Microsolvation and 13C-Li NMR coupling

The empirical expression (1)J(CLi) = L[n(a + d)](-1) is proposed; it claims a reciprocal dependence of the NMR coupling constant (1)J((13)C, Li) in a C-Li compound on two factors: (i) the number n of lithium nuclei in bonding contact with the observed carbanion center and (ii) the sum (a + d) of the numbers a of anions and d of donor ligands coordinated at the Li nucleus that generates the observed (1)J(CLi) value. The expression was derived from integrations of separate NMR resonances of coordinated and free monodentate donor ligands (t-BuOMe, Et2O, or THF) in toluene solutions of dimeric and monomeric 2-(alpha-aryl-alpha-lithiomethylidene)-1,1,3,3-tetramethylindan at moderately low temperatures. This unusually slow ligand interchange is ascribed to steric congestion in these compounds, which is further characterized by measurements of nuclear Overhauser correlations and by solid-state structures of the dimers bearing only one donor per lithium atom (d = 1). Increasing microsolvation numbers d are also accompanied by typical changes of the NMR chemical shifts delta (positive for the carbanionic (13)C(alpha), negative for C(para) and p-H). The aforementioned empirical expression for (1)J(CLi) appears to be applicable to other cases of solvated monomeric, dimeric, or tetrameric C-Li compounds (alkyl, alkenyl, alkynyl, and aryl) and even to unsolvated (d approximately 0) trimeric, tetrameric, or hexameric organolithium aggregates, indicating that (1)J(CLi) might serve as a tool for assessing unknown microsolvation numbers. The importance of obtaining evidence about the (13)C NMR C-Li multiplet splitting of both the nonfluxional and fluxional aggregates is emphasized.     

Interconversion of contact and separated ion pairs in silyl- and arylthio-substituted alkyllithium reagents

Ether-solvated contact and separated ion pairs (CIP and SIP) for two lithium reagents, tris(trimethylsilyl)methyllithium (1) and bis(3,5-bistrifluoromethylphenylthio)methyllithium (2), have been characterized and observed for the first time under conditions of slow exchange by NMR spectroscopy, and barriers to interconversion have been measured. A Saunders isotope perturbation experiment was used to support identification of the CIP and SIP species for 2.     

Optimization and application of lithium parameters for the reactive force field, ReaxFF

To make a practical molecular dynamics (MD) simulation of the large-scale reactive chemical systems of Li-H and Li-C, we have optimized parameters of the reactive force field (ReaxFF) for these systems. The parameters for this force field were obtained from fitting to the results of density functional theory (DFT) calculations on the structures and energy barriers for a number of Li-H and Li-C molecules, including Li(2), LiH, Li(2)H(2), H(3)C-Li, H(3)C-H(2)C-Li, H(2)C=C-LiH, HCCLi, H(6)C(5)-Li, and Li(2)C(2), and to the equations of state and lattice parameters for condensed phases of Li. The accuracy of the developed ReaxFF was also tested by comparison to the dissociation energies of lithium-benzene sandwich compounds and the collision behavior of lithium atoms with a C(60) buckyball.     

Through-shell alkyllithium additions and borane reductions

The through-shell borane reduction and methyllithium addition to benzaldehyde (1), benzocyclobutenone (2), and benzocyclobutenedione (3) incarcerated inside a hemicarcerand (4) with four tetramethylenedioxy bridges are reported. All guests could be reduced and methylated. Selective monoreduction and monomethylation were observed for 3. In the methyllithium addition to 4[symbol: see text]3, the initially formed lithium alcoholate underwent a Moore rearrangement. The reactivity of the incarcerated guests toward methyllithium increased in the order 1 < 2 < 3 and toward borane in the order 1 < 2 approximately equal 3. Guest reactivity was correlated with the inner-phase location of the reacting carbonyl group in the preferred guest inner-phase orientation. The latter was determined from the X-ray structures of 4[symbol: see text]1, 4[symbol: see text]2, and 4[symbol: see text]3, from molecular mechanical calculations, and from the hemicarcerand-induced upfield shift of the guest proton resonances. In the methyllithium and n-butyllithium addition to 4[symbol: see text]1 and 4[symbol: see text]3 at elevated temperatures, selective cleavage of a host's spanner or tetramethylenedioxy bridge, respectively, was observed. The cleavage of one spanner also took place in the methyllithium addition to the 1-methyl-2-pyrrolidinone hemicarceplex. These scission reactions are initiated by the initially formed lithium alcoholates, which show enhanced basicity and nucleophilicity in the inner phase as compared to the bulk phase. Mechanisms for the host scission reactions are discussed.     

