31 research outputs found
Copper-Catalyst-Controlled Site-Selective Allenylation of Ketones and Aldehydes with Propargyl Boronates
A practical and highly site-selective copper-PhBPE-catalyst-controlled allenylation with propargyl boronates has been developed. The methodology has shown to be tolerant of diverse ketones and aldehydes providing the allenyl adducts in high selectivity. The BPE ligand and boronate substituents were shown to direct the site selectivity for which either propargyl or allenyl adducts can be acquired in high selectivity. A model is proposed that explains the origin of the site selectivity
General and Rapid Pyrimidine Condensation by Addressing the Rate Limiting Aromatization
The rate limiting
aromatization within the condensation approach
toward pyrimidines utilizing amidines and activated olefins was addressed
to provide for a general and rapid process. A strong solvent effect
was elucidated to affect the rate for the initial alkoxide elimination
from the intermediate Michael adduct wherein polar aprotic solvents
demonstrate an addition controlled aromatization. Spectroscopic studies
support a solvent dependent equilibrium between the amidine and alkoxide
base wherein the rate for aromatization is optimal when the equilibrium
toward the amidine anion was strongly favored
A Computational Investigation of the Ligand-Controlled Cu-Catalyzed Site-Selective Propargylation and Allenylation of Carbonyl Compounds
A copper-catalyzed
site-selective propargylation/allenylation reaction
toward carbonyl compounds has been mechanistically investigated using
a computational approach. Different reaction pathways and catalytic
cycles were investigated. Control of the site selectivity arises from
a destabilizing interaction introduced by the phenyl-substituted ligand
A copper-catalyzed asymmetric oxime propargylation enables the synthesis of the gliovirin tetrahydro-1,2-oxazine core
Atom-Economical Cross-Coupling of Internal and Terminal Alkynes to Access 1,3-Enynes
Selective carbon–carbon (C–C) bond formation in chemical synthesis generally requires pre-functionalized building blocks. However, the requisite pre-functionalization steps undermine the efficiency of multi-step synthetic sequences, which is particularly problematic in large-scale applications, such as in the commercial production of pharmaceuticals. Herein, we describe a selective and catalytic method for synthesizing 1,3-enynes without pre-functionalized building blocks. This method is facilitated by a tailored P,N-ligand that enables regioselective coupling and suppresses secondary E/Z-isomerization of the product. The transformation enables several classes of unactivated internal acceptor alkynes to be coupled with terminal donor alkynes to deliver 1,3-enynes in a highly regio- and stereoselective manner. The scope of compatible acceptor alkynes includes propargyl alcohols, (homo)propargyl amine derivatives, and (homo)propargyl carboxamides. The reaction is scalable and can operate effectively with 0.5 mol% catalyst loading. The products are versatile intermediates that can participate in various downstream transformations. We also present preliminary mechanistic experiments that are consistent with a redox-neutral Pd(II) catalytic cycle
Distal Stereocontrol Using Guanidinylated Peptides as Multifunctional Ligands: Desymmetrization of Diarylmethanes via Ullman Cross-Coupling
We
report the development of a new class of guanidine-containing
peptides as multifunctional ligands for transition-metal catalysis
and its application in the remote desymmetrization of diarylmethanes
via copper-catalyzed Ullman cross-coupling. Through design of these
peptides, high levels of enantioinduction and good isolated yields
were achieved in the long-range asymmetric cross-coupling (up to 93:7
er and 76% yield) between aryl bromides and malonates. Our mechanistic
studies suggest that distal stereocontrol is achieved through a Cs-bridged
interaction between the Lewis-basic <i>C</i>-terminal carboxylate
of the peptides with the distal arene of the substrate
Total Synthesis of (−)-Lasonolide A
The lasonolides are novel polyketides
that have displayed remarkable biological activity in vitro against
a variety of cancer cell lines. Herein we describe our first-generation
approach to the formal synthesis of lasonolide A. The key findings
from these studies ultimately allowed us to go on and complete a total
synthesis of lasonolide A. The convergent approach unites two highly
complex fragments utilizing a Ru-catalyzed alkene–alkyne coupling.
This type of coupling typically generates branched products; however,
through a detailed investigation, we are now able to demonstrate that
subtle structural changes to the substrates can alter the selectivity
to favor the formation of the linear product. The synthesis of the
fragments features a number of atom-economical transformations which
are highlighted by the discovery of an engineered enzyme to perform
a dynamic kinetic reduction of a β-ketoester to establish the
absolute stereochemistry of the southern tetrahydropyran ring with
high levels of enantioÂselectivity
Copper-Catalyzed Asymmetric Propargylation of Cyclic Aldimines
The copper-catalyzed asymmetric propargylation
of cyclic aldimines
is reported. The influence of the imine trimer to inhibit the reaction
was identified, and equilibrium constants between the monomer and
trimer were determined for general classes of imines. Asymmetric propargylation
of a diverse series of <i>N</i>-alkyl and <i>N</i>-aryl aldimines was achieved with good to high asymmetric induction.
The utility was demonstrated by a titanium catalyzed hydroamination
and reduction to generate the chiral indolizidines (−)-crispine
A and (−)-harmicine