Darzens Reaction Research Articles

Synthesis of a Camphor-Derived Auxiliary and the Application to the Asymmetric Darzens Reaction

A readily available chiral camphor-derived auxiliary was synthesised through a highly efficient and short general route. The Darzens reaction of the auxiliary with aldehydes in the presence of base gave glycidic esters with almost complete diastereocontrol and high yield.

ChemInform Abstract: A Highly Enantioselective Darzens Reaction Between Diazoacetamides and Aldehydes Catalyzed by a (+)‐Pinanediol—Ti(OiPr)4 System.

A highly efficient enantioselective Darzens reaction of aldehydes with diazoacetamides catalyzed by a (+)-pinanediol–Ti(OiPr)4 system has been developed. The cis-glycidic amides were obtained in high yields and with moderate to excellent enantioselectivity (up to 99%).

Facile synthesis of functionalized spiro[indoline-3,2'-oxiran]-2-ones by Darzens reaction

A series of functionalized spiro[indoline-3,2'-oxiran]-2-ones was efficiently synthesized by Darzens reaction of phenacyl bromides with isatins both with N-alkyl groups and without N-substituent in the presence of potassium carbonate as a base catalyst. When two equivalents phenacyl bromides were used in the reaction, the N-substitution reaction of isatin also finished with the formation of spiro-oxirane-oxindoles.

In Situ Generation Technology of β‐But­oxycarbonyliodonium Ylide: A Hyperva­lent Analogue of the Darzens Reagent

AbstractAn ester exchange reaction of β‐butoxy‐β‐acyloxyvinyl‐λ3‐iodane with lithium bases (ROLi and nBuLi) efficiently generates highly labile monoester iodonium ylide at low temperature. The iodonium ylide generated in situ cleanly undergoes Darzens condensation with aromatic aldehydes to afford trans‐epoxy ester selectively.

ChemInform Abstract: KOH‐Promoted Synthesis of Oxirane Functional Derivatives from Diethyl Bromomalonate and Aldehydes under Phase‐Transfer Catalysis Conditions.

AbstractKOH‐promoted Darzens condensation of bromomalonate (II) with aromatic or isoprenoid aldehydes (I) under PTC conditions smoothly affords oxiranedicarboxylates (III) (8 examples).

KOH-Promoted Synthesis of Oxirane Functional Derivatives from Diethyl Bromomalonate and Aldehydes under Phase-Transfer Catalysis Conditions

The Darzens condensation of diethyl bromomalonate with aromatic or isoprenoid aldehydes under heterogeneous conditions (KOH/MeCN) in the presence of Bu 4 NPF 6 as a recoverable phase-transfer catalyst afforded the corresponding diethyl 3-R-oxirane-2,2-dicarboxylates in high yields.

N,N-DIIsopropyl-N-phosphonyl imines lead to efficient asymmetric synthesis of aziridine-2-carboxylic esters.

Highly diastereoselective asymmetric synthesis of chiral aziridine-2-carboxylic esters is reported for 20 examples with good yields (51-87%) and excellent diastereoselectivities (>99:1 dr for most cases). The modified N-phosphonyl imines have proven to be superior to previous imine auxiliaries for the aza Darzens reaction by using a secondary isopropyl group to replace the primary benzyl group for N,N-diamino protection. In the meanwhile, a special operation by slowly adding the pre-cooled imine solution at -78 °C into the preformed β-bromo lithium enolate mixture at this temperature in the presence of 4 Å molecular sieves was found to be crucial in terms of yields and diastereoselectivity. The present method can provide an easy and general access to β-hydroxy α-amino acids and other important amino building blocks.

A highly enantioselective Darzens reaction between diazoacetamides and aldehydes catalyzed by a (+)-pinanediol–Ti(OiPr)4 system

A highly efficient enantioselective Darzens reaction of aldehydes with diazoacetamides catalyzed by a (+)-pinanediol-Ti(O(i)Pr)(4) system has been developed. The cis-glycidic amides were obtained in high yields and with moderate to excellent enantioselectivity (up to 99%).

ChemInform Abstract: Asymmetric Phase Transfer Darzens Reactions Catalyzed by D‐Glucose‐ and D‐Mannose‐Based Chiral Crown Ethers.

AbstractAsymmetric Darzens condensation of various α‐chloro ketones with aromatic aldehydes proceeds readily in the presence of a D‐glucose‐derived chiral crown ether under mild conditions.

Asymmetric phase transfer Darzens reactions catalyzed by d-glucose- and d-mannose-based chiral crown ethers

Liquid–liquid phase asymmetric Darzens condensations were carried out in the presence of d-glucose- and d-mannose-based crown ethers 1 and 2 as the catalyst. The use of d-glucose-based lariat ether 1 as the catalyst gave the best results. The reaction of 4-phenyl-α-chloroacetophenone, 2-chloro-1-tetralone, and 2-chloro-1-indanone with various aromatic aldehydes afforded the corresponding aromatic α,β-epoxyketones in moderate to high enantiomeric excess (ee up to 96%) under mild reaction conditions. The substituents of the benzaldehyde used as the reactants had a significant impact on the chemical yields and enantiomeric excess. The absolute configuration of some epoxyketone products was determined by single-crystal X-ray analysis.

