Regioselective Preparation of Saturated Spirocyclic and Ring-Expanded Fused Pyrazoles

• Published in: Journal of organic chemistry 2014-09, Vol.79 (18), p.8800-8811
• Main Authors: Merchant, Rohan R, Allwood, Daniel M, Blakemore, David C, Ley, Steven V
• Format: Article
• Language: English
• Subjects: Alkynes - chemical synthesis; Alkynes - chemistry; Molecular Structure; Polycyclic Compounds - chemical synthesis; Polycyclic Compounds - chemistry; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Spiro Compounds - chemical synthesis; Spiro Compounds - chemistry; Stereoisomerism
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo501624t

Saturated bicyclic pyrazoles represent an important class of biologically active molecules, but their preparation can be hampered by labor-intensive synthesis of required starting materials. A convenient one- or two-step procedure for the synthesis of saturated spirocyclic and fused pyrazoles is reported. The synthesis benefits from the use of readily available alkynes and bench-stable tosylhydrazones, which are easily prepared from their parent ketones. Sigmatropic rearrangement of spirocyclic pyrazoles to fused analogues occurs with concomitant one-carbon expansion of the saturated ring, allowing rapid access to a range of pharmaceutically and agrochemically relevant polycyclic structures featuring a broad scope of saturated ring sizes.