60 %), the procedure can be adapted to large-scale synthesis and a wide variety of cyclopropenones " including bicyclic derivatives 31a and 31b can be prepared. 

A few 4a-carba-furanoses were synthesized using the same methodology. However, after saturation of the alcohol 40 the syntheses diverged when protection of the hydroxyl, cleavage of the acetonide and oxidative cleavage of the diol afforded the aldehyde 44 (Scheme 8.15). This compound underwent an aldolisation reaction whose stereoselectivity could be controlled by the reaction temperature. Specifically, at — 90°C the bicyclic product 46 was obtained in a yield of 71%. Alternately, bicyclic derivative 45 was the principle product obtained when the reaction was run at room temperature (78%). Reduction of the lactone and desilylation afforded 4a-carba-(3-D-xylofuranose from isomer 45, whereas 4a-carba-(3-D-ribofuranose was formed from 46. Isomerisation of compound 40 led to the synthesis of two other isomeric carba-sugars 4a-carba-(3-L-lyxofuranose and 4a-carba-(3-L-arabinofuranose [36]. 

Intramolecular heterocyclization in polyacrylonitrile 86UK62. a-Isocyano acetates, synthesis of N-heterocycles from 85YGK764. Isonitrosotosyl malonates in synthesis of N-heterocycles 80H(14)1581. Lactams, regioselective formation from bridged bicyclic ketones 81T1283. Malononitrile derivatives, synthesis of N-heterocycles condensed from ... 

A breakthrough in guanidinium-based anion hosts came with the synthesis of the bicyclic derivative 4.28 by Schmidtchen in 1980. The presence of the hydrocarbon backbone reduces dramatically the solvation of the guanidinium moiety and increases its lipophilicity, resulting in complexes with p-nitrobenzoate guest, for example, with association constants of the order of 1.4 X 10 in chloroform. Interestingly, Ci symmetric chiral derivatives may be prepared starting from chiral amino acids via the procedure shown in Scheme 4.2. ... 

The Wittig methodology applied to the synthesis of 7.162 can be used in a variety of situations. Aldehyde 7.165, for example, was converted to 7.166 [methyl 8-(2-N-benzenesulfonylamino-l-cyclopentyl)oct-6-enoate] via a Wittig reaction and diazomethane estetiHcation. The corresponding acid of 7.166 was converted to its sodium carboxylate, and was shown to inhibit arachidonic acid induced blood platelet aggregation in rabbits. A quite different approach converted anhydride 7.167 to 7.168. Note the similarity to cleavage of bicyclic derivatives in section 7.1.B (see 7.75 and 7.78). 

Dihydrocyclopentene derivatives (from cyclopentadiene) after kinetic resolution with a lipase are useful precursors for the synthesis of 1-deoxy-D-nojirimycin, and benzene cis-diol (from benzene by microbial oxidation) has been used as a precursor to 1-deoxy-D-galactonojirimycin and bicyclic derivative 59. The preparation of imino-alditol derivatives in which the imino nitrogen atom is part of a fused tetrazole ring is mentioned in Chapter 10 and the synthesis of imino-lactams is covered in Chapters 10 and 16. 

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