Synthesis of Spirobicyclic Pyrazoles by Intramolecular Dipolar Cycloadditions/[1s, 5s] Sigmatropic Rearrangements

Abstract

Formation of fused pyrazoles via intramolecular 1,3-dipolar cycloadditions of diazo intermediates with pendant alkynes are described. A subsequent thermal [1s, 5s] sigmatropic shift of these pyrazole systems resulted in a ring contraction to form spirocyclic pyrazoles. The limitations of this rearrangement were explored by changing the substituents on the non-migrating aromatic ring and by using substrates lacking an aromatic linkage to the propargyl group.

Enantioselective synthesis of isochromans and tetrahydroisoquinolines by C–H insertion of donor/donor carbenes

“…2). Although the analogous substrates for the synthesis of benzodihydrofurans can suffer from competing dipolar cycloaddition reactions, 36,37 this side reaction was not observed in the reactions leading to isochromans. Stevens-type rearrangement products were also not observed for unsaturated substrates.…”

“…We hypothesize that a larger ring size helps to limit the dipolar cycloaddition pathway. 36,37 Aliphatic substrates also react with high diastereo-and enantioselectivity. There is a clear trend of decreasing yield from substrates that have two alkyl substituents versus one alkyl substituent at the insertion site.…”

tert-Butyl Nitrite-Induced Radical Nitrile Oxidation Cycloaddition: Synthesis of Isoxazole/Isoxazoline-Fused Benzo 6/7/8-membered Oxacyclic Ketones

“…Molecules 2024, 29, x FOR PEER REVIEW 8 of 17 residues were purified by column chromatography using an ethyl acetate/petroleum ether mixture to obtain the desired products (Scheme 5). Compounds 5a-5i were prepared according to the referenced literature [43][44][45]. To a solution of 1-(2-hydroxyphenyl)ethan-1-one) (1.0 equiv.)…”

Diazophosphonates: Effective Surrogates for Diazoalkanes in Pyrazole Synthesis

“…Most examples employ aryl diazo compounds generated in situ from the corresponding ortho ‐substituted benzaldehyde tosylhydrazones, and give fused pyrazoles or spiro‐4 H ‐pyrazoles according to whether the intermediate diazo species is mono‐ or di‐substituted (Scheme 5). [52–57] In contrast, we chose to exploit the electron‐withdrawing properties of the phosphoryl group to enable the first use of such diazo compounds in a range of intramolecular 1,3‐dipolar cycloadditions to give carbocyclic fused pyrazoles (Scheme 5).…”