In this Account, we detail our efforts to develop catalyst-controlled variants of both the Wacker oxidation and the Heck reaction to address synthetic limitations and provide mechanistic insight selleck chemicals into the underlying organometallic processes of these reactions.
In contrast to previous reports, we discovered that electrophilic palladium catalysts with noncoordinating counterions allowed for the use of a Lewis basic ligand to efficiently promote tert-butylhydroperoxide (TBHP)-mediated Wacker oxidation reactions of styrenes. This discovery led to the mechanistically guided development of a Wacker reaction catalyzed by a palladium complex with a bidentate ligand. This ligation may prohibit coordination of allylic heteroatoms, thereby allowing for the application of the Wacker oxidation to substrates that were poorly behaved under classical conditions.
Likewise, we unexpectedly discovered that electrophilic Pd-sigma-alkyl intermediates are capable of distinguishing between electronically inequivalent C-H bonds during beta-hydride elimination. As a result, we have developed E-styrenyl selective oxidative Heck reactions of previously unsuccessful electronically nonbiased alkene substrates using arylboronic acid derivatives. The mechanistic insight gained from the development of this chemistry allowed for the rational design of a similarly E-styrenyl selective classical Heck reaction using aryldiazonium salts and a broad range of alkene substrates. The key mechanistic findings from the development of these reactions provide new insight into how to predictably impart catalyst control in organometallic processes that would otherwise afford complex product mixtures.
Given our new understanding, we are optimistic that reactions that introduce increased complexity relative to simple classical processes may now be developed based on our ability to predict the selectivity-determining nucleopalladation and beta-hydride elimination steps through catalyst design.”
“In an effort to augment or displace petroleum as a source of liquid fuels and chemicals, researchers are seeking lower cost technologies that convert natural gas (largely methane) to products such as methanol. Current methane to methanol technologies based on highly optimized, indirect, high-temperature chemistry (>800 degrees C) are prohibitively expensive.
A new generation of catalysts is needed to rapidly convert methane and O-2 (ideally as air) directly to methanol (or other liquid hydrocarbons) Drug_discovery at lower temperatures (similar to 250 degrees C) and with high selectivity.
Our approach is based on the reaction between CH bonds of hydrocarbons (RH) and transition metal complexes, LnM-X, to generate activated LnM-R Palbociclib Phase 3 intermediates while avoiding the formation of free radicals or carbocations.