Deuterium Labelling to Extract Local Stereochemical Information by VCD Spectroscopy in C-D Stretching Region: A Case Study of Sugars

Stereochemical elucidation of molecules with multiple chiral centers is difficult. Even with VCD spectroscopy, excluding all but one diastereomeric structural candidates is challenging because stereochemical inversion of one chiral center...

Total Synthesis of Resolvin T4

A total synthesis of resolvin T4 was achieved by connecting three intermediates by Wittig reactions. The enal in the C1–C10 part was constructed through reduction of a propargylic alcohol with Red-Al followed by oxidation. The enal moiety in the C11–C16 part was synthesized by a ring-opening reaction of a silyl epoxide followed by a Peterson elimination. The chiral centers at C7 and C13 were constructed by ruthenium-catalyzed asymmetric transfer hydrogenation.

A Novel Dual Organocatalyst for the Asymmetric Pinder Reaction and a Mechanistic Proposal Consistent with the Isoinversion Effect Thereof

In general, the Pinder reaction concerns the reaction between an enolisable anhydride and an aldehyde proceeding initially through a Knoevenagel reaction followed by the ring closing process generating lactones with at least two chiral centers. These scaffolds are frequently present in natural products and synthetic bioactive molecules, hence it has attracted intense interest in organic synthesis and medicinal chemistry, particularly with respect to controlling the diastereo- and enantioselectivity. To the best of our knowledge, there has been only one attempt prior to this work towards the development of a catalytic enantioselective Pinder reaction. In our approach, we designed, synthesized, and tested dual chiral organocatalysts by combining BIMAH amines, (2-(α-(alkyl)methanamine)-1H-benzimidazoles, and a Lewis acid motif, such as squaramides, ureas and thioureas. The optimum catalyst was the derivative of isopropyl BIMAH bearing a bis(3,5-trifluoromethyl) thiourea, which afforded the Pinder products from various aromatic aldehydes with diastereomeric ratio >98:2 and enatioselectivity up to 92 ee%. Interestingly, the enantioselectivity of this catalyzed process is increased at higher concentrations and exhibits an isoinversion effect, namely an inverted "U" shaped dependency with respect to the temperature. Mechanistically, these features, point to a transition state involving an entropy-favored heterodimer interaction between a catalyst/anhydride and a catalyst/aldehyde complex when all other processes leading to this are much faster in comparison above the isoinversion temperature.

Diastereoselective Pd-catalyzed decarboxylative allylation to construct quaternary stereocenters using sulfinimine as the directing group

A robust Pd(0)-catalyzed decarboxylation of allylic alkylation has been developed to construct quaternary stereocenters through the use of chiral tert-butanesulfinamide as the directing group. This strategy provides a simple and efficient route to the construction of quaternary chiral centers at the α-position of chiral sulfinamides, with high diastereoselectivities and high yields.

Iron-catalyzed Stereoselective Allylboration of 3,4-Dihydroisoquinolines with Potassium allyltrifuoroborates

An iron-catalyzed allyation of isoquinoline with potassium allytrifluoborate was described. The operation of this reaction is very simple and highly practical. The diastereoismoer having two adjacent chiral centers were obtained in single anti configuration.

The Price is Right: Predicting Reagent Prices

<div> <p>We present a model for estimating the price of a reagent from its chemical structure. It is intended to be useful when doing reagent selection for library design. The model is a Random Forest regressor which is trained on the MolPort catalog of 302K reagents and the log of their price. For descriptors we use topological fingerprints from RDKit: chiral Morgan fingerprints, its medicinal chemistry descriptors, and counts of undetermined chiral centers. The model has an out-of-bag performance of 34% variance explained in log Price. When predicting on known reagents, the model explains 91% of the variance in log Price. We analyzed the model to understand the errors that the model makes. We show that the compounds with the highest errors have only a subtly different structure from similar molecules, but very different in price. </p> </div>

The Price is Right: Predicting Reagent Prices

<div> <p>We present a model for estimating the price of a reagent from its chemical structure. It is intended to be useful when doing reagent selection for library design. The model is a Random Forest regressor which is trained on the MolPort catalog of 302K reagents and the log of their price. For descriptors we use topological fingerprints from RDKit: chiral Morgan fingerprints, its medicinal chemistry descriptors, and counts of undetermined chiral centers. The model has an out-of-bag performance of 34% variance explained in log Price. When predicting on known reagents, the model explains 91% of the variance in log Price. We analyzed the model to understand the errors that the model makes. We show that the compounds with the highest errors have only a subtly different structure from similar molecules, but very different in price. </p> </div>