Titanium‐mediated living radical styrene polymerizations. V. Cp2TiCl‐catalyzed initiation by epoxide radical ring opening: Effect of solvents and additives

The effects of solvents, additives, ligands, and solvent in situ drying agents as well as catalyst and initiator concentrations have been investigated in the Cp₂TiCl‐catalyzed radical polymerization of styrene initiated by epoxide radical ring opening. On the basis of the solubilization of Cp₂Ti(III)Cl and the polydispersity of the resulting polymer, the solvents rank as follows: dioxane ≥ tetrahydrofuran > diethylene glycol dimethyl ether > methoxybenzene > diphenyl ether ≥ bulk > toluene ? pyridine > dimethylformamide > 1‐methyl‐2‐pyrrolidinone > dimethylacetamide > ethylene carbonate, acetonitrile, and trioxane. Alkoxide additives such as aluminum triisopropoxide and titanium(IV) isopropoxide are involved in alkoxide ligand exchange with the epoxide‐derived titanium alkoxide and lead to broad molecular weight distributions, whereas similarly to strongly coordinating solvents, ligands such as bipyridyl block the titanium active site and prevent the polymerization. By contrast, softer ligands such as triphenylphosphine improve the polymerization in less polar solvents such as toluene. Although mixed hydrides such as lithium tri‐tert‐butoxyaluminum hydride, sodium borohydride, and lithium aluminum hydride react with bis(cyclopentadienyl)titanium dichloride to form mixed titanium hydride species ineffective in polymerization control, simple hydrides such as lithium hydride, sodium hydride, and especially calcium hydride are particularly effective as in situ trace water scavengers in this polymerization. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 2015–2026, 2006     

Efficient Synthesis of a New Series of Piperidine Ring–Modified Alcohol and Methyl Ether Analogs of (±)-threo-Methyl Phenyl(piperidin-2-yl)acetate

A series of novel piperidine ring–modified alcohol and methyl ether analogs of (±)-threo-methyl phenyl(piperidin-2-yl)acetate was synthesized. This series of methyl phenyl(piperidin-2-yl)acetate analogs was developed by piperidine ring alkylation and/or acylation followed by lithium aluminum hydride reduction to give alcohol derivatives. Methylation of the alcohol analogs by extension of standard literature procedures gave the corresponding methyl ether derivatives. The chemical structure of these compounds was established based on mass and ¹H NMR spectral data and CHN elemental analysis data. Several significant modifications to the literature methodologies made the reaction more efficient, and good yields were generally obtained.     

Direct Nucleophilic Addition to N‐Alkoxyamides

While the synthesis of amide bonds is now one of the most reliable organic reactions, functionalization of amide carbonyl groups has been a long‐standing issue due to their high stability. As an ongoing program aimed at practical transformation of amides, we developed a direct nucleophilic addition to N‐alkoxyamides to access multisubstituted amines. The reaction enabled installation of two different functional groups to amide carbonyl groups in one pot. The N‐alkoxy group played important roles in this reaction. First, it removed the requirement for an extra preactivation step prior to nucleophilic addition to activate inert amide carbonyl groups. Second, the N‐alkoxy group formed a five‐membered chelated complex after the first nucleophilic addition, resulting in suppression of an extra addition of the first nucleophile. While diisobutylaluminum hydride (DIBAL‐H) and organolithium reagents were suitable as the first nucleophile, allylation, cyanation, and vinylation were possible in the second addition including inter‐ and intramolecular reactions. The yields were generally high, even in the synthesis of sterically hindered α‐trisubstituted amines. The reaction exhibited wide substrate scope, including acyclic amides, five‐ and six‐membered lactams, and macrolactams.     

A. Critical Evaluation of the Knorr Synthesis of Tpifluoromethylpyrroles and the Reactivity of Diethyl 4-Trifluoromethyl-2-Methylpyrrole-3, 5-Dicarboxylate.

