Chemoselective conversion of α-unbranched aldehydes to amides, esters, and carboxylic acids by NHC-catalysis

Depending on the N-heterocyclic carbene catalyst utilized, α-unbranched aldehydes selectively provided amides, esters, or carboxylic acids through oxidation by NCS. The α-unbranched aldehyde underwent these reactions chemoselectively in the presence of an aromatic or α-branched aldehyde.     

Structure and diastereoselectivity of the α-hydroxylation of chiral ester enolates by molybdenum peroxo complex

Scope and limitations of the diastereoselective α-hydroxylation of chiral ester enolates by MoO₅·Py·HMPT were investigated. An improved synthesis of natural(-)-verrucarinolactone ((-)-(2S,3R)-2-hydroxy-3-methyl-pentanolide) is described.     

A new synthesis of β,γ-unsaturated esters and allenic esters with construction of a carbon-carbon bond between α- and β-positions by the reaction of magnesium alkylidene carbenoids with lithium ester enolates

Treatment of lithium ester enolates with magnesium alkylidene carbenoids, generated from 1-chlorovinyl p-tolyl sulfoxides with isopropylmagnesium chloride via the sulfoxide-magnesium exchange reaction, gave β,γ-unsaturated esters in moderate to good yields. When this reaction was conducted with the lithium ester enolates of α-chlorocarboxylic acid esters, allenic esters were obtained. This procedure provides an unprecedented way for the synthesis of β,γ-unsaturated esters and allenic esters from ketones with the construction of a carbon-carbon bond between α- and β-positions.     

Enantioselective chlorination of β-keto esters and amides catalyzed by chiral copper（Ⅱ） complexes of squaramide-linked bisoxazoline ligand

Enantioselective chlorination of b-keto esters and amides catalyzed by squaramide-linked bisoxazoline ligand–Cu（OAc）2complexes was investigated. The corresponding chlorinated products were obtained in excellent yields with moderate enantioselectivities. The effect of solvent, temperature, Lewis acid, and ligand structure on the reaction is discussed. This was the first investigation of catalytic asymmetric achlorination of b-keto amides. This study has highlighted that a simple chiral squaramide–oxazoline with cheap Cu（OAc）2 H2 O complexes can catalyze this chlorination.     

Preparation of α,β-unsaturated esters and amides via external-CO-free palladium-catalyzed carbonylation of alkenyl tosylates

Palladium-catalyzed carbonylation of tosylates with phenyl formate is described. This procedure needs neither external carbon monoxide nor any pressure-resistant apparatus. A variety of cyclic and acyclic alkenyl tosylates can be converted into the corresponding phenyl esters in good yields. Furthermore, this method is effective for the one-pot synthesis of α,β-unsaturated amides.     

Synthesis of 1,2,4-triazolines: base-catalyzed hydrazination/cyclization cascade of α-isocyano esters and amides

A convenient, efficient synthesis of 1,2,4-triazolines from α-isocyano esters/amides and azodicarboxylates is presented. The developed reaction cascade is based on a base-catalyzed hydrazination-type reaction followed by a subsequent cyclization providing the triazolines in good to excellent yields (75-99%). Phosphine-catalyzed and preliminary asymmetric phase-transfer catalysis approaches have also been investigated.     

A solventless protocol for the Michael addition of aromatic amides to α,β-unsaturated esters promoted by microwave irradiation

A very simple and efficient solvent-free method for the preparation of N-benzoylated β-amino esters (protected β-amino acids) via the microwave-assisted Michael addition of aromatic amides to α,β-unsaturated esters in the presence of Cs₂CO₃ and tetrabutylammonium bromide (TBAB) is described. The advantages of this method are efficiency, high yields and short reaction times.     

Asymmetric α-2-tosylethenylation of N,N-dialkyl-L-amino acid esters via the formation of non-racemic ammonium enolates

Asymmetric α-2-tosylethenylation of (S)-2-(pyrrolidin-1-yl)propanoic acid esters was shown to produce good yields with high enantioselectivities. The reaction proceeds via the formation of a non-racemic ammonium enolate without an external source of chirality.     

Enantioselective α-chlorination of β-keto esters and amides catalyzed by chiral imidodiphosphoric acids

Chiral imidodiphosphoric acids were employed as catalysts for the enantioselective α-chlorination of β-keto esters and amides using NCS as the chlorine source, providing a series of optically active products with good to high enantioselectivities (74–95% ee) and excellent yields (92–99%). This represents the first report of the Brønsted acid catalyzed enantioselective α-chlorination of cyclic β-keto derivatives.     

Can we predict the conformational preference of amides?

To what extent, if any, is the conformation of secondary amides revealed by theory? This question has now been addressed by computational methods using calculations at the B3LYP/6-31G level of theory and (1)H NMR spectroscopy. Both gas-phase and solvent studies predict a Z-anti conformation to be the lowest in energy for an evaluated series of acetamides. Moreover, Z-anti conformations may also be inferred from the chemical shifts of the N-CH alpha protons determined by NMR spectroscopy. Thus, a proton situated anti to the N-H proton consistently appears approximately 0.8 ppm further downfield than a proton situated gauche to the N-H proton. This finding, which could only be derived by using the DFT calculations of conformational preference as a guide to interpret the NMR data, might prove to be useful as a simple and convenient methodology for establishing amide conformation experimentally.     

