15 research outputs found
Total Synthesis of Acortatarin A Using a Pd(II)-Catalyzed Spiroketalization Strategy
The total synthesis of acortatarin A relying on a PdÂ(II)-catalyzed
spiroketalization is reported. This strategy allows a single stereocenter
in the spiroketalization substrate to produce the target efficiently
under mild conditions, installing the necessary oxygenation in the
backbone through an allylic transposition. The synthesis also verifies
that pollenopyrroside B and acortatarin A are the same compound, and
electrochemical studies suggest that the reported bioactivity is not
due to simple antioxidant properties
Enantioselective Alkyne Conjugate Addition Enabled by Readily Tuned Atropisomeric <i>P</i>,<i>N</i>‑Ligands
By
the nature of its structure, the 5-membered chiral biaryl heterocyclic
scaffold represents a departure from 6-membered <i>P</i>,<i>N</i>-ligands that facilitates tuning and enables ligand
evolution to address issues of selectivity and reactivity. In this
vein, the Cu-catalyzed enantioselective conjugate alkynylation of
Meldrum’s acid acceptors is reported using Me-StackPhos. Enabled
by this new ligand, the reaction tolerates a wide range of alkynes
furnishing the products in high yields and excellent enantioselectivity.
The transformation provides access to highly useful chiral β-alkynyl
Meldrum’s acid building blocks as demonstrated by an efficient
enantioselective synthesis of the preclinical agent OPC 51803
Catalytic Enantioselective Alkyne Addition to Nitrones Enabled by Tunable Axially Chiral Imidazole-Based P,N-Ligands
Although catalytic enantioselective alkyne addition is
an established
method for the synthesis of chiral propargylic alcohols and amines,
addition to nitrones presents unique challenges, and no general chiral
catalyst system has been developed. In this manuscript, we report
the first Cu-catalyzed enantioselective alkyne addition to nitrones
utilizing tunable axially chiral imidazole-based P,N-ligands. Our approach effectively overcomes difficulties
in both reactivity and selectivity, resulting in a simple Cu-catalyzed
protocol. The reaction accommodates a wide range of nitrones and alkynes,
enabling the streamlined synthesis of chiral propargyl N-hydroxylamines via the enantioselective C–C bond formation.
A diverse array of optically active nitrogen-containing compounds,
including chiral hydroxylamines, can be accessed directly through
facile transformations of the reaction products
Diastereoselective Synthesis of Protected 1,3-Diols by Catalytic Diol Relocation
A complementary diastereoselective
goldÂ(I) or bismuthÂ(III) catalyzed
tandem hemiacetalization/dehydrative cyclization of 1,5-monoallylic
diols was developed to access 1,3-dioxolanes and dioxanes. This methodology
provides rapid access to protected 1,3-diols under mild conditions
with high levels of diastereoselectivity
Catalytic Enantioselective Synthesis of Amino Skipped Diynes
The Cu-catalyzed synthesis of nonracemic
3-amino skipped diynes
via an enantiodetermining C–C bond formation is described using
StackPhos as ligand. Despite challenging issues of reactivity and
stereoselectivity inherent to these chiral skipped diynes, the reaction
tolerates an extremely broad substrate scope with respect to all components
and provides the title compounds in excellent enantiomeric excess.
The alkyne moieties are demonstrated here to be useful synthetic handles,
and 3-amino skipped diynes are convenient building blocks for enantioselective
synthesis
Design, Preparation, and Implementation of an Imidazole-Based Chiral Biaryl P,N-Ligand for Asymmetric Catalysis
A new
strategy for increasing the barrier to rotation in biaryls
has been developed that allows for the incorporation of 5-membered
aromatic heterocycles into chiral atropisomers. Using this concept,
an imidazole-based biaryl P,N-ligand has been designed and prepared
as a single enantiomer. This ligand performs exceptionally well in
the enantioselective A<sup>3</sup>-coupling, demonstrating the potential
of this new design element
Design, Preparation, and Implementation of an Imidazole-Based Chiral Biaryl P,N-Ligand for Asymmetric Catalysis
A new
strategy for increasing the barrier to rotation in biaryls
has been developed that allows for the incorporation of 5-membered
aromatic heterocycles into chiral atropisomers. Using this concept,
an imidazole-based biaryl P,N-ligand has been designed and prepared
as a single enantiomer. This ligand performs exceptionally well in
the enantioselective A<sup>3</sup>-coupling, demonstrating the potential
of this new design element
Incorporation of Axial Chirality into Phosphino-Imidazoline Ligands for Enantioselective Catalysis
A complementary
strategy for ligand tuning that enables controlling
ligand conformation is described here. The concept is demonstrated
with new ligands that are employed in the catalytic enantioselective
preparation of the highly important C2-aminoalkyl five-membered heterocycle
motif. The alkynylation/cyclization sequence developed here is convergent,
highly modular, and allows for a complementary scope to the heteroarylation
of imines. This new ligand platform should offer new possibilities
for expanding the use of PHIM-type ligands in a large variety of new
transformations
Controlling Regiochemistry in the Gold-Catalyzed Synthesis of Unsaturated Spiroketals
A novel
gold-catalyzed synthesis of unsaturated spiroketals that
addresses regioselectivity issues commonly reported in metal-catalyzed
spiroketalization of alkynes is reported. The reaction sequence is
regulated by an acetonide protecting group which undergoes extrusion
of acetone to deliver the desired spiroketals in good yields and diastereoselectivities.
The reaction, which is carried out under very mild conditions employing
AuCl as the catalyst, should be widely applicable in the synthesis
of a broad range of spiroketals
Design, Preparation, and Implementation of an Imidazole-Based Chiral Biaryl P,N-Ligand for Asymmetric Catalysis
A new
strategy for increasing the barrier to rotation in biaryls
has been developed that allows for the incorporation of 5-membered
aromatic heterocycles into chiral atropisomers. Using this concept,
an imidazole-based biaryl P,N-ligand has been designed and prepared
as a single enantiomer. This ligand performs exceptionally well in
the enantioselective A<sup>3</sup>-coupling, demonstrating the potential
of this new design element