Rapid Access to Azabicyclo[3.3.1]nonanes by a Tandem Diverted Tsuji–Trost Process

Abstract

At hree-step synthesis of the 2-azabicyclo[3.3.1]nonaner ing system from simple pyrroles, employing a combined photochemical/palladium-catalysed approach is reported. Substrate scope is broad,a llowing the incorporation of aw ider ange of functionalityr elevant to medicinal chemistry.M echanistic studies demonstrate that the processo ccurs by acid-assisted CÀNb ond cleavage followed by b-hydride eliminationt of orm ar eactive diene, demonstratingt hat efficient control of what mightb e considered off-cycle reactionsc an result in productive tandem catalytic processes. This represents as hort and versatile route to the biologically important morphan scaffold.

Structural Basis of Metallo-β-lactamase Inhibition byN-Sulfamoylpyrrole-2-carboxylates

“…N1-Sulfonylation. 53 Sodium hydride (2.20 g, 55.0 mmol, 60 wt %, 1.1 equiv) was added portionwise to the solution of pyrrole (3.47 mL, 50.0 mmol, 1.0 equiv) in dry DMF (150 mL) at 0 °C. The obtained mixture was stirred for 1 h at the same temperature (note for this step: a constant flow of nitrogen gas was used to reduce foaming).…”

Stereoselective two-carbon ring expansion of allylic amines via electronic control of palladium-promoted equilibria

“…This is presumed to occur in an anti fashion based on previous reports, 17 leading to an intermediate which is then unable to undergo immediate outer sphere C–N bond formation as this would result in the geometrically unfeasible E -alkene 12. The complex therefore appears to undergo C 1 –C 2 rotation, potentially aided by the adjacent ester, 18 to form N–Pd intermediate 13 which is presumed to be the non-nucleophilic catalyst resting state. Following this, C–N bond formation via an inner sphere process gives the ( S )-stereocentre observed.…”

Stereoselective Two-Carbon Ring Expansion of Allylic Amines via Electronic Control of Palladium-Promoted Equilibria

“…This is presumed to occur in an anti fashion based on previous reports, 16 leading to an intermediate which is then unable to undergo immediate outer sphere C-N bond formation as this would result in the geometrically unfeasible E-alkene 12. The complex therefore appears to undergo C1-C2 rotation, potentially aided by the adjacent ester, 17 to form N-Pd intermediate 13 which is assumed to be the non-nucleophilic catalyst resting state. Following this, C-N bond formation via an inner sphere process gives the (S)stereocentre observed.…”