One of the interesting aspects of this patent is the description of electrophilic aromatic substitution of the positive charge of an iminium cation on an aromatic (e.g., ansiole). Since the iminimum cation must be paired with an anion, the inventors describe the use of large organic anions as phase-transfer catalysts and then incorporate chirality in these anions.
The diagrams show the reaction of the iminium salt with anisole and the structures of three chiral anionic phase-transfer catalysts that are chiral borates or chiral binaphthyl phosphate.
The inventors state: “The chiral ion pair could be a source enantioinduction in the subsequent electrophilic aromatic substitution reaction.”
Unfortunately, the patent does not provide detailed procedures.
The patent also mentions the use of chiral ureas and thioureas as chiral auxiliaries to “facilitate an enantioselective reaction by complexing to the conjugate base of an achiral Bronsted acid via hydrogen bonding.”
As an aside, tetrabutylammonium iodide is used to form an iodide intermediate (see Example 29) used to form the iminium ion.
Much of the value of this patent is in describing concepts as well as providing good references for a variety of related synthetic methods.
About Marc Halpern
Dr. Halpern is founder and president of PTC Organics, Inc., the only company dedicated exclusively to developing low-cost high-performance green chemistry processes for the manufacture of organic chemicals using Phase Transfer Catalysis. Dr. Halpern has innovated PTC breakthroughs for pharmaceuticals, agrochemicals, petrochemicals, monomers, polymers, flavors & fragrances, dyes & pigments and solvents. Dr. Halpern has provided PTC services on-site at more than 260 industrial process R&D departments in 37 countries and has helped chemical companies save > $200 million. Dr. Halpern co-authored five books including the best-selling “Phase-Transfer Catalysis: Fundamentals, Applications and Industrial Perspectives” and has presented the 2-day course “Practical Phase-Transfer Catalysis” at 50 locations in the US, Europe and Asia.
Dr. Halpern founded the journal “Industrial Phase-Transfer Catalysis” and “The PTC Tip of the Month” enjoyed by 2,100 qualified subscribers, now beyond 130 issues. In 2014, Dr. Halpern is celebrating his 30th year in the chemical industry, including serving as a process chemist at Dow Chemical, a supervisor of process chemistry at ICI, Director of R&D at Sybron Chemicals and founder and president of PTC Organics Inc. (15 years) and PTC Communications Inc. (20 years). Dr. Halpern also co-founded PTC Interface Inc. in 1989 and PTC Value Recovery Inc. in 1999. His academic breakthroughs include the PTC pKa Guidelines, the q-value for quat accessibility and he has achieved industrial PTC breakthroughs for a dozen strong base reactions as well as esterifications, transesterifications, epoxidations and chloromethylations plus contributed to more than 100 other industrial PTC process development projects.
Dr. Halpern has dedicated his adult life to his family and to phase-transfer catalysis (in that order!).
