Themed collection Organocatalysis

Showcasing a collection of cutting edge contributions by international leaders in the field of organocatalysis.

Organocatalytic reactions affording achiral compounds opened unexplored pathways in the synthesis of densely functionalized aromatic moieties, olefins and useful molecules such as natural substances.

A critical discussion of recent strategies directed to the development of more sustainable asymmetric organocatalysis is presented.

Enantioselective organocascades creating multiple carbon–heteroatom bonds are rare but these fascinating domino processes lead to highly functionalised optically active building blocks.

It is successfully demonstrated that the nitroalkene Diels–Alder reaction can be rendered enantio- and periselective by helical–chiral hydrogen bond donor catalysts.

An efficient asymmetric Mannich-type reaction of α-cyano α-sulfonyl carbanions has been achieved by exploiting the structural modularity and anion-recognition ability of chiral 1,2,3-triazolium ions. This protocol has proven to be applicable to a variety of N-Boc imines and cyanosulfones, affording β-amino α-cyanosulfones in excellent yields with high stereoselectivities.

An organocatalyst enables chemoselective introduction of an acyl group onto the sterically hindered secondary hydroxy group in the presence of the primary one.

Resin-supported N-terminal prolyl peptide having suitable secondary structure effectively catalyzed asymmetric Michael addition of substituted β-styryl- and heteroarylboronates to 4-hydroxybut-2-enal.

An organocatalyst promotes the enantio- and diastereoselective cycloaddition of aryl succinic anhydrides and aldehydes to generate paraconic acid (γ-butyrolactone) derivatives.

A new approach to anhydride formation is reported via activation of C–O bonds by the Vilsmeier–Haack reagent formed by Ru(bpy)₃Cl₂ and CBr₄ in DMF.

A facile, highly regio- and enantioselective amino-thiocarbamate-catalyzed bromolactonization of cis-1,2-disubstituted olefinic acids has been developed.

Chiral proton catalysis enables an enantioselective synthesis of Lindsley's GlyT1 inhibitor and a general approach to aminomethyl azetidine pharmacophores.

Organocatalytic construction of pyran derivatives via amine-catalyzed Michael addition and subsequent enolization/cyclisation has been described with high enantioselectivities.

A novel and potentially efficient enzymatic Diels–Alder reaction, involving acid–base catalysis, is presented and evaluated.

The first enantioselective directed cross-aldol reaction between simple ketones using trichlorosilyl triflate and a chiral phosphine oxide catalyst is described.

3-Carbethoxy-2-alkyl-3-pyrrolines are formed in high yields by way of phosphine-catalyzed intramolecular γ-umpolung addition of α-aminoalkylallenic esters.

The umpolung reaction of activated α,β-unsaturated aldehydes to saturated esters was obtained in an ionic liquid by organocatalysis of electrogenerated NHC.

A highly stereoselective organocatalyzed chain elongation of carbohydrates is described.

α,β-Unsaturated acyl azoliums generated by oxidative carbene catalysis react stereoselectively with sulfur ylides to give cyclopropyl carboxylic esters.

Quaternary ammonium salts act as efficient neutral additives in organocatalyzed Michael additions to enals, promoting sequential iminium–enolate formation.

We report an enantioselective route to β-hydroxy carboxyl compounds by asymmetric oxy-Michael addition to a γ-hydroxy-α,β-unsaturated thioester via hemiacetal intermediates.

An efficient organocatalytic Michael-aldol cascade for construction of enantioenriched spirocyclic oxindoles fused with tetrahydrothiophenes was investigated.

A highly effective catalytic enantioselective direct aminal synthesis was developed. Chiral ammonium 1,1′-binaphthyl-2,2′-disulfonates, which were prepared in situ from (R)-1,1′-binaphthyl-2,2′-disulfonic acid (BINSA) and achiral amines, promoted the enantioselective addition of primary amides to aromatic aldimines.

The asymmetric direct vinylogous reaction of α,β-unsaturated γ-butyrolactams using a C₁-symmetric guanidine organocatalyst embodied a secondary amine subunit.

A facile and highly enantioselective approach towards 2-substituted 3-bromopyrrolidines has been developed.

Asymmetric Mannich reaction employing phthalides has been developed for the first time, which led to stereocontrolled synthesis of 3,3-disubstituted phthalides. Facile preparation of chiral isoquinolinones and isoquinolines was also demonstrated.

cis-β-thio-α-amino acid derivatives through organocatalytic one pot, cascade thio-Michael/ring opening reaction were synthesized in high yields with good diastereoselectivities and enantioselectivities.

