Enantioselective Synthesis of Spiro Heterocyclic Compounds Using a Combination of Organocatalysis and Transition‐Metal Catalysis

Abstract

Over the last ten years, the combination of organocatalysis with transition metal (TM) catalysis has become one of the most important toolboxes used for synthesizing optically pure compounds containing chiral quaternary centers, including spiro heterocyclic molecules. The dominant method in the enantioselective synthesis of spiro heterocyclic compounds based on synergistic catalysis includes chiral aminocatalysis and NHC catalysis, as already established covalent organocatalytic strategies. Another area of organocatalysis widely combined with TM catalysis producing enantiomerically enriched spiro heterocyclic compounds is non‐covalent catalysis, dominated by chiral phosphoric acids, thiourea, and squaramide derivatives. This review article aims to summarize enantioselective methods used for constructing spirocyclic heterocycles based on a combination of organocatalysis and transition metal catalysis.

Advances in heterocycle synthesis through photochemical carbene transfer reactions

“…Over the past few decades, transition metal-catalyzed or mediated cyclization reactions have surfaced as a highly efficient method for constructing heterocyclic skeletons. 6 The coordination of transition metals serves to facilitate reactions that might not occur otherwise, or with the addition of certain chiral ligands to enantioselectivity achieve heterocyclic compounds. Despite significant advancements in the metal-catalyzed creation of heterocyclic structures, practical applications face significant challenges due to the high cost of transition metals and the necessity for elevated reaction temperatures.…”

Organocatalytic Enantioselective Synthesis of Chiral Spiro‐indoline‐pyrazolones through a formal [4+1] Annulation Reaction of 4‐Bromopyrazolones and aza‐ortho‐Quinone Methides

“…On the other hand, the stereoselective synthesis of chiral spirocyclic compounds is an attractive topic in asymmetric catalysis. [10][11][12] Among the spirocyclic compounds, spiroindolines represent an interesting scaffold present in several compounds with biological activities (Figure 1A). [13][14][15][16] One straightforward way to synthesize chiral C2-spiroindolines is using a formal [4 + 1] cycloaddition through an aza-ortho-quinone methide intermediate.…”

“…On the other hand, the stereoselective synthesis of chiral spirocyclic compounds is an attractive topic in asymmetric catalysis [10–12] . Among the spirocyclic compounds, spiroindolines represent an interesting scaffold present in several compounds with biological activities ( Figure 1 A ) [13–16] .…”

Copper-catalyzed asymmetric allylic substitution of racemic/meso substrates

“…There is a growing interest in the catalytic and enantioselective synthesis of intricate organic compounds using readily accessible materials. [1][2][3][4][5][6] Among them, AAS has emerged as a reliable approach for the synthesis of enantiomerically pure compounds. Since the pioneering work by the Trost group [7][8][9] on Pd-catalyzed AAS, transition metal-catalyzed AAS has been continuously developed as a powerful tool for the efficient construction of chiral C-C and C-X bonds.…”