New synthesis of 3-fluoropyridine derivatives

The reaction of 2,2-bis(dimethylamino)-3,3-difluoro-1-methylcyclobutane-carbonitrile with alkyl lithiums leads to the formation of 6-alkyl-2-(dimethylamino)-3-fluoro-5-methylpyridines in moderate to good yields.     

Preparation and oxidative coupling of bis[o-(hydrosilyl)phenyl]cuprates and bis[o-(fluorosilyl)phenyl]cuprates

Bis[o-(hydrosilyl)phenyl]cuprates and bis[o-(fluorosilyl)phenyl]cuprates were prepared by reacting [o-(hydrosilyl)phenyl]lithiums and [o-(fluorosilyl)phenyl]lithiums, respectively, with copper salts, such as CuCN and Cu(OPiv)₂. The phenylcuprates underwent oxidative coupling to afford 2,2′-bis(hydrosilyl)biphenyls and 2,2′-bis(fluorosilyl)biphenyls.     

An ab Initio Study of Some Phenyl- and (Halophenyl)alkali Compounds

Ab initio calculations are presented for alkali metal derivatives of fluoro- and chlorobenzenes for comparison with previously determined experimental substitutent effects. Calculated substituent effects for one alkali metal are linearly related to those of another. (Difluorophenyl)lithiums show additivity of substituent effects calculated from (monofluorophenyl)lithiums but dichloro derivatives do not, an effect attributed to the higher polarizability of chlorine. meta- and para-fluoro substituents show excellent agreement with experiment. ortho-fluoro and chlorine substituents do not. These differences are rationalized.     

The 13C NMR conformational analysis of 9,10-dihydroanthracene monoanions

The ¹³C NMR chemical shifts and coupling constants for the parent and $\text{t}$-butyl 9,10-dihydroanthraceneyl lithiums indicate sp² hybridization and flattened geometries.     

Ag4V2O6F2 (SVOF): a high silver density phase and potential new cathode material for implantable cardioverter defibrillators

The electrochemical reactivity of the cathode material Ag 4V 2O 6F 2 (SVOF) versus lithium, with a particular emphasis on the lithium insertion mechanism, was studied by means of the complementary techniques in situ X-ray diffraction, electron paramagnetic resonance, and high-resolution transmisssion electron microscopy. This study confirms the initial reports of a high capacity for SVOF of 148 mAh/g above 3 V and that the reduction of silver above 3 V (vs Li (+)/Li (0)) leads to a loss of SVOF crystallinity until it becomes completely amorphous between the third and fourth lithiums inserted. Next, vanadium is reduced between 2.5 and 1.5 V (vs Li (+)/Li (0)) for the fifth and sixth lithiums inserted. In addition, the polarization within the cathode is significantly lower for the vanadium reduction than for the silver reduction. The silver metal morphologies consisted of nanoparticles ( approximately 5 nm diameter) and dendrites and were both seen in samples of lithiated SVOF.     

Facile Synthesis of Oxamides by Efficient Trapping of Carbamoyl Lithiums with Isocyanates

Unsymmetrical oxamides are conveniently synthesized in good yields by a new trapping reaction of unstable carbamoyl lithiums with isocyanates.     

Reaction of beta-ethoxyvinyl lithiums generated from phenyltellanyl- and ethyltellanylacetaldehyde diethyl acetals with aldehydes and ketones and successive hydrations

Reactions of alpha-tellanyl-beta-ethoxyvinyl lithiums of aldehydes and ketones proceeded in good to high yields and the successive treatment with acids gave the alpha-tellanyl alpha,beta-unsaturated aldehydes. alpha-Tellanyl alpha,beta-unsaturated aldehydes easily transformed to more useful compounds.     

Stereo- and regioselective formation of silyl enol ethers via oxidation of vinyl anions

Oxidation of E- and Z-vinyl lithiums with silyl peroxides 5 affords silyl enol ethers 3 in good to excellent yield with retention of configuration. This methodology represents a useful new procedure for the stereo- and regioselective synthesis of ketone enolates.     

A convenient synthesis of quinolines by reactions of o-isocyano-β-methoxystyrenes with nucleophiles

2,4-Disubstituted quinolines have been synthesized by reactions of o-isocyano-β-methoxystyrenes, which can be easily prepared from commercially available o-aminophenyl ketones in three steps, with alkyl(or aryl)lithiums in generally good yields. Subsequently, o-isocyano-β-methoxystyrenes have also proved to react efficiently with lithium dialkylamides to afford the corresponding 4-substituted N,N-dialkylquinolin-2-amines in satisfactory yields.     

