Catalytic and Highly Enantioselective Reactions of α‐Sulfonyl Carbanions with Chiral Bis(oxazoline)s

Abstract

The enantioselective reactions of lithiated benzyl trifluoromethyl sulfones with a substoichiometric amount of a bis(oxazoline) and various aldehydes is disclosed. The products were formed with excellent diastereo- and enantioselectivities. Fluorination of the sulfone with N-fluorobenzenesulfonimide and a stoichiometric amount of a bis(oxazoline) gave products with extremely high enantioselectivities (up to 99% ee; ee=enantiomeric excess). The enantioselective reaction was confirmed to proceed through a dynamic thermodynamic resolution pathway.

Enantioselective Synthesis, Configurational Stability, and Reactivity of Lithium α‐tert‐Butylsulfonyl Carbanion Salts

“…The key feature of the concept depicted in Scheme is the use of chiral lithium α‐sulfonyl carbanion salts II , which are configurationally stable and carry achiral ligands at the Li atom. This is in contrast to the realization of enantioselective reactions of chiral lithium α‐sulfonyl carbanion salts coordinated by chiral ligands,6 which follow a dynamic kinetic6a and dynamic thermodynamic resolution6b,6c pathway 7…”

Experimental and Theoretical Investigation of the Enantiomerization of Lithium α‐tert‐Butylsulfonyl Carbanion Salts and the Determination of Their Structures in Solution and in the Crystal

“…Previous attempts towards an enantioselective synthesis of S ‐phenyl‐substituted derivatives of I and II have been uniformly unsuccessful,1j,8 presumably because of fast racemization even at low temperatures (see below). A few enantioselective reactions of magnesium and lithium α‐sulfonyl carbanion salts have been achieved by treatment with electrophiles in the presence of chiral ligands on the metal atom 6r,9,10. These interesting reactions presumably follow dynamic kinetic9 and dynamic thermodynamic6r resolution pathways.…”

“…A few enantioselective reactions of magnesium and lithium α‐sulfonyl carbanion salts have been achieved by treatment with electrophiles in the presence of chiral ligands on the metal atom 6r,9,10. These interesting reactions presumably follow dynamic kinetic9 and dynamic thermodynamic6r resolution pathways. In the course of our structural studies of α‐sulfonyl carbanions and their salts [3b–3i,3k,3m,6h,6j] we became interested in the design and enantioselective synthesis of derivatives of I and II that are configurationally stable on the timescale of their synthesis, reaction with electrophiles, and structural investigation.…”

Recent Progress on the Synthesis of Chiral Sulfones

“…Two years later, Nakamura and co‐workers further reported the highly enantioselective reactions of lithiated benzyl trifluoromethyl sulfones (Scheme 58). [72] The Li(I) and bis(oxazoline) L 27 as a catalyst, TMSCl was added to inhibit the retro‐aldol‐type reaction by trimethylsilylation of the formed alkoxides of products, promoting the reaction of benzyl trifluoromethyl sulfones 126 and various aldehydes to form corresponding adducts 127 in moderate to high yields (58–94 %) and excellent diastereoselectivities (86 : 16–98 : 2 dr). The six‐membered transition‐state TS‐17 was formed due to the 1,3‐diaxial steric repulsion between the sulfonyl oxygen atom and the aldehyde substituent.…”