Allylic-type diindium reagents. Reactivity toward electrophiles and cascade coupling reactions with imines

The allylic-type diindium reagents A and B were prepared from 3-bromo-1-iodopropene (1a) and 4-bromo-2-iodobut-2-ene (1b), respectively, and their reactions with electrophiles were investigated. The diindium reagents A and B were initially reacted with imines and the resulting vinylindium compounds were then treated with organic halides in the presence of Pd(PPh(3))(4) to give linear N-aryl and N-tosyl homoallylic amines. Diindium A is stable in a small amount of water in solvent, whereas B is easily protonated to give a crotylindium reagent. The reaction of B with benzaldehyde gives mainly the 1,3- and 1,5-diols via a spontaneous coupling with two molecules of the aldehyde, in contrast to A, which reacts with one molecule of carbonyl compounds to give the vinylindium compounds.     

Preparation of 4'-substituted thymidines by substitution of the thymidine 5'-esters

tert-Butyl thymidylate 3 was prepared from thymidine 1 in six steps and 67% overall yield. When the lithium trianion of 3 (prepared by treatment of 3 with excess LDA and then excess tert-butyllithum) is reacted with electrophiles, trapping occurs stereoselectively from either the alpha- or beta-face depending on the electrophile (Scheme 1). Deuterioacetic acid in deuteriomethanol affords mainly the alpha-deuterated product (4a/4b = 2.4:1) while all other electrophiles, e.g., phenylselenenyl chloride, allyl bromide, and N-fluorobenzenesulfonimide (NFSI), give predominately (or completely) the products of attack from the beta-face (5bcd/4bcd = 3.7:1 to 100:0). The structures of the products were determined by coupling constant analysis of both the initial compounds and the diols 6bcd prepared by ester reduction and by formation of the acetonides 7bc. The methyl ester of the 3'-epimer of thymidylic acid 9 was also prepared from thymidine 1 in nine steps and 74% overall yield. When the lithium trianion of 9 (prepared by treatment of 9 with excess LDA and then excess tert-butyllithum) is reacted with electrophiles, trapping also occurs stereoselectively with attack on either the alpha- or beta-face depending on the electrophile (Scheme 2). Again, deuterioacetic acid in deuteriomethanol affords mainly the beta-deuterated product (11a/10a = 1.6:1) while all other electrophiles, e.g., phenylselenenyl chloride, methyl iodide, allyl bromide, and NFSI, gave predominately (or completely) the product of attack from the alpha-face (8.7:1 to 100: 0). Again, the structures of the products were determined by coupling constant analysis of both the initial compounds, and the diols 12b-e were prepared by reduction of the ester and by formation of the acetonides 13bcd. A rationale has been developed using molecular mechanics calculations to explain the diastereoselectivity that involves staggered axial attack on the sp(2) carbon opposite to the pseudoaxial alkoxy group in the most stable half-chair conformation of the enolates, as shown in Schemes 3-5.     

Highly enantioenriched homoenolate reagents by asymmetric gamma-deprotonation of achiral 1-silyl-substituted 1-alkenyl carbamates

1-trimethylsilyl-1-alkenyl carbamates 1 are deprotonated by n-butyllithium/(-)-sparteine (2) with a high degree of enantiotopic differentiation in the gamma-position to form the enantiomerically enriched allyllithium derivatives 3. Trapping these with several electrophiles proceeds stereospecifically in an anti-S(E)' or syn-S(E)' substitution to form products 4 or ent-4, respectively. Compounds 3a (R = Me) and 3b (R = Ph) exhibit toward carbonyl electrophiles opposite senses of almost complete stereospecificity, thus for 3b.2 the involvement of a eta(3)-complex is suggested. [reaction: see text]     

四氟乙烯齐聚体的反应 四氟乙烯四、五聚体和芳香胺的反应

前已报道四氟乙烯四聚体(全氟-3,4-甲基己烯-3)(1)、五聚体(全氟-3,4-二甲基-4-乙基己烯-2)(2)和脂肪烷氧以及脂肪胺的亲核反应.本文报道化合物1,2和芳香胺如苯胺、β-萘胺的反应.由于烯烃1、2双键处于分子中间,因而当亲核试剂进攻时,双键容易发生重排,生成的末端基烯烃更具反应性,故导致一取代、二取代、三取代以及环化降解等复杂产物.     

