143282-42-2Relevant academic research and scientific papers
Asymmetric synthesis of α-amino acids: Preparation and alkylation of monocyclic iminolactones derived from α-methyl trans-cinnamaldehyde
Lu, Ta-Jung,Lin, Cheng-Kun
scheme or table, p. 9527 - 9534 (2009/04/07)
(Chemical Equation Presented) Two novel chiral monocyclic iminolactones 14a and 14b have been prepared. The chiral auxiliary 12 was obtained from α-methyl-trans-cinnamaldehyde through reduction, methylation, Sharpless asymmetric dihydroxylation, and oxidation in 87% overall yield. Esterification of compound 12 with the respective protected amino acids followed by deprotection and cyclization provided the corresponding iminolactones, each in 82% overall yield. Alkylation of the iminolactone 14a afforded the α-methyl-α,α-disubstituted products 15 and 16 in good yields (78-99%) and excellent diastereoselectivity (de >98%). Alkylations of the iminolactone 14b furnished the α-benzyl-α,α-disubstituted products 15a, 16b, 17, and 18 in good yields (51-86%) but moderate diastereoselectivities (43-56%). When HMPA or DMPU was used as a cosolvent, the rate of alkylation of the iminolactone 14b was accelerated with improved yields (56-99%) and diastereoselectivities (50-83%). Hydrolysis of the dialkylated iminolactones yielded the α,α-disubstituted α-amino acids in good yields (80-98%) and high enantiomeric excesses (98-99%) with good recovery of compound 12 (83-92%).
Enantioselective allylations of azlactones with unsymmetrical acyclic allyl esters
Trost, Barry M.,Ariza, Xavier
, p. 10727 - 10737 (2007/10/03)
A catalytic asymmetric synthesis of quaternary amino acids has been developed. The method derives from the asymmetric allylic alkylation (AAA) reaction with chiral palladium catalysts derived from π-allylpalladium chloride dimer and the bis-2-diphenylphosphinobenzamide of R,R-1,2- diaminocyclohexane and related ligands. Highly symmetrical allylating agents such as allyl acetate and 2-methallyl acetate give moderate to low ee. On the other hand, 1-monosubstituted and 1,1-disubstituted allyl systems give excellent results with ee's normally ≥90%. A most interesting dichotomy occurs in the facial selectivity with respect to the azlactone as it depends on the allylating agent as well as the ligand. For example, prenylation gives 99% ee derived from attack on the si face of the azlactone with a R,R-ligand, but cinnamylation gives a 90% ee of the product derived from attack on the re face with the same ligand. A model based upon the catalyst creating a chiral pocket is presented to explain these results. Using a trimethylsilyl- substituted allylating agent, excellent ee (97%) was obtained. Protodesilylation then provides the simple allylated amino acid with high ee. Oxidative cleavage of these allylated systems provides a practical asymmetric synthesis of α-alkylated aspartic acids where variation of the alkyl group derives from using variously substituted azlactones. The ability to modify the double bond provides further flexibility to generate unusual amino acids.
ENANTIOSPECIFIC SYNTHESIS OF AMINO ACIDS: PREPARATION OF (R)- AND (S)-α-METHYLASPARTIC ACID FROM (S)-TRYPTOPHAN
Chan, Chat-On,Crich, David,Natarajan, Swaminathan
, p. 3405 - 3408 (2007/10/02)
The enantiospecific synthesis of both antipodes of α-methylaspartic acid from (S)-tryptophan is described with the key steps being alkylation of the hexahydropyrroloindole 4, oxidative degradation of indoles and, for the preparation of the (R)-isomer, Barton reductive decarboxylation.
