The synthesis of quinolines from N-alkylformanilides and electron-rich alkenes

N-Methylformanilide in phosphoryl chloride reacts with ketones, aldehyde and ketone enamines or enol acetates to give N-methylquinolinium salts in good yields.     

Benzotriazole-assisted synthesis of enamines

A new, facile preparation of enamines was achieved a two-step sequence: (i) the ready formation of an N-(-aminoalkyl)benzotriazole derivative from equimolar amounts of benzotriazole, an aldehyde, and a secondary amine, (ii) the elimination of benzotriazole from the derivative by sodium hydride in tetrahydrofuran (THF). The method provides enamines in good overall yields based on the quantity of amine used.     

Synthesis of γ-amino alcohols from aldehydes, enamines, and trichlorosilane using Lewis base catalysts

The reaction of aldehydes, enamines, and trichlorosilane in the presence of a Lewis base catalyst, particularly N-methylpyrrolidinone and DMF, affords γ-amino alcohols with a high diastereoselectivity. The method consists of C-C bond formation between an aldehyde and an enamine, and a subsequent intramolecular reduction of the resulting iminium ion intermediate. In most cases, one diastereomer is exclusively generated, and we propose a transition state model for the intramolecular reduction of the iminium ion intermediate. Enamines, prepared beforehand from the corresponding ketone and amine, can be used in the reaction without purification. Furthermore, enantioselective catalysis using a chiral Lewis base catalyst is possible, although the enantioselectivity is modest. The current tandem method offers the first, concise synthetic method of γ-amino alcohols from aldehydes and enamines.     

The conversion of 2,x-disubstituted cyclohexanones to their less stable isomers—the stereochemical implications of enamine hydrolysis

When 2-methyl-x-alkylcyclohexanones (x≠2) are converted to their enamines and the latter are hydrolysed under kinetic conditions the process leads to a substantial increase in the proportion of the less stable ketone, over that present at equilibrium. Pyrrolidine appears to be the most effective amine in this process. Hydrolysis of the enamine isomer having a tetrasubstituted double bond proceeds with little or no stereoelectronic control during the protonation step. Low temperature thermal isomerization of simple enamines is shown not to exist; when equilibration does occur, it is due to traces of acid impurity.     

几个烯胺的邻硝基苯甲酰化和在酸水解中发生的重排

为了了解芳酰基化的效率和双酰基衍生物的形成, 对几个典型醛和酮的吗啉烯胺进行了邻硝基苯甲酰化的探索。丁醛和异丁醛吗啉烯胺的酰化正常, 水解分别生成55%的2-(邻硝基苯甲酰基)丁醛(2)和40%的2-(邻硝基苯甲酰基)异丁醛(3)。3-戊酮和1, 3-二甲氧基丙酮的吗啉烯胺在酰化和水解时分别生成37%和14.8%相应的β-二酮的烯醇邻硝基苯甲酸酯(4)和(5)。4和5的酸水解发生意外的1, 5-和1,3-酰基转位, 分别生成3, 5-二甲基-2, 6-双(邻硝基苯基)吡喃-4-酮(6)和2-甲氧基-2-甲氧乙酰基-1, 3-双(邻硝基苯基)-1, 3-丙二酮(7)。环戊酮和环已酮吗啉烯胺的酰化分别产生9%和34%的双酰基烯胺(9a)和(9b),逐次酸水解得到2-(邻硝基苯甲酰基)环戊酮(11a)和-环已酮(11b)。在总酰化产物的直接水解中, 11a的产率可以达到81%, 而11b只有35%。对双酰化进行了一些讨论。     

The resonance energy of amides and their radical cations

Structural Chemistry - The resonance energy of an amide can be calculated through comparison with a model amine and a model ketone (or aldehyde) with subtraction of the “residual”...     

Enamines—XXXIX : Enamines from cyclopropylketones

The enamines from cyclopropyl-methyl-, -ethyl- and -cyclopentylketone have been prepared by reaction of the ketone with a secondary amine and TiCl₄. Their vinylcyclopropane structure has been demonstrated by NMR. The reaction of dicyclopropylketone, cyclopropylphenylketone or cyclopropyl-α-thienylketone with secondary amines and TiCl₄ afforded homoallylic rearrangement products, namely 1-cyclopropyl-, 1-phenyl- and 1-(α-thienyl)-1,4-diamino-1-butene, respectively.     

Effect of additives on the proline-catalyzed ketone–aldehyde aldol reactions

The effect of bases, acids, and water as additives in proline-catalyzed ketone–aldehyde aldol reactions has been studied. While the reaction appears to be relatively tolerant to small amounts of tertiary amine bases or weak acids, it stops completely with strong acids. The use of water as an additive had a highly beneficial effect on reactions that were conducted with a stoichiometric ratio of ketone to aldehyde, especially with cyclic ketones. This allows the efficient use of more precious ketones such as 4-thianone as donors in the direct enantioselective aldol and facilitates purification.     