ChemInform Abstract: Enantioselective Synthesis of Heteroaromatic Epoxyketones under Phase‐Transfer Catalysis Using D‐Glucose‐ and D‐Mannose‐Based Crown Ethers.

AbstractThe use of D‐glucose‐based crown ether (Ia) gives better enantioselectivities than the use of D‐mannose‐based crown ether (Ib) in the Darzens condensation of chloroacetylthiophenes (II) and (VII), and chloroacetylfuran (V) with aldehydes.

ChemInform Abstract: Highly Enantioselective Asymmetric Darzens Reactions with a Phase Transfer Catalyst.

AbstractThe new PTC is used to catalyze an unprecedented highly enantioselective Darzens reaction of α‐chloro ketones with aldehydes to give optically active epoxides.

α,α-dihalocarbonyl compounds and their analogs in the Darzens reaction: An old reaction with new possibilities

Data on reactions that take place in an α,α-dihalocarbonyl compound-carbonyl compound-nucleophile system and related systems under Darzens reaction conditions are generalized, systematized, and analyzed. The features of these reactions depending on substituent nature, method of carbanion generation, and other factors are discussed. Synthetic capabilities of certain products formed in this system are considered.

A Catalytic Asymmetric Darzens Reaction under Phase-Transfer Conditions

Deng and co-workers report the catalytic asymmetric Darzens reaction between cyclic and acyclic α-chloro ketones and aliphatic as well as aromatic aldehydes. A systematic tuning of cinchona alkaloid derived quaternary ammonium salts revealed structure 1 as the phase-transfer catalyst of choice. In the presence of lithium hydroxide as stoichiometric base, catalyst 1 provides the desired products in high yields and high enantioselectivities.

ChemInform Abstract: Asymmetric C—C Bond Formation via Darzens Condensation and Michael Addition Using Monosaccharide‐Based Chiral Crown Ethers.

ChemInform Abstract: Asymmetric C—C Bond Formation via Darzens Condensation and Michael Addition Using Monosaccharide‐Based Chiral Crown Ethers.

Enantioselective synthesis of heteroaromatic epoxyketones under phase-transfer catalysis using d-glucose- and d-mannose-based crown ethers

Heteroaromatic epoxyketones have been synthesized in an asymmetric Darzens condensation of 2-chloroacetylfuran or 2- and 3-chloroacetylthiophene with aromatic aldehydes and in the enantioselective epoxidation of α,β-enones with an N-methylpyrrole unit, in both cases in the presence of d-glucose- 1 or d-mannose-based 2 crown ethers as phase transfer catalysts. The use of d-glucose-based 1 lariat ether as the catalyst gave the best results. The α,β-epoxyketones with a furan or a thiophene moiety were obtained in good enantioselectivities (up to 86% ee) as well as excellent diastereoselectivities (up to 98:2), but the epoxyketones with a pyrrole-ring were formed in the Darzens condensation in low yields and enantioselectivities. The epoxyketones with an N-methylpyrrole moiety isolated from the epoxidation of the corresponding α,β-enones were obtained in significant enantioselectivities (in ee values up to 81%) in the presence of catalyst 1 under mild reaction conditions.

Asymmetric Total Synthesis of the Antimalarial Drug (+)-Mefloquine Hydrochloride via Chiral N-Amino Cyclic Carbamate Hydrazones

Mefloquine hydrochloride is an important antimalarial drug. It is currently manufactured and administered in racemic form; however there are indications regarding the biological activity of the two enantiomers that suggest the superiority of the (+)-form. The asymmetric total synthesis of the (+)-enantiomer of mefloquine hydrochloride is described. The key asymmetric transformation utilized is a novel asymmetric Darzens reaction of a chiral α-chloro-N-amino cyclic carbamate hydrazone derived from an N-amino cyclic carbamate (ACC) chiral auxiliary.

ChemInform Abstract: The Darzens Condensation of α,β‐Unsaturated Aldehydes and Ketones.

AbstractEnolates of α‐bromo esters (I) or ketones (V) undergo one‐pot Darzens condensation to give diastereomeric mixtures of epoxides.

Asymmetric C–C bond formation via Darzens condensation and Michael addition using monosaccharide-based chiral crown ethers

Liquid–liquid phase asymmetric Darzens condensations were promoted by d-glucose- and d-mannose-based crown ethers. The corresponding aromatic and heteroaromatic α,β-epoxyketones were obtained with moderate to high enantioselectivities (up to 96%) as well as diastereoselectivities (up to 98:2) under mild reaction conditions. The absolute configurations of several of the epoxyketones were determined by single crystal X-ray analysis. The Michael additions of diethyl acetylaminomalonate to trans-β-nitroalkenes were carried out in a solid–liquid two-phase system in the presence of a d-glucose-based crown catalyst with up to 99% ee.

The Darzens condensation of α,β-unsaturated aldehydes and ketones

The one-pot Darzens condensation of α,β-unsaturated aldehydes and ketones with enolates of an α-bromo ester or ketone is described.