A versatile synthesis of chiral β-aminophosphines

Abstract

A method for the preparation of chiral β-aminophosphines having substituted P-aryl groups is described. Ring-opening of cyclic sulfamidates with metal diarylphosphinites yields β-aminophosphine oxides, which are then reduced to the corresponding phosphines. Effects of the diarylphosphinite countercation on the regioselectivity of the ring-opening reaction (P- versus O-alkylation) are discussed. This method enables the introduction of electron-deficient, electron-rich and sterically hindered diarylphosphino groups, as demonstrated by the synthesis of a series of novel, P-aryl-substituted β-aminophosphines derived from tert-leucinol, valinol and phenylglycinol. Access to these derivatives will create new opportunities for steric and electronic tuning of β-aminophosphine-derived chiral ligands and organocatalysts.

Enantioselective Access to Chiral Cyclic Sulfamidates Through Iridium‐Catalyzed Asymmetric Hydrogenation

“…Chiral cyclic sulfamidates are versatile intermediates for the construction of some important chemical and biological molecules. [1][2][3] For example, they have wide range of application to work as potential precursors for the synthesis of chiral amines, amino alcohols and amino acids through various synthetic transformations. [2][3] Taking into account of their great synthetic importance, much attention has been paid to the development of highly efficient synthetic methodologies.…”

“…To explore the feasibility of Ir-catalyzed asymmetric hydrogenation of cyclic sulfamidate imines, 4phenyl-5H- [1,2,3] bisphosphine ligands ( Figure 1). As shown in Table 1, several bisphosphine-(thio)urea ligands L1-L3 were applied in this Ir-catalyzed asymmetric hydrogenation ( Table 1, entries 1-3).…”

“…The 2-napthyl (1 n) and heteroaromatic (1 o) substrates worked well to provide the 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 desired products (2 n-2 o) with excellent results (> 99% conversion, 97%-98% yields, 96%-97% ee). In addition, the alkyl substrate 4-benzyl-5H- [1,2,3]-oxathiazole 2,2-dioxide (1 p) could also be hydrogenated smoothly to achieve full conversion, high yield and moderate enantioselectivity (98% yield and 73% ee).…”

“…As shown in Scheme 2, the gram-scale asymmetric hydrogenation of 4-(3,5-difluorophenyl)-5H- [1,2,3]-oxathiazole 2,2-dioxide 1 h could be performed well in the presence of 0.02 mol% (S/C = 5000) Ir/N-methylated ZhaoPhos L2 catalyst, and the desired product chiral cyclic sulfamidate 2 h was provided with excellent result (97% conversion, 94% yield, TON = 4850, 93% ee). The desired chiral cyclic sulfamidate 2 h is an important intermediate for the construction of piperazinone acid, its enantiomer was one of the two main molecular fragments containing in clinical candidate Moreover, the chiral cyclic sulfamidate 2 h was easily reduced by LiAlH 4 to generate (S)-difluorophenylglycinol in 92% yield and nearly without loss of ee value (92% ee).…”

“…[13] Table 2. Screening solvents for the Ir/NÀMe-ZhaoPhos L2catalyzed asymmetric hydrogenation of 4-phenyl-5H- [1,2,3] oxathiazole 2,2-dioxide (1 a). [a] entry solvent conv.…”