Reports: GB3
46387-GB3 Enantioselective Dearomatization Agents Based on Chiral C2-Symmetric Ligands
Research in our group is directed at the broad area of organic reactions facilitated by metal complex bearing chiral C2-symmetric tetraamine ligands. Nonracemic samples of trans-N,N'-bis(pyridyl-2-methyl)cyclohexane-1,2-diamine and analogues thereof have been used to give a variety of enantioselective catalysts, but most reported studies of these ligands have involved small first-row transition metals. Following from the work of Harman and coworkers, we have been developing a series of low-valent molybdenum and tungsten complexes with chiral C2-symmetric tetraamine ligands which we hope to use in enantioselective dearomatization sequences. In recent months, we have expanded our work to include trans-N,N'-bis(pyridyl-2-methyl)-2,2'-bispyrrolidine and related ligands based on a chiral C2-symmetric 2,2'-bispyrrolidine backbone.
In earlier work, we showed that trans-N,N'-bis(pyridyl-2-methyl)cyclohexane-1,2-diamine and variations involving different heterocycles and N,N,-dimethyl groups react with Mo(CO)6 and W(CO)6 to give the corresponding tricarbonyl complexes (Scheme 1). Nitrosylation reactions under various conditions gave dicarbonyl mononitrosyl complexes, some of which spontaneously proceeded to the corresponding monocarbonyl mononitrosyl complexes, and others of which react further only under reflux. Differences in stereoisomeric preferences were noted for the different tetraamine ligands, with those bearing N-methylimidazolyl groups tending to favor a non-C2-symmetric cis-beta configuration. Monocarbonyl mononitrosyl molybdenum complexes of trans-N,N'-bis(pyridyl-2-methyl)cyclohexane-1,2-diamine and trans- N,N'-dimethyl-N,N'-bis(pyridyl-2-methyl)cyclohexane-1,2-diamine were each oxidized by one electron using iodine and bromine respectively, but attempts to bind aromatics through reduction of the resulting d5 metal centers were not successful, likely owing to insufficient pi-basicity of the metal.
Scheme 1. Established reaction series for molybdenum complexes of trans-N,N'-bis(pyridyl-2-methyl)cyclohexane-1,2-diamine.
In the past year, we have determined conditions to give monocarbonyl mononitrosyl tungsten complexes of trans-N,N'-bis(pyridyl-2-methyl)cyclohexane-1,2-diamine and trans- N,N'-dimethyl-N,N'-bis(pyridyl-2-methyl)cyclohexane-1,2-diamine in which the tetraamine is complexed exclusively in a C2-symmetric cis-alpha configuration (Scheme 2). We note that tungsten complexes tend to be inherently more pi-basic than their molybdenum analogs. Unfortunately, extensive attempts to oxidize the monocarbonyl mononitrosyl tungsten complexes under conditions similar to those used for the molybdenum complexes have been uniformly unsuccessful.
Scheme 2. Synthesis and attempted oxdidation of monocarbonyl mononitrosyl tungsten trans-N,N'-bis(pyridyl-2-methyl)cyclohexane-1,2-diamine and trans- N,N'-dimethyl-N,N'-bis(pyridyl-2-methyl)cyclohexane-1,2-diamine complexes.
Our most recent work has involved chiral C2-symmetric tetraamine ligands based on a bispyrrolidine rather than cyclohexyl backbone (Scheme 3). Though reports of these ligands are more scarce than those of the cyclohexyl-based versions, molecules such as (R,R)-N,N'-bis(pyridyl-2-methyl)-2,2'-bisypyrrolidine are potentially advantageous in the current work, as they are thought to be restricted to the C2-symmetric cis-alpha configuration in an octahedral coordination sphere. With stricter enforcement of the C2-symmetric configuration, we expect to be able to use variations of the ligand heterocycles in order to modulate the amount of electron density donated to the metal fragment. IR spectroscopic data confirmed the viability of this approach for the cyclohexyl-based ligands, but a preference of some of the tetramine ligand variants for the non-C2-symmetric cis-beta configuration stymied its application.
Scheme 3. Results of initial work with nonracemic N,N'-bis(N-methylimidazolyl-2-methyl)-2,2'-bisypyrrolidine.
ACS-PRF funds spent during the past year were used as summer salary for the PI and to purchase a Rayonet UV photoreactor needed for the synthesis of the shown bispyrrolidine salt. During the reported grant year, one of the students who worked on this project (Burgess) successfully defended an undergraduate thesis for departmental honors, received her degree, and began graduate study in chemistry at the University of Virginia. The cyclohexyl-based ligand work outlined above was presented by three students at the American Chemical Society 2009 spring national meeting in Salt Lake City, and we anticipate submission of a paper on this work in due time.
