Synthesis of Dihydropyrano[3,2-c]pyrazoles via Double Bond Migration and Ring-Closing Metathesis

Abstract

Three types of pyrazole-fused heterobicycles, i.e., 1,5-, 1,7-, and 2,5-dihydropyrano[3,2-c]pyrazoles, were synthesized from 4-allyloxy-1H-pyrazoles. A sequence of the Claisen rearrangement of 4-allyloxy-1H-pyrazoles, ruthenium-hydride-catalyzed double bond migration, O-allylation, and ring-closing metathesis was employed in this study.

CuI-Catalyzed Coupling Reactions of 4-Iodopyrazoles and Alcohols: Application toward Withasomnine and Homologs

“…All reactions were Scheme 1. Versatile intermediate 4-allyloxy-1H-tritylpyrazole (4a), developed in our previous works (adapt from references [22][23][24][29][30][31]).…”

“…4-Allyloxy-1H-1-tritylpyrazole 4a (Scheme 1), derived from 4-iodopyrazole (1), played a key role as a versatile intermediate in our previous studies for the total synthesis of the pyrazole alkaloid, withasomnine (7) [22,23], and its six-membered homolog 11 [23][24][25][26][27], which were reported to exhibit COX-2 inhibitory activities [23,27,28]. Compound 4a was also extensively utilized as an important intermediate for the construction of new pyrazolefused heterobicyclic molecules 9 via ring-closing metathesis (RCM) (Scheme 1) [29][30][31]. However, the synthesis of compound 4a requires six steps from commercially available pyrazole, through 4-iodopyrazole (1), 4-iodo-1H-1-tritylpyrazole (2a), and aldehyde 3.…”

3-Trifluoromethanesulfonyloxy-4,7-dihydropyrazolo[1,5-a]pyridine via Ring-Closing Metathesis: Synthesis and Transformation to Withasomnine Homologs

“…8 We have studied functionalization of pyrazoles at the C4-position via several types of metal-catalyzed coupling reactions, including the synthesis of oxygen-containing pyrazole heterobicyclic systems 4 (Scheme 1), which was developed using ring-closing metathesis (RCM) as the cyclization step. [9][10][11] In those studies, the N-1 position of the pyrazole ring was protected by a trityl or benzyl group. Provided the N-1 position was protected by an appropriate substituent group, RCM would, thus, enable the construction of various different types of pyrazole-fused hetero-bicyclic compounds.…”