16 research outputs found
Mechanism of Nakamuraās Bisphosphine-Iron-Catalyzed Asymmetric C(sp<sup>2</sup>)āC(sp<sup>3</sup>) Cross-Coupling Reaction: The Role of Spin in Controlling Arylation Pathways
Quantum
mechanical calculations are employed to investigate the
mechanism and origin of stereoinduction in asymmetric iron-catalyzed
CĀ(sp<sup>2</sup>)āCĀ(sp<sup>3</sup>) cross-coupling reaction
between Grignard reagents and Ī±-chloroesters. A coherent mechanistic
picture of this transformation is revealed. These results have broad
implications for understanding the mechanisms of iron-catalyzed cross-coupling
reactions and rational design of novel iron-based catalysts for asymmetric
transformations
Stereocontrol in a Combined Allylic Azide Rearrangement and Intramolecular Schmidt Reaction
Pre-equilibration of an interconverting set of isomeric
allylic
azides is coupled with an intramolecular Schmidt reaction to afford
substituted lactams stereoselectively. The effect of substitution
and a preliminary mechanistic study are reported. The synthetic potential
of this method is demonstrated in the context of an enantioselective
synthesis of an advanced intermediate leading toward pinnaic acid
Catalytic Kinetic Resolution of Disubstituted Piperidines by Enantioselective Acylation: Synthetic Utility and Mechanistic Insights
The catalytic kinetic resolution
of cyclic amines with achiral
N-heterocyclic carbenes and chiral hydroxamic acids has emerged as
a promising method to obtain enantio-enriched amines with high selectivity
factors. In this report, we describe the catalytic kinetic resolution
of disubstituted piperdines with practical selectivity factors (<i>s</i>, up to 52) in which we uncovered an unexpected and pronounced
conformational effect resulting in disparate reactivity and selectivity
between the cis- and trans-substituted piperidine isomers. Detailed
experimental and computational studies of the kinetic resolution of
various disubstituted piperidines revealed a strong preference for
the acylation of conformers in which the Ī±-substituent occupies
the axial position. This work provides further experimental and computational
support for the concerted 7-member transition state model for acyl
transfer reagents and expands the scope and functional group tolerance
of the secondary amine kinetic resolution
Mechanism of Rh<sub>2</sub>(II)-Catalyzed Indole Formation: The Catalyst Does Not Control Product Selectivity
Possible
mechanisms for Rh-promoted indole formation from vinyl/azidoarenes
were examined computationally, and a mechanism is proposed in which
the Rh catalyst promotes generation of a nitrene but is not directly
involved in cyclization
Concerted Amidation of Activated Esters: Reaction Path and Origins of Selectivity in the Kinetic Resolution of Cyclic Amines via NāHeterocyclic Carbenes and Hydroxamic Acid Cocatalyzed Acyl Transfer
The
N-heterocyclic carbene and hydroxamic acid cocatalyzed kinetic
resolution of cyclic amines generates enantioenriched amines and amides
with selectivity factors up to 127. In this report, a quantum mechanical
study of the reaction mechanism indicates that the selectivity-determining
aminolysis step occurs via a novel concerted pathway in which the
hydroxamic acid plays a key role in directing proton transfer from
the incoming amine. This modality was found to be general in amide
bond formation from a number of activated esters including those generated
from HOBt and HOAt, reagents that are broadly used in peptide coupling.
