Synthesis of Fluorine‐Containing Molecular Entities Through Fluoride Ring Opening of Oxiranes and Aziridines

Abstract

The current minireview highlights the most relevant methodologies for the creation of fluorinated scaffolds accessed through transformations of three‐membered heterocycles (oxiranes and aziridines) involving their opening with various nucleophilic fluorinating agents reported over recent years. The purpose of the review is also to provide an overview of the ring‐opening synthetic practices with fluoride towards different functionalized, fluorine‐containing scaffolds with the focus on regioselectivity/regiocontrol and enantioselectivity including symmetric or unsymmetric monoheterocycles, cycloalkane‐fused oxiranes and aziridines.

Boron Reagents and Catalysts for the Functionalization of Strained Heterocycles

“…Of historical importance is the combination of BF 3 −Et 2 O with organometallic reagents, [3] which increase dramatically their reactivity towards epoxides and oxabicyclic alkenes [9] . It is known all three fluorine atoms of BF 3 −Et 2 O can be incorporated in products deriving from the ring opening of epoxides and aziridines, and this topic has been recently reviewed [10] . The use of BF 3 −Et 2 O in catalytic amounts has also been reported in the intramolecular oxa‐cyclization of epoxyalcohols en route to complex natural compounds such as (+)‐sorangicin A, hemibrevetoxin B [11] .…”

Base-Mediated Claisen Rearrangement of CF3-Containing Bisallyl Ethers

“…It is widely understood that strategic entry of fluorine atoms or fluorinated groups to adequate molecules gave strong impact to the original character in many instances, and thus development of novel methods for the construction of a variety of such compounds has attracted significant attention of researchers working in the field of synthetic organic chemistry, material science, and biologically active compounds [1][2][3][4][5]. For this reason, we have been studying to realize facile preparation of such molecules, and recently reported an interesting proton transfer starting from both propargylic [6] and allylic alcohols [7], enabling to form diverse ,-enones and saturated ketones, respectively, just by their treatment with very convenient as well as easy-to-handle tertiary amines.…”

Switchable Regioselectivity in the Opening of Aziridine by Fluoride: DFT Calculation and Synthesis of Fluorinated Piperidines

“…Selected examples having promising biological activities are shown in Figure . we envisioned that the ring‐opening of aziridine‐containing piperidines by fluoride would provide a direct means to synthesize piperidines bearing a β‐fluoroamine motif . However, the issue of regioselectivity is a roadblock to realize this strategy.…”

“…However, the issue of regioselectivity is a roadblock to realize this strategy. Many different methods have been developed for the ring opening of aziridine and aziridinium by fluoride, However, most of the methods focus on the reactivity, and very few investigated the regioselectivity …”

“…[4] we envisioned that the ring-opening of aziridine-containing piperidines by fluoride would provide a direct means to synthesize piperidines bearing a β-fluoroamine motif. [5] However, the issue of regioselectivity is a roadblock to realize this strategy. Many different methods have been developed for the ring opening of aziridine [6] and aziridinium by fluoride, [7] However, most of the methods focus on the reactivity, and very few investigated the regioselectivity.…”