Lithium n-benzyltrimethylsilylamide (LSA): a new reagent for conjugate addition - enolate trapping reactions

Lithium N-benzyltrimethylsilyl amide (LSA) adds to crotonates in a 1,4-manner, though the reaction of ordinary lithium amides with α,β-unsaturated carbonyl compounds is accompanied with a 1,2-addition and hydrogen abstraction at the γ-position. The conjugate addition via LSA followed by enolate trapping with electrophiles produces the corresponding α-substituted β-amino esters, which are, in turn, converted into β-lactams and α-substituted α, β-unsaturated esters.     

Photopolymerization initiated by carbonyl compounds. VII. Solvent effects on biacetyl photoinitiation

Biacetyl is solvated by methanol or water giving an α-substituted alkanone. Irradiation of the solvated species at 300 nm in the presence of vinyl acetate or vinyl pyrrolidone, produces a significant amount of polymer. The photoprocesses leading to active free radicals are considered to be a type I photocleavage of the α-substituted alkanone.     

Methods of synthesis and synthetic application of α-diazomethylphosphonates

Data on methods of synthesis and reactivity of α-diazomethylphosphonic acid esters are classified. Main approaches to obtain diazomethylphosphonate ester (the Seyferth—Gilbert reagent) as well as α-substituted diazomethylphosphonates are considered. The most important reactions of α-diazomethylphosphonates are discussed: [1+2] cycloaddition to alkenes, insertion into heteroatom—heteroatom bonds, reactions with aldehydes and ketones, being of interest as preparative methods to obtain cyclopropane phosphonates, α-substituted methylphosphonic esters and alkynes, correspondingly.     

Synthesis and application of enantioenriched functionalized α-tetrasubstituted α-amino acids from biocatalytic desymmetrization of prochiral α-aminomalonamides

Catalyzed by Rhodococcus erythropolis AJ270, an amidase-containing microbial whole cell catalyst in neutral phosphate buffer at 30 °C, a number of prochiral α-substituted α-aminomalonamides underwent highly efficient and enantioselective hydrolytic desymmetrization to afford functionalized α-tetrasubstituted α-amino acids in 74-98% chemical yields and 94.0 to >99.5% ee. The presence of a free α-amino (NH(2)) substituent in the substrates was deemed important to ensure high biocatalytic efficiency and enantioselectivity. The synthetic application of biocatalytic desymmetrization was demonstrated by practical chemical transformations of (R)-2-amino-2-carbamoylpent-4-enoic acid to α-substituted serine analogues and a bioactive diamino alcohol derivative.     

Synthesis of 1-hydrocarbon substituted cyclopropyl silyl ketones

The synthesis of cyclopropyl silyl ketones possessing a hydrocarbon group at 1-position of three-membered ring was investigated. The reaction of sulfoxonium ylide with α,β-unsaturated acylsilanes derived from α,β-unsaturated aldehydes did not afford the desired acylsilane derivatives. Instead, the corresponding silyl enol ethers were yielded exclusively. On the other hand, the Corey-Chaykovsky cyclopropanation of α-substituted α,β-unsaturated aldehydes proceeded well to give 1-substituted cyclopropyl aldehydes. The silyl substitution of formyl proton in the obtained aldehydes via umpolung of carbonyl group afforded the target acylsilanes.     

(E)-γ-Substituted Allylic Alcohols and α-Substituted Homoallylic Alcohols via Acidic Treatment of the Acetonides Derived from γ-Substituted Vinyl Diols

Treatment of the acetonides of γ-substituted vinyl diols under acidic deprotection conditions afforded γ-substituted allylic alcohols and α-substituted homoallylic alcohols.     

