Low-valent Titanium Induced Reductive Coupling Reaction of Aryl Sulfonyl Chlorides with α,β-Unsaturated Esters

Thereductivecouplingreactionofthecarbonylcompoundsbylow-valenttiboiumSPecieshasbeenstUdiedindepthandhaswidelybeenusedinorganicsynthesis"'.However,theintermolecu1arreductivecouplingreactionoftWocompoundscontainingdifferentfunctionalgroupsinducedbylow-valenttitaniumhasnot'beenreported.Recently,wehavereportedthelow-valenttitaluminducedintermolecularreductivecouplingreactionsofcarboxylicderivativeswithketones',andcarboxylicderivativeswithnitrocompounds'.Wenowdescribetliereactionofarylsulfonylchl…     

Highly Enantioselective Iridium-Catalyzed Hydrogenation of α,β-Unsaturated Esters

α,β-Unsaturated esters have been employed as substrates in iridium-catalyzed asymmetric hydrogenation. Full conversions and good to excellent enantioselectivities (up to 99?%?ee) were obtained for a broad range of substrates with both aromatic- and aliphatic substituents on the prochiral carbon. The hydrogenated products are highly useful as building blocks in the synthesis of a variety of natural products and pharmaceuticals.     

1,2-Addition of Activated Vinyl Carbanions to α,β-Unsaturated Carbonyls

Methyl acrylate reacts with α,β-unsaturated aldehydes in the presence of a tertiary amine to afford 1,2-addition products.     

Enantioselective Organocatalytic Aza-Michael Additions of Phthalimide Derivatives to α,β-Unsaturated Aldehydes

Phthalimide derivatives as nitrogen nucleophiles with α,β‐unsaturated aldehydes for asymmetric aza‐Michael additions have been reported. The reactions proceed smoothly to afford corresponding Michael adducts in good yields (up to 98%) and enantioselectivities (up to 95% ee).     

Co(Salox)-Catalyzed Enantioselective Reduction of α,β-Unsaturated Esters

Co-Salox complexes are suitable catalysts for the reduction of prochiral α,β-unsaturated esters. These ligands can be prepared in a single step from available and inexpensive materials, thus representing an easily accessible alternative to previously reported Co-catalysts. NaBH₄ is employed as reducing agent in the presence of EtOH as proton source, leading to the stereoselective formation of chiral esters, amides, and nitriles in up to 99 % yield and 96.5 : 3.5 er. The concentration of the reductant counter cation (Na⁺) and the solvent polarity have been shown to correlate with reactivity and enantioselectivity, suggesting that a relatively complex mechanistic manifold is in place.     

Organocatalytic Enantioselective Diels–Alder Reaction of 2-Trifluoroacetamido-1,3-dienes with α,β-Unsaturated Ketones

We report herein the first examples of chiral phosphoric acid-catalyzed enantioselective Diels–Alder reactions between 2-trifluoroacetamido-1,3-dienes 1 and α,β-unsaturated carbonyl compounds 2 . Polysubstituted 1-acetamido cyclohexenes 3 were formed in high yields with excellent diastereo- and enantioselectivities. The reaction proceeds through a stepwise process as shown by deuterium labelling experiments. A catalytic enantioselective three-component reaction of 1 , 2 and ortho-hydroxybenzhydryl alcohols 4 was subsequently developed furnishing the densely functionalized hexahydroxanthenes 5 in a highly stereoselective manner. This multicomponent reaction generates four chemical bonds with concurrent creation of five contiguous stereocenters.     

Reactions of β-Sulfinyl α,β-Unsaturated Ketones with Dienes

β-Sulfinyl α,β-unsaturated ketones (2a-f) reacted in a regioselective manner with dienes such as butadiene (3a) and 1,3-pentadiene (3b) to give 1,4-cyclohexadiene derivatives (4-8) with the concomitant elimination of sulfenic acid, while the ketones (2a-c) reacted with cyclopentadiene (3c) to yield the norbornenes (9).     

Reaction of Trialkyl Phosphites with α,β-Unsaturated Carbonyl Compounds

Abstract

Reaction of trialkyl phosphites 1 with α,β-unsaturated oxo-compounds 2 gives oxaphospholenes 3 or/and two types of Arbuzov products, γ-keto-phosphonates 4 and alkyl-enol-ethers 5.     

γ-Methylenation of α,β-Unsaturated Ketones

γ-Methylene derivatives of α,β-unsaturated ketones are obtained readily by a one-pot procedure exploiting the reaction of O-silylated dienolates with commercially available formaldehyde N, N-dimethyliminium chloride in anhydrous N, N-dimethylformamide, in situ oxidation of the Mannich reaction product with hydrogen peroxide, and elimination of N,N-dimethylhydroxylamine from the resultant N-oxide.     

Intertwining Olefin Thianthrenation with Kornblum/Ganem Oxidations: Ene-type Oxidation to Furnish α,β-Unsaturated Carbonyls

A widely applicable, practical, and scalable synthetic method for efficient ene-type double oxidation of alkenes is reported via a two-step alkenyl thianthrenium umpolung/Kornblum-Ganem oxidation strategy. This chemo- and stereoselective procedure allows easy access to various α,β-unsaturated carbonyls that may be otherwise difficult or cumbersome to synthesize by conventional methods. For α-olefins, this metal-free transformation can be tuned according to synthetic needs to produce either the elusive (Z)-unsaturated aldehydes or their (E) counterparts. Moreover, this strategy has enabled streamlined synthesis of distinct butadienyl pheromones and kairomones.     

