BOGER Heterocycle synthesis

BOGER Heterocycle synthesis 40 BOORO Enol ether synthesis 4i BORCH Reduction 42 Bormann 404 Borodin 183 Borsche 123... 

The Boger pyrrole synthesis based on a heterocyclic azadiene Diels-Alder strategy (1,2,4,5-tetrazine to 2,2-diazine to pyrrole) was employed by the author for the total synthesis of ningalin B . Thus a Diels-Alder reaction of the electron-rich acetylene 52 with the electron deficient 1,2,4,5-tetrazine 53 proceeded to give the desired diazine 54 which underwent subsequent ring contraction to afford the core pyrrole structure 55. 

Stoichiometric palladium-mediated cyclization was used in natural product synthesis by Boger a number of years ago, as was noted in the introduction. More recently, an intramolecular palladium-catalyzed amination of a heteroaromatic halide has been used as a step in the synthesis of an a-carboline natural product analog [146]. As discussed above, the diphenylhydrazone arylation can also be used for nitrogen heterocycle synthesis [140]. 

Boger D. L. Heterocyclic and Acyclic Azadiene Diels-Alder Reactions Total Synthesis of Nothapodytine B. J. Heterocycl. Chem. 1998 35 1003-1011 Keywords inverse electron-demand Diels-Alder reactions, acyclic azadienes, synthesis of natural products... 

Boger et al. reported the first total synthesis of ningaline D (282) starting from the diphenylacetylene 1092 and dimethyl l,2,3,4-tetrazine-3,6-dicarboxylate (1093) (687). In this synthesis, the key step is the formation of the fully substituted pyrrole core using an inverse electron demand heterocyclic azadiene Diels-Alder reaction followed by a reductive ring contraction of the resultant 1,2-diazine. 

Additionally, Boger and Panek reported an intramolecular amine arylation mediated by stoichiometric quantities of Pd (0), Eq. (2) [15]. Efforts to render this transformation catalytic in palladium were fruitless, however. The resulting heterocycle was utilized in the total synthesis of lavendamycin. 

Boger has devised numerous synthetic schemes for the synthesis of six-membered nitrogen heterocycles based upon DA addition with subsequent rDA extrusion, and has reviewed the subject. Representative examples are shown for the synthesis of substituted pyridines (equation 95), substituted pyrimidines (equation 96) ° and substituted 1,2-diazines (equation 97). ... 

The Diels-Alder reaction with inverse electron demand has been one of the most intensively studied reactions of 1,2,4-triazines. In this reaction 1,2,4-triazines behave as electron-deficient dienes and react with electron-rich dienophiles to give, generally, pyridines (see Houben-Weyl, Vol. E7b, p 471 ff). [4 + 2] Cycloadditions of 1,2,4-triazines have been observed with alkenes, alkynes, strained double bonds, electron-rich double and triple bonds, but in a few cases also with electron-deficient alkynes C—N double and triple bonds can also be used as dienophiles. In addition to intermolecular Diels-Alder reactions, intramolecular [4 + 2] cycloaddition reactions of 1,2,4-triazines have also been studied and used for the synthesis of condensed heterocyclic systems. A review on the intermolecular Diels-Alder reaction was published by Boger and Weinreb 14 Sauer published a review on his studies in 1992,381 and E. C. Taylor published a summary of his own work on intramolecular Diels-Alder reactions in 1988.382... 

A stoichiometric, intramolecular variant of the Buchwald-Hartwig amination was reported by D, L. Boger and J, S. Panek as early as 1984 in the synthesis of lavendamycin.7 They showed that 1.2 equiv of Pd(PPh3)4 could effect the intramolecular cyclization of an amino bromide 1 to the desired heterocycle 2. The absence of an external base to sequester the generated HBr rendered this reaction super-stoichiometric in palladium. 

D. L. Boger and S. N. Weinreh, Hetero Diels-Alder Methodology in Organic Synthesis, Academic Press, New York, NY, 1987 A. R. Katritzky and C. W. Rees, Comprehensive Heterocyclic Chemistry, Pergamon Press, New York, NY, 1985. 

Diels-Alder reactions of heterocyclic azadienes scope and applications , Boger, D. L., Chem. Rev., 1986, 86, 781 Hetero Diels-Alder methodology in organic synthesis , Ch. 10, Boger, D. L. and Weinreb, S. M., Academic Press, 1987. 

Boger - Diels-Alder reactions of heterocyclic azadienes for the total synthesis of complex molecules [87JACS2717]... 

Ishikawa H, Boger DL (2007) Total synthesis of (—)- and ent-(+)-4-desacetoxy-5-desethyl-vindoline. Heterocycles 72 95-102... 

Boger DL (1996) Azadiene Diels-Alder reactions scope and applications. Total synthesis of natural and ent-fredericamycin A. J Heterocycl Chem 33 1519-1531... 

Several examples of intramolecular Boger reactions toward the synthesis of pyridine-containing heterocyclic systems were reported by the Taylor group and the Snyder group, For instance, intramolecular cyclization of triazine 219, after loss of nitrogen, afforded 220. Alternatively, triazine 221 generated bicyclic systems 222, which was then oxidized to 223. ... 

Overall, while this excursion has been brief, the above examples should provide a preliminaiy indication of the power of azadiene-based inverse-electron-demand Diels—Alder reactions in the context of total synthesis, particularly for the synthesis of highly substituted heterocyclic systems such as pyridines, diazines, and pyrimidines. Arguably, few if any other methods enable such facile, diverse, and consistent constructions of these challenging aromatic systems. With this background in place, we are now prepared to analyze the total synthesis of isochrysohermidin (1) by Boger and Baldino. 

Diels-Alder reactions in which carbon-heteroatom bonds are formed are useful for the synthesis of heterocyclic compounds. Many examplesof hetero Diels-Alder reactions are described in the recent monograph by Boger and Weinreb, including some which involve carbohydrates 30). 

Nitrogen-containing heterocycles are also available via intramolecular hetero Diels-Alder reactions. Williams employed an aza diene to prepare a complex polycyclic synthetic intermediate in his synthesis of versicolamide B. Boger reported a tandem intramolecular hetero Diels-Alder/l,3-dipolar cycloaddition sequence for the synthesis of vindorosine. Cycloaddition precursor 137 undergoes an inverse electron demand Diels-Alder reaction to yield 138. This compound decomposes via a retro dipolar cycloaddition to generate nitrogen gas and a 1,3-dipole that completes the cascade by reacting with the indole alkene to afford 139. Seven more steps enable the completion of vindorosine. ... 

Boger, D.L. and M. Patel. 1988. Total synthesis of prodigiosin, prodigiosene, and des-methoxyprodigiosin Diels-Alder reactions of heterocyclic azadienes and development of an effective paUadium(ii)-promoted 2,2 -bipyrroUe coupling procedure. J Org Chem 53 1405-1415. 

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