The effect of HMPA on the reactivity of epoxides,aziridines, and alkyl halides with organolithium reagents

A kinetic study of the effect of added HMPA cosolvent on the reaction of 2-lithio-1,3-dithiane (1), bis(phenylthio)methyllithium (2), and bis(3,5-bistrifluoromethylphenylthio)methyllithium (3) with methyloxirane (propylene oxide), N-tosyl-2-methylaziridine, and the several alkyl halides (BuCl, BuBr, BuI, allyl chloride) was carried out. Widely varied rate effects of HMPA on these SN2 substitutions were observed, ranging from >108 rate increases for 1 and butyl chloride to >103 rate decreases for 3 and methyloxirane. These reactions appear to go through separated ion pair intermediates, so a key effect is the ease of ion pair separation of the lithium reagent (3 > 2 > 1). Because 3 is already almost fully separated in THF, HMPA has no effect on the rate of halide substitution, but a large reduction is observed with the epoxide as substrate, a consequence of strong lithium assistance to the ring opening which is suppressed when excess HMPA is present. When ion pair separation is difficult (1), modest rate increases (104) are seen for epoxide opening, but very large increases are seen for aziridine (106) and alkyl halide reactions (108), for which lithium assistance is much less important. Reagent 2 shows more complicated behavior in reaction with the epoxide: 1-2 equiv of HMPA causes a small rate increase, while larger amounts cause a large rate decrease. Here the rate-accelerating effects of SIP formation are more nearly balanced with the rate-retarding effects of suppression of lithium catalysis.     

Furopyridines. XII . Reaction of 3-bromo, 2-phenylthio and 2-phenylthio-3-bromo derivatives of furo[2,3-b]-, furo[3,2-b]-, furo[2,3-c]- and furo[3,2-c]pyridine with several alkyllithiums

This paper describes reactions of 3-bromo- 1a-d , 2-phenylthio- 5a-d and 2-phenylthio-3-bromofuropyridines 6a-d with n-butyl-, t-butyl- and methyllithium and lithioacetonitrile. Lithiation of compounds 1a-d with n-butyl- or methyllithium gave the parent furopyridines 2a-d and o-ethynylpyridinols 3a-d. Reaction of compounds 5a-d with methyllithium afforded o-(phenylthioethynyl)pyridinols 7a-d , which were also yielded by reaction of compounds 6a-d with t-butyl- or methyllithium. The phenylthio group in compounds 7a-d were substituted with t-butyl group by the reaction with excess t-butyllithium. In contrast, 2-phenylthio group in compounds 5a-d and 6a-d was substituted with cyanomethyl group by reaction with lithioacetonitrile to give compounds 11a-d and 10b, c respectively.     

Theoretical study on the lithium-halogen exchange reaction of 1,1-dihaloalkenes with methyllithium and the nucleophilic substitution reaction of the resulting alpha-halo alkenyllithiums

Transition structures for the lithium-bromine exchange reaction of 1,1-dibromoalkenes with methyllithium have been located by both the B3LYP and the MP2 levels of theory with the 6-31+G basis set. The reaction with methyllithium dimer gave similar results with lower activation energies. These calculations predict both the kinetic and the thermodynamic stereoselectivity correctly. That is, the sterically more constrained bromine atom of 1,1-dibromoalkenes was predominantly reacted with alkyllithium (dimer) in the kinetic condition. The intramolecular substitution reaction of 4,4-dibromo-3-methyl-3-pentenol in the presence of methyllithium has been investigated. After deprotonation of the alcohol and the lithium-bromine exchange reaction, the intramolecular substitution reaction occurs to give dihydrofuran in a concerted manner. The intermolecular substitution of alpha-chloro alkenyllithium with methyllithium was also studied for comparison. The formation of the indene derivative from 3-(o-bromophenyl)-1,1-dibromo-1-propene in the presence of methyllithium occurs in a similar manner. The lithium-bromine exchange reaction of bromobenzene with methyllithium occurs in an S(N)2 mechanism and the solvent plays an important role.     

