Ian D. Jenkins

Convenient synthetic routes to bidentate and monodentate 2-, 3- and 4-pyridyl phosphines: potentially useful ligands for water-soluble complex catalysts

The monodentate and bidentate pyridyl phosphines, PR3 and R2P(CH2)2PR2, where R=3- or 4-pyridyl can be prepared in high yields by treatment of butyllithium/TMEDA/3- or 4-bromopyridine with PCl3 or Cl2P(CH2)2PCl2 at low temperature. 1,2-Bis(di-2-pyridylphosphino)ethane is conveniently synthesised by an alternative route involving reaction of 1,2-dibromoethane with lithium di-2-pyridylphosphide.

The Hendrickson reagent and the Mitsunobu reaction: a mechanistic study

The alkoxytriphenylphosphonium ion intermediate of the Mitsunobu reaction can be generated using the Hendrickson reagent, triphenylphosphonium anhydride trifluoromethanesulfonate, 1. Strangely, while the reagent 1 can be used in place of the Mitsunobu reagents (triphenylphosphine and a dialkylazodicarboxylate) for the esterification of primary alcohols, secondary alcohols such as menthol undergo elimination. Evidence is presented to show that this unexpected result is due to the presence of trialkylammonium triflate salts. Such salts lead to a dramatic decrease in the rate of esterification relative to competing elimination. The Mitsunobu esterification of menthol with p-nitrobenzoic acid was re-examined and the occurrence of elimination reported for the first time. The presence of traces of tetrabutylammonium triflate led to a dramatic reduction in the yield of inverted ester and a corresponding increase in the yield of anti elimination product 2-menthene. The mechanism of the Mitsunobu reaction is discussed in the light of the dramatic salt effect on both the rate and outcome of the reaction and the possible involvement of ion pair clustering. In contrast, use of the reagent 1 resulted in syn elimination to give a 1:2 mixture of 2- and 3-menthenes. Finally, 1 and sodium azide can be used to convert a primary alcohol into an azide in high yield. There was no reaction under Mitsunobu conditions.

Improved synthesis of ‘cord factor’ analogues

Treatment of trehalose or sucrose with triphenylphosphine, di-isopropyl azodicarboxylate, and palmitic acid results in the formation of the corresponding 6,6′-dipalmitates–analogues of ‘cord factor’–in good yield under exceptionally mild conditions.

The reactivity of nitroxides towards alkenes

At elevated temperatures, nitroxides (e.g. 1,1,3,3-tetramethyl-2,3-dihydroisoindol-2-yloxyl) undergo a slow addition reaction with acrylonitrile, methyl acrylate and styrene to give the bis-nitroxide adducts. With alkenes containing an allylic hydrogen such as methyl methacrylate and 6-methylene-1,4-oxathiepan-7-one, the major reaction observed was hydrogen abstraction. The resulting hydroxylamines can be trapped as Michael addition products.

Derivatives of sucrose 3′,4′-epoxide

Abstract A facile, one-pot synthesis of α- d -glucopyranosyl 3,4-anhydro-β- d -tagatofuranoside (1) from sucrose in good yield is reported. Derivatives of 1 can also be obtained from 4,6:2,1′-di-O-isopropylidenesucrose and from 2,3,6,1′,6′-penta-O-benzoylsucrose by treatment with triphenylphosphine and diethyl azodicarboxylate. The n.m.r. spectra (13C,1H) and conformation of derivatives of 1 are discussed. A new anhydrosucrose (1′,4′) is reported.

MONO- AND DIALKYLATION OF ISOPROPYL PHOSPHINATE-A SIMPLE PREPARATION OF ALKYLPHOSPHINATE ESTERS1

Abstract Base-catalysed alkylation of isopropyl phosphinate with primary alkyl halides under mild conditions affords the corresponding alkyl phosphinate esters in fair to excellent yields.

The mechanism of initiation in the free radical polymerization of N-vinylcarbazole and N-vinylpyrrolidone

Abstract The reactions of N-vinylcarbazole and of N-vinylpyrrolidone with benzoyl peroxide and with di-t-butyl peroxalate in the presence of the nitroxide scavenger 1,1,3,3-tetramethyl-1,3-dihydroisoindol-2-yloxyl are reported. Use of di-t-butyl peroxalate leads to the expected radical intermediates which are efficiently scavenged by the nitroxide. When benzoyl peroxide is used as initiator however, both ionic and radical processes are involved. The importance of electron-transfer processes is discussed.

Selective mono reduction of bis-phosphine oxides under mild conditions

Bis-phosphine oxides can be selectively reduced to bis-phosphine monoxides under exceptionally mild conditions using triflic anhydride and a thiol.

Ionic and Neutral Mechanisms for C–H Bond Silylation of Aromatic Heterocycles Catalyzed by Potassium tert-Butoxide

Exploiting C-H bond activation is difficult, although some success has been achieved using precious metal catalysts. Recently, it was reported that C-H bonds in aromatic heterocycles were converted to C-Si bonds by reaction with hydrosilanes under the catalytic action of potassium tert-butoxide alone. The use of Earth-abundant potassium cation as a catalyst for C-H bond functionalization seems to be without precedent, and no mechanism for the process was established. Using ambient ionization mass spectrometry, we are able to identify crucial ionic intermediates present during the C-H silylation reaction. We propose a plausible catalytic cycle, which involves a pentacoordinate silicon intermediate consisting of silane reagent, substrate, and the tert-butoxide catalyst. Heterolysis of the Si-H bond, deprotonation of the heteroarene, addition of the heteroarene carbanion to the silyl ether, and dissociation of tert-butoxide from silicon lead to the silylated heteroarene product. The steps of the silylation mechanism may follow either an ionic route involving K+ and tBuO- ions or a neutral heterolytic route involving the [KOtBu]4 tetramer. Both mechanisms are consistent with the ionic intermediates detected experimentally. We also present reasons why KOtBu is an active catalyst whereas sodium tert-butoxide and lithium tert-butoxide are not, and we explain the relative reactivities of different (hetero)arenes in the silylation reaction. The unique role of KOtBu is traced, in part, to the stabilization of crucial intermediates through cation-π interactions.

Novel polymer-supported coupling/dehydrating reagents for use in organic synthesis

Two novel dehydrating reagents and, based on a phosphonium anhydride and an oxyphosphonium triflate respectively, were prepared by reaction of the corresponding polymer-supported phosphine oxides with triflic anhydride. Reagent, based on the novel phosphorus heterocycle 1,1,3,3-tetraphenyl-2-oxa-1,3-diphospholanium bis(trifluoromethanesulfonate), was found to be a useful reagent for ester and amide formation. A wide range of coupling/dehydration-type reactions, such as ester, amide, anhydride, peptide, ether and nitrile formation, were performed in high yield using the more readily prepared polymer-supported triphenylphosphine ditriflate, which was easily recovered and re-used several times without loss of efficiency. With primary alcohols, both reagents and provide an alternative to the Mitsunobu reaction, where the use of azodicarboxylates and chromatography to remove the phosphine oxide by-product can be avoided. The use of 4-dimethylaminopyridine allowed the esterification of secondary alcohols with to proceed in high yield but with retention of configuration.