Synthesis and stereochemistry of 6-membered ring phosphonates (original) (raw)
Tetrahedron-asymmetry, 2003
Chiral, non-racemic α-hydroxyphosphonates have been prepared in high enantiomeric excess (96–98% ee), via stereoselective oxaziridine-mediated hydroxylation of diallyl benzylphosphonates. The enantiomeric purity and absolute configuration of the α-hydroxyphosphonates was established from 1H and 31P NMR spectroscopy of the (S)-O-methylmandelate esters. Deprotection of the diallyl α-hydroxyphosphonates under neutral conditions furnished the corresponding free phosphonic acids, retaining a high degree of stereochemical purity (90 to >98% ee).
Tetrahedron: Asymmetry, 1996
Steret~ontrol in the asymmetric phosphonylation of aldehydes via organophosphorous esters has bccn obtained starting from chiral aldehydes. The nature of the O-protecting group is crucial to obtain, in terms of diastereoseleetivity and chemical yields, the best results. An ab/n/t/o molecular orbital study on 2-silyioxy propanal and MM2 studies on 2-alkoxy propanai show the existence of stable cyclic and acyclic conformers, which are presumably responsible for the high syn diastereoseleetivity observed in the addition of non-metal carrying phosphites.
European Journal of Medicinal Chemistry, 2011
A novel and efficient method for the one-pot synthesis of diamide (bis-amidate) prodrugs of acyclic nucleoside phosphonates, starting from free phosphonic acids or phosphonate diesters is reported. The approach from phosphonate diesters via their bis(trimethylsilyl) esters is highly convenient, eliminates isolation and tedious purification of the phosphonic acids, and affords the corresponding bis-amidates in excellent yields (83e98%) and purity. The methodology has been applied to the synthesis of the potent anticancer agent GS-9219, and symmetrical bis-amidates of other biologically active phosphonic acids. Anti-HIV, antiproliferative, and immunomodulatory activities of the compounds are discussed including the bis-amidate prodrugs 14 and 17 that exhibited anti-HIV activity at submicromolar concentrations with minimal cytotoxicity. Prepared from acid 5. 1 H NMR (DMSO-d 6 , 500 MHz) d 8.10 (s, 1H, H-8), 7.73 (bs, 2H, 6-NH 2 ), 4.49 (dd, 1 H, J HeNeP ¼ 12.1, J NHeCH ¼ 10.3, NH), 4.34 (dd, 1H, J HeNeP ¼ 11.3, J NHeCH ¼ 10.3, NH), 4.20 (dd, 1H, J gem ¼ 14.4, J 1 0 ae2 0 ¼ 3.7, H-1 0 a), 4.12e3.98 (m, 5H, COOeCH 2 and H-1 0 b), 3.98 (m, 1 H, H-2 0 ), 3.86e3.76 (m, 2H, NHeCH), 3.63 (dd, 1H, J gem ¼ 13.0, J HeCeP ¼ 8.0, OeCH 2 eP), 3.55 (dd, 1H, J gem ¼ 13.0, J HeCeP ¼ 9.1, OeCH 2 eP), 1.24e1.21 (m, 6H, NHeCHeCH 3 ), 1.18 (t, 3H, J CH3eCH2 ¼ 7.1, COOeCH 2 eCH 3 ), 1.16 (t, 3H, J CH3eCH2 ¼ 7.1, COOeCH 2 eCH 3 ), 1.02 (d, 3H, J 3 0 e2 0 ¼ 6.3, H-3 0 ). 13 C NMR (DMSO-d 6 , 126 MHz) d 174.20e174.16 (m, COO), 158.86 (d, J 2-F ¼ 203.2, C-2), 5.2.8. (2S,2 0 S)-Diethyl 2,2 0 -{[({2 -[(2,6-diaminopyrimidin-4-yl)oxy] ethoxy}methyl)phosphoryl]bis(azanediyl)}dipropanoate (20) Prepared from diester 12 [33]. 1 H NMR (DMSO-d 6 , 500 MHz) d 6.02 (bs, 2 H, NH 2 ), 5.87 (bs, 2H, NH 2 ), 5.03 (s, 1H, H-5), 4.57 (dd, 1H, J HeNeP ¼ 11.2, J NHeCH ¼ 10.9, NHP), 4.50 (t, 1H, J HeNeP ¼ J NHeCH ¼ 10.3, NHP), 4.20 (t, 2H, H-1 0 ), 4.10e4.00 (m, 4H, COOeCH 2 ), 3.88e3.82 (m, 2H, CHCOO), 3.71 (t, 2H, H-2 0 ), 3.62 (d,
Tetrahedron Letters, 2001
A short, practical stereospecific synthesis of triphenylphosphonium salts bearing an L-(N -benzoyl)-alanyl substituent from L-serine is described. The key step is the ring opening of an oxazoline salt derived from serine with trimethylsilyl halide, giving b-bromo or b-iodo alanine, which were used for the quaternization of triphenylphosphine. The phosphonium salts were obtained in 80% overall yield from serine, and their enantiomeric purity was easily determined by 31 P NMR in the presence of a cinchona alcaloid.
Tetrahedron: Asymmetry, 2012
Salen-like compounds, such as bis-aminophosphonic systems bearing a (R,R)-1,2-diamino-cyclohexyl (DACH) moiety, were synthesized by the addition of dialkyl phosphites to the azomethine bond of N,N 0-dibenzylidene-1,2-diaminocyclohexane 2. Five bis-aminophosphonates, dimethyl, diethyl, diisopropyl, dibenzyl, and diallyl derivatives, were obtained in high diastereoselectivity. Three of these compounds, dimethyl 3a, diethyl 3b, and diisopropyl 3c derivatives, had the predominant diastereoisomers separated. A hypothetical explanation of the diastereoselectivity is also reported.
Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates
Beilstein Journal of Organic Chemistry, 2016
Multicomponent reactions (MCRs) are one of the most important processes for the preparation of highly functionalized organic compounds in modern synthetic chemistry. As shown in this review, they play an important role in organophosphorus chemistry where phosphorus reagents are used as substrates for the synthesis of a wide range of phosphorylated heterocycles. In this article, an overview about multicomponent reactions used for the synthesis of heterocyclic compounds bearing a phosphonate group on the ring is given.
ChemInform Abstract: Facile and Stereoselective Synthesis of Vinylphosphonates
ChemInform, 2010
Facile and Stereoselective Synthesis of Fused γ-Butyrolactones of Carbohydrates.-The previously reported [2 + 2] photocycloadducts (I) and (III) of homochiral butenolides and vinylene carbonate are found to be useful precursors for the preparation of fused γ-butyrolactone carbohydrates.-(GREGORI, A.;