Enantioselective Formal C(sp2)−H Vinylation

An enantioselective formal C(sp²)?H vinylation of prochiral 2,2‐disubstituted cyclopentene‐1,3‐dione is presented. This vinylative desymmetrization is realized by using a two‐step procedure that consists of a catalytic enantioselective vinylogous Michael addition of deconjugated butenolides to cyclopentene‐1,3‐dione and a base‐mediated decarboxylation. The overall process utilizes deconjugated butenolides as the source of the highly substituted vinyl unit. Five‐membered carbocycles containing a remote all‐carbon quaternary stereogenic center are obtained in good yields and with good to high enantioselectivities.     

Catalytic enantioselective construction of quaternary stereocenters by direct vinylogous Michael addition of deconjugated butenolides to nitroolefins

A direct vinylogous Michael reaction of γ-substituted deconjugated butenolides with nitroolefins has been developed with the help of a newly identified quinine-derived bifunctional catalyst, allowing the synthesis of densely functionalized products with contiguous quaternary and tertiary stereocenters in excellent yield with perfect diastereoselectivity (>20:1 dr) and high enantioselectivity (up to 99:1 er).     

Catalytic alkenylation of γ-substituted butenolides with cyclic N-sulfonylated imines in water leading to α-arylidene butenolide derivatives

An efficient Et₃N-catalyzed alkenylation of γ-substituted deconjugated butenolides with cyclic N-sulfonylated imines in water is described. The reaction proceeds efficiently under mild reaction conditions to give α-arylidene butenolide derivatives in high yield (82–96%).     

α-Bromo-β,γ-unsaturated ketenes for the synthesis of α-benzylamino-β,γ-unsaturated acids

The synthesis of α-benzylamino-β,γ-unsaturated acids has been developed starting from α-bromo-α,β-unsaturated chlorides. Via treatment of the acyl chlorides with (R)-pantolactone in the presence of TEA, the in situ formation of the deconjugated ketenes and their direct transformation into chiral esters was performed. The substitution of bromine with benzylamine, followed by acid hydrolysis, allowed to us obtain enantiomerically enriched α-benzylamino-β,γ-unsaturated acids.     

Regioselective α‐Addition of Deconjugated Butenolides: Enantioselective Synthesis of Dihydrocoumarins

The enantioselective α‐addition of deconjugated butenolides has rarely been exploited, in contrast to the well‐studied γ‐addition of deconjugated butenolides. In this study, an unprecedented asymmetric α‐addition/transesterification of deconjugated butenolides with ortho ‐quinone methides generated in situ afforded a series of functionalized 3,4‐dihydrocoumarins containing two contiguous stereogenic centers with excellent diastereo‐ and enantioselectivity. DFT calculations suggested that the rarely observed regioselectivity was due to the distortion energy that resulted from the interaction between the nucleophilic dienolate and the electrophilic ortho ‐quinone methide.     

Heteroatom‐Guided Torquoselective Olefination of α‐Oxy and α‐Amino Ketones via Ynolates

Ynolates were found to react with α‐alkoxy‐, α‐siloxy‐, and α‐aryloxyketones at room temperature to afford tetrasubstituted olefins with high Z selectivity. Since the geometrical selectivity was determined in the ring opening of the β‐lactone enolate intermediates, the torquoselectivity was controlled by the ethereal oxygen atoms. From experimental and theoretical studies, the high Z selectivity is induced by orbital and steric interactions rather than by chelation. In a similar manner, α‐dialkylamino ketones provided olefins with excellent Z selectivity. These products can be easily converted into multisubstituted butenolides and γ‐butyrolactams in good yield.     

Direct Catalytic Asymmetric Mannich‐type Reaction of α,β‐Unsaturated γ‐Butyrolactam with Ketimines

We report a direct catalytic asymmetric Mannich‐type addition of α,β‐unsaturated γ‐butyrolactam to α‐ethoxycarbonyl ketimines promoted by a soft Lewis acid/Brønsted base cooperative catalyst. A thiophosphinoyl group on the nitrogen of ketimines was crucial for both electrophilic activation and α‐addition of γ‐butyrolactams. The obtained aza‐Morita–Baylis–Hillman‐type products bear an α‐amino acid architecture with a tetra‐substituted stereogenic center.     

The preparation of perfluoroalkenyl allenes (trienes) and pentafluorophenyl allenes

Trifluorovinyl- and (Z)-pentafluoropropenylcopper reagents readily react with propargylic halides or tosylates. With primary propargylic substrates, the major product is the alkyne. With secondary propargylic substrates, mixtures of alkyne/allene are obtained; the allene product is the major product. With tertiary propargylic substrates, the allene is regiospecifically and stereospecifically formed in good isolated yields. With pentafluorophenyl copper and primary propargylic substrates, the major product is pentafluorobenzene. With secondary and tertiary propargylic substrates, the allene is regiospecifically formed in good isolated yields.     

Microwave-assisted N-debenzylation of amides with triflic acid

A new and facile microwave-assisted protocol for the debenzylation of N-benzylamides with triflic acid has been developed. Both secondary and tertiary aliphatic or aromatic amides are obtained in moderate to good yields.     

Efficient oxidative N-dealkylative addition of trialkylamines to dimethyl acetylenedicarboxylate using BrCCl3 as the terminal oxidant

Herein we present a continuous improvement of visible-light mediated N-dealkylative addition of tertiary amines to dimethyl acetylenedicarboxylates (DMAD) using alkyl halogenides as external oxidants together with base additives. This method is highlighted by excellent tolerance with various tertiary amines and good to excellent yields in short reaction time under mild conditions.     

