The mechanistic foundation behind the identity of a phosphine ligand that best promotes a desired reaction outcome is often non-intuitive, and thus has been addressed in numerous experimental and theoretical studies. In this work, multivariate correlations of reaction outcomes using 38 different phosphine ligands were combined with classic potentiometric analyses to study a Suzuki reaction, for which the site selectivity of oxidative addition is highly dependent on the nature of the phosphine. These studies shed light on the generality of hypotheses regarding the structural influence of different classes of phosphine ligands on the reaction mechanism(s), and deliver a methodology that should prove useful in future studies of phosphine ligands.
Synthetically useful radical thiol–ene
reactions can be
initiated by visible light irradiation in the presence of transition
metal polypyridyl photocatalysts. The success of this method relies
upon the use of p-toluidine as an essential additive.
Using these conditions, high-yielding thiol–ene reactions of
cysteine-containing biomolecules can be accomplished using biocompatibile
wavelengths of visible light, under aqueous conditions, and with the
thiol component as the limiting reagent. We present evidence that p-toluidine serves as a redox mediator that is capable of
catalyzing the otherwise inefficient photooxidation of thiols to the
key thiyl radical intermediate. Thus, we show that co-catalytic oxidants
can be important in the design of synthetic reactions involving visible
light photoredox catalysis.
Despite the enormous potential for the use of stereospecific cross-coupling reactions to rationally manipulate the three-dimensional structure of organic molecules, the factors that control the transfer of stereochemistry in these reactions remain poorly understood. Herein we report a mechanistic and synthetic investigation into the use of enantioenriched alkylboron nucleophiles in stereospecific Pd-catalyzed Suzuki cross-coupling reactions. By developing a suite of molecular descriptors of phosphine ligands, we could apply predictive statistical models to select or design distinct ligands that respectively promoted stereoinvertive and stereoretentive cross-coupling reactions. Stereodefined branched structures were thereby accessed through the predictable manipulation of absolute stereochemistry, and a general model for the mechanism of alkylboron transmetallation was proposed.
Herein, we report the integration of simple linear regressions with gold(I) catalysis to interrogate the influence of phosphine structure on metal-catalyzed organic transformations. We demonstrate that observed product ratios in [4 + 3]/[4 + 2] cycloisomerization processes are influenced by both steric and electronic properties of the phosphine, which can be represented by the Au-Cl distance. In contrast, the observed selectivity of a similar [2 + 3]/[2 + 2] cycloisomerization is governed by L/B1, a steric parameter. Using this correlation, we were able to accurately predict the selectivity of a previously untested, Buchwald-type ligand to enhance selectivity for the same transformation. This ligand found further utility in increasing the selectivity of a previously reported gold-catalyzed cycloisomerization/arylation of 1,6-enynes by ~1 kcal/mol.
Three
types of dirhodium tetrakis(triarylcyclopropanecarboxylate)
complexes were generated and shown to adopt disparate high-symmetry
structures. These catalysts were evaluated in the intermolecular C–H
functionalization of an array of terminally substituted n-alkanes and displayed various site-selectivity as a function of
catalyst and substrate structure, which could be correlated through
quantitative relationships.
A new catalyst system capable of selective chloride functionalization in the Pd-catalyzed amination of 3,2- and 5,2- Br/Cl-pyridines is reported. A reaction optimization strategy employing ligand parametrization led to the identification of 1,1'-bis[bis(dimethylamino)phosphino]ferrocene "DMAPF", a readily available yet previously unutilized diphosphine, as a uniquely effective ligand for this transformation.
Computed descriptors for acyclic diaminocarbene ligands are developed in the context of a gold catalyzed enantioselective tandem [3,3]-sigmatropic rearrangement-[2+2]-cyclization. Surrogate structures enable the rapid identification of parameters that reveal mechanistic characteristics. The observed selectivity trends are validated in a robust multivariate analysis facilitating the development of a highly enantioselective process.
Delineating complex ligand effects
on enantioselectivity is a longstanding
challenge in asymmetric catalysis. With α-amino acid ligands,
the essential difficulty lies in accurately describing integrated
perturbations induced by simultaneous variation about the α
side chain and N protecting group of the ligand, which hampers an
intuitive understanding of the structure–enantioselectivity
relationships. To deconvolute such complexity in chiral amino acid
enabled enantioselective C–H functionalization reactions, a
computational organometallic model system was developed. Whereas a
model based only on a conventional results in diminished predictive
power, the ground state Pd(II)-based models display an excellent ability
to describe the observed enantioselectivity. These structures were
leveraged using a multivariate modeling approach to successfully describe
Pd(II)-catalyzed C–H alkylation, alkenylation, and two C–H
arylation reactions, wherein descriptors of torsion angle, percent
buried volume, and NBO charge showed quantitative relevance to predict
enantiomeric excess. On the basis of the insights revealed in these
case studies, an optimal set of amino acid ligands is suggested to
provide maximum information in a screening campaign.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.