Bicycles synthesis

Studies on the potential of the electrochemical approach to pyrazolotriazoles 117 showed that under the conditions of bicycle synthesis from 3-amino-4-hydrazonopyrazoles the N-l-unsubstituted triazole ring of 117 was further oxidized in a one-electron peak, followed by proton removal to yield the bis-(l,l )-2-phenylpyrazolo[3,4-i/][l,2,3]triazoles 118. This observation is significant, since in spite of pronounced pharmaceutical applications of pyrazoles, the redox characteristics of substituted pyrazoles have received limited attention (Scheme 13) <2001MI1022>. 

The 6,5-bicyclic synthesis outlined above has been extended to indolizidines, formed by AHR of a suitable prochiral alkenyl iodide such as 28, which can be easily prepared by allylation of the lactam 27. In contrast to purely carbogenic systems, however, the most effective ligand proves to be BPPFOH ((R)-a-[(S)-l ,2-bis(diphenylphosphino)ferrocenyl] ethyl alcohol) 31 [35] which gives results clearly superior to those obtained with BINAP (Scheme 8) [36,37]. 

Synthesis by high-dilution techniques requires slow admixture of reagents ( 8-24 hrs) or very large volumes of solvents 100 1/mmol). Fast reactions can also be carried out in suitable flow cells (J.L. Dye, 1973). High dilution conditions have been used in the dilactam formation from l,8-diamino-3,6-dioxaoctane and 3,6-dioxaoctanedioyl dichloride in benzene. The amide groups were reduced with lithium aluminum hydride, and a second cyclization with the same dichloride was then carried out. The new bicyclic compound was reduced with diborane. This ligand envelops metal ions completely and is therefore called a cryptand (B. Dietrich, 1969). 

J.E. Baldwin (1975, 1976A) has developed a biomimetic synthesis which is loosely analogous to the biosynthetic pathway which starts with the so-called Amstein tripeptide. Baldwin used bicyclic dipeptides more suitable for stereoselective in vitro syntheses. 

In his cephalosporin synthesis methyl levulinate was condensed with cysteine in acidic medium to give a bicyclic thiazolidine. One may rationalize the regioselective formation of this bicycle with the assumption that in the acidic reaction mixture the tMoI group is the only nucleophile present, which can add to the ketone. Intramolecular amide formation from the methyl ester and acid-catalyzed dehydration would then lead to the thiazolidine and y-lactam rings. The stereochemistry at the carboxylic acid a-... 

The intramolecular coupling of organostannanes is applied to macrolide synthesis. In the zearalenone synthesis, no cyclization was observed between arylstannane and alkenyl iodide. However, intramolecular coupling take.s place between the alkenylstannane and aryl iodide in 706. A similar cyclization is possible by the reaction of the alkenylstannane 707 with enol triflate[579]. The coupling was applied to the preparation of the bicyclic 1,3-diene system 708[580]. 

A-4-Thiazoline-2-ones and ring substituted derivatives are usually prepared by the general ring-closure methods described in Chapter II. Some special methods where the thiazole ring is already formed have been used, however. An original synthesis of 4- 2-carboxyphenyl)-A-4-thiazoline-2-one (18) starting from 2-thiocyanato-2-halophenyl-l-3-indandione (19) has been proposed (Scheme 8) (20, 21). Reaction of bicyclic quaternary salts (20) may provide 3-substituted A-4-thiazoline-2-one derivatives (21) (Scheme 9) (22). Sykes et al. (23) report the formation of A-4-thiazoline-2-ones (24) by treatment ef 2-bromo (22) or 2-dimethylaminothiazole (23) quaternary salts with base (Scheme 10). 

One of the widely used cinnoline syntheses is the transformation of diazotized o-aminoarylethylenes into this bicyclic system (Widman-Stoermer synthesis) (Scheme 69). 

Examination of the pyrazino[2,3-rf]pyrimidine structure of pteridines reveals two principal pathways for the synthesis of this ring system, namely fusion of a pyrazine ring to a pyrimidine derivative, and annelation of a pyrimidine ring to a suitably substituted pyrazine derivative (equation 76). Since pyrimidines are more easily accessible the former pathway is of major importance. Less important methods include degradations of more complex substances and ring transformations of structurally related bicyclic nitrogen heterocycles. 

A synthesis of ( )-cocaine proceeded through an initial cycloaddition of (526) to (527) to produce the bicyclic structure (528) (78JA3638). 

Azetidin-2-one, l-benzyl-3,3,4-triphenyl-, 7, 249 Azetidin-2-one, l-(2-bromophenyl)-X-ray crystallography, 7, 247 Azetidin-2-one, 3-carboxy-synthesis, 7, 262 Azetidin-2-one, 3-halo-synthesis, 7, 77 ring contraction, 7, 81-82 Azetidin-2-one, 4-imino-IR spectroscopy, 7, 248 Azetidin-2-one, 1-phenyl-irradiation, 7, 255 Azetidin-2-one, 4-phenyl-reductive ring cleavage, 7, 252 Azetidin-2-one, 4-thio-IR spectroscopy, 7, 248 Azetidinones bicyclic, 7, 348-356 C NMR, 7, 348 H NMR, 7, 348 reactivity, 7, 356-358 spectroscopy, 7, 357 structure, 7, 349 synthesis, 7, 358-359 fused ring... 

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... 

Pyrylium salts alkyl groups reactivity, 3, 662 aromaticity, 3, 640 arylammes from, 3, 657 benzenoid compounds from, 3, 656, 658 benzisoxazol-3-yl-synthesis, 6, 124 bicyclic... 

NMR, 7, 409 Thietane, 2-thioxo-rearrangements, 7, 422 Thietane, triimino-cycloadducts, 7, 433 synthesis, 7, 41 Thietane-2,4-diones synthesis, 7, 435 Thietanes, 7, 403-447 5-amination, 7, 444 basicity, 7, 424 bicyclic... 

A number of bridged crown ethers have been prepared. Although the Simmons-Park in-out bicyclic amines (see Sect. 1.3.3) are the prototype, Lehn s cryptands (see Chap. 8) are probably better known. Intermediates between the cryptands (which Pedersen referred to as lanterns ) and the simple monoazacrowns are monoazacrowns bridged by a single hydrocarbon strand. Pedersen reports the synthesis of such a structure (see 7, below) which he referred to as a clam compound for the obvious reason . Although Pedersen appears not to have explored the binding properties of his clam in any detail, he did attempt to complex Na and Cs ions. A 0.0001 molar solution of the clam compound is prepared in ethanol. The metal ions Na and Cs are added to the clam-ethanol solutions as salts. Ultraviolet spectra of these solutions indicate that a small amount of the Na is complexed by the clam compound but none of the Cs . 

During the course of a mass spectrometric study of D-homo-14-hydroxy steroids, it was necessary to prepare the corresponding C-8 deuterium labeled analogs. The preparation of these uncommon steroid derivatives has been achieved by repeating the Torgov total synthesis [(257) (262)] with a deuterium-labeled bicyclic starting material (258). Both of the resulting 14-hydroxy epimers, (261) and (262), exhibited better than 90% isotopic purity. ... 

The Boger pyridine synthesis involves the reaction of triazine 1 with activated alkene 2 in a hetero-Diels-Alder fashion. The intermediate bicyclic species 3 is unstable and a facile cycloreversion takes place due to the loss of nitrogen gas to afford the appropriately substituted pyridine derivative 4. 

Methylpyrido[2,3-d]pyrimidin-2,4(l//,3/7)-dione has also been prepared by this method, which has also been used for the synthesis of other bicyclic systems. ... 

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