Synthesis of Fluorinated β-Aminophosphonates and γ-Lactams

Abstract

The functionalized polyfluorophosphorylated 1-azadienes I have been prepared by a Wittig reaction of ethyl glyoxalate and perfluorophosphorylated conjugated phosphoranes, obtained by reaction of phosphazenes and fluorinated acetylenic phosphonates. Subsequent reduction of both carbon-carbon and carbon-nitrogen double bonds of these 1-azadienes I affords the fluorine-containing β-aminophosphonates II, with the syn β-aminophosphonate being obtained as the major diastereoisomer. Base-mediated cyclocondensation of a diastereomeric mixture of aminophosphonates II leads exclusively to a new type of functionalized trans-γ-lactams III in a diastereoselective way. A computational study has also been used to explain the observed diastereoselectivity of these reactions.

Telescoping Reactions with Trifluorodiazoethane‐Derived Aza‐Wittig Reagents and Allenyl esters

“…[23][24][25][26][27] First, we utilized phosphorane 3a,w hich featured the triphenylphosphine group, but no reaction occurred. [23][24][25][26][27] First, we utilized phosphorane 3a,w hich featured the triphenylphosphine group, but no reaction occurred.…”

“…Next, a-iminophosphoranes 3 were anticipated to react with aldehydes in aW ittig reaction, similar to work reported by the group of Wittig and others. [23][24][25][26][27] First, we utilized phosphorane 3a,w hich featured the triphenylphosphine group, but no reaction occurred. Next, we attempted thes ame reaction with tributylphosphorane 3g.S urprisingly,t he Wittig product was not detected;i nstead, b-enamino ester 4a was obtained in good yield with complete Z-stereoselectivity (Scheme 6a).…”

“…Next, α‐iminophosphoranes 3 were anticipated to react with aldehydes in a Wittig reaction, similar to work reported by the group of Wittig and others . First, we utilized phosphorane 3 a , which featured the triphenylphosphine group, but no reaction occurred.…”

Chemistry of α-Oxoesters: A Powerful Tool for the Synthesis of Heterocycles

“…In the proposed reaction mechanism, Mannich-type reaction of 83 occurred with in situ generated glyoxalate imine to give intermediate 84, and then lactamization took place by nucleophilic addition of nitrogen at the activated carbonyl group (Scheme 23). 72 Recently, Alonso et al 73 By treatment of β,γ-unsaturated α-iminoester 93 with NaBH 4 in THF at 25°C, ethyl 5-oxopyrrolidine-2-carboxylate 94 was obtained in 73% yield. Starting β,γ-unsaturated α-iminoester 93 was generated by aza-Wittig reaction of β,γ-unsaturated α-oxoester 92 with in situ formed phosphazene in DCM at room temperature for 30 min (Scheme 25).…”

Nucleophilic trifluoromethylation of carbonyl compounds and derivatives

“…Therefore, the synthetic access to fluorinated compounds was difficult in the past and largely restricted to the use as starting materials of a very limited amount of commercially available fluorinated building blocks 10 or simple synthetic fluorinated templates. 11,12 Taking into account that many biologically active compounds contain the trifluoromethyl group as the essential motif, the introduction of this moiety is a challenging topic, and the development of highly efficient methodologies for trifluoromethylation is of significant importance for wide fields of science and technology.…”