4493-08-7Relevant articles and documents
Enantioselective allylation of nitro group-stabilized carbanions catalyzed by chiral crown ether phosphine-palladium complexes
Sawamura, Masaya,Nakayama, Yuki,Tang, Wen-Ming,Ito, Yoshihiko
, p. 9090 - 9096 (1996)
Enantioselective allylations of α-nitro ketones (3) and α-nitro esters (15) with allyl acetate were carried out in the presence of 2 equiv of alkali metal fluorides (KF, RbF, CsF) and 1 mol % of palladium catalysts prepared in situ from Pd2(dba)3·CHCl3 and chiral phosphine ligands. Moderate enantioselectivities were observed in the reaction of nitro ketones 3, giving products 4 (4a, 49% ee; 4b, 58% ee; 4c, 44% ee) when rubidium fluoride and ferrocenylphosphine ligands bearing monoaza-15-crown-5 (1b) or monoaza-18-crown-6 (1c) moieties were used as a base and a chiral ligand, respectively. Optically active allylation product 4a was converted into 1-methyl-1-azaspiro[4.5]-decan-10-amine (13), a precursor to opioid receptor binding agents. Enantioselectivity in the reaction of nitro esters 15 increased in accord with increasing steric demand of the ester alkyl group (Me 4 (1 equiv). The pronounced effect of the crown ether moiety for both enantioselection and rate acceleration can be explained by assuming the formation of a ternary complex involving the crown ether, rubidium cation, and enolate anion at the stereodifferentiating transition state. Optically active nitro ester (R)-16c was converted into (R)-α-methylglutamic acid (20).
Chiral 3,6-dihydro-2H-1,4-oxazin-2-ones as alanine equivalents for the asymmetric synthesis of α-methyl α-amino acids (AMAAs) under mild reaction conditions
Chinchilla, Rafael,Galindo, Nuria,Nájera, Carmen
, p. 704 - 717 (2007/10/03)
3,6-Dihydro-2H-1,4-oxazin-2-ones 1 act as very reactive chiral cyclic alanine equivalents and can be diastereoselectively alkylated or allylated using mild reaction conditions: potassium carbonate under phase-transfer catalysis (PTC) conditions when using activated alkyl halides, organic bases such as tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2- diazaphosphorine (BEMP) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) when using unactivated alkyl halides, and neutral Pd(0)-catalysis when allylic carbonates are used. In most cases, the diastereoselectivity under all these different reaction conditions is excellent although the reactions are always carried out at room temperature. Hydrolysis of the obtained alkylated or allylated oxazinones allows the preparation of enantiomerically enriched (S)- α-methyl α-amino acids (S)-AMAAs. The PTC and organic base methodologies have also been applied to the synthesis of (R)-α-methyl α-amino acids starting from (R)-alanine. When dihalides are used as electrophiles under PTC or BEMP conditions, a spontaneous N-alkylation also takes place giving bicyclic oxazinones, which can be hydrolyzed to enantiomerically pure cyclic (S)-AMAAs.
A Novel Synthesis of (R)- and (S)-α-Alkylated Aspartic and Glutamic Acids: α-Alkylated Aspartic Succinimides as New Type of β-Turn Type II and II' Mimetics
Obrecht, Daniel,Bohdal, Udo,Daly, John,Lehmann, Christian,Schoenholzer, Peter,Mueller, Klaus
, p. 10883 - 10900 (2007/10/02)
A novel and efficient synthesis of optically pure (R)- and (S)-α-methyl glutamic acid (1), (R)-and (S)-α-methyl aspartic acid (2a) and (R)- and (S)-α-isobutyl aspartic acid (2b) using L-phenylalanine cyclohexylamide 4 as chiral auxiliary is described.Crystal structures show that the (R)- and (S)-α-methyl glutamic acid derivatives (S,S)-5 and (R,S)-6 adopt β-turn type I geometries, whereas the corresponding aspartimide derivatives (R,S)-12a,b form a β-turn type II and (S,S)-11a a β-turn type II'.These findings suggest, that the succinimide derivatives of (R)- and (S)-α-alkyl aspartic acids can serve as building blocks to stabilise β-turns of type II (or II') in peptides depending on their absolute configuration.
