The Chemistry of Cyclopropanes and New Insights into Organocatalyzed Asymmetric Cyclopropanation

Abstract

Cyclopropane structure has been the object of interest in multiple investigations due to its prevalence in different natural products. In addition, this structure has a particular reactivity, specifically the 1,1‐cyclopropanedicarboxylate compounds, which act as acceptor‐donor cyclopropanes. Its reactivity could be compared with that of an α,β‐unsaturated carbonyl, which undergoes conjugate addition reaction and depending on the nature of the nucleophile this can lead to a cycloaddition reaction. Therefore, cyclopropane can be transformed into several useful structures in organic synthesis. Different methods have been described to achieve cyclopropanes such as, Simmons‐Smith reaction, decomposition of diazoalkanes and Michael‐Initiated ring closure (MIRC). Due to the absence of metals, this last method has been applied to the asymmetric organocatalytic synthesis of cyclopropanes, where the substrates activation is through the imine‐enamine intermediates formation or by hydrogen bonds. The asymmetric reaction consists of a domino reaction composed of a conjugate addition reaction and a cyclization reaction via intramolecular nucleophilic substitution. In this review, different asymmetric organocatalytic syntheses of the last two decades until 2021 are presented. With the intention to facilitate the reading of the review, an example of each paper was selected with the optimal reaction conditions and with the best organocatalyst producing the best yield and high stereoselectivity.

Recent Advances on Direct Functionalization of Indoles in Aqueous Media

“…Cyclopropanes and spirocyclopropanes are important design elements in pharmaceutical chemistry because they can improve the metabolic stability of drugs and have good properties of restricting molecular conformational rigid scaffolds. [124,125] Among them, compounds with spirocyclopropyl oxindole motifs have extensive and interesting biological properties. [126,127] In 2019, Li et al described an unprecedented on-water cyclopropanation reaction of diazo compounds 164 and electron-deficient alkenes 165 via a catalyst-free process (Scheme 36).…”

“…Cyclopropanes and spirocyclopropanes are important design elements in pharmaceutical chemistry because they can improve the metabolic stability of drugs and have good properties of restricting molecular conformational rigid scaffolds [124,125] . Among them, compounds with spirocyclopropyl oxindole motifs have extensive and interesting biological properties [126,127] .…”

Highly selective catalyst- and additive-free iodosulfonylation of cyclopropenes in water

“…Functionalized cyclopropanes broadly exist in natural products, 1 and they are synthetically valuable starting materials in the construction of complex molecules as 3C building blocks. 2,3 On the other hand, cyclopropyl groups, especially the cyclopropyl sulfone moieties, are privileged structures that frequently appear in drugs and drug candidates (Scheme 1). 4,5 Therefore, the construction of functionalized cyclopropanes is of high importance in synthetic and medicinal chemistry, and has attracted great attention from the chemical community.…”

Synthesis of cyclopropanes through gold-catalyzed [2 + 1] cycloaddition of allenamides with sulfoxonium ylides

“…2 Due to the innate ring strain and similar properties to double bonds, cyclopropanes possess higher reactivity than ordinary alkanes, and their application as precursors or key reaction intermediates benefits the development of a wide range of reactions. 3 Therefore, efficient and versatile methods for the synthesis of cyclopropanes have been of great concern for organic chemists for many years, including transition metal-catalyzed cyclopropanation relying on metal carbenes as divalent carbon sources, 4 photo-induced carbene-transfer cyclopropanation and radical-involved photocatalytic cyclopropanation. 5 Other transition metal-free reactions include the use of bases, Lewis acids, and various ylides that can also form cyclopropanes.…”