A Novel Synthesis of α-Tellanyl α,β-Unsaturated Aldehydes Using α-Tellanyl β-Alkoxyalkenyl Lithiums

Abstract

β-Ethoxy-α-phenyltellanylvinyl lithiums were successfully generated in situ from phenyltellanylacetaldehyde diethyl acetal with lithium 2,2,6,6-tetrame-thylpiperidide (LTMP) and underwent methylation or nucleophilic addition with aldehydes and ketones. The successive dehydration of the allylic alcohols with trimethylsilyl trifluoromethanesulfonate (TMSOTf) gave α-phenyltellanyl α,β-unsaturated aldehydes, which transformed to some useful compounds.     

Ionization energies of hypervalent Li2F,Li2Cl and Na2Cl molecules obtained by surface ionization electron impact neutralization mass spectrometry

Ionization energies of hypervalent Li(2)F, Li(2)Cl and Na(2)Cl molecules detected by surface ionization electron impact neutralization mass spectrometry are reported. The ionization energies were 3.78 +/- 0.2 eV for Li(2)F, 4.93 +/- 0.2 eV for Li(2)Cl, and 4.21 +/- 0.2 eV for Na(2)Cl. The ionization energies (IE) agree with theoretical ionization energies calculated by ab initio methods, supporting the theoretical prediction that Li(2)F has a hyperlithiated configuration in which the odd electron delocalizes over the two lithiums and with photoionization measurement. The first ionization energy of Na(2)Cl was experimentally confirmed earlier and for Li(2)Cl as well.8 We have developed and used this new approach for the problem--in the present work ions were first formed by surface ionization, followed by electron attachment (neutralization).     

Synthesis of 2-Mercapto- and 2-Hydroxy-Substituted Diphenylphosphines for use as Dianionic Bidentate Ligands and Polydentate Ligand Precursors

Abstract

As part of our studies into the synthesis of polydentate phosphine-containing ligands, we have investigated the preparation of the phosphines (4; X[dbnd]O) and (4; X[dbnd]S). These are of interest both as potential dianionic bidentate ligands and as useful precursors of more complex polydentate ligand systems. A synthesis of the thiol system (4; X[dbnd]S) from 1,2-dinitrobenzene has been previously reported [1], but the observation [2], that 2-bromoaryl esters of phosphoric acid rearrange to give esters of arylphosphonic acids in the presence of alkyl lithiums, led us to consider whether a similar type of rearrangement might provide a convenient approach to both (4; X[dbnd]S) and (4; X[dbnd]O).     

Synthesis of 1,3‐Dihydro‐3‐oxo‐2‐benzofuran‐1‐carboxylates via Intramolecular Cyclization of 2‐[2‐(Dimethoxymethyl)phenyl]‐ 2‐hydroxyalkanoates Followed by Oxidation

A novel and efficient method for the preparation of 1,3‐dihydro‐3‐oxo‐2‐benzofuran‐1‐carboxylates 4 under mild conditions has been developed. Thus, the reaction of [2‐(dimethoxymethyl)phenyl]lithiums, generated easily from 1‐bromo‐2‐(dimethoxymethyl)benzenes 1 , with α‐keto esters gives the corresponding 2‐[2‐(dimethoxymethyl)phenyl]‐2‐hydroxyalkanoates 2 . The TsOH‐catalyzed cyclization of these hydroxy acetals is followed by the oxidation of the resulting cyclic acetals 3 with PCC to give the desired products in satisfactory yields. The reaction of [2‐(dimethoxymethyl)‐4,5‐dimethoxyphenyl]lithium with (MeOC?O)₂, followed by treatment with NaBH₄ or organolithiums, affords 2‐[2‐(dimethoxymethyl)‐4,5‐dimethoxyphenyl]‐2‐hydroxyalkanoates 6 , which can similarly be transformed into the corresponding 1,3‐dihydro‐3‐oxo‐2‐benzofuran‐1‐carboxylates 7 in reasonable yields.     

