Synthesis of trifluoromethyl γ-aminophosphonates by nucleophilic aziridine ring opening

Abstract

Phosphonated derivatives of trifluoromethyl aziridine were obtained with good yield from aziridine-2-carbaldehyde by two distinct methods, which resulted in different diastereoselectivities. Using thiols as nucleophiles ring opening reactions of trifluoromethylated derivatives of aziridine-2-phosphonates proceeded regio- and diastereoselectively, giving rise to γ-amino-γ-trifluoromethyl phosphonates.

Functionalization of α-hydroxyphosphonates as a convenient route toN-tosyl-α-aminophosphonates

“…All aldehydes were prepared from the corresponding alcohols. Compounds 1a, 26 2–3, 27 b 4a, 50 4c, 51 5a, 52 5b 53 were prepared as described. The NMR data for 2–3, 54 4b, 27 b 5c 55 were in good agreement.…”

“…1 and Nbenzyl protected aziridines 6a,b). 26 In the case of Boc protected aziridine, the reaction gave only one diastereoisomer 8b as the sole product, where 7a was le unreacted in the reaction mixture. Moreover, 8b existed as a mixture of two rotamers (1.9 : 1 NMR ratio) that could be separated by chromatography techniques.…”

“…Surprisingly, when para-toluenesulfonamide (TsNH 2 ) was used along with K 2 CO 3 , aminophosphonates 23a,b were obtained as the sole products. The structure and stereochemistry of compound 23a was determined by X-ray diffraction analysis and indicated the rac(1S,2R,3S)-23a conguration, analogous to 6a, 26 obtained by Pudovik addition (Fig. 3).…”

Palladium-Catalyzed Isomerization-Coupling Reactions of Allyl Chloride with Amines to Generate Functionalized Phosphorus Derivatives

“…For example, Palacios reported the introduction of the γ-amino via an aza-Michael addition to a β-unsaturated imine [20]. Cytlak reported the preparation of trifluoromethyl γ-aminophosphonates by nucleophilic aziridine ring opening [21]. The compounds could be prepared starting from an α-amino aldehyde via a Horner-Wadsworth-Emmons (HWE) reaction and subsequent conversions [10,22].…”

Synthesis of β-alkoxy-N-protected phenethylamines via one-pot copper-catalyzed aziridination and ring opening

“… 2 Aziridines are suitable synthetic scaffolds or intermediates for the synthesis of many kinds of organic compounds through their ring opening by different nucleophiles including cyanide, aromatic and olefinic compounds, hydride, alcohols, thiols, amines, and halogens, affording various 1,2-difunctionalised compounds. 3 Among these 1,2-difunctionalised products, vicinal amino ethers have been obtained using different methodologies including inorganic protic or Lewis acids such as BF 3 ·Et 2 O, Sn(OTf) 2 , (NH 4 ) 2 Ce(NO 3 ) 6 , ionic liquids, [Ag(COD) 2 ]PF 6 , and also by an aprotic imidazolium zwitterion, an N , N ′-dioxide–Mg(OTf) 2 complex, sulphated zirconia, Ag( i ), Au( i ), phosphomolybdic acid supported on silica gel, montmorillonites and ceric ammonium nitrate, but always using previously isolated aziridines. 4 In addition, very recently, the aziridination of alkenes with subsequent ring opening using alcohols under continuous flow was reported.…”