Computational Study on the Mechanism and Selectivity of C–H Bond Activation and Dehydrogenative Functionalization in the Synthesis of Rhazinilam

Abstract

The key platinum mediated C-H bond activation and functionalization steps in the synthesis of (-)-rhazinilam (Johnson, J. A.; Li, N.; Sames, D. J. Am. Chem. Soc. 2002, 124, 6900) were investigated using the M06 and B3LYP density functional approximation methods. This computational study reveals that ethyl group dehydrogenation begins with activation of a primary C-H bond in preference to a secondary C-H bond in an insertion/methane elimination pathway. The C-H activation step is found to be reversible while the methane elimination (reductive elimination) transition state controls rate and diastereoselectivity. The chiral oxazolinyl ligand induces ethyl group selectivity through stabilizing weak interactions between its phenyl group (or cyclohexyl group) and the carboxylate group. After C-H activation and methane elimination steps, Pt-C bond functionalization occurs through β-hydride elimination to give the alkene platinum hydride complex.

CH Activation: A Complementary Tool in the Total Synthesis of Complex Natural Products

“…Despite the modest yield and diastereoselectivity, together with the necessity using a stoichiometric amount of platinum, the success of this early example of CH activation was remarkable and highly instructive. A recent computational study based on density functional approximation methods reported by Ellis and Ess also provided further insights on the mechanism and selectivity of this CH activation/dehydrogenation reaction 10. Finally, isomerically pure imine 9 was subjected to transamination (NH 2 OH) followed by a palladium‐catalyzed macrolactamization11 and subsequent decarboxylation to complete the total synthesis of (−)‐rhazinilam ( 1 ).…”

Rational Design in Catalysis: A Mechanistic Study of β-Hydride Eliminations in Gold(I) and Gold(III) Complexes Based on Features of the Reaction Valley

“…This work was triggered by the following findings: (1) gold­(I) alkyl complexes are inert toward β-elimination reactions, and very detailed experimental evidence exists that accounts for this behavior; (2) on the contrary, gold­(III) has a d 8 electron configuration [valence isoelectronic with palladium­(II) and platinum­(II)], for which β-hydride eliminations are common; ,− (3) gold­(III)-catalyzed β-hydride eliminations have recently been suggested to occur in a gold complex featuring a highly strained cycloalkyl ligand . Guided by (1)–(3), we performed a detailed mechanistic study of β-hydride eliminations for a variety of gold­(I) and gold­(III) alkyl complexes to shed light onto the different mechanisms involving gold­(I) and gold­(III).…”