Synthesis and Nucleophilic Addition Reactions of Tricarbonyl[η5‐2‐(phenylthio)hexadienyl]iron Hexafluorophosphate

3‐Phenylthio‐3‐sulfolene ( 1 ) was readily converted to a C‐5 substituted product 2 , which upon thermolysis and complexation with Fe₂(CO)₉ gave (η⁴‐diene)iron complexes 3a and 3b . Treatment of 3a and 3b with aq. HPF₆ and Ac₂O provided the title compound 5 , which reacted regio‐ and stereospecifically with some nucleophiles to give the addition products 3b and 7 .     

Preparation and configurational stability of chiral chloro-[D1]methyllithiums of 98% enantiomeric excess

Enantiopure stannyl-[D1]methanol was converted to chloro-[D1]methylstannane under complete inversion of configuration using Ph3P/N-chlorosuccinimide in THF. It was transmetalated to stereospecifically give chloro-[D1]methyllithium (ee up to 98%). Its microscopic configurational stability was tested by performing tin-lithium exchange in the presence of benzaldehyde as the electrophile under various conditions. The macroscopic configurational stability was addressed by using the same electrophile but by adding it 30 s after the addition of MeLi used for transmetalation. Chloro-[D1]methyllithium is chemically very labile, however completely configurationally stable on both time scales up to the temperature of rapid decomposition (-78 degrees C).     

Reaction of Oxiranes with Ethyl 3-Phenyl-1H-pyrazole-5-carboxylate

Russian Journal of Organic Chemistry - Ethyl 3-phenyl-1H-pyrazole-5-carboxylate reacted with oxiranes to give mixtures of 2-phenyl-6-R-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-4-ones and ethyl...     

2-Lithiated-2-phenyloxetane: a new attractive synthon for the preparation of oxetane derivatives

A valuable and direct method to access 2-substituted-2-phenyloxetanes by electrophilic quenching of the corresponding 2-lithiated derivative has, for the first time, been described. 2-Lithiated-2-phenyloxetane was found to be configurationally unstable. Evidence is presented to show that electron-transfer processes are also operative in the coupling reactions with electrophiles.     

The reactions of tetrafluoroethylene oligomers: V. The reactions of perfluoro-3,4-dimethyl-4-ethylhexene-(2) with thionucleophiles and the chemical transformations of reaction products

The reactions of perfluoro-3,4-dimethyl-4-ethylhexene-(2) (1) with s-nucleophiles such as benzylthiol, allylthiol, phenylthiol and the chemical transformations of these reaction products were reported. 1 reacted with S-nucleophiles to give four types of isomeric products. At ?30～ ?60°C, in ether, kinetically controlled product 2 (a, b, c) were formed. Compound 2 might be converted directly into the thermodynamically stable products 3 (a, b,) in DMF-KF at r.t., At 100°C, 2 was converted to 4 (a, b, c) via intramolecular rearrangement. In KF-DMF at r.t., 4 was isomerized to 5 (a, b, c). 2a also reacted with another mole of thiol to give the corresponding disulfide 6 and hydrogen-containing olefin 7a as well as the disubstituted product 8a in DMF, but only give 3a and 9a in ether-Et₃N. The reaction of 2a with methyl alcohol gave only a small amounts of 3a and 10a. The reaction of 2b with dimethylamine was complex and 3b and 11 were obtained in low yield.     

An efficient synthesis and reactions of novel indolylpyridazinone derivatives with expected biological activity

Reaction of 4-anthracen-9-yl-4-oxo-but-2-enoic acid (1) with indole gave the corresponding butanoic acid 2. Cyclocondensation of 2 with hydrazine hydrate, phenyl hydrazine, semicarbazide and thiosemicarbazide gave the pyridazinone derivatives 3a-d. Reaction of 3a with POCl(3) for 30 min gave the chloropyridazine derivative 4a, which was used to prepare the corresponding carbohydrate hydrazone derivatives 5a-d. Reaction of chloropyridazine 4a with some aliphatic or aromatic amines and anthranilic acid gave 6a-f and 7, respectively. When the reaction of the pyridazinone derivative 3a with POCl(3) was carried out for 3 hr an unexpected product 4b was obtained. The structure of 4b was confirmed by its reaction with hydrazine hydrate to give hydrazopyridazine derivative 9, which reacted in turn with acetyl acetone to afford 10. Reaction of 4b with methylamine gave 11, which reacted with methyl iodide to give the trimethylammonium iodide derivative 12. The pyridazinone 3a also reacted with benzene- or 4-toluenesulphonyl chloride to give 13a-b and with aliphatic or aromatic aldehydes to give 14a-g. All proposed structures were supported by IR, (1)H-NMR, (13)C-NMR, and MS spectroscopic data. Some of the new products showed antibacterial activity.     