Diastereo- and Enantioselective Synthesis of syn-alpha-Vinylchlorohydrins and cis-Vinylepoxides

A new method to generate chiral syn-vinylchlorohydrins and cis-vinyloxiranes is reported. Reaction of (alpha-haloallyl)lithiums with methoxy-9-BBN or Ipc(2)BOMe followed by treatment with BF(3).OEt(2) leads to (Z)-(gamma-haloallyl)boranes which react with aldehydes to yield cis-vinylepoxides (de >/= 90%) upon oxidative workup. Alternatively, addition of ethanolamine to the allylboration product yields syn-alpha-halohydrins (de >/= 90%) that are also easily cyclized to cis-vinylepoxides. Extension of this protocol using [(Z)-gamma-chloroallyl]BIpc(2) leads to chiral syn-alpha-chlorohydrins and cis-vinylepoxides in high de (>/=90%) and ee (90-99%). Enantioselectivity of reactions of chiral (Z)-(gamma-chloroallyl)boranes with aldehydes are more sensitive to reaction conditions than enantioselectivity of reactions of other alpha-or gamma-substituted allylboranes. The effects of proportion of BF(3).OEt(2) and the relative efficacies of LiNR(2) bases on diastereo- and enantioselectivity of the chloroallylation are reported.     

Asymmetric syntheses of (R)-4-halo-6,6a,7,8,9,10-hexahydro-5H-pyrazino[1,2-a][1,n]naphthyridines,important 5-HT2C agonist precursors

Asymmetric syntheses of N-protected (R)-4-halo-6,6a,7,8,9,10-hexahydro-5H-pyrazino[1,2-a][1,n]naphthyridines, advanced intermediates for the synthesis of highly potent and selective 5-HT_2C agonists, are described. The key transformation involves ring opening of N-protected bicyclic sulfamidate (R)-hexahydro-3H-pyrazino[1,2-c][1,2,3]oxathiazine 1,1-dioxide with (4-halo-2-fluoropyridin-3-yl)lithiums or (3-bromo-5-fluoropyridin-4-yl)lithium. In situ hydrolyses of the resultant sulfamic acids and subsequent intramolecular nucleophilic aromatic substitutions (S_NAr) produce the enantiopure tricycles. The two step procedure represents new methodology for the stereoselective syntheses of tetrahydronaphthyridines.     

Synthesis and characterization of low-coordinate divalent aryl transition-metal halide analogues of grignard reagents: precursors for reduction to metal-metal-bonded complexes

The synthesis and characterization of the series of divalent first-row aryl transition-metal(II) halide compounds [Cr(mu-Cl)Ar']2 (1) and (Li(OEt2)Ar'MI2]2 (M=Mn (2), Fe (3), and Co (4); Ar'=C6H3-2,6-(C6H3-2,6-iPr2)2) are described. 1-4 were prepared by the addition of one equiv of Ar'Li to the respective transition-metal dihalides. They were characterized by UV-vis spectroscopy, magnetic measurements, and by X-ray crystallography. In dimeric 1, each chromium center has quasi-four-coordinate, square-planar geometry, in which the metal is terminally bound to a terphenyl ligand through the ipso carbon of the central ring and to two bridging chloride ligands. There is a further interaction between chromium and an ipso carbon from one of the flanking -C6H3-2,6iPr2 rings. In contrast, for the iodo derivatives 2-4, LiI is not eliminated upon addition of LiAr' to MI2. Instead, the diethyl ether solvated adducts, [Li(OEt2)Ar'MI2]2 (M=Mn (2), Fe (3), or Co (4)) were isolated. These possess a distorted cubane Li2M2I4 core, in which the lithiums are bound to an ether and the transition metals are bound to a terphenyl group. Magnetic measurements between 2 and 300 K reveal the expected weak antiferromagnetic exchange coupling in each of the complexes.     

Generation of carbanions through stibine-metal and bismuthine-metal exchange reactions and its applications to precision synthesis of ω-end-functionalized polymers