Synthesis and reactions of 3-acetyl-6-methyl-2-(methylthio)pyridine

A reaction of methyllithium with 3-cyano-6-methylpyridine-2(1 H)-thione followed by alkylation of the resulting 3-acetylpyridinethione, or a direct reaction of methyllithium with 3-cyano-6-methyl-2-(methylthio)pyridine, afforded 3-acetyl-6-methyl-2-(methylthio)pyridine. The ketone obtained was examined in bromination reactions under various conditions. Bromi-nation in methanol or chloroform, proceeding through the formation of sulfonium bromides, gave substituted 3-(bromoacetyl)pyridine. A reaction of 3-acetyl-6-methyl-2-(methyl-thio)pyridine with N-bromosuccinimide in CCl4 afforded N-(pyridinesulfenyl)succinimide. The bromo ketone was used for the synthesis of various heterocyclic compounds.     

Amine-chelated aryllithium reagents--structure and dynamics

Multinuclear NMR studies of five-membered-ring amine chelated aryllithium reagents 2-lithio-N,N-dimethylbenzylamine (1), the diethylamine and diisopropylamino analogues (2, 3), and the o-methoxy analogue (4), isotopically enriched in (6)Li and (15)N, have provided a detailed picture of the solution structures in ethereal solvents (usually in mixtures of THF and dimethyl ether, ether, and 2,5-dimethyltetrahydrofuran). The effect of cosolvents such as TMEDA, PMDTA, and HMPA has also been determined. All compounds are strongly chelated, and the chelation is not disrupted by these cosolvents. Reagents 1, 2, and 3 are dimeric in solvents containing a large fraction of THF. Below -120 degrees C, three chelation isomers of the dimers are detectable by NMR spectroscopy: one (A) with both nitrogens coordinated to one lithium of the dimer, and two (B and C) in which each lithium bears one chelating group. Dynamic NMR studies have provided rates and activation energies for the interconversion of the 1-A, 1-B, and 1-C isomers. They interconvert either by simple ring rotation, which interconverts B and C, or by amine decoordination (probably associative, DeltaG(++)(-93) = 8.5 kcal/mol), which can interconvert all of the isomers. The dimers of 1 are thermodynamically more stable than those of model systems such as phenyllithium, o-tolyllithium, or 2-isoamylphenyllithium (5, DeltaDeltaG > or = 3.3 kcal/mol). They are not detectably deaggregated by TMEDA or PMDTA, although HMPA causes partial deaggregation. The dimers are also more robust kinetically with rates of interaggregate exchange, measured by DNMR line shape analysis of the C-Li signal, orders of magnitude smaller than those of models (DeltaDeltaG(++) > or = 4.4 kcal/mol). Similarly, the mixed dimer of 1 and phenyllithium, 13, is kinetically more stable than the phenyllithium dimer by >2.2 kcal/mol. X-ray crystal structures of the TMEDA solvate of 1-A and the THF solvate of 3-B showed them to be dimeric and chelated in the solid state as well. Compound 4, which has a methoxy group ortho to the C-Li group, differs from the others in being only partially dimeric in THF, presumably for steric reasons. This compound is fully deaggregated by 1 equiv of HMPA. Excess HMPA leads to the formation of ca. 15% of a triple ion (4-T) in which both nitrogens appear to be chelated to the central lithium.     

