有机锂化合物催化合成均三嗪

The imine salt was formed initially by the addition of an organolithium compound to the aromatic nitricle. This type of reaction usually leads to cyclic products, such as triazines. We discussed the mechanism of organolithium compounds catalyzed trimerization of nitriles and study the catalystic charateristics. Using this new method, the yield of triazines was improved.     

Orthoacylimines: a new class of chiral auxiliaries for nucleophilic addition of organolithium reagents to imines

A new class of orthoacylimine-derived chiral auxiliaries has been synthesized and tested in the nucleophilic addition of organolithium reagents to imines. The precursors can be prepared by an aza-Wittig reaction between the corresponding orthoacyl azide and a variety of aldehydes in the presence of trialkylphosphines. The nucleophilic addition of organolithium reagents led to the addition products in good yields and with good to excellent diastereoselectivities (from 85:15 to 99:1). The chiral, nonracemic secondary amines could be readily obtained under mild hydrolytic condition. Furthermore, the chiral auxiliary can be recovered in quantitative yield and reconverted to the starting orthoacyl azide precursor. This method was applied to the synthesis of (S)-t-leucine.     

Synthesis of difunctional initiator via the Peterson reaction

This paper presents an improved method to prepare divinylphenyl compounds which are a useful class of precursors in preparing difunctional organolithium initiators. In the past, most of the divinylphenyl compounds reported were prepared from reactions of phosphorus-substituted carbanions with aldehydes and ketones (Wittig reaction). The phosphorus by-product of the Witting reaction was difficult to be completely removed from the final products. In this paper, we apply the Peterson reaction (silane substituted carbanions) to the synthesis of divinylphenyl compounds. This reaction appears to be operationally simpler and cleaner than the Wittig reaction since the by-product of silane is easily removed by silica Gel chromatography. The syn-elimination of β-hydroxylsilane is complete and clean under NaH condition with no detectable isomers in the final product. The reaction of the divinylphenyl compound with S-butylithium forms a difunctional organolithium initiator which is used to prepare triblock copolymers with the desirable microstructure in each block.     

Metal Free Dötz-Type Aminobenzannulation Reaction via 1,1-Dipoles Cross-Coupling

Aryl amines are of constant interest in organic synthesis owing to their ubiquity in natural products, pharmaceuticals, and organic materials. However, C−H amination or pre-functionalization frequently results in uncontrollable site selectivity, over activation and the generation of inseparable mixtures of regio-isomers. Here we present a novel metal free Dötz-type aminobenzannulation reaction that circumvents the selectivity issues inherent in aromatic chemistry, as well as the use of stoichiometric unstable organolithium reagents and toxic chromium complexes. The concept of utilizing readily available isocyanides and Morita–Baylis–Hillman (MBH) carbonates to achieve 1,1-dipoles cross-coupling to construct ketenimine is the key to success, which has been experimentally and computationally verified. The tandem 6π-electrocyclization/aromatization process offers a versatile method for synthesizing functionalized anilines, fused aryl amines and fused heteroaryl amines.     

A method for the synthesis of 2-aminobenzoxazoles

A synthesis of 2-aminobenzoxazoles from the parent C–H compound is described. The procedure involves deprotonation at the 2-position of the benzoxazole and quenching the intermediate organolithium species with a halogen electrophile. The 2-halobenzoxazole is then treated in the same pot with an amine nucleophile to afford the desired product. The substrate scope and selectivity of the reaction are presented. The method is operationally simple and provides access to a variety of amine products bearing additional nucleophilic heteroatoms.     

Coupling reactions of zirconocene complexes and heterosubstituted alkenes

This tutorial review surveys recent advances in the field of zirconium promoted coupling reactions of unsaturated molecules (and/or organolithium compounds) and heterosubstituted alkenes. This reaction has recently emerged as a powerful tool in organic chemistry to access a variety of synthetically useful building blocks not easily available by other methods. In particular, three different reaction pathways are discussed: i) the reaction involving alkyne-zirconocene and aryne-zirconocene complexes which allows access to dienyl and aryl zirconocene complexes; ii) the reaction of alkene-zirconocene complexes and enol ethers which has shown to be highly dependent on the structure of the enol ether used, allowing the synthesis of simple vinyl zirconocenes or multicomponent coupling products, and; iii) the reaction involving imine-zirconocene complexes which supposes a new entry to allylic amines.     

A convenient synthesis of unsymmetrical secondary amines. Insitu formation of unstable formaldehyde imines.

The monoalkylation of aliphatic and aromatic primary amines can be accomplished by the reaction of organolithium or Grignard reagents with N-(cyanomethyl) or N-(aminomethyl) derivatives.     

