Metal-Ligand Cooperative Catalysis and Methods for Metal Removal from Organic Transformations

Organometallic catalysis has revolutionized the synthesis of complex organic molecules. Methods for C-C, C-X and C-H bond formation and cleavage are exploited throughout the areas of fine chemicals synthesis, with major applications for pharmaceuticals. This situation raises duel challenges: 1) high-performance catalysts for environmentally and economically sustainable synthesis and 2) efficient methods of catalyst (i.e. metal) removal must be identified. This work tackles both of these areas. The highly tunable cooperative PR2NR\u272 ligands have been implemented for the first time for catalytic organic transformations. I show that [Ru(Cp)(PtBu2NBn2)(MeCN)][PF6] is an effective catalyst for the cyclization of alkynyl alcohols and have characterized a deactivated species, [Ru(Cp)(PtBu2NBn2)(-C=CHPh)][PF6], from the attempted hydration of alkynes. Directions in metal removal from catalytic reactions have been investigated, using both a solid-supported catalyst and an insoluble metal scavenger

Substrate-Mediated Deactivation of a Ru(P\u3csup\u3et\u3c/sup\u3e\u3csup\u3eBu\u3c/sup\u3e2N\u3csup\u3eBn\u3c/sup\u3e2) Cooperative Complex

Ligand design for metal-ligand cooperative (MLC) catalysis is inherently more complex than that for traditional non-cooperative ligands. The basicity, sterics and structure of the acid/base group in MLC proton-transfer (PT) complexes, for instance, undoubtedly influence catalyst performance. Herein, we evaluate the highly tunable PR2NR′2 (1,5-R′-3,7-R-1,5-diaza-3,7-diphosphacyclooctane) ligand family for the first time in an organic transformation. With [Ru(Cp)(PtBu2NBn2)(MeCN)][PF6] as the catalyst, no turnover was observed in the anti-Markovnikov hydration of alkynes, a known PT MLC reaction. Treatment of the cooperative complex with phenylacetylene affords a vinylammonium product in which the pendant nitrogen atom of the PtBu2NBn2 ligand forms a Lewis acid-base adduct with the alpha-carbon atom of the vinylidene intermediate. Characterization by X-ray crystallography and NMR spectroscopy conclusively assign this structure in both the solid and the solution state. The adduct formation is irreversible, and the adduct is characterized as a catalyst deactivation product. Snapping Shut: The PR2NR′2 ligand family (R and R′ are removed for clarity in the graphic) open the door for easily tuned catalysts for cooperative organic transformations. However, the ligand swings toward the vinylidene, forming a stable (and catalytically inactive) Lewis acid-base adduct. (□ = open coordination site

New Phosphine-Functionalized NHC Ligands: Discovery of an Effective Catalyst for the Room-Temperature Amination of Aryl Chlorides with Primary and Secondary Amines

We report convenient and high-yielding syntheses of new phosphine-functionalized dihydroimidazolium salts and demonstrate their utility as ligand precursors for Buchwald–Hartwig amination. Several examples of the general formula [1-Mes-3-{2-(PR₂)­phenyl}­imidazolidin-2-ylium]­[BF₄] have been prepared, where phosphines of varying steric and electronic properties (R = Ph (<b>9</b>), Cy (<b>10</b>), 1-Ad (<b>11</b>)) are tethered by an <i>o</i>-phenylene group. The synthesis was not adaptable to <i>N</i>-aryl groups other than mesityl, giving unexpected phosphonium salt species instead. The synthesis was adapted to flexible benzyl-linked variants of the formula [1-Ar-3-{2-(PCy₂)­benzyl}­imidazolidin-2-ylium]­[BF₄], which allowed more steric variation of the dihydroimidazolium <i>N</i>-aryl group (Ar = Mes (<b>21</b>), Dipp (<b>22</b>)). A preliminary study of these hybrid NHC/P ligands in Buchwald–Hartwig amination catalysis (in situ precatalyst formation) revealed <b>11</b> to be the most active of the series. Premixing the isolated free NHC ligand 1-Mes-3-{2-(PAd₂)­phenyl}­imidazolidin-2-ylidene (<b>23</b>) with [Pd­(cinnamyl)­Cl]₂ provided a highly active precatalyst that performed well at room temperature and 1 mol % catalyst loading. The system was shown to have an unprecedented ability to arylate both primary alkylamines (monoarylation) and secondary dialkylamines with aryl chlorides at room temperature. Electron-rich and -poor aryl and heteroaryl halides, as well as those featuring <i>ortho</i> substitution, were well tolerated, while substrates featuring both primary and secondary amine groups were selectively arylated at the NH₂ position. Furthermore, a preliminary examination of performance in ammonia arylation and acetone α-arylation showed promising results, giving good conversion and high selectivity for monoarylation in both cases

New Phosphine-Functionalized NHC Ligands: Discovery of an Effective Catalyst for the Room-Temperature Amination of Aryl Chlorides with Primary and Secondary Amines

We report convenient and high-yielding syntheses of new phosphine-functionalized dihydroimidazolium salts and demonstrate their utility as ligand precursors for Buchwald–Hartwig amination. Several examples of the general formula [1-Mes-3-{2-(PR₂)­phenyl}­imidazolidin-2-ylium]­[BF₄] have been prepared, where phosphines of varying steric and electronic properties (R = Ph (<b>9</b>), Cy (<b>10</b>), 1-Ad (<b>11</b>)) are tethered by an <i>o</i>-phenylene group. The synthesis was not adaptable to <i>N</i>-aryl groups other than mesityl, giving unexpected phosphonium salt species instead. The synthesis was adapted to flexible benzyl-linked variants of the formula [1-Ar-3-{2-(PCy₂)­benzyl}­imidazolidin-2-ylium]­[BF₄], which allowed more steric variation of the dihydroimidazolium <i>N</i>-aryl group (Ar = Mes (<b>21</b>), Dipp (<b>22</b>)). A preliminary study of these hybrid NHC/P ligands in Buchwald–Hartwig amination catalysis (in situ precatalyst formation) revealed <b>11</b> to be the most active of the series. Premixing the isolated free NHC ligand 1-Mes-3-{2-(PAd₂)­phenyl}­imidazolidin-2-ylidene (<b>23</b>) with [Pd­(cinnamyl)­Cl]₂ provided a highly active precatalyst that performed well at room temperature and 1 mol % catalyst loading. The system was shown to have an unprecedented ability to arylate both primary alkylamines (monoarylation) and secondary dialkylamines with aryl chlorides at room temperature. Electron-rich and -poor aryl and heteroaryl halides, as well as those featuring <i>ortho</i> substitution, were well tolerated, while substrates featuring both primary and secondary amine groups were selectively arylated at the NH₂ position. Furthermore, a preliminary examination of performance in ammonia arylation and acetone α-arylation showed promising results, giving good conversion and high selectivity for monoarylation in both cases