Origin of the detrimental effect of lithium halides on an enantioselective nucleophilic alkylation of aldehydes

The effect of lithium halides on the enantioselectivity of the addition of methyllithium on o-tolualdehyde, in the presence of chiral lithium amides derived from chiral 3-aminopyrrolidines (3APLi), has been investigated. The enantiomeric excess of the resulting 1-o-tolylethanol was found to drop upon addition of significant amounts of LiCl, introduced before the aldehyde. The competitive affinity between the lithium amide, the methyllithium, and the lithium halides in THF was examined by multinuclear NMR spectroscopy and DFT calculations. The results showed that the original mixed aggregate of the chiral lithium amide and methyllithium is rapidly, totally, and irreversibly replaced by a similar 1:1 complex involving one lithium chloride or bromide and one lithium amide. While the MeLi/LiX substitution occurs with some degree of epimerization at the nitrogen for the endo-MeLi:3APLi complex, it is mostly stereospecific for the exo-type arrangements of the aggregate. The thermodynamic preference for mixed aggregates between 3APLi and LiX was confirmed by static DFT calculations: the data show that the LiCl and LiBr aggregates are more stable than their MeLi counterparts by more than 10 kcal.mol(-1) provided THF is explicitly taken into account. These results suggest that a sequestration of the source of chirality by the lithium halides is at the origin of the detrimental effect of these additives on the ee of the model reaction.     

Stereoselective synthesis of vinylsilanes from alkynylsilanes by reductive alkylation via hydroboration,transmetallation and carbodemetallation

Hydroboration of 1-trimethylsilyl-1-alkynes with dicyclohexylborane gives 1-trimethylsilylvinylboranes regio- and stereoselectively whose successive treatment with methyllithium, cuprous iodide and alkyl halides affords (Z)-1,2-dialkylvinylsilanes in high yields. Functionalized 1-trimethylsilyl-1-alkynes give analogous results. Successive treatment of the intermediary 1-trimethylsilylvinylboranes with methyllithium and methyl iodide gives 2-trimethylsilyl-2(Z)-alkenes. Allyl halides give 4-trimethylsilyl-1,4(Z)-alkadienes analogously.     

Pyridyl group assisted deprotonation of a methyl group on silicon: complex induced proximity effect and novel hydroxymethylation

A novel methodology for the deprotonation of a methyl group on silicon has been developed. This newly developed alpha-lithiation protocol is based on the intramolecular pyridyl group coordination to stabilize the alpha-silyl carbanion together with the inherent silicon alpha effect. It was found that the deprotonation (t-BuLi/Et(2)O/-78 degrees C) occurs with 2-pyridyltrimethylsilane but not with other related silanes such as phenyltrimethylsilane, 3-pyridyltrimethylsilane, and 4-pyridyltrimethylsilane. It seems that this deprotonation proceeded through the agency of the complex-induced proximity effect (CIPE) of a 2-pyridyl group on silicon. (1)H NMR analysis of (2-pyridyldimethylsilyl)methyllithium revealed the intramolecular coordination of a pyridyl group to lithium. (2-Pyridyldimethylsilyl)methyllithium was found to react with chlorosilanes, hydrosilanes, chlorostannanes, bromine, iodine, organic bromides, aldehydes, and ketones in good to excellent yields. The resultant adducts were further oxidized with H(2)O(2)/KF to give the corresponding alcohols in excellent yields. Thus, this two-step transformation provides an efficient method for the nucleophilic hydroxymethylation.     

Phosphate-phosphonate conversion: Nucleophilic displacement reactions involving phosphoric esters and methyllithium

The alkylation-metalation reaction of phosphoric esters depends on the way the lithium reagent has been prepared. With salt-containing methyllithium (LiBr or LiI), the alkylation is never complete. On the contrary, with salt-free methyllithium, the alkylation is completed at – 10°C. This reaction is performed independently of the substituents at the phosphoryl group.     