N-tert-Butyldimethylsilyl Imines as Intermediates for the Synthesis of Amines and Ketones

Grignard reagents add to benzonitrile at low temperature catalyzed by CuBr and TBSCl affording N-TBS ketimines, which were investigated as intermediaries for the synthesis of primary amines and ketones. N-silylimines were easily obtained by an organolithium addition to benzonitrile followed by a reaction with TBSCl in CH₂Cl₂. In situ reduction of these imines by BH₃ and 1,3,2-oxazaborolidines 1 or 2 as chiral templates afforded the corresponding amines with modest to good enantiomeric excess.     

Formation of an organolithium derivative of 2-(α-aminobenzyl)-1-methylbenzimidazole in the reaction of 2-benzoyl-1-methylbenzimidazole oxime with lithium naphthalenide

It was shown with the reaction of 2-benzoyl-1-methylbenzimidazole oxime with lithium naphthalenide that ketoximes can be used to obtain difficultly accessible organolithium derivatives of primary nonaromatic amines.     

Transition metal-catalyzed α-alkylation of amines by C(sp3)‒H bond activation

α-Substituted amines are present in a myriad of biologically active natural and synthetic products. With the objective of developing atom-economical reactions, a panel of synthetic methods allowing the direct functionalization of C(sp³)?H bonds adjacent to the nitrogen atom have been developed. The field remains dominated by the sequence α-lithiation/addition on an electrophile even if the use of reactive organolithium reagents is not compatible with all functional groups. Over the past ten years, an increasing interest has been devoted to metal-catalyzed CH-activation, some studies being specially dedicated to C(sp³)?H bond activation. Notably, this approach has been envisioned to perform direct α-functionalization of amines. The aim of this article is to give an overview of synthetic methods for transition metal-catalyzed α-alkylation of amines by C(sp³)?H bond activation.     

Synthesis of [11C]/(13C)amines via carbonylation followed by reductive amination

Twelve 11C-labelled amines were prepared via 11C-carbonylation followed by reductive amination. The 11C-carbonylation was performed in the presence of tetrakis(triphenylphosphine)palladium using aryl iodides or aryl triflates, [11C]carbon monoxide and phenyl-/methylboronic acid. The [11C]ketones formed in this step were then transformed directly into amines by reductive amination using different amines in the presence of TiCl4 and NaBH3CN. The 11C-labelled amines were obtained with decay-corrected radiochemical yields in the range 2-78%. The radiochemical purity of the isolated products exceeded 98%. (13C)Benzhydryl-phenyl-amine was synthesised and analysed by NMR spectroscopy for confirmation of the labelling position. Specific radioactivity was determined for the same compound. The reference compounds were prepared by reductive amination of ketones using conventional reaction conditions and three of the compounds were novel. The presented approach is a new method for the synthesis of [11C]/(13C)amines.     

Palladium‐Catalysed Direct Cross‐Coupling of Organolithium Reagents with Aryl and Vinyl Triflates

A palladium‐catalysed cross‐coupling of organolithium reagents with aryl and vinyl triflates is presented. The reaction proceeds at 50 or 70 °C with short reaction times, and the corresponding products are obtained with moderate to high yields, with a variety of alkyl and (hetero)aryl lithium reagents.     

6,6-二烷基富烯与有机锂的反应-双(取代环戊二烯基)钛, 锆衍生物的合成

本文研究了6,6-二烷基富烯与有机锂反应的立体效应。6,6二甲基、甲基乙基、二乙基、甲基苯基富烯与乙基锂易发生环外双键的还原反应。6-甲基-6-正丙基、异丁基富烯同正丁基锂则发生环外双键的加成反应。6,6-多亚甲基富烯[C5H4=C(CH2)n]与有机锂的反应随n值不同而异, n=4的富烯同正丙基锂和正丁基锂进行α-攫氢和环外双键还原的竞争反应; n=5,6 的富烯与乙基锂, 异丙基锂和异丁基锂发生还原反应, 与正丙基俚和正丁基锂则进行加成与还原的竞争反应,n=4 的富烯与芳基锂发生α-攫氢反应, 随n值增大则倾向于加成反应。通过上述反应所得的锂化合物合成了一系列新的仲、叔烷基和烯基取代的环戊二烯基钛、锆衍生物。应用^1HNMR证明了化合物的结构。     

A convenient rhodium-catalyzed intermolecular hydroamination procedure for terminal alkynes

The first rhodium-catalyzed intermolecular hydroamination of alkynes is presented. Terminal alkynes react efficiently with anilines in the presence of cationic rhodium(I) catalysts under very mild reaction conditions (e.g., base and acid free at room temperature) to yield up to 99% of the corresponding imines. An easy one-pot protocol for the synthesis of secondary amines was developed by combining this alkyne amination reaction with in situ addition of organolithium reagents.     

