Lithiation directed by amino alkoxides. Application to the synthesis of new disubstituted dihydrodipyridopyrazines

The synthesis of new 4,6-disubstituted dihydrodipyridopyrazines starting from corresponding carboxaldehydes via lithiation directed by alpha-amino alkoxides is described. The N,N,N'-trimethylethylenediamine was used as amine component for in situ formation of the alpha-amino alkoxides. After optimization, this reaction allowed easy access to new interesting starting materials for further applications by palladium-catalyzed reactions.     

二苯并噻吩类硫化物在非负载型NiMoW催化剂上加氢脱硫反应机理

研究了二苯并噻吩(DBT)、4-甲基二苯并噻吩(4-MDBT)和4,6-二甲基二苯并噻吩(4,6-DMDBT)在非负载型NiMoW催化剂上的加氢脱硫反应产物分布及反应机理,给出了它们在非负载型催化剂上加氢脱硫反应网络.研究发现,由于甲基的空间位阻效应,二苯并噻吩类化合物加氢脱硫转化率顺序为4,6-DMDBT≈4-MDBT＜DBT,而非负载型NiMoW催化剂具有很高的芳环加氢活性,有利于烷基取代的芳环加氢,减弱空间位阻效应,使烷基取代的二苯并噻吩类化合物得到有效脱除.DBT的脱硫产物会被进一步加氢,其产物分布与联苯加氢产物相似.4-MDBT有两种预加氢脱硫反应路径,甲基取代的苯环由于甲基的供电子效应会被优先加氢.非负载型催化剂存在的L酸中心会使部分4-MDBT和4,6-DMDBT通过脱甲基反应生成DBT再进行脱硫反应.     

CpRu(CO)2(BF4) and [CpFe(CO)2(THF)]+ on mesoporous silica as adsorbents for the removal of dibenzothiophenes from hydrocarbon solutions

The complexes, CpRu(CO)2(BF4) and [CpFe(CO)2(eta2-2-methylpropene)][BF4], react with dibenzothiophene (DBT) and 4,6-dimethyldibenzothiophene (4,6-Me2DBT) to give [CpRu(CO)2(DBT)][BF4] and [CpFe(CO)2(4,6-Me2DBT)][BF4], whose structures were established by X-ray diffraction studies. The same types of products are obtained when dibenzothiophenes react with CpRu(CO)2(BF4) and [CpFe(CO)2(THF)][BF4] that are adsorbed on the mesoporous silica SBA-15. DRIFT and XPS studies indicate that CpRu(CO)2(BF4) and [CpRu(CO)2(DBT)][BF4] are adsorbed on the SBA-15 by hydrogen-bonding of the BF4- anions to surface Si-O-H groups. CpRu(CO)2(BF4)/SBA-15 removes 99% of the DBT in a 45% toluene/55% hexanes simulated petroleum feedstock. This solid phase extractant is less successful for sterically-hindered 4,6-Me2DBT, as only 72% of it is removed. The results show that CpRu(CO)2(BF4) can be immobilized by adsorption on mesoporous silica and that it reacts with dibenzothiophenes in the adsorbed form, CpRu(CO)2(BF4)/SBA-15, in much the same way that it reacts in solution.     

Synthesis and reactions of lithio derivatives of 1-allenylbenzotriazole

1-(2-Chloropropen-2-yl)benzotriazole ( 6 ) is converted by heating with sodium hydroxide or by lithium diisopropylamide at -78° into 1-allenylbenzotriazole ( 1 ) in high yield. Allene 1 undergoes in situ lithiation at the α-carbon and subsequent reactions with iodomethane or carbonyl compounds to produce 1-(1-substituted allenyl)benzotriazoles 9 and 2a-c , respectively. Three equivalents of lithium diisopropylamide dilithiated 1 and afforded symmetrical 1-(1,3-disubstituted allenyl)benzotriazoles 11a,b upon reaction with ketones. The unsymmetrical 1-(1,3-disubstituted allenyl)benzotriazole 5 was obtained via a stepwise addition of benzophenone to the lithio derivative of 1 followed by a second lithiation and quenching with acetone. Monosubstituted allenes 2a and 8 were cyclized into the benzotriazolyl substituted dihydrofuran 3 and dihydropyrrole 4 respectively.     