Chemistry of siloles. The reactions of siloles with organolithium reagents

The chemical behaviour of siloles toward various organolithium reagents in THF has been investigated. The reaction of 1-methyl-1-(trimethylsilyl)-, 1-phenyl-1-(trimethylsilyl)- and 1,1-bis(trimethylsilyl)dibenzosilole (I, II and III) with a large excess of an alkyllithium such as methyllithium or butyllithium afforded 1,1-dialkyldibenzosiloles in quantitative yields. Treatment of I with an excess of phenyllithium gave a mixture of 1-methyl-1-phenyl- and 1,1-diphenyldibenzosilole quantitatively, while with an excess of tert-butyllithium, I afforded 1,1-dimethyl- and 1-tert-butyl-1-methyldibenzosilole in low yield. Similar treatment of I and II with 1 equiv. of methyl- or butyl-lithium yielded a mixture of the corresponding mono- and dialkyl-substituted dibenzosiloles. 1-Methyl-3,4-diphenyl-1,2,5-tris(trimehylsilyl)silole reacted with methyllithium in THF to give 1,1-dimethyl-3,4-diphenyl-2,2,5-tris(trimethylsilyl) silole. Similarly, both 2,4-diphenyl-1,1,3,5-tetrakis(trimethylsilyl)silole and 4,5-diphenyl-1,1,2,3-tetrakis(trimethylsilyl)silole with methyllithium afforded two isomers of 1-methyl-2,4-diphenyl-1,2,3,5-tetrakis(trimethylsilyl)-1-silacyclopent-3-ene in a ratio of 3 : 2 in high yields.     

Tetrahedranyllithium: synthesis, characterization, and reactivity

The first representative of stable tetrahedranyl anion, tris(trimethylsilyl)tetrahedranyllithium (3), has been synthesized by the reaction of tetrakis(trimethylsilyl)tetrahedrane (2) with methyllithium in tetrahydrofuran. The structural characterization of the tetrahedranyllithium has been achieved by X-ray crystallography, showing that the structure of 3.(TMEDA)1.5 represents a stretched tetrahedron. The endocyclic C(Li)-C(SiMe3) bond lengths range from 1.5408(15) to 1.5441(15) A (av 1.5425(15) A), and are longer than the endocyclic C(SiMe3)-C(SiMe3) bond lengths, which range from 1.4961(15) to 1.5009(15) A (av 1.4986(15) A). Methyl- and hydrogen-substituted tetrahedranes have also been prepared by the reaction of 3 with dimethyl sulfate and cyclopentadiene, respectively.     

New and efficient synthesis of 5′-amino-5′-(S)-methyl-2′,5′-dideoxynucleosides

A short, efficient synthesis of 5′-amino-5′-(S)-methyl-2′,5′-dideoxynucleosides 1 has been developed through the diastereoselective addition of methylmagnesium bromide or methyllithium to an intermediate tert-butylsulfinimide.     

CO2 on a Tightrope: Stabilization,Room‐Temperature Decarboxylation,and Sodium‐Induced Carboxylate Migration

A sterically shielded 3‐substituted zwitterionic N,N‐dimethylisotryptammonium carboxylate has been synthesized by consecutive chemoselective double alkylation of indole. The carboxylate undergoes a quantitative and unusually facile decarboxylation in dimethyl sulfoxide (DMSO) or dimethyl formamide (DMF) at room temperature. The breaking of a nearly equidistant hydrogen bond by solvent molecules initiates heterolytic C? C cleavage. The decarboxylation rate decreases with increasing CO₂ partial pressure, proving the competitiveness of protonation and re‐carboxylation of the carbanionic intermediate. Corresponding spiro compounds containing silylene and stannylene moieties show high thermal stability. Addition of an excess of methyllithium to the sodium salt triggers a reaction sequence comprising a deprotonation, carboxylate transfer, and nucleophilic trapping of the rearranged carboxylate by another equivalent of methyllithium. Hydrolytic work‐up of the geminal diolate leads to an acetyl product. The role of the sodium counterion and the mechanism of the rearrangement have been unraveled by deuteration experiments.     