β-Trifluoromethyl pyrroles are readily obtained by the Knorr synthesis, but the procedure fails for the preparation of the the α-isomers. The β-trifluoromethyl group reacts with alkoxide anions and is reduced with lithium aluminium hydride.     

Reduction of 1,2-diaroyl-1,2-diazetidines by lithium aluminum hydride

Reaction of a series of four-membered ring hydrazides (1,2-diaroyl-1,2-diazetidines) with lithium aluminum hydride at 80° results in reductive saturation of both carbonyl groups affording 1,2-diaryl-1,2-diazetidines in modest yield. Reactions at 22° result in reductive fragmentation at one carbonyl moiety, producing a monoaroyl-1,2-diazetidine as the exclusive product. A mechanism similar to that postulated for the temperature-dependent reduction of amides by lithium aluminum hydride is proposed for the reduction of these 1,2-diazetidines.     

Reduction of the benzoyl group in substituted 5-benzoyl-4,5-dihydro-1,2,4-oxadiazoles

The carbonyl group of substituted 5-benzoyl-4,5-dihydro-1,2,4-oxadiazoles can be reduced by lithium aluminium hydride at low temperature without ring opening. Mixtures of the two related diastereoisomeric benzylalcohols are obtained. Configurations were assigned by ¹H-nmr.     

Addition of phosphorus-stabilized carbanions to cyclic enones and further transformations of the reaction products

a-Lithiated diethyl alkylphosphonates react with cyclic enones according to a 1,2-addition, yielding the corresponding allylic alcohols (β-hydroxyalkylphosphonates). The alcohols undergo acid-catalyzed dehydration with preferential exocyclic location of the new olefinic bond; in some cases, allylic rearrangement to a 2° alcohol was observed. In pure methanol, allylic rearrangement is accompanied by the formation of an allyl methyl ether. Lithiated prop-2-enylphosphonate adds to the β-carbon (1,4-addition) via its γ-carbon; the only exception is 3-methylcyclohexenone, in which the methyl group directs the nucleophile toward the carbonyl center. © 1996 John Wiley & Sons, Inc.     

Redox Reorganization: Aluminium Promoted 1,5-Hydride Shifts Allow the Controlled Synthesis of Multisubstituted Cyclohexenes

An efficient synthesis of cyclohexenes has been achieved from easily accessible tetrahydropyrans via a tandem 1,5-hydride shift–aldol condensation. We discovered that readily available aluminium reagents, e.g. Al₂O₃ or Al(O^tBu)₃ are essential for this process, promoting the 1,5-hydride shift with complete regio- and enantiospecificity (in stark contrast to results obtained under basic conditions). The mild conditions, coupled with multiple methods available to access the tetrahydropyran starting materials makes this a versatile method with exceptional functional group tolerance. A wide range of cyclohexenes (>40 examples) have been prepared, many in enantiopure form, showing our ability to selectively install a substituent at each position around the newly forged cyclohexene ring. Experimental and computational studies revealed that aluminium serves a dual role in facilitating the hydride shift, activating both the alkoxide nucleophile and the electrophilic carbonyl group.     

Ready Access to Fluorinated Phosphonate Mimics of Secondary Phosphates. Synthesis of the (alpha,alpha-Difluoroalkyl)phosphonate Analogues of L-Phosphoserine, L-Phosphoallothreonine, and L-Phosphothreonine