Synthetic,structural and binding studies of the 4,6-dimethyldibenzothiophene complex [(eta(5)-C(5)Me(5))Ru(CO)(2)(eta(1)(S)-4,6-Me(2)DBT)]BF(4): toward an understanding of deep hydrodesulfurization

The synthesis of the first completely characterized transition-metal complex containing a sulfur-bound 4,6-dimethyldibenzothiophene (4,6-Me(2)DBT) ligand, [CpRu(CO)(2)(eta(1)(S)-4,6-Me(2)DBT)]BF(4) (1) (Cp = eta(5)-C(5)Me(5)), is reported. X-ray studies of 1 and its 4-methyldibenzothiophene and dibenzothiophene analogues, [CpRu(CO)(2)(eta(1)(S)-4-MeDBT)]BF(4) (2) and [CpRu(CO)(2)(eta(1)(S)-DBT)]BF(4) (3), show that the Ru-S bond distances increase in the order, 3 < 2 < 1. Equilibrium studies on the series of [CpRu(CO)(2)(eta(1)(S)-DBTh)](+) compounds, where DBTh = DBT, 4-MeDBT, 4,6-Me(2)DBT, and 2,8-Me(2)DBT, show that the relative binding strengths of the dibenzothiophene ligands increase in the order 4,6-Me(2)DBT (1) < 4-MeDBT (20.2(1)) < DBT (62.7(6)) < 2,8-Me(2)DBT (223(3)). These results are the first to quantify the steric effect of 4- and 6-methyl groups on the sulfur-coordinating ability of dibenzothiophenes to transition-metal centers. They are also consistent with the proposal that 4- and 6-methyl groups reduce the coordination of dibenzothiophenes to active metal sites on hydrodesulfurization catalysts, which could account for the slow rate of 4-MeDBT and 4,6-Me(2)DBT hydrodesulfurization in petroleum feedstocks.     

2,8(4,6)-二取代半瞬烯及其BCO衍生物的Cope重排

运用从头计算量化方法计算了一系列Cope重排的2,8(或4,6)-二取代半瞬烯(1和2), 以及2,8:4,6-四取代半瞬烯(3和4)的过渡态结构、活化能、能量差和核独立化学位移. 在2,8(或4,6)-二取代半瞬烯体系里, π电子基均使得Cope重排向2进行, 这与Hoffmann早年对此的定性预测相反. 它们的过渡态是离域双同芳香性的. 本文重点讨论了π电子基与BCO共同取代的2,8:4,6-四取代半瞬烯体系, 由于BCO的稳定效应和π电子基共轭效应, π电子基均使得结构4具有优先稳定性, 其Cope重排活化能也大大降低甚至消除. 随着卤素主量子数的变化, 它们的取代半瞬烯Cope重排相关参数也有相应的规律性变化.     

Regioselective ortho lithiation of 3-aryl and 3-styryl furans

[structure: see text]. An unusual regioselectivity pattern for the ortho lithiation of 3-aryl and 3-styryl furans has been uncovered wherein lithiation occurs preferentially at the sterically encumbered 2-position. The results are attributed, at least in part, to stabilization of the intermediate furyl anion by through-space donation of pi-electron density from the substituent appended at the 3-position to the lithium cation. This ortho lithiation reaction may be applied as a useful synthetic tool for accessing 2,3-disubstituted furans.     