A novel catalytic process for trifluoromethylation of bromoaromatic compounds

The palladium-catalyzed trifluoromethylation of aryl bromides has been achieved in micellar media. The micellar conditions result in enhanced yields and are applicable to bromoaromatics with ketone, aldehyde, hydroxyl and amine functionalities.     

三甲基硅化腈在有机合成中的应用

三甲基硅化腈是一种常用的有机合成试剂. 对近年来三甲基硅化腈在有机合成中的应用进行了简要的总结和概述, 重点介绍了三甲基硅化腈作为强的亲核试剂广泛用于环氮和环氧化合物的开环反应、亚胺和醛酮类化合物的加成、胺与醛或酮参与的多组分反应、偶联反应以及对炔和具有较高活性的碳碳双键的氰化加成等反应.     

Enamines a halogene allylique—II: Action des organometalliques

In the condensation of organometallic reagents (Mg, Li, Cu) with halogenated enamines, there is a competition between substitution of the allylic halogen and rearrangement with loss of halogen, to give bicyclic compounds3 (6-pyrrolidino 6-alkyl bicyclo [3.1.0] hexanes). The reaction can be oriented toward the formation of the α-substituted ketone or of the bicyclic amine by an appropriate choice of the organometallic derivative, of the solvent and of the amino group of the enamine. The structure of the bicyclic amine3 could be the result of a selective attack on the least hindered side of the postulated intermediate immonium.     

UPS on Weinreb resin: a facile solid-phase route to aldehyde and ketone derivatives of "unnatural" amino acids and peptides

The solid-phase synthesis of "unnatural" amino aldehydes, amino ketones, peptide aldehydes, and peptide ketones was accomplished from commercially available resin in a series of room temperature reactions. The initial step involved addition of an "unnatural" side chain to the N-terminus of a benzophenone imine-activated Weinreb resin-bound amino acid or peptide derivative. The alkylated imine was hydrolyzed, and the amine was converted to the Boc-, Cbz-, or naphthoyl derivative. The resin-bound substrate was then cleaved with DIBAL-H or a Grignard reagent to give the amino aldehyde, amino ketone, peptide aldehyde, or peptide ketone products. Twenty-four reactions were carried out simultaneously using a "Billboard" reaction apparatus to give products in 27-87% (59% average) isolated yield.     

Similarities and differences between azomethines and ketimines: synthesis, materials characterization and structure of novel imines compounds

Imines (ketimines and azomethines) derived from p-dibenzoylbenzene (DB) and terephthalic aldehyde (TA) and two aromatic amines: aniline and 2,6-dimethylaniline have been investigated. Compounds were synthesized via condensation of amines with carbonyl monomers in DMA or amine solution. When using DMA as a solvent, azomethines with high yields were obtained. On the other hand, the amines used as a monomers served also as an effective solvent for the synthesis of the ketanils. This different reactivity of the aldehyde and ketone groups in DMA and in amine depends on the dehydration mechanism being dominated by a kinetic process or thermodynamic one. On the basis of FTIR, 13C and 1H NMR, UV-vis spectra, thermal characteristic and theoretical calculations conclusions are drawn regarding the similarities and differences between azomethines and ketimines.     

Pt-Sn/γ-Al2O3-catalyzed highly efficient direct synthesis of secondary and tertiary amines and imines

Versatile syntheses of secondary and tertiary amines by highly efficient direct N‐alkylation of primary and secondary amines with alcohols or by deaminative self‐coupling of primary amines have been successfully realized by means of a heterogeneous bimetallic Pt–Sn/γ‐Al₂O₃ catalyst (0.5 wt % Pt, Pt/Sn molar ratio=1:3) through a borrowing‐hydrogen strategy. In the presence of oxygen, imines were also efficiently prepared from the tandem reactions of amines with alcohols or between two primary amines. The proposed mechanism reveals that an alcohol or amine substrate is initially dehydrogenated to an aldehyde/ketone or NH‐imine with concomitant formation of a [PtSn] hydride. Condensation of the aldehyde/ketone species or deamination of the NH‐imine intermediate with another molecule of amine forms an N‐substituted imine which is then reduced to a new amine product by the in‐situ generated [PtSn] hydride under a nitrogen atmosphere or remains unchanged as the final product under an oxygen atmosphere. The Pt–Sn/γ‐Al₂O₃ catalyst can be easily recycled without Pt metal leaching and has exhibited very high catalytic activity toward a wide range of amine and alcohol substrates, which suggests potential for application in the direct production of secondary and tertiary amines and N‐substituted imines.     