In addition to the previously recorded reactions of diethyl lithio(difluoromethyl)phosphonate (8) with primary triflates and aldehydes, we report here that 8 reacts with functionalized, but unactivated, methyl esters to give efficient acyl substitution. Thus, 8 reacts cleanly (-78 degrees C, THF) with the following methyl esters (product, yield): methyl (S)-isopropylideneglycerate (14, 99%), methyl (S)-3-O-(tert-butyldimethylsilyl)-2 -O-tetrahydropyranylglycerate (16, 85%), and the Garner ester derived from D-serine (15, 77%). Expeditious treatment of the resultant alpha,alpha-difluoro-beta-keto phosphonates with hydride or Grignard reagents followed by alcohol deoxygenation provides a general method for the synthesis of (alpha,alpha-difluoroalkyl)phosphonate analogues of secondary phosphates. For tertiary alcohols, Dolan-MacMillan deoxygenation conditions are employed. The requisite methyl oxalate esters are obtained by an improved procedure wherein the lithium alkoxide of the hindered tertiary alcohol is irreversibly generated at low temperature and then condensed with methyl oxalyl chloride. Relative stereochemistry is assigned via conversion of the Garner ester derived Boc-amino alcohols to the corresponding cyclic, six-membered phosphonate esters and examination of their (1)H NMR spectra. The relevant vicinal coupling constants are extracted from these spectra by performing double quantum-filtered phase-sensitive COSY experiments. This new (difluoromethylene)phosphonate anion-methyl ester condensation, Grignard (hydride) addition, deoxygenation sequence has been applied to the synthesis of (alpha,alpha-difluoroalkyl)phosphonate analogues of L-phosphoserine (>/=96% ee) and L-phosphoallothreonine (93% ee) from D-serine and of L-phosphothreonine (91% ee) from L-glycerate, respectively.     

Ultrasound-induced heterogeneous reduction of halo,alkoxy and amino derivatives of group ivb elements with lithium aluminium hydride

Hydrides of group IVB elements have been prepared in high yield by heterogeneous reduction of the corresponding halo, alkoxy and amino derivatives using lithium aluminium hydride in non-polar solvents under ultrasonic irradiation.     

Enantioselective Syntheses of Conformationally Rigid,Highly Lipophilic Mesityl‐Substituted Amino Acids

Three N‐Boc‐protected amino acids substituted with a mesityl (=2,4,6‐trimethylphenyl) group were synthesized in enantiomerically pure form, either by asymmetric epoxidation or by aminohydroxylation as the source of chirality. The 3‐mesityloxirane‐2‐methanol 7 , easily available in high enantiomer purity by Sharpless epoxidation, was converted into 3‐{[(tert‐butoxy)carbonyl]amino}‐3‐mesitylpropane‐1,2‐diol 9 by a regio‐ and stereoselective ring opening with an ammonia equivalent (sodium azide or benzhydrylamine), followed by hydrogenation and in situ treatment with (Boc)₂O (Boc=[(tert‐butoxy)carbonyl]) (Scheme 3). Oxidative cleavage of the diol fragment in 9 afforded N‐[(tert‐butoxy)carbonyl]‐α‐mesitylglycine 1 of >99% ee. This amino acid was also prepared in enantiomerically pure form starting from 2,4,6‐trimethylstyrene ( 11 ) by a regioselective Sharpless asymmetric aminohydroxylation, followed by a 2,2,6,6‐tetramethylpiperidin‐1‐yloxyl (TEMPO)‐catalyzed oxidation (Scheme 4). On the other hand, 1‐[(tert‐butoxy)carbonyl]‐2‐{{[(tert‐butyl)dimethylsilyl]oxy}methyl}‐3‐mesitylaziridine 14 was prepared from 9 by a sequence involving selective protection of the primary alcohol (as a silyl ether), activation of the secondary alcohol as a mesylate, and base‐induced (NaH) cyclization (Scheme 5). The reductive cleavage of the aziridine ring (H₂, Pd/C), followed by alcohol deprotection (Bu₄NF/THF) and oxidation (pyridinium dichromate (PDC)/DMF or (TEMPO)/NaClO) provided, in high yield and enantiomeric purity, N‐[(tert‐butoxy)carbonyl]‐β‐mesitylalanine 2 . Alternatively, the regioselective ring opening of the aziridine ring of 14 with lithium dimethylcuprate, followed by silyl‐ether cleavage and oxidation lead to N‐[(tert‐butoxy)carbonyl]‐β‐mesityl‐β‐methylalanine 3 . A conformational study of the methyl esters of the N‐Boc‐protected amino acids 1 and 3 carried out by variable‐temperature ¹H‐NMR and semi‐empirical (AM1) calculations shows the strong rotational restriction imposed by the mesityl group.     