Cationic cyclization of keto-epoxides mediated by zirconium(IV) tetrachloride: diastereoselective synthesis of cis-decalinols

10-Methyl-cis-9-decalinols are important motifs in several natural products and key intermediates in total synthesis. Herein, we wish to describe a highly chemo- and diastereoselective cyclization of keto-epoxides leading to 10-methyl-cis-9-decalinols. This method based on the use of zirconium(IV) tetrachloride permits the access to a wide variety of cis-decalinols in good to excellent yields. The cationic cyclization could also be performed with chiral keto-epoxide with complete control of the diastereoselectivity affording cis-bicyclic tertiary alcohol with good enantiomeric excess. The chemo- and the diastereoselectivity are assumed to result from the ability of Zr(IV) to generate highly stable bidentic complexes with α-hydroxy-ketone intermediates.     

Poly(urethaneimides) (PUIs) containing tertiary amine groups as precursors for original PUI cationomers

This paper details the synthesis and characterisation of poly(urethaneimides) (PUIs) containing tertiary amine groups and obtained from a polytetramethylene oxide diol (PTMO1000), N-methyldiethanolamine (MDEA), 4,4′-methylene-bis-phenylisocyanate (MDI) and 4,4′-hexafluoroisopropylidene-bis-phthalic anhydride (6FDA). The polymers PTMO1000 (1 − x equiv.) + MDEA (x equiv.)/MDI (2 equiv.)/6FDA (1 equiv.) were obtained in high yields (>90%) through original synthesis, involving the reaction of macrodiisocyanates with an aromatic dianhydride in two steps only. A wide range of complementary techniques including two-dimensional NMR showed that the new method enabled a very good control of the polymer structure. In particular, the tertiary amine content of the PUI copolymers was easily varied over the whole composition range (x: 0 → 1), with interesting prospects for the design of a wide range of ion-containing poly(urethaneimides) by quaternising the tertiary amine groups. The PUI properties (e.g. solubility, viscosity, film-forming ability, etc.) clearly depended upon their tertiary amine content. Up to a tertiary amine content of x = 0.7 equiv., the very good film-forming character of the PUIs enabled to cast strong films suitable for permeability investigations.     

Synthesis of 4-amino-1,2,3,4-tetrahydropyridine derivatives by intramolecular nucleophilic addition of tertiary enamides to in-situ generated imines

The reactivity of stable tertiary enamides in nucleophilic addition reaction with various in-situ generated imines was explored. Under very mild conditions, formyl-bearing tertiary enamides reacted with both aromatic and aliphatic amines to form imine intermediates. In the absence or presence of p-toluenesulfonic acid as a catalyst, intramolecular nucleophilic addition of enamide to imine functionality proceeded effectively to produce diverse 4-amino-1,2,3,4-tetrahydropyridine derivatives in good to excellent yields.     

Rh-catalyzed intramolecular debenzylative cyclization of amines. Butyrolactams from benzylamines having a chloroacetylene moiety

When benzylamines having a chloroacetylene moiety were heated in wet toluene with a catalytic amount of rhodium trifluoroacetate dimer, intramolecular debenzylative cyclization took place to give butyrolactams. This method is a new entry to selective debenzylation of amines.     

Ferrocenophane-based bifunctional organocatalyst for highly enantioselective Michael reactions

Highly enantioselective Michael reactions between acetylacetone and trans-β-nitroolefins are achieved by a novel ferrocenophane-based tertiary amine-thiourea organocatalyst to provide the corresponding products in good to excellent yields (up to 95%) and enantioselectivities (up to 99% ee).     

Practical cleavage of trifluoroacetamides with p-toluensulfonic acid

A practical and efficient cleavage of trifluoroacetamides with p-TsOH·H₂O has been developed. The deprotected amines are isolated directly from the reaction mixture as tosylate salts. This method can be applied to both secondary and tertiary trifluoroacetamides in good isolated yields.     

Direct Catalytic Asymmetric Doubly Vinylogous Michael Addition of α,β‐Unsaturated γ‐Butyrolactams to Dienones

An asymmetric doubly vinylogous Michael addition (DVMA) of α,β‐unsaturated γ‐butyrolactams to sterically congested β‐substituted cyclic dienones with high site‐, diastereo‐, and enantioselectivity has been achieved. An unprecedented DVMA/vinylogous Michael addition/isomerization cascade reaction affords chiral fused tricyclic γ‐lactams with four newly formed stereocenters.     

Enantioselective preparation of N-chirogenic tertiary amine oxides

We found that PLE can be used as an efficient catalyst for desymmetrization of prochiral tertiary amine N-oxides and demonstrated that they were hydrolyzed by PLE efficiently to afford N-chirogenic tertiary amine oxides up to 99% ee in moderate to good yields.     

nBu4NI-catalyzed oxidative amidation of aldehydes with tertiary amines

An efficient oxidative coupling protocol for amide formation has been developed. Various tertiary amines and aromatic aldehydes were oxidized to their corresponding tertiary amides in moderate to good yields in the presence of a simple nBu₄NI-catalyst.     

Chiral tertiary amine N-oxides in asymmetric epoxidation of α,β-unsaturated ketones

Chiral tertiary amine N-oxides have been shown to undergo stereoselective oxygen transfer reaction in the epoxidation of chalcone derivatives with modest to good enantioselectivity.