Frustrated Radical Pairs in Organic Synthesis.

Frustrated radical pairs (FRPs) describe the phenomenon that two distinct radicals─which would otherwise annihilate each other to form a closed-shell covalent adduct─can coexist in solution, owing to steric repulsion or weak bonding association. FRPs are typically formed via spontaneous single-electron transfer between two sterically encumbered precursors─an oxidant and a reductant─under ambient conditions. The two components of a FRP exhibit orthogonal chemical properties and can often act in cooperativity to achieve interesting radical reactivities.

Regioselective aliphatic C-H functionalization using frustrated radical pairs.

Frustrated Lewis pairs (FLPs) are well documented for the activation of small molecules such as dihydrogen and carbon dioxide. Although canonical FLP chemistry is heterolytic in nature, recent work has shown that certain FLPs can undergo single-electron transfer to afford radical pairs. Owing to steric encumbrance and/or weak bonding association, these radicals do not annihilate one another, and they have thus been named frustrated radical pairs (FRPs).

Working at the interfaces of data science and synthetic electrochemistry.

Electrochemistry is quickly entering the mainstream of synthetic organic chemistry. The diversity of new transformations enabled by electrochemistry is to a large extent a consequence of the unique features and reaction parameters in electrochemical systems including redox mediators, applied potential, electrode material, and cell construction. While offering chemists new means to control reactivity and selectivity, these additional features also increase the dimensionalities of a reaction system and complicate its optimization.

Using Data Science To Guide Aryl Bromide Substrate Scope Analysis in a Ni/Photoredox-Catalyzed Cross-Coupling with Acetals as Alcohol-Derived Radical Sources.

Ni/photoredox catalysis has emerged as a powerful platform for C(sp)-C(sp) bond formation. While many of these methods typically employ aryl bromides as the C(sp) coupling partner, a variety of aliphatic radical sources have been investigated. In principle, these reactions enable access to the same product scaffolds, but it can be hard to discern which method to employ because nonstandardized sets of aryl bromides are used in scope evaluation.

Predicting Reaction Yields via Supervised Learning.

Numerous disciplines, such as image recognition and language translation, have been revolutionized by using machine learning (ML) to leverage big data. In organic synthesis, providing accurate chemical reactivity predictions with supervised ML could assist chemists with reaction prediction, optimization, and mechanistic interrogation.To apply supervised ML to chemical reactions, one needs to define the object of prediction (e.

Bayesian reaction optimization as a tool for chemical synthesis.

Reaction optimization is fundamental to synthetic chemistry, from optimizing the yield of industrial processes to selecting conditions for the preparation of medicinal candidates. Likewise, parameter optimization is omnipresent in artificial intelligence, from tuning virtual personal assistants to training social media and product recommendation systems. Owing to the high cost associated with carrying out experiments, scientists in both areas set numerous (hyper)parameter values by evaluating only a small subset of the possible configurations.

Direct Use of Carboxylic Acids in the Photocatalytic Hydroacylation of Styrenes To Generate Dialkyl Ketones.

A general protocol for the hydroacylation of styrenes from aliphatic carboxylic acids is reported. These reactions proceed via β-scission of a phosphoranyl radical that is accessed by photoredox catalysis, followed by addition of the resulting acyl radical to the styrenyl olefin. We show that phosphine tunability is critical for efficient intermolecular coupling due to competitive quenching of the photocatalyst by the olefin.

Direct C-C Bond Formation from Alkanes Using Ni-Photoredox Catalysis.

A method for direct cross coupling between unactivated C(sp)-H bonds and chloroformates has been accomplished via nickel and photoredox catalysis. A diverse range of feedstock chemicals, such as (a)cyclic alkanes and toluenes, along with late-stage intermediates, undergo intermolecular C-C bond formation to afford esters under mild conditions using only 3 equiv of the C-H partner. Site selectivity is predictable according to bond strength and polarity trends that are consistent with the intermediacy of a chlorine radical as the hydrogen atom-abstracting species.

Asymmetric Organocatalytic Reductive Coupling Reactions between Benzylidene Pyruvates and Aldehydes.

An organocatalytic three-component reductive coupling reaction between dimethyl phosphite, benzylidene pyruvates, and aldehydes is reported. A chiral triaryliminophosphorane catalyst promotes Pudovik addition, which is followed by phospha-Brook rearrangement to transiently generate enolates that are trapped stereoselectively by aldehydes. This reductive coupling provides vicinal polyfunctionalized stereocenters from readily available prochiral starting materials with excellent diastereoselectivity, enantioselectivity, and yield.