Ion–molecule reactions of methoxymethyl cations with some organic substrates studied by ion cyclotron resonance spectrometry

The reactions of methoxymethyl cations generated from dimethyl ether with propene, butene-2, vinyl methyl ether, acetaldehyde and acetone have been studied. The collision complexes, generated with the olefines, may eliminate an olefine, a methanol and a formaldehyde molecule as shown by double resonance experiments. From deuterium labelling it is found, that in the cases of propene and butene-2 the elimination of an olefine is accompanied by an extensive H/D interchange in the collision complexes, which has been shown not to occur in the long-lived reactant methoxymethyl cations if the internal energy of the methoxymethyl cations is less than 2.3 eV. The H/D interchange in these collision complexes is reduced in the elimination of methanol and is almost completely suppressed in the elimination of formaldehyde. In reactions with vinyl methyl ether, however, the eliminations of methanol and formaldehyde from the corresponding collision complexes appear to proceed with extensive H/D interchange. These observations point to acyclic collision complexes rather than 4-membered ring complexes. The collision complexes generated with acetaldehyde and acetone decompose by elimination of formaldehyde only. Deuterium labelling has shown that the formaldehyde molecule contains the original methylene group of the reactant methoxymethyl cations. In addition, ¹⁸O labelling in acetone has shown that the original oxygen atom of the methoxymethyl cations is retained completely in the eliminated formaldehyde. These observations exclude any formation of 4-membered ring collision complexes and can only be explained by acyclic complexes. Possible mechanisms of all reactions mentioned are discussed in the light of these results.     

A DFT study of the mechanism of polymerization of epsilon-caprolactone initiated by organolanthanide borohydride complexes

The mechanisms of polymerization of epsilon-caprolactone (CL) initiated by either the rare-earth hydride [Cp2Eu(H)] or the borohydrides [Cp2Eu(BH4)] or [(N2NN')Eu(BH4)] were studied at the DFT level (Cp=eta5-C5H5; N2NN'=(2-C5H4N)CH2(CH2CH2NMe)2). For all compounds the reaction proceeds in two steps: a hydride transfer from the rare earth initiator to the carbonyl carbon of the lactone, followed by ring-opening of the monomer. In the last step a difference is observed between the hydride and borohydride complexes, because for the latter the ring-opening is induced by an additional B-H bond cleavage leading to a terminal--CH2OBH2 group. This corresponds to the reduction by BH3 of the carbonyl group of CL. Upon reaction of [Cp2Eu(H)] with CL, the alkoxy-aldehyde complex produced, [Cp2Eu(O(CH2)5C(O)H)], is the first-formed initiating species. In contrast, for the reaction of CL with the borohydride complexes [(Lx)Eu(BH4)] (Lx=Cp2 or N2NN'), an aliphatic alkoxide with a terminal--CH2OBH2 group, [(Lx)Eu(O(CH2)6OBH2)] is formed and subsequently propagates the polymerization. The present DFT investigations are fully compatible with previously reported mechanistic studies of experimental systems.     

Stereochemistry of some reactions between alkyl S-methyl methylphosphonothioates and chiral alkoxides

With R-(+) ethyl (or methyl) S-methyl methylphosphonothioate and (+)-pinacolyl alkoxide competitive and highly stereoselective displacements of O-alkyl and S-methyl occur, both reactions being with inversion of configuration. With the enantiomeric S-(-) ethyl (and methyl) S-methyl methylphosphonothioates and (+)-pinacolyl alkoxide the reactions, although still competitive, are no longer stereoselective. In contrast similar reactions with the sodium salt of (-)-menthol, (which might be considered to be the mirror image of (+)-pinacolyl alkoxide) occur highly stereoselectively with the S-(-) but not with R-(+) enantiomers. The displacement of O-alkyl from alkyl S-methyl methyl-phosphonothioates by ethoxide, pinacolyl alkoxide and menthyl alkoxide is not observed when methoxide is the nucleophile; in this case only displacement of S-alkyl group occurs.     

