Expansion of the applicability of the Truce-Smiles rearrangement

Abstract

The Truce-Smiles rearrangement is a synthetically useful and easily performed reaction which can be used to condense multiple steps of a synthesis. The nucleophilic aromatic substitution in this reaction produces a chiral center in the rearrangement product. A variety of rearrangement substrates has been prepared and investigated. Investigations into tether functionalization, tether length, pyridyl ring systems and introduction of a second heteroatom into the tether are reported. It has been shown that the rearrangement prefers nitrile tether functionalization. For ethyl ester tethers that perform the rearrangement, there is a secondary cyclization that results in the formation of an aryl lactone. The rearrangement favours a tether length that proceeds through a 5-membered ring intermediate. Rearrangement was successfully reported for a substrate which utilizes two heteroatoms in the tether, something which has not appeared in the literature previously. Use of a microwave reactor resulted in increased rearrangement yields, in addition to facilitating rearrangements that were previously unsuccessful using conventional heating with an oil bath. Use of chiral ionic liquids (CILs) is an excellent approach toward green chemistry due to their high solubility power, coupled with their ability to be recycled and reused over multiple reactions. Over recent years, there has been an increasing interest in investigating the use of CILs as solvent systems to selectively induce chirality in reactions; resulting in the enantioselective formation of products and reduced waste. A variety of CILs have been prepared and tested for their ability to serve as solvents and impart chirality on the reaction. The CILs were successfully used as reaction solvents, however, there is no strong chiral induction observed.