Rafael Chinchilla

Enantiomerically pure guanidine-catalysed asymmetric nitroaldol reaction

Abstract Enantiomerically pure guanidines with and without C 2 symmetry have been prepared and used as catalysts in the addition of nitromethane to aldehydes (Henry reaction). The influence of the structure and amount of the guanidine, the solvent and the temperature in the enantioselectivity of the nitroaldol reaction has also been studied.

NEW TRENDS IN PEPTIDE COUPLING REAGENTS

INTRODUCTION .............................................................................................................................. 205 I . PREPARATION OF REAGENTS ............................................................................................... 205 1 . Phosphonium Salts ............................................................................................................... 205 2 . Aminium Salts ....................................................................................................................... 209 3 . Phosphinic and Phosphoric Acid Derivatives ..................................................................... 214 4 . Other Coupling Reagents ..................................................................................................... 217 5 . Polymer-Supported Reagents .............................................................................................. 218 I1 . COUPLING MECHANISMS ...................................................................................................... 219 I . Carbodiimides ...................................................................................................................... 219 2 . Phosphonium Salts ............................................................................................................... 222 3 . Aminium Salts ....................................................................................................................... 222 4 . Phosphinic and Phosphoric Acid Derivatives ..................................................................... 223 5 . Other Coupling Reagents ..................................................................................................... 224 6 . Amino Arid Halides ............................................................................................................. 226 In . PEPTIDE SYNTHESIS ............................................................................. I . Carbodiimides ...................................................................................................................... 227 2 . Phosphonium Salts ............................................................................................................... 228 3 . Aminium Salts ....................................................................................................................... 237 4 . Phosphinic and Phosphoric Acid Derivatives ..................................................................... 244 5 . Other Coupling Reagents ..................................................................................................... 251 6 . Polymer-Supported Reagents ............................................... 7 . Active Esters ......................................................................................................................... 255 ................................................... 262 9 . Amino Acid Halides ............................................................................................................. 263 10 . Comparative Studies .......................................................................................................... 264 ..................................................... 267 1 . Carbodiimides ...................................................................................................................... 267 8 . Amino Acid Anhydrides ............................................

Asymmetric synthesis of α-amino acids using polymer-supported Cinchona alkaloid-derived ammonium salts as chiral phase-transfer catalysts

Abstract Cinchonidine and cinchonine have been N -alkylated with Merrifield resin and employed as chiral phase-transfer catalysts for the enantioselective alkylation of enolates from N -(diphenylmethylene)glycine esters with activated electrophiles (up to 90% ee ). The use of the polymer-supported cinchonidine ammonium salt afforded the corresponding ( S )-isomers, whereas the ( R )-isomers were obtained using related cinchonine-supported polymers.

New dimeric anthracenyl-derived Cinchona quaternary ammonium salts as phase-transfer catalysts for the asymmetric synthesis of α-amino acids

New dimeric cinchonidine- and cinchonine-derived ammonium salts which incorporate a dimethylanthracenyl bridge have been prepared and used as phase-transfer catalysts in the asymmetric alkylation of N-(diphenylmethylene)glycine esters in good yields and up to 90% ee.

Glycine and Alanine Imines as Templates for Asymmetric Synthesis of α‐Amino Acids

The present paper is an overview of new methods for the asymmetric synthesis of different types of α-amino acids. These methods are based on alkylation and condensation reactions of glycine and alanine imine derivatives, which can be carried out under very mild and simple reaction conditions. The enolates generated from these types of reagents are very soft and can be alkylated in a highly diastereoselective manner, even at room temperature, by using chiral templates or asymmetric PTC conditions. These methodologies afford monoalkylated and dialkylated α-amino acids as well as heterocyclic derivatives. In the case of cyclic imine derivatives with oxazinone or pyrazinone structures, the condensation reaction under PTC conditions or with Eschenmoser’s salt allows the preparation of chiral α,β-didehydro-α-amino acid derivatives which can be hydrogenated, cyclopropanated or submitted to Diels−Alder cycloadditions to afford N-methylated and cyclic α-amino acids.

Unexpected metal base-dependent inversion of the enantioselectivity in the asymmetric synthesis of α-amino acids using phase-transfer catalysts derived from cinchonidine

Abstract New cinchonidinium salts bearing a 3,5-dialkoxybenzyl group show an alkaline metal base-dependent reversal of enantioselectivity when used as phase-transfer catalysts in the asymmetric alkylation of N -(diphenylmethylene)glycine isopropyl ester with benzyl bromide. The use of potassium hydroxide as base in this alkylation reaction afforded the ( S )-enantiomer, whereas using sodium hydroxide under the same conditions afforded the corresponding ( R )-enantiomer.

A new polymer-supported reagent for the Fmoc-protection of amino acids

A new polymer-supported Fmoc-OSu (Fmoc-P-OSu) has been prepared from polymer-bound N-hydroxysuccinimide (P-HOSu), and used as a solid-supported reagent for the Fmoc-protection of amino groups. The residual P-HOSu generated after the protection reaction can be separated by simple filtration and reused.

Polymer-bound TBTU as a new solid-supported reagent for peptide synthesis

Abstract A new polymer-supported TBTU (P-TBTU) has been prepared from polystyrene-bound 1-hydroxybenzotriazole (P-HOBT) and used efficiently as a solid-supported reagent for peptide-coupling reactions, and is even effective with wet solvents. The P-HOBT can be recovered by simple filtration and reused for the preparation of new P-TBTU.

Direct synthesis of hydroxamates from carboxylic acids using 2-mercaptopyridone-1-oxide-based thiouronium salts

Tetrafluoroborate and hexafluorophosphate thiouronium salts derived from 2-mercaptopyridone-1-oxide and tetramethylurea (TOTT and HOTT) or N,N′-dimethylpropyleneurea (TODT and HODT) convert carboxylic acids to Weinreb amides and N-methoxy or N-benzoxyamides in high yields by reaction with N,O-dimethylhydroxylamine and O-methyl- or O-benzyl-hydroxylamine hydrochlorides, respectively, in the presence of triethylamine or DIEA.

Polymer-Supported Cinchona Alkaloid-Derived Ammonium Salts as Recoverable Phase-Transfer Catalysts for the Asymmetric Synthesis of α-Amino Acids †

Alkaloids such as cinchonidine, quinine and N-methylephedrine have been N-alkylated using polymeric benzyl halides or co-polymerized and then N-alkylated, thus affording a series of polymer-supported chiral ammonium salts which have been employed as phase-transfer catalysts in the asymmetric benzylation of an N-(diphenylmethylene)glycine ester. These new polymeric catalysts can be easily recovered by simple filtration after the reaction and reused. The best ees were achieved when Merrifield resin-anchored cinchonidinium ammonium salts were employed.