General and efficient method for the synthesis of alkoxymethylsilanes

Although alkoxymethylsilanes serve as useful building blocks, various efforts to synthesize them by substitution reaction with an alkoxide ion at the carbon adjacent to the silicon failed. To solve this synthetic problem a new route which is very simple to perform was developed. Bromination of (methoxymethyl)trimethylsilane by using N‐bromosuccinimide/2,2′‐azobisisobutyronitrile (NBS/AIBN) was followed by a substitution by alcohols in the presence of triethylamine to give the corresponding [alkoxy‐­(methoxy)methyl]trimethylsilanes. These acetals can be used directly for the next reduction with di‐isobutylaluminium hydride (DIBAL‐H) or Et₃SiH/BF₃·OEt₂ to give alkoxymethylsilanes in good to moderate yields. The success of the substitution reaction with the alcohols suggests that the mechanism is of somewhat S_N1 by nature and formation of the cationic intermediate seems to release the steric hindrance around the carbon, allowing the attack of alcohols. Copyright © 1999 John Wiley & Sons, Ltd.     

Aziridinyl ketones XVII. The hydrogenation of 2-phenyl-3-aroylaziridines to aziridinylcarbinols

The sodium borohydride reduction of both cis and trans-1-cyclohexyl-2-phenyl-3-aroylaziridines provides in each case the corresponding carbinol as a mixture of the two possible diastereoisomeric racemates, whereas reduction of these ketones with lithium aluminum hydride or with lithium diisopropylamide provides only the racemate resulting from attack on the carbonyl group from the least hindered side. Catalytic hydrogenation of a cis aziridinyl ketone cleaved the aziridine ring and provided an amino carbinol.     

Vibrational Spectroscopic Study on Ion Solvation and Association of Lithium Perchlorate in 4-Methoxymethyl-ethylene Carbonate

Solvation interaction and ion association in solutions of lithium perchlorate/4-methoxymethyl-ethylene carbonate （MEC） have been studied by using Infrared and Raman spectra as a function of concentration of lithium perchlorate. The splitting of ring deformation band and ring ether asymmetric stretching band, and the change of carbonyl stretching band suggest that there should be a strong interaction between Li^＋ and the solvent molecules, and the site of solvation should be the oxygen atom of carbonyl group. The apparent solvation number of Li^＋ was calculated by using band fitting technique. The solvation number was decreased from 3.3 to 1.1 with increasing the concentration of LiClO4/MEC solutions. On the other hand, the band fitting for the ClO4^- band revealed the presence of contact ion pair, and free ClO4^- anion in the concentrated solutions.     

Ring contraction and other reactions of azidobenzene-and azidotoluene-tricarbonylmanganese cations

Azidobenzene- and azidotoluene-tricarbonylmanganese cations are reduced to the corresponding aniline and toluiden complexes not ony by lithium aluminium hydride but also by azide ion in polar solvents. Direct substitution of the azido group by methoxy occurs with sodium methoxide in methanol. Above 130°C nitrogen is lost from the azido compounds and ring contraction occurs yielding the corresponding (cyanocyclopentadienyl)tricarbonylmanganese complexes.     

Synthesis of α-Functionalized Allenes

It is known, since the work of Landor et al, that α-allenic alcohols can be specifically obtained by treating the monotetrahydropyranyl ether of a butyn-1,4-diol with lithium aluminium hydride (1). In this reaction, which can be also realized with another leaving group (halogen, ammonium) (2), the allenic linkage is formed by an S_N ^2′ process where the nucleophilic hydride is transferred from the initially formed alcoholate (scheme 1).     

氢化铝锂新合成方法的研究

在略高溫度下,通过氯化锂和金属钠在氫气氛中的反应,得到了氢化锂和氯化钠的混合物。用通常的Schlesinger法将得到的混合物用于合成氢化铝锂。反应的副产物是氯化锂和氯化钠的混合物,可用不同方法将其分离,所得氯化锂用于再循环。