Synthesis of multisulfur-containing substituted dibenzothiophenes

New substituted dibenzothiophenes have been prepared and characterized. Selective functionalizations utilized substitutions of lithiodibenzothiophenes available from established methodology. New dibenzothiophenes prepared include 2-(bromomethyl)dibenzothiophene (5) , 2-(thiomethyl)dibenzothiophene (6) , 2-S-phenylthiomethyldibenzothiophene (24) , 2-S-(2′-dibenzothiophenylmethyl)thiomethyldibenzothiophene (25) , 2-S-methyldibenzothiophene (30) , 2-S-(p-bromophenyl)dibenzothiophene (31) , and 2-S-benzyldibenzothiophene (33). Dibenzothiophenes prepared from 4-lithiodibenzothiophene include 4-(bromomethyl)dibenzothiophene (13) , 4-(thiomethyl)dibenzothiophene (14) , 4-S-(4′-dibenzothiophenylmethyl)thiomethyldibenzothiophene (26) , 4-S-(p-tolyl)dibenzothiophene (34) , 4-S-methyldibenzothiophene (35) , 4-S-benzyldibenzothiophene (37) , and 4-S-(p-bromophenyl)dibenzothiophene (36). Similarly new 2,8-disubstituted dibenzothiophenes prepared include 2,8-bis(thiomethyl)dibenzothiophene (19) , 2,8-bis(S-benzyl)dibenzothiophene (27) , 2,8-bis(S-p-tolyl)dibenzothiophene (28) and 2,8-bis(S-methyl)dibenzothiophene (29). The cmr chemical shift data for these dibenzothiophenes are also included.     

Synthesis and thermal rearrangement of 2-(2-chloroethoxy)-4,6-disubstituted <Emphasis Type="Italic">sym</Emphasis>-triazines

On thermolysis of 4-methoxy- and 4-alkylamino-2-(2-chloroethoxy)-6-morpholino(piperidino)-sym-triazines, the corresponding oxazolo- or imidazo-sym-triazinones are formed by elimination of methyl chloride or hydrogen chloride, and 4,6-disubstituted 3-(2-chloroethyl)-sym-triazin-2-ones are formed from 4,6-dimorpholino(dipiperidino) derivatives.     

Synthesis of [2.2]paracyclophane-pseudo-ortho-dicarboxylic acid

An efficient three-step synthesis of [2.2]paracyclophane-pseudo-ortho-dicarboxylic acid by dibromination of [2.2]paracyclophane, thermal isomerization of the resultingpseudopara-dibromide topseudo-ortho-isomer, followed by lithiation/carboxylation was developed. The possibility of preparation of two other novelpseudo-ortho-disubstituted carbonyl derivatives, 4-carboxy-12-(1-oxopenthyl)-[2.2]paracyclophane and di(4-carboxy[2.2]paracyclophanyl-12)ketone, was demonstrated when an excess of lithiation reagent (4 or 10 eq.) was used in the final step. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2001–2004, November, 1997.     

Regioselective ortho lithiation of halopyridines

Regioselective ortho lithiation of 2-, 3-, and 4-halopyridines is achieved with lithium diisopropylamide (?78°, tetrahydrofuran) to afford, upon quenching with electrophilic reagents, 2,3- and 3,4-disubstituted pyridines in good to excellent yield.     

Preparation of 1,3-disubstituted isoquinoline derivatives from N-boc-3-substituted-1,2-dihydroisoquinolines

3-Substituted N-Boc-1,2-dihydroisoquinolines 2 can be functionalized at the 1-position via lithiation and subsequent electrophilic trapping. The resulting products 3 can be deprotected and oxidized to afford the corresponding 1,3-disubstituted isoquinolines 5 . Deprotection of dihydroisoquinoline 3k followed by sodium borohydride reduction affords the cis-1,3-disubstituted tetrahydroisoquinoline 11 . The 1,3-disubstituted N-Boc-1,2-dihydroisoquinoline 3g is efficiently alkylated at the 1-position to give 1,1,3-trisubstituted analogs 12 .     

<Emphasis Type="Italic">sym</Emphasis>-triazines. 8. Synthesis and some reactions of 4,6-disubstituted 2-(1H-pyrrolyl)-1,3,5-triazines

We have studied the reaction of 2,5-dimethoxytetrahydrofuran with 4,6-disubstituted 2-amino-1,3,5-triazines with the aim of obtaining novel coupled polyheterocyclic systems with potential bioactivity. Reaction conditions were optimized. A series of novel 4,6-disubstituted 2-(1H-1-pyrrolyl)-sym-triazines was obtained. It was found that the product yields depended on the nature of the substituent in the 4 and 6 positions of the triazine ring and on the reaction conditions. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 440–451, March, 2008.     