Intramolecular and intermolecular diels-alder reactions of acylhydrazones derived from methacrolein and ethylacrolein

The intramolecular Diels-Alder reactions of hydrazones derived from methacrolein or ethylacrolein and terminally unsaturated N-acyl-N-methylhydrazines have been investigated. The hydrazones 7b and 7c derived from N-methyl-N-pent-4-enoylhydrazine 3b were found to undergo intramolecular [4 + 2] cycloaddition above 140 °C and the pyridopyridazines 12 were isolated. The corresponding hydrazones 8b and 8c from N-methyl N-pent-4-ynoylhydrazone 4a reacted similarly and gave as the final products the pyridines 13. The scope of the reaction is limited, as was shown by the failure of several other terminally unsaturated hydrazones of β-unsaturated aldehydes to undergo intramolecular cycloaddition. These hydrazones did, however, undergo intermolecular [4 + 2] cyctoaddition to N-phenylmaleimide. Other hydraiones 15 of methacrolein. including the benzoylhydrazone and the phenylhydrazone, also reacted with N-phenylmaleimide to give the pyridine 14b by way of an isolable dihydropyridine 16.     

Highly diastereoselective formation and reactions of a non-mesomerically stabilized, lithiated alpha-thiocarbanion

A new class of non-mesomerically stabilized, unbranched, configurationally stable lithiated alpha-thiocarbanion has been synthesized and its stereospecific reactions with several electrophiles were investigated.     

Lithiation of 3-(Acylamino)-2-unsubstituted-, 3-(Acylamino)-2-ethyl-, and 3-(Acylamino)-2-propyl-4(3H)-quinazolinones: Convenient Syntheses of More Complex Quinazolinones(1)

3-(Pivaloylamino)- and 3-(acetylamino)-4(3H)-quinazolinones react with alkyllithium reagents to give 1,2-addition products in very good yields. Lithiation takes place with LDA and is regioselective at position 2. The lithium reagents thus obtained react with a variety of electrophiles to give the corresponding substituted derivatives in very good yields. Reactions of the lithium reagents with iodine give oxidatively dimerized cyclic structures. 3-(Pivaloylamino)- and 3-(acetylamino)-2-ethyl-4(3H)-quinazolinones and 3-(pivaloylamino)- and 3-(acetylamino)-2-propyl-4(3H)-quinazolinones are lithiated at the benzylic position with LDA. The lithium reagents so produced also react with a variety of electrophiles to give the corresponding 2-substituted-4(3H)-quinazolinone derivatives in very good yields. However, lithiation of 3-(acylamino)-2-(1-methylethyl)-4(3H)-quinazolinones was unsuccessful, as were lithiations of compounds having a diacetylamino group at position 3. The amide groups have been cleaved in good yield under basic or acidic conditions from some of the products to provide access to the free amino compounds.     

立体控制合成紫杉醇侧链丙酮化合物

利用β-内酰胺的形成引入两个紫杉醇侧链所需要的手性中心, 然后水解开环得紫杉醇侧链物, 形成丙酮化物后再转化为目的物。     

Conformationally constrained 2'-N,4'-C-ethylene-bridged thymidine (aza-ENA-T): synthesis, structure, physical, and biochemical studies of aza-ENA-T-modified oligonucleotides

