Stereodivergent Mannich reaction of bis(trimethylsilyl) ketene acetals with N-tert-butanesulfinyl imines by Lewis acid or Lewis base activation, a one-pot protocol to obtain chiral beta-amino acids

• Published in: Organic & biomolecular chemistry Vol. 15; no. 36; pp. 7705 - 7709
• Main Authors: Cantu-Reyes, Margarita, Alvarado-Beltran, Isabel, Ballinas-Indili, Ricardo, Alvarez-Toledano, Cecilio, Hernandez-Rodriguez, Marcos
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 20.09.2017
• Subjects: Acetals - chemistry; Amino Acids - chemical synthesis; Amino Acids - chemistry; Chemistry; Chemistry, Organic; Ethylenes - chemistry; Imines - chemistry; Ketones - chemistry; Lewis Acids - chemistry; Lewis Bases - chemistry; Molecular Structure; Physical Sciences; Science & Technology; Stereoisomerism; ASYMMETRIC-SYNTHESIS; ENANTIOSELECTIVE SYNTHESIS; TETRABUTYLAMMONIUM TRIPHENYLDIFLUOROSILICATE; ARYL; DIASTEREOSELECTIVE ADDITION; GAMMA-LACTONES; DERIVATIVES; CARBOXYLATE ESTERS
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c7ob01853c

We report a one-pot synthesis of chiral beta(2,2,3)-amino acids by the Mannich addition of bistrimethylsilyl ketene acetals to N-tert-butanesulfinyl imines followed by the removal of the chiral auxiliary. The synthesis and isolation of pure beta-amino acid hydrochlorides were conducted under mild conditions, without strong bases and this method is operationally simple. The stereoselective reaction was promoted by two different activation methods that lead to different stereoisomers: (1) Lewis Acid (LA) catalysis with boron trifluoride diethyl etherate and (2) Lewis Base (LB) catalysis with tetrabutylammonium difluorotriphenylsilicate. The reaction presented good diastereoselectivity with LB activation and moderate to good dr with LA catalysis. The exceptions in both protocols were imines with electron donating groups in the aromatic ring.