Enantioselective, NHC-Catalyzed Annulations of Trisubstituted Enals and Cyclic N-Sulfonylimines via α,β-Unsaturated Acyl Azoliums

All aboard please! A new reaction of enals and cyclic sulfonylimines, as the nucleophiles(!), is the first highly enantioselective NHC-catalyzed annulation of trisubstituted enals. The catalytically generated α,β-unsaturated acyl azolium undergoes a reaction with the enamine tautomer of the imine via an aza-Claisen rearrangement as the key C?C bond-forming step. High yields and enantioselectivities were achieved using β-, α,β-, and β,β'-substituted enals.     

Interaction of α,β-Unsaturated Ketones of the Adamantane Series with N,N'-Binucleophiles

The influence has been established of the structure of the initial ketone, the reactants, and the reaction conditions on the direction of the interaction of ,-unsaturated ketones of the adamantane series with hydrazine, phenylhydrazine, semicarbazide, thiosemicarbazide, urea, and thiourea. It was found that on interaction with hydrazine and phenylhydrazine both intermediate hydrazones and the final cyclization products, pyrazolines, were formed. Reaction with semicarbazide and thiosemicarbazide leads only to the synthesis of derivatives at the carbonyl group, semicarbazones and thiosemicarbazones, but with urea and thiourea leads to products of addition at the double bond.     

Bifunctional Iminophosphorane-Catalyzed Enantioselective Nitroalkane Addition to Unactivated α,β-Unsaturated Esters**

Herein we describe the enantioselective intermolecular conjugate addition of nitroalkanes to unactivated α,β-unsaturated esters, catalyzed by a bifunctional iminophosphorane (BIMP) superbase. The transformation provides the most direct access to pharmaceutically relevant enantioenriched γ-nitroesters, utilizing feedstock chemicals, with unprecedented selectivity. The methodology exhibits a broad substrate scope, including β-(fluoro)alkyl, aryl and heteroaryl substituted electrophiles, and was successfully applied on a gram scale with reduced catalyst loading, and, additionally, catalyst recovery was carried out. The formal synthesis of a range of drug molecules, and an enantioselective synthesis of (S)-rolipram were achieved. Additionally, computational studies revealed key reaction intermediates and transition state structures, and provided rationale for high enantioselectivities, in good agreement with experimental results.     

Synthesis of α,β-Unsaturated Ketones via Enamines

Acylation of an enamine followed by acid hydrolysis constitutes the well-known Stork's reaction of synthesizing β-diketones.^1,2 This article reports that the acylated enamine 1 which corresponds to monoenamine of a β-diketone can be hydrogenated to a Mannich base 2 which on elimination by heating or treatment with acid yields the α, β-unsaturated ketone 3; further hydrogenation gives saturated ketone 4 in good yield (Scheme 1). A similar transformation effected by hydroboration has been reported by Montury and Góre.     

Condensation of 1-Amino-4-azafluorene with α-Diketones and α,β-Unsaturated Ketones

Condensation of 1-amino-4-azafluorene with -diketones and with unsaturated ketones in basic medium gives novel substituted 1,4-diazafluoranthenes and also dihydro-4-azafluoreno[9,9a,1-b,c]cyclohexano[2',3'-e]- and indano[1',2'-e]azepines.     

Selective Phosphorylation of α,β-Unsaturated Carbonyl Compounds

Abstract

Elaboration of effective methods of selective phosphorylation of α,β-unsaturated carbonyl compounds containing simultaneously C[dbnd]C and C[dbnd]O bonds, which may compete with each other or react consistently one after another, is one of the most complex problems in the modern organophosphorus synthesis. On the basis of our previous systematic investigations of kinetics and mechanism of the Pudovik and Abramov reactions in the series of α,β-unsaturated carbonyl compounds we have suggested three possible ways to solve this problem: a) soft reaction conditions, regulated by solvent, catalyst and temperature; b) interface catalysis; c) metallocomlex catalysis (reaction in the coordination sphere of transition metal).     

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.     

Stereoselective Cycloaddition of N-Acyliminium Ions with α,β-Unsaturated Ketones and Esters

The [4+2] reactions of N‐acyliminium ions, produced from 2‐aryl‐3‐hydroxy‐2,3‐dihydroisoindol‐1‐ones or 5‐hydroxy‐1‐phenyl‐2,5‐dihydro/2,3,4,5‐tetrahydropyrrol‐2‐ones in the presence of BF₃OEt₂, with α,β‐unsaturated ketones or esters were examined, and the dependence of these reactions on the substituents at double bonds was clarified. For β‐aryl substituted α,β‐unsaturated ketones and esters such as 4‐aryl‐3‐buten‐2‐ones, chalcones and methyl cinnamate, the [4+2] reactions could proceed smoothly at room temperature to afford 6‐acyl‐5,6,6a,11‐tetrahydroisoindolo[2,1‐a]quinolin‐11‐ones and 4‐acyl‐1,3a,4,5‐tetrahydropyrrolo[1,2‐a]quinolin‐ 1‐ones or 4‐acyl‐1,2,3,3a,4,5‐hexahydropyrrolo[1,2‐a]quinolin‐1‐ones in moderate to high yields; while for simple α,β‐unsaturated ketones and esters such as methyl crotonate and ethyl 3‐methylbut‐2‐enoate, except mesityloxide, the [4+2] reactions were difficult to proceed. The cycloaddition reactions were highly stereoselective, and only one stereoisomer was produced in each reaction.