Appel Reaction Research Articles

Neighboring group participation: Part 16. Stereoselective synthesis and receptor-binding examination of the four stereoisomers of 16-bromomethyl-3,17-estradiols

The four possible isomers of 3-benzyloxy-16-hydroxymethylestra-1,3,5(10)-trien-17-ol ( 1a– 4a) with proven configurations were converted into the corresponding 3-benzyloxy-16-bromomethylestra-1,3,5(10)-triene-3,17-diols ( 5e– 8e). Depending on the reaction conditions the cis isomers of 3-benzyloxy-16-hydroxymethylestra-1,3,5(10)-trien-17-ol ( 1a and 2a) were transformed into 3-benzyloxy-16-bromomethylestra-1,3,5(10)-trien-17-yl acetate ( 5b and 6b) or 16-bromomethyl-3-hydroxyestra-1,3,5(10)-trien-17-yl acetate ( 5c and 6c) on treatment with HBr and acetic acid. The mechanism of the process can be interpreted as involving front-side neighboring group participation. Under similar experimental conditions, the trans isomers ( 3a and 4a) yielded only 3-benzyloxy-16-acetoxymethylestra-1,3,5(10)-trien-17-yl acetates ( 3b and 4b) or 16-acetoxymethylestra-1,3,5(10)-triene-3,17-diyl diacetates ( 3d and 4d). Both the cis ( 1a and 2a) and the trans ( 3a, and 4a) isomers were transformed into 16-bromomethylestra-1,3,5(10)-trien-17-ol ( 5a– 8a) by the Appel reaction on treatment with CBr 4/Ph 3P. Debenzylation of 5a– 8a was carried out with HBr and acetic acid to yield 5e– 8e. The debenzylation process in the presence of acetic anhydride produces the diacetates 5d– 8d. The structures of the compounds were determined by means of MS, 1H NMR and 13C NMR spectroscopic methods. Compounds 5c– 8c and 5e– 8e were tested in a radioligand-binding assay. Except for the affinity of 7e for the estrogen receptor ( K i = 2.55 nM), the affinities of the eight compounds ( 5c– 8c and 5e– 8e) for the estrogen, androgen and progesterone receptors are low ( K i > 0.55, 0.52 and 0.21 μM, respectively).

Studies on the structure behavior of triphenyldichlorophosphorane in different solvents

Triphenyldichlorophosporane, which was prepared according to Appel reaction, was an efficient reagent for alkyl halide synthesis by virtue of having two replaceable groups on “pentavalent” phosphorus. The reaction of triphenylphosphine with hexachloroethane was investigated in different solvents and 31P NMR traced the processes of these reactions. As results, it was found that there was similar high coordinated phosphorus species formed in aromatic solvents and in ring ether type solvents, which had large 1JP–C (about 140Hz) according to 13C NMR experiments. It is indicated that, for some solvent such as benzene or dioxane, solvent molecules might be locked in the high coordinated phosphorus compounds, which in turn would affect the triphenyl groups situated at the equatorial position.

Bis(hydroxymethyl)phosphinic acid analogues of acyclic nucleosides; synthesis and incorporation into short DNA oligomers

Novel analogues of acyclic nucleosides based on a bis(hydroxymethyl)phosphinic acid (BHPA) backbone were obtained by condensation of the bis(4,4′-dimethoxytrityl) derivative of BHPA with N-1- or N-3-(2-hydroxyethyl)thymine in the presence of MSNT, or by an Appel reaction with N-1- or N-3-(2-aminoethyl)thymine. After selective deprotection and phosphitylation they were used as monomers for automated solid support synthesis of short oligomers by the phosphoramidite approach.

A Practical Route to Regiospecifically Substituted (R)- and (S)-Oxazolylphenols

New, diversely substituted phenolic oxazolines 14a−d and 15a−d were prepared by two complementary routes A and B, starting from salicylic derivatives 4−7 and various enantiomerically pure 1,2-amino alcohols 13a−d. In route A, the 1,2-amino alcohols 13a−d were directly condensed with the salicylic acids 5 and 7, using the Appel reaction, whereas in route B the amino alcohols 13b−d were treated with the 2-hydroxybenzonitriles 4 and 6, under Witte−Seeliger conditions. The latter route was advantageous for L-valinol 13b and L-tert-leucinol 13c, while route A was the method of choice for the new, sterically demanding amino alcohol 13a, prepared from D- and L-serine. The nitro group in the salicylic derivatives 5 and 6 was introduced by means of a regiospecific ipso substitution of a tert-butyl group by nitric acid. The structure of the nitro product 5 was unambiguously assigned by NOE spectroscopy on the basis of the recently developed DPFGSE-ROE pulse sequence.