An extremely efficient three-component reaction of aldehydes/ketones, amines, and phosphites (Kabachnik-Fields reaction) for the synthesis of alpha-aminophosphonates catalyzed by magnesium perchlorate

Commercially available magnesium perchlorate is reported as an extremely efficient catalyst for the synthesis of alpha-aminophosphonates. A three-component reaction (3-CR) of an amine, an aldehyde or a ketone, and a di-/trialkyl phosphite (Kabachnik-Fields reaction) took place in one pot under solvent-free conditions to afford the corresponding alpha-aminophosphonates in high yields and short times. The use of solvent retards the rate of the reaction and requires a much longer reaction time than that for neat conditions. The reactions involving an aldehyde, an aromatic amine without any electron-withdrawing substituent, and a phosphite are carried out at rt. The reactions involving cyclic ketones, aromatic amines with an electron-withdrawing substituent, and aryl alkyl ketone (e.g., acetophenone) require longer reaction times at rt or heating. Magnesium perchlorate was found to be superior to other metal perchlorates and metal triflates during the reaction of 4-methoxybenzaldehyde, 2,4-dinitroaniline, and dimethyl phosphite. The catalytic activity of various magnesium compounds was influenced by the counteranion, and magnesium perchlorate was found to be the most effective. The reaction was found to be general with di-/trialkyl phosphites and diaryl phosphite. The Mg(ClO4)2-catalyzed alpha-aminophosphonate synthesis in the present study perhaps represents a true three-component reaction as no intermediate formation of either an imine or alpha-hydroxy phosphonate was observed that indicated the simultaneous involvement of the carbonyl compound, the amine, and the phosphite in the transition state.     

Rigorous Conformational Analysis of Pyrrolidine Enamines with Relevance to Organocatalysis

It has been suggested that the origin of regio‐ and stereoselectivity in Michael additions of pyrrolidine enamines is achieved by thermodynamic rather than kinetic control through distinct conformational preferences of the enamines. We assess this proposal by elaboration of a computational protocol that warrants sufficient accuracy. The small energy differences between the conformers necessitate a high accuracy of the electronic structure method which, in addition, must allow for computationally feasible calculations of a large number of conformers. Our protocol is based on density functional theory which we validated against explicitly correlated coupled cluster theory. The results are in agreement with the available experimental data, but illustrate that conformational preferences determined for one enamine are not readily transferable to other types of enamines. We found that an appropriate conformational sampling is inevitable to arrive at meaningful conclusions. Most prominently, s‐cis and s‐trans conformers are similarly stable for aldehyde‐ and ketone‐derived enamines. The regio‐ and stereoselectivity in Michael additions of pyrrolidine‐derived enamines can not be explained by pronounced stability differences of the enamine isomers and conformers in general, disproving the thermodynamic‐control hypothesis. The elucidation of the origin of regio‐ and stereoselectivity requires further theoretical investigations of the elementary steps of Michael additions.     

Reductive amination of aldehydes and ketones to their corresponding amines with N-methylpyrrolidine zinc borohydride

A simple and convenient procedure for reductive amination of aldehydes and ketones using N-methylpyrrolidine zinc borohydride (ZBHNMP) as a reducing agent is described. The reactions are carried out with 1 equiv of amine and 1 equiv of aldehyde or ketone using 1 equiv of ZBHNMP in methanol under neutral conditions at room temperature.     

Direct α‐Vinylidenation of Aldehydes and Subsequent Cascade: Gold and Amine Catalysts Work Synergistically

Carbonyl‐substituted allenes are highly important synthetic intermediates for a number of heterocycles and strained‐ring systems. However, chemistry of allenyl aldehydes has not been explored as extensively as their ketone, ester, or amide analogues because of a lack of general synthetic methods. Described herein is the first direct α‐vinylidenation of aldehydes and an α‐vinylidenation/γ‐functionalization cascade to access tri‐ and tetrasubstituted allenyl aldehydes using a combination of a gold catalyst and an secondary amine. The reactive enamine intermediate of an aldehyde reacts with the gold‐activated hypervalent silylethynyl benziodoxolone to selectively generate the corresponding trisubstituted allenyl aldehyde. The allenyl aldehyde can further react with another equivalent of the alkynylation reagent or other electrophiles to afford tetrasubstituted allenes bearing an aldehyde group, an acetylene, and a halogen functionality. This method enables rapid access to polysubstituted furans from aldehydes.     

Direct-type catalytic three-component Mannich reaction in aqueous media

Bismuth triflate catalyzed direct-type Mannich reaction of cyclohexanone, aromatic aldehyde, and aromatic amine proceeded smoothly in water to afford the corresponding β-amino ketone with very good yield and moderate to good anti selectivity.     

Enamines. II. A theoretical and photoelectron spectroscopic study of the molecular and electronic structures of aliphatic enamines

Comparison of PE. spectroscopic data for four series of enamines (including azetidine and some aziridine derivatives) for studying the influence of amine-ring size on electronic structure show the pyrrolidino group to exhibit the strongest amine/double bond coupling in sterically unconstrained enamines. However, the azetidino group accommodates best steric congestion due to dialkyl substitution at the β-position of the enamine unit. Quantum-chemical calculations of equilibrium structures and energy profiles for amine rotations in model enamines by the PRDDO SCF method agree satisfactorily with experimental results. Notable exceptions are pyrrolidine derivatives for which PRDDO overestimates the amount of N-pyramidality.