**1. Introduction**

Enantiomerically pure cyclopropane derivatives are ubiquitous, nature inspired [1–8] building blocks abundantly employed in organic synthesis [9–13], asymmetric catalysis [14–17], and medicinal chemistry [18–25]. These advanced synthons are typically accessed via diastereoselective 1,3-ring closure reactions [26–30] or asymmetric cyclopropanation [31–41]. A less established, complementary approach relies on chemo- and diastereoselective installation of additional substituents into pre-formed chiral or prochiral cyclopropanes [42–45]. Strain-release-driven additions of different entities to cyclopropenes proved useful for the assembly of enantiomerically enriched cyclopropane derivatives that are not easily accessible via other methods [46–53]. Synthetic methodologies exploiting stereoselective ring-retentive, metal-catalyzed [13,54,55], and organocatalytic [56,57] additions to cyclopropenes were developed by several research groups and have eventually evolved into a rapidly growing area. Our group recently disclosed an efficient diastereoselective route to cyclopropanes **3** via a formal substitution of bromocyclopropanes **1** with oxygen, nitrogen, or sulfur-based nucleophiles (Scheme 1) [51,58]. The reaction proceeds via a base-assisted dehydrohalogenation, affording a highly reactive cyclopropene intermediate **2** and the subsequent nucleophilic addition across the double bond of cyclopropene. Herein, we report our progress on extending this methodology for the preparation of enantiomerically enriched cyclopropanes.

**Citation:** Straub, H.; Ryabchuk, P.; Rubina, M.; Rubin, M. Preparation of Chiral Enantioenriched Densely Substituted Cyclopropyl Azoles, Amines, and Ethers via Formal S*N*2 Substitution of Bromocylopropanes. *Molecules* **2022**, *27*, 7069. https:// doi.org/10.3390/molecules27207069

Academic Editors: Alison Rinderspacher, Gloria Proni and Mircea Darabantu

Received: 23 September 2022 Accepted: 17 October 2022 Published: 20 October 2022

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**Scheme 1.** Different modes of formal nucleophilic substitution of bromocyclopropanes (notations used: EWG—electron-withdrawing group; DG—directing group; RS—small substituent; RL—large substituent).