The direct aldol reaction of an α-alkyl-α-oxo aldehyde was catalyzed by trifluoromethyl-substituted diarylprolinol to afford a γ-oxo-β-hydroxy-α-substituted aldehyde in good yield with excellent anti-selectivity and excellent enantioselectivity.

The chiral phosphoric acid-catalyzed enantioselective reductive amination of aliphatic ketones with aromatic amines was successfully achieved by the use of benzothiazoline as the hydrogen donor. Corresponding chiral aliphatic amines were obtained in good yield with excellent enantioselectivities under mild reaction conditions.

Imidazole reacts with the iminium ion 2, and the failure to observe organocatalytic aza-Michael additions of imidazoles to enals is due to unfavourable proton transfer from the imidazolium fragment to the enamine unit in 3c.

A biomimetic organocatalytic enantioselective decarboxylative ketone aldol reaction of β-ketoacids with trifluoromethyl ketones was realized.

β-Trifluoromethyl-β-alanine of either (R) or (S) absolute configuration was selectively prepared using base-catalyzed reaction of (S)-N-tert-butanesulfinyl (3,3,3)-trifluoroacetaldimine with dialkyl malonates.

One-pot enantioselective synthesis of β-trifluoromethylated pyrrolines was developed by the organocatalyzed-conjugated addition of nitromethane to β-trifluoromethylated enones.

Cyclopropanes were prepared in high yields, complete diastereoselection and high enantioselectivity by reacting 4-nitro-5-styrylisoxazoles with 2-bromomalonate esters under phase-transfer catalysis.

NHC-catalysed highly diastereoselective synthesis of multifunctionalised piperidines from azalactones is developed.

β-Trifluoromethylated pyrroline carboxylates were synthesized by organocatalytic conjugated addition of a glycine imine to β-trifluoromethylated enones, followed by a deprotection/cyclization/dehydration sequence.

The asymmetric Michael addition of dioxindoles (3-hydroxy-2-oxindoles, 1) to β-substituted nitroalkenes is presented. The bifunctional primary amine-thiourea catalyst A, by means of a non-covalent-based mode of activation, secures direct and easy access to valuable 3-substituted 3-hydroxyoxindole derivatives with high stereocontrol.

New, recyclable PMHS-supported chiral imidazolinones promoted the Diels–Alder reaction of dienes with unsaturated aldehydes (up to 93% ee).

A fluorous organocatalyst promotes direct asymmetric aldol reactions of aromatic aldehydes with ketones in brine to afford the corresponding anti-aldol products in high yield with up to 96% ee.

We report the first example of catalytic asymmetric direct amination of α-monosubstituted nitroacetates using di-tert-butyl azodicarboxylate, catalyzed by Hatakeyama's catalyst β-ICD.

An oligopeptide equipped with catalytic moieties converts simple alkenes into enantiomerically enriched (monoprotected) 1,2-trans-diols and serves as proof-of-principle for multicatalysis.

Enantioselective total synthesis of (+)-galbulin via organocatalytic domino Michael–Michael–aldol condensation.

Enantioselective oxidative domino reactions of allylic alcohols to functionalized esters have been developed. The domino oxidation iminium–enamine activation represents a convenient strategy for the enantioselective synthesis of differently substituted aldehydes starting from readily available allylic alcohols.

We present herein for the first time the asymmetric synthesis of drug-like spiranes having five to six contiguous stereocenters through the reflexive-Michael reaction by using 2-aminobuta-1,3-enyne-catalysis under mild conditions.

A dramatic enhancement of stereoselectivity has been observed when using C₆F₆ as an unconventional solvent in the nitro-Michael reaction of 1,3-dicarbonyl compounds catalysed by a commercially available α,α-L-diaryl prolinol. DFT calculations clarified the origin of stereoselectivity and the role of C₆F₆.

The NHC-catalyzed thioesterification of aldehydes with thiols in the presence of phenazine as a stoichiometric oxidant.

We report the first example of highly enantioselective organocatalytic synthesis of 3-difluoroalkyl substituted 3-hydroxyoxindoles. The total synthesis of the difluoro analogue of convolutamydine E was achieved by this method.

Catalytic [2+2] and [3+2] annulations of allenoates with cyclic ketimines afforded functionalized sultam-fused azetidines and dihydropyrroles in good yields with high selectivities.

The first catalytic aryl-λ³-iodane-induced Hofmann rearrangement of primary carboxamides using iodobenzene (5 mol%) and m-CPBA was developed.

A conceptually novel chiral Brønsted base/Brønsted acid catalytic method for the enantioselective synthesis of α-amino thioesters through a tandem condensation–intramolecular rearrangement–protonation has been developed which provides a number of important synthetic building blocks in good yield and with moderate to good enantioselectivities.

