Shiroshi Shibuya

Enantioselective hydrophosphonylation of aromatic aldehydes catalyzed by chiral titanium alkoxides

Abstract The enantioselective hydrophosphonylation of aromatic aldehydes with silylphosphite (1) or diethyl phosphonate (5a) assisted by chiral titanium alkoxides as catalyst is examined. Titanium alkoxide (7), derived from L -tratrate and Ti(O-iPr)4, was found to be an effective catalyst and induce modest enantioselectivity in the reaction.

Enantioselectivity for hydrophosphonylation of aromatic aldehydes catalyzed by lanthanum binaphthol complex. Remarkable electronic effect of aromatic substituents

Abstract Hydrophosphonylation of aromatic aldehydes with diethyl phosphite in the presence of catalytic amount of La-BINOL complex ( 2 ) proceeded enantioselectively to give the corresponding α-hydroxyphosphonates in good yield. Enantioselectivity was found to depend on the electronic nature of para -substituents.

Enantioselective synthesis of α-amino phosphonic acids by an application of stereoselective opening of homochiral dioxane acetals with triethyl phosphite

Abstract Stereoselective opening of homochiral acetals ( 2a–c ) with triethyl phosphite was applied to the enantioselective synthesis of phosphono alcohols ( 1a–c ), which were succssefully converted to the α-amino phosphonic acid diethyl esters ( 6a–c ).

Facile synthesis of aryl(difluoromethyl)phosphonates through CuBr-mediated cross coupling reactions of [(diethoxyphosphinyl)difluoromethyl]zinc bromide with aryl iodides

Abstract The CuBr-promoted coupling reaction of [(diethoxyphosphinyl)difluoromethyl]zinc bromide 6 with aryl iodides in either DMF or DMA was examined to give a series of aryl(difluoromethyl)phosphonates. The coupling reaction was applicable to the selective synthesis of α,α-difluoro-4- iodobenzylphosphonale 11e, a useful intermediate for the preparation of F2Pmp. 1-[(Diethylphosphono)difluoromethyl] naphthalene 15 and the regioisomer 16 were obtained in high yields from 1- and 2-iodonaphthalene, respectively. The phosphonate 16 was transformed to the free acid 4a, a low molecular-mass inhibitor of protein phosphatases.

Stereodivergent synthesis of β-amino-α-hydroxyphosphonic acid derivatives by lewis acid mediated stereosclective hydrophosphonylation of α-amino aldehydes

Abstract The highly diastereoselective synthesis of β-amino-α-hydroxyphosphonic acid derivatives was achieved by Lewis acid mediated hydrophosphonylation of α-dibenzylamino aldehyde. Diastereofacial differentiation could be controlled in either a chelation or a non-chelation manner by simple tuning of the nature of phosphoric nucleophiles.

Enantioselective synthesis of α-hydroxyphosphinic acid derivatives through hydrophosphinylation of aldehydes catalyzed by Al-Li-BINOL complex

Abstract The first catalytic asymmetric synthesis of (S)-α-hydroxy-H-phosphinates and (S,S)-α,α′-dihydroxyphosphinates were achieved by the reaction of methyl phosphinate with aldehydes in the presence of Al-Li-BINOL complex.

Stereocontrolled synthesis of hydroxymethylene phosphonate analogues of phosphorylated tyrosine and their conversion to monofluoromethylene phosphonate analogues

Abstract A stereocontrolled synthesis of protected variants 13 and 15 of HPmp 2 , a mimic of phosphorylated tyrosine, was achieved through either chiral-auxiliary assisted or chiral heterobimetal catalyzed stereoselective hydrophosphonylation of 4-formyl- l -phenylalanine derivative 7 . Fluorination of HPmp derivatives 13 and 15 thus obtained was carried out to give FPmp derivatives 16 and 17 .

A new facile diastereoconversion of 2-amino alcohols involving a novel cyclocarbamation

Abstract A new practical method for diastereoconversion of 2-amino alcohols was performed by treatment of N-Cbz- derivatives with trifluoromethanesulfonic anhydride or thionyl chloride, followed by ring cleavage of the resulting oxazolidin-2-ones

Synthesis of 1,1-difluoro-5-(1H-9-purinyl)-2-pentenylphosphonic acids and the related methano analogues. Remarkable effect of the nucleobases and the cyclopropane rings on inhibitory activity toward purine nucleoside phosphorylase.

A series of 1,1-difluoro-5-(1H-9-purinyl)-2-pentenylphosphonic acids, (E)-2a,b and (Z)-2a,b, as well as the related methano analogues (+/-)-3a,b and (+/-)-4a,b were prepared for evaluation of their PNP inhibitory activities. The cyclopopane ring and the hypoxanthine residue were found to increase the profile of inhibitory activity. The IC50 and Ki values of difluoro¿(1R*,2S*)-2-[2-(6-oxo-6,9-dihydro-1H-9-purinyl)ethyl]cycl opropyl¿methylphosphonic acid (+/-)-3b toward PNP purified from Cellulomonas sp. were determined to be 70 nM and 8.8 nM, respectively.

Enantioselective synthesis of threo-α,β-dihydroxyphosphonates by asymmetric dihydroxylation of 1(E)-alkenylphosphonates with AD-mix reagents

Abstract Asymmetric dihydroxylation (AD) of 1(E)-alkenylphosphonates with an AD-mix-α or -β reagent was examined to give a series of optically active threo-α,β-dihydroxyphosphonates. Good enantioselectivity (>88% ee) was observed in the AD reaction of 1(E)-alkenylphosphonates with conjugated aromatic substituents. The steric effects of the ester functionality in the course of the dihydroxylation were also evaluated. Enantioselectivity and yield were significantly improved when the AD reaction was carried out with dimethyl phosphonate instead of diethyl phosphonate.