The 2'-deoxy-2'-N,4'-C-ethylene-bridged thymidine (aza-ENA-T) has been synthesized using a key cyclization step involving 2'-ara-trifluoromethylsufonyl-4'-cyanomethylene 11 to give a pair of 3',5'-bis-OBn-protected diastereomerically pure aza-ENA-Ts (12a and 12b) with the fused piperidino skeleton in the chair conformation, whereas the pentofuranosyl moiety is locked in the North-type conformation (7 degrees < P < 27 degrees, 44 degrees < phi m < 52 degrees). The origin of the chirality of two diastereomerically pure aza-ENA-Ts was found to be due to the endocyclic chiral 2'-nitrogen, which has axial N-H in 12b and equatorial N-H in 12a. The latter is thermodynamically preferred, while the former is kinetically preferred with Ea = 25.4 kcal mol-1, which is thus far the highest observed inversion barrier at pyramidal N-H in the bicyclic amines. The 5'-O-DMTr-aza-ENA-T-3'-phosphoramidite was employed for solid-phase synthesis to give four different singly modified 15-mer antisense oligonucleotides (AONs). Their AON/RNA duplexes showed a Tm increase of 2.5-4 degrees C per modification, depending upon the modification site in the AON. The relative rates of the RNase H1 cleavage of the aza-ENA-T-modified AON/RNA heteroduplexes were very comparable to that of the native counterpart, but the RNA cleavage sites of the modified AON/RNA were found to be very different. The aza-ENA-T modifications also made the AONs very resistant to 3' degradation (stable over 48 h) in the blood serum compared to the unmodified AON (fully degraded in 4 h). Thus, the aza-ENA-T modification in the AON fulfilled three important antisense criteria, compared to the native: (i) improved RNA target affinity, (ii) comparable RNase H cleavage rate, and (iii) higher blood serum stability.     

Double deprotonation of acetylenic oxiranes: synthesis of allenic ketones through Dilithio Ynenolates

[reaction: see text] The double deprotonation of acetylenic oxiranes gives allenic ketones through the 1,2-H or 1,2-Ar shift on the transient oxiranyl dianion intermediates. The resulting dilithium ynenolates give allenic ketones upon hydrolysis or can be quenched with various electrophiles.     

Ate complexes of secondary boronic esters as chiral organometallic-type nucleophiles for asymmetric synthesis

The addition of an aryllithium reagent to a secondary boronic ester leads to an intermediate boron-ate complex that behaves as a chiral nucleophile, reacting with a broad range of electrophiles with inversion of stereochemistry. Depending on the electrophile, the C-B bond can be converted into C-I, C-Br, C-Cl, C-N, C-O, and C-C, all with very high levels of stereocontrol. This discovery now adds a new, readily available, configurationally stable, chiral organometallic-type reagent to the arsenal of methods for use in asymmetric organic synthesis.     

The configurational stability of an enantioenriched alpha-thiobenzyllithium derivative and the stereochemical course of its electrophilic substitution reactions; synthesis of enantiomerically pure, tertiary benzylic thiols

The lithium compound (S)-7, formed by deprotonation of the (S)-S-1-phenylethyl thiocarbamate (S)-10, is configurationally stable at -70 degrees C. Even at elevated temperatures it racemizes only very slowly. It represents the first essentially enantiopure alpha-thiocarbanion derivative and can be utilized in asymmetric synthesis. Most electrophiles (except proton acids) add to (S)-7 with complete stereoinversion. Cleavage of the substitution products leads to practically enantiopure, tertiary 1-phenylalkanethiols.     

脱卤亚磺化研究——连二亚硫酸钠作为新的脱卤亚磺化试剂

全氟碘代烷与亚硫酸盐发生单电子转移反应生成全氟亚磺酸盐;连二亚硫酸钠水溶液热分解时,ESR表明生成SO_2~-主阴离子自由基,这两者促使我们尝试用连二亚硫酸钠代替亚硫酸盐与全氟卤代烷反应.实验表明对于全氟碘代烷及溴代烷它是一种有效的     

Selective mono- and 1,2-difunctionalisation of cyclopentene derivatives via Mg and Cu intermediates

A single Br/Mg exchange of 1,2-dibromocyclopentene with iPrMgCl LiCl provides the corresponding beta-bromocyclopentenylmagnesium reagent, which can then be reacted with various electrophiles (yields: 65-82 %). In the presence of a secondary alkylmagnesium halide and Li2CuCl4 (2 mol %), these 2-bromoalkenylmagnesium compounds undergo bromine substitution and can then further react with electrophiles to give 1,2-difunctionalised cyclopentenes (63-79 %). The mechanism of this process is discussed.