Intramolecular carbolithiation promoted by a DTBB-catalysed chlorine-lithium exchange

The reaction of 6-chlorohex-1-ene 1 with lithium powder and a catalytic amount of 4,4′-di-tert-butylbiphenyl (DTBB, 5% molar) in THF at −78°C gives the corresponding organolithium intermediate 2, which by reaction with different electrophiles affords, after hydrolysis with diluted hydrochloric acid, the expected products 3. The same reaction performed at −30°C gives cyclopentyl derivatives 5, probably by cyclisation of the open-chain intermediate 2 to give the cyclic organolithium compound 4. When the double bond in the starting material contains an alkyl substituent, for instance compounds 6 and 9, the corresponding cyclisation is inhibited, so the corresponding acyclic products 8 and 11 are respectively, obtained. However, when the substituent at the same positions is a phenyl group, like in starting materials 12 and 15, the cyclised products 14 and 17 were respectively, isolated. In the case of the secondary starting chlorinated material 18, the reaction can be directed to both, the acyclic products 20 or the cyclic ones 22, working at −78 or −30°C, respectively, as it happens in the case of the unsubstituted chlorinated material 1. For the tertiary chloro derivative 23, only the cyclic compound 27 could be isolated at −30°C due to the great instability of the corresponding tertiary organolithium intermediate 24, which undergoes a proton abstraction even at −78°C. From allyl 2-chlorophenyl ether 28 or N,N-diallyl-2-chloroaniline 32, only the corresponding cyclic compounds 31 and 33, respectively, are isolated either at −78 or at −30°C. In all cases a carbanionic cyclisation, better than a radical one, is postulated to occur as mechanistic pathway.     

Asymmetric control in Diels–Alder cycloadditions of chiral 9-aminoanthracenes by relay of stereochemical information

Two approaches to the synthesis of chiral 9-amino anthracenes are described. The first, by nucleophilic addition of organolithium reagents to imines promoted by BF₃·OEt₂, unexpectedly provided stable aminoboranes as products. The second approach, using palladium catalysed cross coupling, was more successful for primary amines, and the key 9-(α-methylbenzylamino)anthracene subjected to cycloadditions with N-methyl maleimide and maleic anhydride. Excellent reactivity was achieved with good levels of diastereoselectivity, through a favourable combination of electrostatic and hydrogen bonding effects. Trial studies of the retro Diels–Alder reaction of these cycloadducts were also performed.     

Tertiary alcohols by tandem β-carbolithiation and N→C aryl migration in enol carbamates

Enol carbamates (O-vinylcarbamates) derived from aromatic or α,β-unsaturated compounds and bearing an N-aryl substituent undergo carbolithiation by nucleophilic attack at the (nominally nucleophilic) β position of the enol double bond. The resulting carbamate-stabilized allylic, propargylic, or benzylic organolithium rearranges with N→C migration of the N-aryl substituent, creating a quaternary carbon α to O. The products may be readily hydrolyzed to yield multiply branched tertiary alcohols in a one-pot tandem reaction, effectively a polarity-reversed nucleophilic β-alkylation-electrophilic α-arylation of an enol equivalent.     

Aryl triflates and [11C]/(13C)carbon monoxide in the synthesis of 11C-/13C-amides

Palladium(0)-mediated carbonylation reactions using aryl triflates, amines, and a low concentration of [(11)C]carbon monoxide were used in the syntheses of 13 (11)C-labeled amides. Lithium bromide was used as an additive to facilitate the reaction. The (11)C-labeled products were obtained with decay-corrected radiochemical yields in the range of 2-63%. The radiochemical purity of the final products exceeded 98%. As an example, a reaction starting with 1.79 GBq [(11)C]carbon monoxide gave 0.38 GBq of LC-purified N-isopropyl-4-nitro-[(11)C]benzamide within 27 min from the start of the carbonylation reaction (54% decay-corrected radiochemical yield). The specific radioactivity of this compound was 191 GBq/micromol, 35 min after the end of a 10 microAh bombardment. N-Benzylisoquinoline-1-((13)C)carboxamide was prepared and analyzed by NMR for confirmation of the labeling position. The triflates 16, 20, 21, and 22 were synthesized from the corresponding alcohols and trifluoromethanesulfonic anhydride. The reference compounds 30a and 30b were prepared from the corresponding carboxylic acids and benzylamine. The other nine reference compounds 32a to 32i were synthesized from the respective acid chlorides and amines. The presented report shows that the sometimes more easily obtainable aryl triflates can be a useful alternative to the commonly used aryl halides in palladium(0)-mediated synthesis of (11)C/(13)C-amides.     

Asymmetric allylic alkylation of acyclic allylic ethers with organolithium reagents

A highly efficient, regio- and enantioselective Cu(I) /phosphoramidite-catalyzed asymmetric allylic alkylation of allyl ethers with organolithium reagents is reported. The use of organolithium reagents is essential for this catalytic C?C bond formation due to their compatibility with different Lewis acids. The versatility of allylic ethers under the copper-catalyzed reaction conditions with organolithium reagents is demonstrated in the shortest synthesis of (S)-Arundic acid.