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 β-amino acids

Abstract

We report a one-pot synthesis of chiral β-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 β-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.

Chiral N‐tert‐Butylsulfinyl Imines: New Discoveries

“…When imines 16 react with trimethylsilyl ketene acetal 264 in the presence of TBAT gave the corresponding protected aminoalcohols, which in situ where desulfinylated to yield the expected amino acids 265 , isolated as their hydrochlorides (Scheme 113). [152] Some of the obtained products are cyclic amino acids isolated with good yields (49–99 %) and diastereoselectivities (90 : 10–94 : 6 dr).…”

Reactions of Bis(trimethylsilyl)ketene Acetals with Several Activated Organic Substrates

“…Finally, another BF 3 · Et 2 O‐activated reaction was reported for the one‐pot transformation of N ‐ tert ‐butanesulfinylimines 105 into chiral β 2,2,3 ‐amino acids 106 and 107 by Mannich addition of 1 to the N ‐ tert ‐butanesulfinyl imines followed by the removal of the chiral auxiliary, Scheme . (TBAT: tetrabutylammoniumtriphenyldifluorosilicate).…”