2-[1-(1,2,4-三唑)甲基]-3-乙酰基-2,5-二取代芳基-1,3,4-噁二唑啉类化合物的合成

在冰醋酸存在下, 4-取代苯乙酮和溴素容易进行溴代反应, 得到α-溴-4-取代苯乙酮; 将其和1,2,4-三唑在丙酮中反应, 得到α-(1,2,4-三唑-1-基)-4-取代苯乙酮2; 在冰醋酸催化下, 2和4-取代苯甲酰肼1进行缩合, 得到相应酰腙衍生物3; 化合物3在乙酸酐的作用下环化生成一系列2-[1-(1,2,4-三唑)甲基]-3-乙酰基-2,5-二取代芳基-1,3,4-噁二唑啉4. 化合物4的结构经IR, 1H NMR, MS, 元素分析和单晶衍射确证.     

Synthesis of 8-substituted naphtho[2,1-b]thiophenes with cationic side chains at position 4

A series of five 8-substituted α-[bis(2-hydroxyethyi)aminoethyl]naphtho[2,1-b]thiophenes 7 and a series of seven N-(3-dimethylaminopropyl)-8-substituted naphtho[2,1-b]thiophene-4-carboxamides 8 have been synthesized. The naphtho[2,1-b]thiophene-4-carboxylic acids 4 were prepared by photooxidative cyclization of α-(2-thienyi)-β-arylacrylic acids 3. The carboxylic acids 4 were converted by a conventional five step route involving α-bromoketone intermediates to the a-[bis(2-hydroxyethyl)aminomethyl]-8-substituted naphtho-[2,1-6]thiophene-4-methanols 7 and by a standard two-step amide preparation to the N-(3-dimethylaminopropyl)-8-substituted naphtho[2,1-6]thiophene-4-carboxamides 8 .     

Carbon dioxide: A reagent for the protection of nucleophilic centers and the simultaneous activation of alternative locations to electrophilic attack: 15. A synthetic method for the α-substitution of N-phenylbenzylamine

N-Phenylbenzylamine has been converted into a variety of α-substituted derivatives in one-pot sequences, using carbon dioxide both for N-protection and α-carbon activation, and then subsequent lithiation at the α-carbon atom by either tert- or n-butyllithium. The resulting lithium carbamate reacts with electrophiles, followed smooth acid-catalyzed decarboxylation under mild condition to give α-substituted N-phenylbenzylamines in good yields.     

Diastereoselective synthesis of β-substituted α-hydroxyphosphinates through hydrophosphinylation of α-heteroatom-substituted aldehydes

The diastereoselective synthesis of β-substituted α-hydroxyphosphinates was achieved by hydrophosphinylation of α-oxy aldehydes and α-amino aldehydes with ethyl allylphosphinate catalyzed by lithium phenoxide.     

Desymmetrizing asymmetric ring expansion of cyclohexanones with α-diazoacetates catalyzed by chiral aluminum Lewis acid

Chiral aluminum Lewis acid catalyst composed of Me(3)Al and 3,3'-bis(trimethylsilyl)-BINOL in a 2:1 ratio was found to promote novel catalytic asymmetric ring expansion of cyclohexanone with α-substituted α-diazoacetates to give seven-membered rings with an all-carbon quaternary center. Application of this strategy to 4-substituted cyclohexanones opened up a novel way for the catalytic desymmetrizing asymmetric construction of cycloheptanones bearing remote α,δ-chiral centers.     

Asymmetric Synthesis of Cα-Substituted Prolines through Curtin–Hammett-Controlled Diastereoselective N-Alkylation

Asymmetric synthesis of α-substituted proline derivatives has been accomplished by an efficient chirality-transfer method. High diastereoselectivity of the N-alkylation of the proline ester (C→N chirality transfer) was achieved when a 2,3-disubstituted benzyl group was used as the N-substituent. DFT calculations provided a mechanistic rationale for the high degree of stereoselectivity. The generated N-chirality of the quaternary ammonium salt was transferred back to the α-carbon through a stereoselective [2,3]-Stevens rearrangement (N→C chirality transfer) to give α-substituted proline ester.     

Solid-phase synthesis of α-substituted proline hydantoins and analogs

The manual solid-phase preparation of racemic α-substituted bicyclic proline hydantoins and analogs, which can potentially contain up to four sites of structural diversity (ring size and substitution on the ring or at the ring fusion), is described. Key steps involved alkylation of aldimines of resin-bound amino acids with α,ω-dihaloalkanes and intramolecular displacement of the halide to generate α-substituted prolines and homologs. After formation of resin-bound ureas by reaction of these sterically-hindered secondary amines with isocyanates, base-catalyzed cyclization/cleavage yielded the desired hydantoin products.     

