Stereoselective Aldol Reaction of Glutarimides Using PseudoC₂Symmetry

Abstract

The boron aldol reaction of beta-substituted glutaric imides bearing an oxazolidinone-based auxiliary proceeds with excellent diastereoselectivity; switching the tertiary amine employed between i-Pr(2)EtN or Et(3)N affords enantiomeric lactone product.

Diastereoselective Mannich reactions of pseudo-C2-symmetric glutarimide with activated imines

“…On the basis of our previous study [ 4 ], the chiral glutarimide 1a was employed as the starting material and optimization of reaction conditions with benzaldehyde-based imines 2 was performed ( Table 1 ). Lithium enolate by the action of LDA to 1a was found to be ineffective as long as the imines with benzyl ( 2aa ) or Boc ( 2ab ) as substituents R were employed ( Table 1 , entries 1 and 2).…”

“…During these decades, we have been keenly interested in the 3-(trifluoromethyl)glutaric acid derivatives and developed a couple of routes to get successful access to such target molecules with a variety of substituents at the 2-position [ 1 – 3 ]. Previously, the oxazolidinone-installed bisimide 1a was employed for the crossed aldol reactions by the way of boron enolate which allowed the isolation of optically active lactones in good to excellent yields [ 4 – 5 ]. One of the most intriguing features of this protocol is the fact that the enantiomers at the lactone part were readily obtained only by the selection of the tertiary amines employed in the reaction.…”