Synthesis and conformational study of 1,2,3,4,5,6,7,8-octahydro-1,6-naphthiridines

A new class of endocyclic enamines, 1,6-disubstituted 1,2,3,4,5,6,7,8-octahydro-1,6-naphthiridines, was synthesized from 4-piperidone imines by successive subjecting the latter to lithiation with lithium diethylamide, to alkylation with 1-bromo-3-chloropropane, and to intramolecular cyclization. All stages were carried out as a unique process without isolation of the intermediate compounds. A thorough optimization of the process conditions, workup, and product storage was carried out. The conformational study of 1,6-disubstituted 1,2,3,4,5,6,7,8-octahydro-1,6-naphthiridines was performed.     

Synthesis of phosphonium 1,3,2,5-dioxaborataphosphorinanes

Conclusions Reaction of ammonium 2,2,5-triphenyl-4,6-disubstituted 1,3,2,5-dioxaborataphosphorinane oxides or the sodium salt of methoxy(diphenyl)borataoxybenzyl(hydroxybenzyl)phenylphosphine oxide with methyltriphenylphosphonium iodide yields methyltriphenylphosphonium 2,2,5-triphenyl-4,6-disubstituted 1,3,2,5-dioxaborataphosphorinane oxides.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2607–2609, November, 1988.     

Synthesis and structure of new 1,3,5-triazine-pyrazole derivatives

We have studied the reaction of methylenedicarbonyl compounds with 4,6-disubstituted 2-hydrazinyl-1,3,5-triazine in order to obtain novel coupled biheterocyclic aromatic systems with potential bioactivity. Reaction conditions were studied and optimized, and a series of 4,6-disubstituted 2-(1H-pyrazolyl)-1,3,5-triazines were obtained with good yield.     

New, simple and versatile synthesis of 4,6-disubstituted pyridazin-3(2H)-ones

A simple, two-step synthesis of 4,6-disubstituted pyridazin-3(2H)-ones starting from 2-diethoxyphosphoryl-4-oxoalkanoates and hydrazines is described. The intermediate 4-diethoxyphosphoryl-4,5-dihydropyridazin-3(2H)-ones obtained in this way are used in a Horner-Wadsworth-Emmons olefination of aldehydes to give a variety of disubstituted pyridazin-3(2H)-ones.     

High-yield syntheses of 2,3-disubstituted furans and thiophenes

The course of lithiation of furan- and thiophene-2-carboxylic acids is critically dependent on the identity of the lithium base allowing high-yielding syntheses of 2,3- and 2,5-disubstituted thiophenes: the proposed use of a trimethylsilyl blocking group to control metallation in the furan acid provides a useful route to 2,3-disubstituted furans.     

Synthesis of substituted indoles via a highly selective 7-lithiation of 4,7-dibromoindoles and the effect of indole-nitrogen on regioselectivity

We have developed an efficient synthetic pathway to rapidly access 4-bromoindoles, 4-substituted indoles, 4-bromo-7-substituted indoles, and 4,7-disubstituted indoles using a highly selective lithiation at the 7-position of 1-alkyl-4,7-dibromoindoles when treated with t-BuLi in ether. Based upon the selectivity obtained with 5,7-dibromoindoles in our previous study and with 4,7-dibromoindoles in the current study, we conclude that the alkylated indole nitrogen plays an important role in controlling selectivity.     

Strategy for the enantioselective synthesis of trans-2,4-disubstituted piperidines: application to the CCR3 antagonist IS811

A strategy for the enantioselective synthesis of trans-2,4-disubstituted piperidines is proposed and applied to the preparation of IS811, a potent CCR3 antagonist. The C2 stereocenter is derived from commercial (R)-epichlorohydrin, while the C4 stereocenter is installed via diastereoselective hydrogenation of an alpha,beta-unsaturated lactone intermediate. Inversion of the original stereocenter via an efficient intramolecular S(N)2 amination affords the piperidine core of IS811. An improved protocol for the lithiation of ethyl propiolate is reported.