Preparation of TADDOL Derivatives for New Applications

Substitution of one or both TADDOL OH groups by other functional groups X, Y is key to new applications of this cheap chiral auxiliary. The Appel reaction and treatment with SOCl2 provide the mono- and dichlorides, respectively. The chlorides are, in turn, replaced by various nucleophiles, and further modifications give a large variety of derivatives, including mono- and ditritylated dioxolanes. The new compoundsavailable in either enantiomeric formare ready to be used in enantioselective synthesis and as dopants in liquid crystals.

Additions and Corrections - A Highly Efficient One-Flask Method for the Preparation of the Individual Diastereoisomers of Ribonucleoside 3',5'-Cyclic N-Substituted Phosphoramidates via the Direct Appel Reaction. X-Ray Structure of trans-5-Isopropyl-2'-deoxyuridine 3',5'-Cyclic N-Benzylphosphoramidate.

Additions and Corrections - A Highly Efficient One-Flask Method for the Preparation of the Individual Diastereoisomers of Ribonucleoside 3',5'-Cyclic N-Substituted Phosphoramidates via the Direct Appel Reaction. X-Ray Structure of trans-5-Isopropyl-2'-deoxyuridine 3',5'-Cyclic N-Benzylphosphoramidate.

Studies of Phosphazenes: Part 271. Synthesis of (Triphenylphosphazenyl)Pentachloro and Pentafluoro-Cyclotriphosphazenes

The triphenylphosphazenyl cyclophosphazene, N3P3(N=PPh3)Cl5 (1) has been prepared by two new methods using Appel and Staudinger reactions. The effect of solvent on the synthesis of 1 from the reaction of gem-N3P3 (NH2)2Cl4 with Ph3PCl2 (Kirsanov method) has been investigated. The fluoro compound, N3P3(N=PPh3)F5(2), is obtained readily in good yields (85%) by the treatment of 1 with KF in methyl cyanide.

A highly efficient one-flask method for the preparation of the individual diastereoisomers of ribonucleoside 3',5'-cyclic N-substituted phosphoramidates via the direct Appel reaction. X-ray structure of trans-5-isopropyl-2'-deoxyuridine 3',5'-cyclic N-benzylphosphoramidate

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA highly efficient one-flask method for the preparation of the individual diastereoisomers of ribonucleoside 3',5'-cyclic N-substituted phosphoramidates via the direct Appel reaction. X-ray structure of trans-5-isopropyl-2'-deoxyuridine 3',5'-cyclic N-benzylphosphoramidateJozsef Beres, Wesley G. Bentrude, Laszlo Parkanji, Alajos Kalman, and Alan E. SopchikCite this: J. Org. Chem. 1985, 50, 8, 1271–1278Publication Date (Print):April 1, 1985Publication History Published online1 May 2002Published inissue 1 April 1985https://doi.org/10.1021/jo00208a023RIGHTS & PERMISSIONSArticle Views508Altmetric-Citations22LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Geminal bis[(triphenylphosphoranylidene)amino]cyclotriphosphazenes synthesis: substitution reactions, and nuclear magnetic resonance spectra

Cyclotriphosphazenes bearing an amino ligand are readily converted into the corresponding (triphenylphosphoranylidene)amino (–NPPh3) derivatives by means of an excess of triphenylphosphine–tetrachloromethane in an acetonitrile–triethylamine medium (Appel reaction). Thus prepared, N3P3Cl4(NPPh3)2 reacts with dimethylamine in various solvents according to a geminal substitution pattern; this is an indication of SN1-type reactions, as a result of the strong electron-donating character of the ligands. The ultimate substitution product N3P3(NMe2)4(NPPh3)2, also prepared from N3P3(NMe2)4(NH2)2, is isolated as its HCl or 2HCl adduct, depending on the method of preparation. In both adducts the protons are attached to ring nitrogen atoms, and variable-temperature 1H and 31P n.m.r. measurements show prototropic behaviour at elevated temperatures. Trends within the 31P n.m.r. parameters of the derivatives are discussed in terms of the electron-donating ability of the ligands.