For the kinetic resolution, the proposed model accurately predicts
the faster reacting enantiomer. A breakdown of the steric and electronic
control elements shows that a gearing effect in the transition state
is responsible for the observed selectivity
Alkenes as Chelating Groups in Diastereoselective Additions of Organometallics to Ketones
Alkenes have been discovered to be
chelating groups to ZnĀ(II),
enforcing highly stereoselective additions of organozincs to Ī²,Ī³-unsaturated
ketones. <sup>1</sup>H NMR studies and DFT calculations provide support
for this surprising chelation mode. The results expand the range of
coordinating groups for chelation-controlled carbonyl additions from
heteroatom Lewis bases to simple CāC double bonds, broadening
the 60 year old paradigm
Mild Aromatic Palladium-Catalyzed Protodecarboxylation: Kinetic Assessment of the Decarboxylative Palladation and the Protodepalladation Steps
Mechanism studies of a mild palladium-catalyzed
decarboxylation
of aromatic carboxylic acids are described. In particular, reaction
orders and activation parameters for the two stages of the transformation
were determined. These studies guided development of a catalytic system
capable of turnover. Further evidence reinforces that the second stage,
protonation of the arylpalladium intermediate, is the rate-determining
step of the reaction. The first step, decarboxylative palladation,
is proposed to occur through an intramolecular electrophilic palladation
pathway, which is supported by computational and mechanism studies.
In contrast to the reverse reaction (CāH insertion), the data
support an electrophilic aromatic substitution mechanism involving
a stepwise intramolecular protonation sequence for the protodepalladation
portion of the reaction
Nickel-Catalyzed Cross-Coupling of Photoredox-Generated Radicals: Uncovering a General Manifold for Stereoconvergence in Nickel-Catalyzed Cross-Couplings
The cross-coupling of sp<sup>3</sup>-hybridized organoĀboron
reagents via photoredox/ānickel dual catalysis represents a
new paradigm of reactivity for engaging alkylĀmetallic reagents
in transition-metal-catalyzed processes. Reported here is an investigation
into the mechanistic details of this important transformation using
density functional theory. Calculations bring to light a new reaction
pathway involving an alkylĀnickelĀ(I) complex generated by addition
of an alkyl radical to Ni(0) that is likely to operate simultaneously
with the previously proposed mechanism. Analysis of the enantioĀselective
variant of the transformation reveals an unexpected manifold for stereoĀinduction
involving dynamic kinetic resolution (DKR) of a NiĀ(III) intermediate
wherein the stereoĀdetermining step is <i>reductive elimination</i>. Furthermore, calculations suggest that the DKR-based stereoĀinduction
manifold may be responsible for stereoĀselectivity observed in
numerous other stereoĀconvergent Ni-catalyzed cross-couplings
and reductive couplings
Stereocontrol in Asymmetric S<sub>E</sub>ā² Reactions of Ī³āSubstituted Ī±,Ī²-Unsaturated Aldehydes
Asymmetric
S<sub>E</sub>ā² reactions of (<i>E</i>)- and (<i>Z</i>)-Ī³-substituted-Ī±,Ī²-unsaturated
aldehydes have been studied for the stereocontrolled preparation of
nonracemic alcohols. Mild exchange reactions of allylic stannanes
provide access to chiral 1,3-bisĀ(tolylsulfonyl)-4,5-diphenyl-1,3-diaza-2-borolidines.
These reagents display reactivity with the Ī³-substituted Ī±,Ī²-unsaturated
aldehydes, which is characterized by matched and mismatched elements
of stereocontrol. Computational analysis (using density functional
theory) provides valuable insights to guide reaction development
Highly Selective Radical Relay 1,4-Oxyimination of Two Electronically Differentiated Olefins
Radical
addition reactions of olefins have emerged as an attractive
tool for the rapid assembly of complex structures, and have plentiful
applications in organic synthesis, however, such reactions are often
limited to polymerization or 1,2-difunctionalization. Herein, we disclose
an unprecedented radical relay 1,4-oxyimination of two electronically
differentiated olefins with a class of bifunctional oxime carbonate
reagents via an energy transfer strategy. The protocol is highly chemo-
and regioselective, and three different chemical bonds (CāO,
CāC, and CāN bonds) were formed in a single operation
in an orchestrated manner. Notably, this reaction provides rapid access
to a large variety of structurally diverse 1,4-oxyimination products,
and the obtained products could be easily converted into valuable
biologically relevant Ī“-hydroxyl-Ī±-amino acids. With a
combination of experimental and theoretical methods, the mechanism
for this 1,4-oxyimination reaction has been investigated. Theoretical
calculations reveal that a radical chain mechanism might operate in
the reaction