Synthesis of fully functionalised spiropyran pyrazolone skeletons via a formal [4+2] cascade process using β-nitro-styrene-derived MBH-alcohols

An efficient protocol was established to construct spiro pyrazolone tetrahydropyran scaffolds at ambient temperature under metal-free conditions. The reaction proceeded via formal [4 + 2] cyclisation of trans-beta-nitro-styrene-derived Morita-Baylis-Hillman (MBH) alcohol with alpha-arylidene pyrazolone. The reaction followed an oxa-Michael/Michael cascade pathway, resulting in the formation of new C-C and C-O bonds. Organocatalytic synthesis of spiropyrazolones using quinine-derived catalyst resulted in 94% enantiomeric excess (ee) and excellent (>20 : 1) diastereoselectivity.

Automated summary

An efficient protocol was developed for the construction of spiro pyrazolone tetrahydropyran scaffolds at ambient temperature without the use of any metal catalyst. The reaction involved the formal [4 + 2] cyclisation of trans-beta-nitro-styrene-derived Morita-Baylis-Hillman alcohol with alpha-arylidene pyrazolone. The synthesis followed an oxa-Michael/Michael cascade pathway and yielded new C-C and C-O bonds. The use of quinine-derived catalyst resulted in high enantiomeric excess (ee) and excellent diastereoselectivity (>20:1).