A novel class of tartaric acid-derived N-spiro quaternary ammonium salts was synthesised starting from known TADDOLs. These compounds were found to catalyse the asymmetric α-alkylation of glycine Schiff bases with high enantioselectivities and in good yields.

Synthesis and preliminary biological evaluation of various modified chromanes via a highly enantioselective Friedel–Crafts alkylation reaction is disclosed for the first time.

A new thiourea–tertiary amine bifunctional catalyst from L-tert-leucine provides excellent stereocontrol in a Michael addition of 5H-oxazol-4-ones to α,β-unsaturated ketones with broad substrate scope and applicability.

An efficient organocatalytic enantioselective conjugate addition of new carbonylmethyl 2-pyridinylsulfone to enals has been developed for synthesis of chiral 3-substituted 1,5-aldehyde carbonyls.

An efficient highly diastereo- and enantioselective direct Michael addition of nitroalkanes to nitroalkenes catalyzed by chiral squaramide catalyst with a low catalyst loading (2 mol%) afforded synthetically useful 1,3-dinitro compounds in high yields with high diastereoselectivities (up to 95 : 5 dr) and excellent enantioselectivities (up to 97% ee).

Graphene oxide is reported as a highly efficient and cost-effective organocatalyst for the aza-Michael addition of amines to activated alkenes.

The use of stable isoquinolinium and phthalizinium methylides in the organocatalytic enantioselective (3+2) cycloaddition with enals is presented.

Merging Jørgensen's and MacMillan's organocatalytic aldehyde chlorinations enables the synthesis of chiral vinylcyclopropanes and (−)-cis-aerangis lactone via terpene-derived 1,2-epoxides.

A highly enantioselective Friedländer condensation has been established by using chiral Brønsted acids in combination with achiral amines to give quinolines in high yields (up to 99%) and with excellent enantioselectivities (up to 95%).

An effective spirocyclization procedure for installing nucleophiles via iodonium(III) salts has been developed using the combination of bis(iodoarene) and mCPBA.

syn-Selective asymmetric cross-aldol reactions of aldehydes with tert-butyl glyoxylate and glyoxamide 2 were realized by the use of an axially chiral amino sulfonamide (S)-1. The cross-aldol products are readily converted to useful chiral building blocks such as γ-lactone and γ-lactam.

Highly diastereo- and enantioselective conjugate addition of α-substituted nitroacetates to maleimides under base-free neutral phase-transfer conditions was developed.

An efficient enantioselective Michael addition of 4-hydroxycoumarin to α,β-unsaturated ketones catalysed by primary amine–phosphinamide bifunctional catalysts afforded Warfarin and its analogs in moderate to excellent yields (up to 99%) and good to excellent enantioselectivities (up to 99% ee).

A highly enantio- and diastereoselective sulfa-Michael addition of thioacetic acid to α,β-disubstituted nitroalkenes catalysed by a chiral squaramide organocatalyst (0.2 mol%) afforded β-nitro sulfides in excellent yields with good diastereoselectivities and high enantioselectivities (up to 94 : 6 dr, 95% ee). This catalytic reaction can be performed on a 10 gram scale.

Carbonate, acetate and phenolate phosphonium salts are excellent organocatalysts for the transesterification of dimethyl and diethyl carbonate with primary and secondary alcohols, including benzyl alcohol, cyclopentanol, cyclohexanol, and the rather sterically hindered menthol.

Michael addition of α-branched aldehydes to β-nitroacrylates was successfully carried out by using a mixed catalyst consisting of a primary amino acid, L-phenylalanine, and its lithium salt to give β-formyl-β′-nitroesters having a quaternary carbon centre in good yields with high enantioselectivity.

A general approach to high-yielding asymmetric synthesis of (2-ethynylphenyl)alcohols as synthons in medicinal chemistry was achieved through Barbas–List aldol reaction on ketones with 2-alkynylbenzaldehydes in the presence of a catalytic amount of trans-4-OH-L-proline or L-prolinamide derivative.

A tripeptide-like prolinamide-thiourea catalyst with (S)-proline, (1S,2S)-diphenylethylenediamine and (S)-di-tert-butyl aspartate as building blocks provides the products of the reaction between ketones and aromatic aldehydes in high to quantitative yields and high stereoselectivities (up to 99 : 1 dr and 99% ee).

A short synthetic route to diastereoisomeric atropos dihydro-5H-dibenz[c,e]azepinium salts via reaction of a single enantiomer of (R)-α-methylbenzylamine with a racemic atropos biphenol derivative is described.

Polystyrene-supported TBD (PS-TBD) catalyzes the ring-opening of N-tosylaziridines with silylated nucleophiles to give the corresponding products in high yields. PS-TBD was easily recovered and reused without significant loss of catalytic activity.