Aryne cycloadditions

Intramolecular aryne cycloaddition.1 A new approach to the basic skeleton of ergot alkaloids involves an intramolecular cyclization of the amide 1 to form 2, effected with LDA at —30°. 

Aryne cycloadditions to furans have been employed in the synthesis of bio-related molecules. For example, adduct 272 served as the starting point for the preparation of the aromatic segment of rifamycin W (an antibiotic). Previously unreported benzyne 274 (its precursor 273 was prepared in several steps from piperonal) readily gave cycloadduct 275 with furan, but unfortunately for a proposed route to podophyllotoxin, did not undergo... 

Aryne cycloadditions have been coupled with radical cyclizations to rapidly assemble multiring systems For example, benzyne addition to furan 278 followed by radical cyclization onto the newly formed double bond gave 280 in two steps and fair yield. 

The synthesis of benzo[l, 2-c 3,4-c 5,6-c"]trifuran 459 (the furan analog of triphenylene) was accomplished by three aryne cycloadditions onto a single benzene ring. The arynes were generated by two different methods. The dibromodiazonium carboxylate hydrochloride 455 and furan gave adduct 456, which was then treated with excess potassium amide. 

The aporphinoid skeleton 683 could be constructed via an mtermoleculav aryne cycloaddition to the styrene moiety of an alkylidenetetrahydroisoquinoline, thus simultaneously creating bonds b and c of the C-ring cf the intramolecular aryne approach in 677 679,... 

The third approach, like the first, constructs the B-ring. The key step, applied to the synthesis of A -nornitidine 710, involved aryne cycloaddition to a vinyl isocyanate. 4,5-Dimethoxybenzyne, generated from aminobenzotriazole 707 by Pb(OAc)4 oxidation, added to vinyl isocyanate 708 to give 709, which was not purified but converted directly to 710 (overall yield in the 30-35% range). 

Buszek and coworkers next conducted additional studies to further understand the regioselectivity of these indole-aryne cycloaddition reactions [54], They chose to generate the indole-aryne systems either from the 4,5- or 5,6-ort/io-dibromo species 100c and 100b by treatment with n-BuLi (2.2 equiv) in toluene, or from the corresponding o-trimethylsilyl triflates 104 and 108 by treatment with tetrabuty-lammonium triphenyldifluorosilicate (TBAT, 2.5 equiv) in THF or CsF (3 equiv) in acetonitrile. It was observed that for either the 4,5- or 5,6- indolyne systems thus prepared, there are no regiochemical preferences in the cycloaddition reactions with t-butylfuran (105a) (Scheme 29). 

Buszek KR, Brown N et al (2009) Concise total synthesis of (-1—)-cis-trikentrin A and (-1—)-herbindole A via intermolecular indole aryne cycloaddition. Org Lett 11 201-204... 

Intramolecular aryne cycloaddition. A new approach to the basic skeleton of... 

In conclusion, the results described above prove the utility of aryne cycloaddition, and hint strongly at the synthetic promise of pyrroiinediones. More research will be needed to determine the extent of this potential. 

SCHEME 21 Aryne cycloaddition with stable munchnones [46]. 

D. Perez, D. Pena, E. Guitian, Aryne cycloaddition reactions in the synthesis of large polycyclic aromatic compounds, Eur. J. Org. Chem. 

F. Yuesi, R.C. Larock, F. Shi, Aryne cycloaddition with stable munchnones synthesis of 9,10-dihydro-9,10-epiminoanthracenes and isoindoles, Asian J. Org. Chem. 3 (2014) 5 57. 

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