Hydrogenation of α-cyanoacrylic acid and its esters by organohydridesilanes

The C=C bond in -cyanoacrylic acid is readily hydrogenated by organohydridesilanes in the absence of catalyst. The hydrogenation of -cyanoacrylate esters requires the presence of acid.A. N. Nesmeyanov Institute of Organometallic Compounds, Russian Academy of Sciences, 117813 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 7, pp. 1655–1657, July, 1992.     

Synthesis of functional derivatives ofN-carboxamidomethyl- andN-phthalimidomethyl-a-amino acids and peptides by reaction of amides and nitriles of α-amino acids with formaldehyde and primary amides or phthalimide

A direct method for the synthesis of functional derivatives ofN-carboxatnidomethyl- and N-phthalimidomethyl-a-amino acids by the reaction of nitriles and amides of -amino acids (including peptides) with formaldehyde and NH-compounds (amides and imides) in DMF in the presence of TsOH was developed. The reactions of the compounds synthesized with acetic anhydride, tosyl chloride, and phcnylalanine benzylamide in the presence of dicyclohexylcarbodiimide affording the corresponding N-acyl and N-sulfonyl derivatives or peptides containing carboxamido- and phthalimidomethyl substituents at the terminal N-atom of the peptide chain, were studied.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1480–1488, June, 1996.     

On the mechanism of the palladium-catalyzed β-arylation of ester enolates

The palladium‐catalyzed β‐arylation of ester enolates with aryl bromides was studied both experimentally and computationally. First, the effect of the ligand on the selectivity of the α/β‐arylation reactions of ortho‐ and meta‐fluorobromobenzene was described. Selective β‐arylation was observed for the reaction of o‐fluorobromobenzene with a range of biarylphosphine ligands, whereas α‐arylation was predominantly observed with m‐fluorobromobenzene for all ligands except DavePhos, which gave an approximate 1:1 mixture of α‐/β‐arylated products. Next, the effect of the substitution pattern of the aryl bromide reactant was studied with DavePhos as the ligand. We showed that electronic factors played a major role in the α/β‐arylation selectivity, with electron‐withdrawing substituents favoring β‐arylation. Kinetic and deuterium‐labeling experiments suggested that the rate‐limiting step of β‐arylation with DavePhos as the ligand was the palladium–enolate‐to‐homoenolate isomerization, which occurs by a β? H‐elimination, olefin‐rotation, and olefin‐insertion sequence. A dimeric oxidative‐addition complex, which was shown to be catalytically competent, was isolated and structurally characterized. A common mechanism for α‐ and β‐arylation was described by DFT calculations. With DavePhos as the ligand, the pathway leading to β‐arylation was kinetically favored over the pathway leading to α‐arylation, with the palladium–enolate‐to‐homoenolate isomerization being the rate‐limiting step of the β‐arylation pathway and the transition state for olefin insertion its highest point. The nature of the rate‐limiting step changed with PCy₃ and PtBu₃ ligands, and with the latter, α‐arylation became kinetically favored. The trend in selectivity observed experimentally with differently substituted aryl bromides agreed well with that observed from the calculations. The presence of electron‐withdrawing groups on these bromides mainly affected the α‐arylation pathway by disfavoring C? C reductive elimination. The higher activity of the ligands of the biaryldialkylphosphine ligands compared to their corresponding trialkylphosphines could be attributed to stabilizing interactions between the biaryl backbone of the ligands and the metal center, thereby preventing deactivation of the β‐arylation pathway.     

1H NMR evaluation of the enantiomeric purity of a series of heterocyclic β-dimethylamino esters and amides by using (S)-mandelic acid derivatives as chiral solvating agents

(S)-OR-Mandelic acid derivatives have been used as chiral solvating agents to induce significant non-equivalences in the ¹H NMR spectra of several heterocyclic structures bearing a β-dimethylamino ester or amide pattern.     

Synthesis ofN-(amidomethyl)- andN- (imidomethyl)-α-amino acid esters by reactions of α-amino acid esters with formaldehyde and amides or imides

Reactions of hydrochlorides of glycine, alanine, phenylalanine, L-isolcucinc, and L-valine esters with aromatic and heteroaromatic carboxamides afforded hydrochlorides of the correspondingN-(amidomethyl)--amino acid esters.N-(Phthalimidomethyl)--amino acid esters were obtained by reactions of -amino acid esters containing free amino groups with formaldehyde and phthalimide, The¹H NMR studies demonstrated that the chiral centers of -amino acids may be retained in the course of condensation. Reactions of the Mannish bases obtained and their hydrochlorides with acetic anhydride and tosyl chloride afforded the correspondingN-aryl andN-sulfonyl derivatives.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp, 1761–1769, July, 1996.     

Novel synthesis of β-siloxy esters by condensation of carbonyls and trimethylsilane with α,β-unsaturated esters catalyzed by RhCl3

A novel one pot reaction of α,β-unsaturated esters with carbonyls and trimethylsilane gave good yields of β-siloxy esters. This RhCl₃ catalyzed method improves upon the two step reaction of silyl ketene acetals with carbonyls.