Synthons, annulating

Mootoo and co-workers disclosed a procedure for the preparation of C-l substituted galactals based on the intramolecular capture of an oxocarbenium ion by an enol ether residue.79 In their approach, the key intermediate 1 -thio-1,2-O-isopropylidene acetals (TIA) are activated with methyl triflate to generate the crucial annulating synthon (1,2-O-isopropylidenated oxocarbenium ion). 

Thio-l, 2-0-Isopropylidene Acetals Annulating Synthons for Highly Hydroxylated... 

Analogues of complex saccharides, in which one or other of the acetal oxygens is replaced by a methylene residue or other heteroatoms, have received attention as biochemical probes and as potential therapeutic agents. The use of l-thio-1,2-isopropylidene acetals (TIA s) as annulating synthons for highly hydroxylated systems is illustrated by the synthesis of (3-C-, p-aza-C- and P-carba- galacto disaccharides. 

Hudlicky, T., Reddy, D.B., Govindan, S.V., Kulp, T., Still, B. and Sheth, J.P., Intramolecular cyclopentene annulation. 3. Synthesis and carhon-13 nuclear magnetic resonance spectroscopy of bicyclic cyclopentene lactones as potential perhydroazulene and/or monoterpene synthons. J. Org. Chem., 1983, 48, 3422. 

Most syntheses of TPs start either from a 1,2,4-triazole derivative or from a pyrimidine residue and need annulation of a second heterocyclic ring. Preferably 5-amino-1,2,4-triazoles (AT) and 2-hydrazinopyrimidines (HP), respectively, are used as starting synthons. 

B. J. Fitzsimmons and B. Fraser-Reid, Annulated pyranosides as chiral synthons for carbo-cyclic systems. Enantiospecific routes to both (+) and (-) chrysanthemum carboxylic acids from a single progenitor, J. Am. Chem. Soc. 101 6123 (1979). 

Enamines are also involved in the classical Hantzsch synthesis, which is usually performed by annulation of an enamine intermediate derived from ammonia and a suitable /3-ketoester or an equivalent 1,3-diketo synthon, with an a-haloketone. A new development is the adaptation of this reaction to solid-phase conditions <1998TL2381>. Heating of the /3-aminoacrylonitrile 276 with the ketone 277 gave a decent yield of the pyrrole 278 (Equation 85), a member of a series of similar compounds which were synthesized using this approach <1997S530>. An additional solid-phase variant of the Hantzsch synthesis provided a set of pyrrole-/3-carboxamide derivatives <1998BML2381>. 

A synthesis of a set of 2-pyridylpyrroles has been described, involving annulation of 1,3-dicarbonyl compounds with 2-(aminomethyl)pyridine under acidic conditions, as illustrated by the construction of compound 437 (Equation 121) <20020L435>. Likewise, pyrroles have also been obtained from reactions between 1,3-diaryl-l,3-dicarbonyl compounds and imines or oximes promoted by the TiCU/Zn-system <2004SL2239>. Yet another approach involves rhodium-catalyzed reactions of isonitriles with 1,3-dicarbonyl synthons, which enables for instance preparation of fluorinated pyrroles <20010L421>. 

Ethyl diazoacetate can also serve as an acetate enolate synthon under acidic conditions, engaging in [2+1] annulation with A -alkyl aldimines (e.g., 595) to provide the corresponding aziridine (597) with very high air-selectivity. The conditions are mild enough that acid-catalyzed ring opening of the products is not observed (Scheme 144) <2004JA1612>. 

CH2CH2C0CH synthon. While the term synthon was not known at the time this remarkable annulation protocol was elaborated (1937), this reaction is undoubtedly one of the earliest (and probably the first ) examples illustrating the value of a synthon designed and specifically tailored to achieve the assemblage of a complex structure. 

The Pd -catalyzed [3 + 2] cycloaddition reactions of (97) exhibit very different selectivities from those of the corresponding methylenecyclopropane codimerizations. One major distinction is the chemoselec-tivity only electron-deficient alkenes will react to form methylenecyclopentane. The nucleophilic nature of this TMM synthon is indicated in the exclusive annulation of the electron-poor double bond of 2,3-di-methoxycarbonylnorbomadiene (equation 109). - No such differentiation of alkenes is evident in the methylenecyclopropane codimerization with the same diene (equation 65). 

Kim, S., Emeric, G., Fuchs, P. L. Use of 3-silylethyl vinyl ketone as a 3-hydroxyethyl vinyl ketone synthon in the Robinson annulation reaction. J. Org. Chem. 1992, 57, 7362-7364. 

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