Copper(I)-Catalyzed Conjugate Addition/Enantioselective Protonation with Selenols and α-Substituted α,β-Unsaturated Thioamides

Herein, a copper(I)-catalyzed asymmetric conjugate addition/protonation with selenols and α-substituted α,β-unsaturated thioamides is disclosed, which affords a series of chiral selenides in high to excellent enantioselectivity. As for both selenols and α-substituted α,β-unsaturated thioamides, the reaction enjoys broad substrate scopes. The present catalytic system is also successfully applied to asymmetric selenation of β-substituted α,β-unsaturated thioamides. A [Cu-(R,R_P)-TANIAPHOS]-SePh species is characterized by its ⁷⁷Se NMR spectra, which gives a chemical shift at δ 462 ppm. Moreover, a {[Cu-(R)-TOL-BINAP]-SePh}₂ species is characterized by X-ray analysis, which confirms the formation of Cu−Se bond in the reaction. Finally, the transformations of the thioamide group to amine and thioester are demonstrated to be straightforward.     

Click-chemistry approach to isoxazole-containing α-CF3-substituted α-aminocarboxylates and α-aminophosphonates

A convenient strategy for the synthesis of isoxazole-containing α-CF(3)-substituted α-aminocarboxylates and α-aminophosphonates have been developed. The method is based on copper-catalyzed 1,3-dipolar cycloaddition of different aromatic nitrile oxides to functionalized acetylenes.     

Conformation et reactivite de systemes (4.n.0) bicycliques a jonction trans—XIX: Synthese,conformation et configuration de methyl-4 et halogeno-4 bicyclo (4.2.0) octanols-3 et octanones-3 trans. Equilibres d'epimerisation des bicyclo (4.2.0) octanones α-substituees

4-substituted trans bicyclo (4.2.0) octan-3 ols et octan-3 ones were prepared. The conformation of these compounds and the configuration of the α-substituents were established by UV, IR and NMR spectroscopy.The epimerisation equilibrium constants for α-substituted bicyclo (4.2.0) octanones (substituents = F, Cl, Br, Me) were determined.     

Regio-controlled synthesis of N-substituted imidazoles

A regio-specific synthesis of N-substituted imidazoles is described. Readily available α-amino acids are converted to α-aminocarbonyl derivatives and reacted with various isothiocyanates to give N-substituted cyclic thioureas. Oxidative or reductive desulfurization of the cyclic thioureas affords structurally diversified imidazoles in good to excellent yields.     

Diastereo- and enantioselective conjugate addition of α-substituted nitroacetates to maleimides under base-free neutral phase-transfer conditions

Highly diastereo- and enantioselective conjugate addition of α-substituted nitroacetates to maleimides under base-free neutral phase-transfer conditions was developed for the synthesis of α,α-disubstituted α-amino acid derivatives.     

Organocatalytic asymmetric 1,4-addition of organoboronic acids to γ-hydroxy α,β-unsaturated aldehyde: facile synthesis of chiral β-substituted γ-lactones

Catalytic asymmetric 1,4-addition of arylvinyl- and arylboronic acids to a γ-hydroxy α,β-unsaturated aldehyde, which affords β-substituted γ-lactols, has been established using a diarylprolinol silyl ether as an organocatalyst. The β-substituted γ-lactols have been obtained in good yields and with up to 91% ee, which lead to chiral β-substituted γ-lactones followed by oxidation.     

Sur la regio specificite de la reaction de reformatsky appliquee au γ-bromocrotonate et au γ-bromosenecioate de trimethylsilyle

The regiospecificity of Reformatsky reactions of γ-bromocrotonic and γ-bromosenecioic timethylsilyl esters are discussed. One-step reactions lead to a majority of α-substituted derivatives, while in two-step reactions, the γ-substituted products are obtained exclusively.