Generation of carbanions from organostibines and organobismuthines through heteroatom-metal exchange reactions was examined from synthetic and mechanistic viewpoints. The exchange reaction proceeded spontaneously upon treatment with various organometallic reagents, such as alkyl lithiums, tetraalkyl zincates, and alkyl magnesium halides to afford the corresponding carbanions quantitatively. Due to the high reactivity of these heteroatom compounds, the exchange reactions took place exclusively even in the presence of various polar functional groups, which potentially react with organometallic species. The advantage of this method was exemplified by the end-group transformation of living polymers that bear these heteroatom species at the ω-polymer end, prepared by using organostibine and bismuthine-mediated living radical polymerizations. Various polymers that bear polar functional groups and acidic hydrogen-for example, poly(methyl methacrylate), poly(butyl acrylate), poly(N-isopropyl acrylamide), and poly(2-hydroxyethyl methacrylate)-could be used in the exchange reactions, and subsequent trapping with electrophiles afforded the corresponding polymers with controlled molecular weights, molecular weight distributions, and end-group functionalities. Competition experiments showed that organostibines and organobismuthines were among the most reactive heteroatom compounds towards organometallic reagents and that their high reactivity was responsible for the high chemoselectivity in the exchange reaction.     

Synthesis and electro-spectroelectrochemistry of ferrocenyl naphthaquinones

A practical approach to ferrocenyl naphthaquinone derivatives involving thermal rearrangement of variously substituted 4-aryl-4-hydroxycyclobutenones was described. The reaction of 3-ferrocenyl-4-isopropoxy-3-cyclobutene-1,2-dione with different aryl lithiums gave the corresponding 4-aryl-4-hydroxycyclobutenones, which were heated in p-xylene at reflux open to the air to yield ferrocenyl naphthaquinones. The redox chemistry of the ferrocenyl naphthaquinones was studied by electrochemical and in situ spectroelectrochemical techniques in CH₂Cl₂ solution and in CH₃CN solution with water, weak and strong acidic additives. Ferrocenyl naphthaquinones displayed reversible two reduction processes involving semiquinone radical anion (Fc-snq⁻), dianion (Fc-nq²⁻) species and a one-electron oxidation process based on the ferrocenium/ferrocene (Fc⁺-nq/Fc-nq) couple in CH₂Cl₂. The redox reaction mechanism of the ferrocenyl naphthaquinones in the presence of the additives proceeded via hydrogen bonding or proton-coupled electron transfer. Effects of the substituents on the reduction potentials and intramolecular charge-transfer bands of ferrocenyl naphthaquinones were also discussed.     

Synthesis and structure of two lithium terphenyls and a “halide rich” terphenyl lithium species

The syntheses and characterization of two new terphenyl iodides 2,6-(2,3,4,5,6-Me₅C₆)₂C₆H₃I (Ar^Pmp₂I) and (Ar^Dbp₂I) are described. Treatment of these with LiBuⁿ or LiBu^t afforded their lithium salts [Ar^Pmp₂Li]₂ (2), Ar^Dbp₂{Li(OEt₂)}₂I (3), and [Ar^Dbp₂Li]₂ (4), which were spectroscopically characterized. The X-ray crystal structures of 2 and the “halide-rich” species 3 as well as that of the previously known [2,6-(2,6-Me₂C₆H₃)₂C₆H₃Li]₂ (i.e. [Ar^Xyl₂Li]₂, 1) were determined. The structures of both 1 and 2 are dimers in which the lithiums bridge the ipso carbons of the central aryl ring of each terphenyl ligand and also interact with the ipso carbons of the flanking aryl rings. The structure of 3 is a rare example of a structurally characterized “halide rich” organolithium complex and has a monomeric arrangement in which two ether-coordinated lithiums are bridged by an ipso-carbon of the central aryl ring as well as an iodine atom.     

Asymmetric homologation of boronic esters bearing azido and silyloxy substituents

In the asymmetric homologation of boronic esters with a (dihalomethyl)lithium, substituents that can bind metal cations tend to interfere. Accordingly, we undertook the introduction of weakly basic oxygen and nitrogen substituents into boronic esters in order to maximize the efficiency of multistep syntheses utilizing this chemistry. Silyloxy boronic esters cannot be made efficiently by direct substitution, but a (hydroxymethyl)boronic ester has been silylated in the usual manner. Conversion of alpha-halo boronic esters to alpha-azido boronic esters has been carried out with sodium azide and a tetrabutylammonium salt as phase-transfer catalyst in a two-phase system with water and either nitromethane or ethyl acetate. These are safer solvents than the previously used dichloromethane, which can form an explosive byproduct with azide ion. Boronic esters containing silyloxy or alkoxy and azido substituents have been shown to react efficiently with (dihalomethyl)lithiums, resulting in efficient asymmetric insertion of the halomethyl group into the carbon-boron bond.