Domino β‐C−H Functionalization and [3+2] Cycloaddition for Efficient Synthesis of Diverse Spiro and Polycyclic Compounds

Abstract

The acetic acid catalyzed three-component reaction of pyrrolidine, aromatic aldehydes and 4-arylidene-5-methyl-2-phenylpyrazol-3-one in refluxing toluene gave functionalized 7'-(E)benzylidenespiro[pyrazole-4,1'-pyrrolizines] in good yields and with high diastereoselectivity. The similar reaction with 2arylidene-N,N'-dimethylbarbiturates resulted in mixture of Z/Eisomers of 7'-arylidenespiro[pyrimidine-5,1'-pyrrolizines] in good yields. However, the three-component with N-phenylmaleimides and sequential oxidation with DDQ reaction gave 8-(E)-arylidenedihydropyrrolo[3,4-a]pyrrolizines in satisfactory yields. The reaction mechanism included sequential β-CÀ H functionalization of pyrrolidine, generation of conjugated azomethine ylides, and sequential [3 + 2] cycloaddition with active alkenes.

Iminium and azonium-activated metal and oxidant-free C–H functionalization of aliphatic amines

“…The same group has shown that a similar reaction proceeded with other dipolarophiles (Scheme 21). 46 A series of 7 0 -(E)-benzylidenespiro [pyrazole-4,1 0 -pyrrolizines] 221 were synthesized in high yields and with high diastereoselectivity employing 4-arylidene-5methyl-2-phenylpyrazol-3-one 220 as the dipolarophile. In contrast to this, a mixture of Z/E isomers of 7 0 -arylidenespiro[pyrimidine-5,1 0 -pyrrolizines] 223 were isolated when 2-arylidene-N,N 0 -dimethylbarbiturates 222 was used as a dipolarophile.…”

Condensation-Based Methods for the C–H Bond Functionalization of Amines

“…In 2019-2020, Yan and co-workers reported transformations resembling reactions shown in Scheme 76, with the modification that N-methylmaleimide is replaced by other electron-deficient alkenes. 133,134 Several other research groups have reported condensation-based reactions involving the -C-H bond functionalization of cyclic amines. Wu, Wu, and co-workers reported a process in which a mixture of pyrrolidine, an -ketoaldehyde, and an acrylate undergo a reaction that leads to simultaneous -and -C-H bond functionalization of the amine to furnish bicyclic 2,3-dihydro-1H-pyrrolizines 166 (Scheme 78).…”