Search for: All records

Abstract Recently, Huang and co‐workers reported a catalytic reaction that utilizes H₂as the sole reductant for a C−C coupling of allyl groups with yields up to 96 %. Here we use computational quantum chemistry to identify several key features of this reaction that provide clarity on how it proceeds. We propose the involvement of a Pd−Pd bound dimer precatalyst, demonstrate the importance of ligand π‐π interactions and counterions, and identify a new, energetically viable, mechanism involving two dimerized, outer‐sphere reductive elimination transition structures that determine both the rate and selectivity. Although we rule out the previously proposed transmetalation step on energetic grounds, we show it to have an unusual aromatic transition structure in which two Pd atoms support rearranging electrons. The prevalence of potential metal‐supported pericyclic reactions in this system suggests that one should consider such processes regularly, but the results of our calculations also indicate that one should do so with caution. 

Abstract Density functional theory was used to elucidate the mechanism and the pericyclicity of chromium‐catalyzed bicyclization reactions that purportedly involve 8‐electron electrocyclization steps. Our computational results indicate that these reactions do indeed proceed via 8‐electron electrocyclization rather than an alternative pathway involving 4‐electron electrocyclization followed by Cope rearrangement. The role of C=[M] groups on the electrocyclization, specifically its pericyclicity, was examined in detail using modern theoretical tools. 

Abstract Asymmetric catalysis is an advanced area of chemical synthesis, but the handling of abundantly available, purely aliphatic hydrocarbons has proven to be challenging. Typically, heteroatoms or aromatic substructures are required in the substrates and reagents to facilitate an efficient interaction with the chiral catalyst. Confined acids have recently been introduced as tools for homogenous asymmetric catalysis, specifically to enable the processing of small unbiased substrates¹. However, asymmetric reactions in which both substrate and product are purely aliphatic hydrocarbons have not previously been catalysed by such super strong and confined acids. We describe here an imidodiphosphorimidate-catalysed asymmetric Wagner–Meerwein shift of aliphatic alkenyl cycloalkanes to cycloalkenes with excellent regio- and enantioselectivity. Despite their long history and high relevance for chemical synthesis and biosynthesis, Wagner–Meerwein reactions utilizing purely aliphatic hydrocarbons, such as those originally reported by Wagner and Meerwein, had previously eluded asymmetric catalysis. 

Abstract Herein, we describe our synthetic efforts toward the pupukeanane natural products, in which we have completed the first enantiospecific route to 2‐isocyanoallopupukeanane in 10 steps (formal synthesis), enabled by a key Pd‐mediated cyclization cascade. This subsequently facilitated an unprecedented bio‐inspired “contra‐biosynthetic” rearrangement, providing divergent access to 9‐isocyanopupukeanane in 15 steps (formal synthesis). Computational studies provide insight into the nature of this rearrangement. 

Abstract Stereoselective Zweifel olefination using boronate complexes carrying two different reactive π‐systems was achieved to synthesize vinyl heteroarenes and conjugated 1,3‐dienes in good yield and up to 100 % stereoselectivity, which remains unexplored until now. Most importantly, we report the unprecedented formation ofEvs.Z‐vinyl heteroarenes for different heteroarenes under identical conditions. Density functional theory (DFT) investigations unveil the mechanistic dichotomy between olefin and heteroarene activation followed by 1,2‐migration, leading toEorZ‐vinyl heteroarenes respectively. We also report a previously unknown reversal of stereoselectivity by using 2,3‐Dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ) as an electrophile. The Zweifel olefination using a boronate complex that carries two different olefins was previously unexplored due to significant challenges associated with the site‐selective activation of olefins. We have solved this problem and reported the site‐selective activation of olefins for the stereoselective synthesis of 1,3‐dienes. 

Abstract A site‐selective C(3)/C(4)‐alkylation ofN‐pyridylisoquinolones is achieved by employing C−C bond activation of cyclopropanols under Ru(II)‐catalyzed/Cu(II)‐mediated conditions. The regioisomeric ratios of the products follow directly from the electronic nature of the cyclopropanols and isoquinolones used, with electron‐withdrawing groups yielding predominantly the C(3)‐alkylated products, whereas the electron‐donating groups primarily generate the C(4)‐alkylated isomers. Density functional theory calculations and detailed mechanistic investigations suggest the simultaneous existence of the singlet and triplet pathways for the C(3)‐ and C(4)‐product formation. Further transformations of the products evolve the utility of the methodology thereby yielding scaffolds of synthetic relevance. 

Abstract The [3s,5s]‐sigmatropic shift is an example of an orbital‐symmetry forbidden pericyclic reaction that is outcompeted by the allowed [3s,3s]‐sigmatropic shift. Density functional theory calculations are used to show that Pd^II‐complexed systems with strategically placed substituents engaging in key stereoelectronic effects can select for the [3s,5s] process, thereby outcompeting both orbital‐symmetry‐allowed [3s,3s]‐ and [3s,5a]‐shifts.