(MeLi)4(dem)1.5]infinity] and [(thf)3Li3M3[(NtBu)3S--how to reduce aggregation of parent methyllithium

Organolithium compounds play the leading role among the organometallic reagents in synthesis and in industrial processes. Up to date industrial application of methyllithium is limited because it is only soluble in diethyl ether, which amplifies various hazards in large-scale processes. However, most reactions require polar solvents like diethyl ether or THF to disassemble parent organolithium oligomers. If classical bidentate donor solvents like TMEDA (TMEDA= N,N,N',N'tetramethyl-1,2-ethanediamine) or DME (DME=1,2-dimethoxyethane) are added to methyllithium, tetrameric units are linked to form polymeric arrays that suffer from reduced reactivity and/or solubility. In this paper we present two different approaches to tune methyllithium aggregation. In [[(MeLi)4(dem)1,5)infinity] (1; DEM = EtOCH2OEt, diethoxymethane) a polymeric architecture is maintained that forms microporous soluble aggregates as a result of the rigid bite of the methylene-bridged bidentate donor base DEM. Wide channels of 720 pm in diameter in the structure maintain full solubility as they are coated with lipophilic ethyl groups and filled with solvent. In compound 1 the long-range Li3CH3...Li interactions found in solid [[(MeLi)4]infinity] are maintained. A different approach was successful in the disassembly of the tetrameric architecture of [((MeLi)4]infinity]. In the reaction of dilithium triazasulfite both the parent [(MeLi)4] tetramer and the [[Li2[(NtBu)3S]]2] dimer disintegrate and recombine to give an MeLi monomer stabilized in the adduct complex [(thf)3Li3Me-[(NtBu)3S]] (2). One side of the Li3 triangle, often found in organolithium chemistry, is shielded by the tripodal triazasulfite, while the other face is mu3-capped by the methanide anion. This Li3 structural motif is also present in organolithium tetramers and hexamers. All single-crystal structures have been confirmed through solid-state NMR experiments to be the same as in the bulk powder material.     

Insertion of CO2, ketones, and aldehydes into the C-Li bond of 1,3,5-triaza-7-phosphaadamantan-6-yllithium

The synthesis and structures of a series of new water-soluble phosphine ligands based on 1,3,5-triaza-7-phosphaadamantane (PTA) are described. Insertion of aldehydes or ketones into the C-Li bond of 1,3,5-triaza-7-phosphaadamantan-6-yllithium (PTA-Li) resulted in the formation of a series of slightly water-soluble beta-phosphino alcohols (PTA-CRR'OH, R = C6H5, C(6)H(4)OCH(3), ferrocenyl; R' = H, C(6)H(5), C(6)H(4)OCH(3)) derived from the heterocyclic phosphine PTA. Insertion of CO(2) yielded the highly water-soluble carboxylate PTA-CO(2)Li, S(2)5 degrees approximately 800 g/L. The compounds have been fully characterized in the solid state by X-ray crystallography and in solution by multinuclear NMR spectroscopy. The addition of PTA-Li to symmetric ketones results in a racemic mixture of PTA-CR(2)OH ligands with a single resonance in the (31)P{(1)H} NMR spectrum between -95 and -97 ppm. The addition of PTA-Li to aldehydes results in a mixture of diasteromeric compounds, PTA-CHROH, with two (31)P{(1)H} NMR resonances between -100 and -106 ppm. Three (eta(6)-arene)RuCl(2)(PTA-CRR'OH) complexes of these ligands were synthesized and characterized, with the ligands binding in a kappa1 coordination mode. All the ligands and ruthenium complexes are slightly soluble in water with S25 degrees = 3.9-11.1 g/L for the PTA-CRR'OH ligands and S(25) degrees = 3.3-14.1 g/L for the (eta(6)-arene)RuCl(2)(PTA-CRR'OH) complexes.     

17β-羟基-17α-甲基-雌甾-4-烯-3-酮的合成

分别以酸性脱羧物和碱性脱羧物为起始原料,经官能团的保护制备甲基诺龙。考察了酸性对保护3位羰基的影响,确定了无水乙醇/石油醚是目标分子重结晶的最佳溶剂体系。考擦了格氏试剂(CH3MgI)和甲基锂(CH3Li)对17位羰基的亲核加成反应,发现用甲基锂试剂反应收率可达86.7% 。