Dispersive Fluorine/Bromine Interactions as Key Selectivity Determinant: Asymmetric Cyclopropanations with 3,3,3-Trifluoro-2-diazopropionate Catalyzed by a Heterochiral-at-The-Metal Centers Dirhodium Paddlewheel Complex

TL;DR

A new dirhodium catalyst enables selective asymmetric cyclopropanation reactions using fluorine and bromine interactions.

Contribution

A novel paddlewheel complex with backbone chirality achieves high selectivity via dispersive fluorine/bromine interactions.

Findings

A chiral-at-the-metal dirhodium complex enables asymmetric cyclopropanation of 3,3,3-trifluoro-2-diazopropionate.

Interhalogen dispersion interactions between CF3 and bromine enhance diastereoselectivity and optical purity.

The catalyst design benefits other fluorinated carbene donor reactions like [2 + 1] cycloadditions.

Abstract

Asymmetric cyclopropanation
reactions of 3,3,3-trifluoro-2-diazopropionate
have so far been largely beyond the scope of dirhodium catalysts.
This significant gap in coverage is now closed with the aid of a new
class of paddlewheel complex with “backbone chirality”,
in which an array of only three different achiral ligands (acetamidate,
trifluoroacetate, calix[4]­arene dicarboxylate) renders the two rhodium
centers inequivalent and chiral-at-the-metal each. The –NH
group of the acetamidate engages the ester carbonyl of the metal carbene
intermediate into favorable interligand hydrogen bonding, which in
turn controls the trajectory of the incoming olefinic reaction partner.
In addition, a dispersive interaction between the −CF3 group flanking the carbene center and a strategically placed bromine
substituent on the calixarene dicarboxylate locks the conformation
of the reactive intermediate in place within the chiral binding site,
which translates into high diastereoselectivity and optical purity
alike. The same type of interhalogen London dispersion interaction
can also benefit [2 + 1] cycloadditions of other fluorinated carbene
donors.

Figures