14 research outputs found
CaptureâCollapse Heterocyclization:1,3-Diazepanes by CâN Reductive Elimination from Rhodacyclopentanones
Rhodacyclopentanones derived from
carbonylative CâC activation
of cyclopropyl ureas can be âcapturedâ by pendant nucleophiles
prior to âcollapseâ to 1,3-diazepanes. The choice of
N-substituent on the cyclopropane unit controls the oxidation level
of the product, such that C4âC5 unsaturated or saturated systems
can be accessed selectively
New Initiation Modes for Directed Carbonylative C-C Bond Activation:Rhodium-Catalyzed (3+1+2) Cycloadditions of Aminomethylcyclopropanes
Under carbonylative conditions, neutral
RhÂ(I)-systems modified
with weak donor ligands (AsPh<sub>3</sub> or 1,4-oxathiane) undergo
N-Cbz, N-benzoyl, or N-Ts directed insertion into the proximal CâC
bond of aminoÂmethylÂcycloÂpropanes to generate rhodacycloÂpentanone
intermediates. These are trapped by N-tethered alkenes to provide
complex perhydroisoindoles
Branch-selective, iridium-catalyzed hydroarylation of monosubstituted alkenes via a cooperative destabilization strategy
Carbonylative C-C Bond Activation of Electron-Poor Cyclopropanes:RhodiumâCatalyzed (3+1+2) Cycloadditions of Cyclopropylamides
Branch-Selective, Iridium-Catalyzed Hydroarylation of Monosubstituted Alkenes via a Cooperative Destabilization Strategy
Highly branch-selective, carbonyl-directed
hydroÂarylÂations
of monoÂsubstituted alkenes are described. The chemistry relies
upon a cationic IrÂ(I) catalyst modified with an electron deficient,
wide bite angle bisÂphosphine ligand. This work provides a regioÂisomeric
alternative to the Murai hydroÂarylÂation protocol
Branch-Selective, Iridium-Catalyzed Hydroarylation of Monosubstituted Alkenes via a Cooperative Destabilization Strategy
Highly branch-selective, carbonyl-directed
hydroÂarylÂations
of monoÂsubstituted alkenes are described. The chemistry relies
upon a cationic IrÂ(I) catalyst modified with an electron deficient,
wide bite angle bisÂphosphine ligand. This work provides a regioÂisomeric
alternative to the Murai hydroÂarylÂation protocol
Reversible CâC Bond Activation Enables Stereocontrol in Rh-Catalyzed Carbonylative Cycloadditions of Aminocyclopropanes
Upon exposure to neutral or cationic
RhÂ(I)-catalyst systems, amino-substituted
cyclopropanes undergo carbonylative cycloaddition with tethered alkenes
to provide stereochemically complex N-heterocyclic scaffolds. These
processes rely upon the generation and trapping of rhodacyclopentanone
intermediates, which arise by regioselective, Cbz-directed insertion
of Rh and CO into one of the two proximal aminocyclopropane CâC
bonds. For cyclizations using cationic RhÂ(I)-systems, synthetic and
mechanistic studies indicate that rhodacyclopentanone formation is
reversible and that the alkene insertion step determines product diastereoselectivity.
This regime facilitates high levels of stereocontrol with respect
to substituents on the alkene tether. The option of generating rhodacyclopentanones
dynamically provides a new facet to a growing area of catalysis and
may find use as a (stereo)Âcontrol strategy in other processes
New Initiation Modes for Directed Carbonylative CC Bond Activation: Rhodium-Catalyzed (3 + 1 + 2) Cycloadditions of Aminomethylcyclopropanes
Controlled Thiol-Ene Functionalization of Polyferrocenylsilane-block-Polyvinylsiloxane Copolymers
Copper-Catalyzed Racemization-Recycle of a Quaternary Center and Optimization Using a Combined Kinetics-DoE/MLR Modeling Approach
The copper-catalyzed racemization of a complex, quaternary
center
of a key intermediate on route to lanabecestat has been identified.
Optimization and mechanistic understanding were achieved through the
use of an efficient, combined kinetic-multiple linear regression approach
to experimental design and modeling. The use of a definitive screening
design with mechanistically relevant factors and a mixture of fitted
kinetic descriptors and empirical measurements facilitated the generation
of a model that accurately predicted complex reaction time course
behavior. The synergistic model was used to minimize the formation
of dimer byproducts, determine optimal conditions for batch operation,
and highlight superheated conditions that could be accessed in flow,
leading to a further increase in yield which was predicted by the
original model