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New technologies in green chemistry; Atroposelective synthesis towards korupensamine D

  • Author(s): Fennewald, James Carl
  • Advisor(s): Lipshutz, Bruce H
  • et al.
Abstract

Chemists and chemical companies alike are well aware of the large amounts of waste they generate, although until recently little attention has been paid to the waste flow in terms of cost and environmental consequences. By most estimates (roughly 85%) of organic waste produced comes in the form of organic solvents. Thus, our goal continues to be the reduction of waste by focusing on organic solvents, and getting those solvents out of reactions via replacement by micellar catalysis, as quantified by E Factors.

Fluorinated compounds have blossomed in the pharmaceutical industry due to the better bioavailability through an increase in membrane permeability when compared to their non-fluorinated analogues. Micellar catalysis has been found to be amenable to radical-based trifluoromethylation of various heterocyclic compounds. Nanoreactors composed of the designer surfactant TPGS-750-M enable these substitution reactions to be performed in water at room temperature in modest to good yields in combination with Langlois’ reagent (NaSO2CF3) and t-BuOOH, negating the need for pre-functionalization. Trifluoromethylation of several heterocyclic arrays has been accomplished, including heteroaromatics.

Aromatic halogens have long served as excellent handles for transition metal catalysis and directing groups in synthesis, with subsequent need for removal. Current protocols for such dehalogenations are cost prohibitive at scale, energy intensive, and generally call for harsh reaction conditions. The new surfactant, SPGS-550-M, (‘Nok’) in water with Fu’s catalyst and a mild hydride source is used for facile debromination of aromatic compounds. These reactions take place at ambient temperatures. Furthermore, the aqueous mediums can be recycled, thus greatly reducing our dependence on organic solvents while furthering technologies in green chemistry.

Chiral compounds and their syntheses have been an intellectual curiosity of organic chemists since the first chiral resolution of tartaric acid in 1848 by Louis Pasteur. We have taken on the challenge to induce axial chirality for the natural product korupensamine D with use of an internal aromatic auxiliary blocking one face of the coupling partner via π-stacking. Korupensamine D has yet to be synthesized in its natural form, due to the inherent instability of the cis tetrahydroisoquinoline ring presenting an exciting, challenging exercise in stereo control.

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