Phase separation as a strategy toward controlling dilution effects in macrocyclic Glaser-Hay couplings.
Macrocycles are abundant in numerous chemical applications, however the traditional strategy for the preparation of these compounds remains cumbersome and environmentally damaging; involving tedious reaction set-ups and extremely dilute reaction media. The development of a macrocyclization strategy conducted at high concentrations is described which exploits phase separation of the catalyst and substrate, as a strategy to control dilution effects. Sequestering a copper catalyst in a highly polar and/or hydrophilic phase can be achieved using a hydrophilic ligand, T-PEG(1900), a PEGylated TMEDA derivative. Similarly, phase separation is possible when suitable copper complexes are soluble in PEG(400), a green and efficient solvent which can be utilized in biphasic mixtures for promoting macrocyclization at high concentrations. The latter phase separation technique can be exploited for the synthesis of a wide range of industrially relevant macrocycles with varying ring sizes and functional groups.
Département de Chimie, Centre for Green Chemistry and Catalysis, Université de Montréal, CP 6128 Station Downtown, Montréal, Québec H3C 3J7 Canada.
Anne-Catherine
AC
Bédard
Shawn K
SK
Collins
D002384:Catalysis; D003300:Copper / Q000737:chemistry; D047028:Macrocyclic Compounds / Q000737:chemistry / Q000302:isolation & purification*; D009942:Organometallic Compounds / Q000737:chemistry; D044367:Phase Transition; D011092:Polyethylene Glycols / Q000737:chemistry
D047028:Macrocyclic Compounds; D009942:Organometallic Compounds; C450681:phenyllithium; D011092:Polyethylene Glycols; D003300:Copper