ChemInform Abstract: Enantioselective gem‐Chlorofluorination of Active Methylene Compounds Using a Chiral Spiro Oxazoline Ligand.

Abstract

Enantioselective gem-Chlorofluorination of Active Methylene Compounds Using a Chiral Spiro Oxazoline Ligand. -The reaction of phosphonates proceeds with a lower selectivity toward monochlorination and thus dichlorinated by-products are also formed. The dihalo-β-ketoester (IIa) is converted into fluorinated derivatives without loss of optical purity including a fully protected β-amino acid (XIX) with a α-chlorofluoromethylene function. -(SHIBATOMI*, K.; NARAYAMA, A.; SOGA, Y.; MUTO, T.; IWASA, S.; Org. Lett. 13 (2011) 11, 2944-2947, http://dx.doi.org/10.1021/ol201007e ; Dep. Environ. Life Sci., Toyohashi Univ. Technol., Toyohashi, Aichi 441, Japan; Eng.) -H. Simon

Monofluorination of Organic Compounds: 10 Years of Innovation

“…The copper-catalyzed enantioselective one-pot gem -chlorofluorination of β-ketoesters and β-ketophosphonates was described by Shibatomi in 2011 (Scheme ) . The desired compounds were obtained in good yields and enantioselectivities using NCS as the chlorinating agent, an excess of NFSI (3 equiv) as the fluorinating agent and ( R )-SPYMOX as the chiral ligand.…”

“…The copper-catalyzed enantioselective one-pot gem-chlorofluorination of β-ketoesters and β-ketophosphonates was described by Shibatomi in 2011 (Scheme 168). 246 The desired compounds were obtained in good yields and enantioselectivities using NCS as the chlorinating agent, an excess of NFSI (3 equiv) as the fluorinating agent and (R)-SPYMOX as the chiral ligand. Two years later, they also applied this system to the enantioselective monofluorination of α-substituted-β-keto-tertbutylesters, leading to good yields (>76%) and high enantioselectivities (>86% ee).…”

Catalytic Reactions in Fluorinated Phosphonates Synthesis

“…The first enantioselective synthesis of chiral gemchlorofluoromethylenephosphonates (isosteric to gemdifluoromethylene derivatives) was reported in 2011 by Shibatomi et al [24]. The one-pot enantioselective gemchlorofluorination of appropriate -ketophosphonates was carried out by applications of chiral Cu(OTf) 2 complex of SPYMOX catalyst 7 [25] which constitutes 2-pyridyl monooxazoline ligand having a spiro-fused axial chiral binaphtyl backbone (Scheme 4).…”

Synthesis of (2S)-2-Chloro-2-fluororibolactone via Stereoselective Electrophilic Fluorination

“…8 Regarding the formation of gem-Cl-F-carbons, there are only a few examples in the literature and most of them are synthesized via electrophilic fluorination of an α-chloro carbonyl compound. 9 Partial stereoselectivity is usually achieved by using chiral transition metal complexes (Ni, Pd, Ti) 10 with or without organocatalysts such as spiro oxazoline ligands, 11 cinchona alkaloid esters, 12 N-acyloxazolidinones, 13 and the Jørgensen catalyst. 14 It is worth mentioning that there are only a few examples reporting the stereoselective electrophilic chlorination of α-fluoro carbonyl compounds.…”