Stephen D. Pastor

Enantioselective synthesis of β-hydroxy-α-aminophosphonic acid precursors

The gold(I) catalyzed aldol reaction of diethyl α-isocyanomethylphosphonate with benzaldeyde gave the oxazoline 3, a β-hydroxy-α-aminophosphonic acid precursor, with high enantio- and diastereoselectivity (98 % trans, 85 % ee) by employing a chiral ferrocenylamine ligand. The use of 31P NMR spectroscopy with the chiral solvating agent (S)-(+)-2,2,2-trifluoro-1-(9-anthryl)ethanol was found to be a powerful tool for determination of optical purity.

12H-DIBENZO[d,g][1,3,2]DIOXAPHOSPHOCINS: Synthesis and Evidence for Long-Range Coupling to Phosphorus

Abstract The synthesis of the 12H-dibenzo[d,g][1,3,2]dioxaphosphocin ring system from 2,2′-alkylidene bisphenols and phosphorus trichloride is described. The 1H NMR shows evidence for long range through-space coupling of the C-12 methine proton to phosphorus.

The Reaction of Seven- and Eight- Membered Cyclic Phosphorochloridites with Polyols

Abstract The syntheses of novel bridged dibenzo[d,f][1,3,2]dioxaphosphepin and dibenzo[d,g][1,3,2]dioxaphosphocin ring systems are described. The 1H NMR spectral data of the eight-membered bridged dioxaphosphocins suggest the observation of a single conformational isomer. The 1H NMR spectrum of the dibenzo[d,g][1,3,2]dioxaborocin 5 requires that either a single nonplanar conformation is being observed or that ring inversion is slow on the NMR time scale. A lower limit of δG ‡ for ring inversion of 5 has been calculated to be 14.4 Kcal/mole. The 1H NMR of the C-12 methyl substituted dioxaphosphocins 4h-i showed the presence of a cis-trans isomer mixture.

Enantioselective synthesis: Catalysis of the aldol reaction by neutral gold(I)-chiral ferrocenylphosphine complexes. Crystal structure of the complex [{(η5-C5H4PPh2)(η5-C5H3(PPh2)CH(Me)N(Me)CH2CH2NMe2)Fe}2(AuCl)3] · Et2O

Abstract The chiral aminoferrocenylphosphine [(η 5 -C 5 H 4 PPh 2 )(η 5 -C 5 H 3 (PPh 2 )CH(CH 3 )-N(CH 3 )CH 2 CH 2 N(CH 3 ) 2 )Fe] ( 1 ) reacts with (H 3 C) 2 SAuCl to give neutral gold(I) complexes that are active catalysts for the enantioselective coupling of isocyanoacetate esters with aldehydes, forming dihydrooxazoles. The structure of the trimeric complex [(rac- 1 ) 2 (AuCl) 3 ] · Et 2 O has been determined by X-ray diffraction.

Asymmetric synthesis: Modification of chiral ferrocenylamine ligands for the gold(I)-catalyzed aldol reaction

Abstract The synthesis of a chiral ferrocenylamine ligand, ( R )-( S )- 11 , with a modifiable ester group is described. High diastereo- and enantioselectivity were obtained in the gold(I)-catalyzed aldol reaction using ( R )-( S )- 11 as a ligand.

2,4,8,10-TETRASUBSTITUTED DIBENZO[d,f][1,3,2]DIOXAPHOSPHEPINS

Abstract The synthesis of the dibenzo[d,f][1,3,2]dioxaphosphepin ring system from substituted biphenyl-2,2′-diols and alkylphosphonous dichlorides is described. The NMR spectral data are consistent with either rapidly interconverting ring conformers or a static non-planar ring conformation.

REACTION OF SEVEN- AND EIGHT-MEMBERED CYCLIC PHOSPHOROCHLORIDITES WITH ALKANOLAMINES

Abstract The reactions of substituted 6-chloro-12H-dibenzo[d,g][1,3,2]dioxaphosphocins and 6-chlorodibenzo[d,f][1,3,2]dioxaphosphepins with primary, secondary and tertiary alkanolamines are described. The primary and sec-aminoalkyl phosphites prepared show no IR or NMR spectroscopic evidence for formation of their tautomeric pentacoordinate form.

The gold(I)-catalyzed aldol reaction utilizing chiral ferrocenylamine ligands : synthesis of N-benzyl-substituted ligands

The synthesis and characterization of (R)-N-{2-[(R)-N-2-hydroxy-1-propyl-N-benzyl]aminoethyl}-N-benzyl-1-[(S)-1′,2-bis(diphenylphosphino)ferrocenyl]ethyl amine (9) and selected carbamate esters is described. The stereoselectivity of the gold(I)-catalyzed reaction of benzaldehyde with methyl iso-cyanoacetate was compared using the N-benzyl-substituted versus the corresponding N-methyl-substituted ferrocenylamine ligands. The lower diastereo- and enantioselectivity obtained using the N-benzyl-substituted ferrocenylamine ligands is consistent with the transition-state model proposed for the stereoselective step of the gold(I)-catalyzed aldol reaction utilizing ferrocenylamine ligands possessing both central and planar chirality.

6H-DIBENZ[c,e][1,2]OXAPHOSPHORINS: SYNTHESIS AND CHEMISTRY

Abstract The reaction of 1-phenylphenol with phosphorus trichloride at elevated temperature using zinc chloride as a catalyst gave the 6H-dibenz[c,e][1,2]oxaphosphorin 1. The reaction of 1 with the phenols 3a–e gave the corresponding 6-phenoxy derivatives 4a–e. In the case of the sterically hindered phenol 3e, an improved procedure involved the reaction of the sodium phenolate of 3e with 1. The reaction of the benzenethiols 5a–b with 1 using triethylamine as an acid acceptor gave the corresponding derivatives 6a–b.

CONFORMATION OF EIGHT-MEMBERED DIOXATHIASILOCIN HETEROCYCLES IN SOLUTION

Abstract The dibenzo[d,g][1,3,6,2]dioxathiasilocin derivatives 3a-f were prepared by the reaction of the thiobisphenols 1a-b with the corresponding dichlorosilanes 2a-e using triethylamine as an acid acceptor. The free energy of activation for ring inversion of the 2,4,8,10-tetra-tert-butyl-substituted 3a was determined by variable temperature 1H NMR to be 13.9 kcal/mol. The 1H NMR spectral data of 3a requires that the ring conformer possess a σ plane of symmetry passing through the silicon and bridging sulfur atoms. In the variable temperature 1H NMR spectra of the 2,4,8,10-tetramethyl-substituted 3b no evidence was observed for the slowing of ring inversion at-55oC, suggesting that the energy of activation for ring inversion is less than 10.9 kcal/mol. The 1H NMR spectral data of 3e-f indicates the presence of equilibrating conformational isomers. The results of this study supports the suggestion that steric factors are a major contributor to the barrier of ring inversion for the dibenzo-[d, g][1,3,6,2]...