New methods and strategies for the direct functionalization of C-H bonds are beginning to reshape the field of retrosynthetic analysis, affecting the synthesis of natural products, medicines and materials. The oxidation of allylic systems has played a prominent role in this context as possibly the most widely applied C-H functionalization, owing to the utility of enones and allylic alcohols as versatile intermediates, and their prevalence in natural and unnatural materials. Allylic oxidations have featured in hundreds of syntheses, including some natural product syntheses regarded as "classics". Despite many attempts to improve the efficiency and practicality of this transformation, the majority of conditions still use highly toxic reagents (based around toxic elements such as chromium or selenium) or expensive catalysts (such as palladium or rhodium). These requirements are problematic in industrial settings; currently, no scalable and sustainable solution to allylic oxidation exists. This oxidation strategy is therefore rarely used for large-scale synthetic applications, limiting the adoption of this retrosynthetic strategy by industrial scientists. Here we describe an electrochemical C-H oxidation strategy that exhibits broad substrate scope, operational simplicity and high chemoselectivity. It uses inexpensive and readily available materials, and represents a scalable allylic C-H oxidation (demonstrated on 100 grams), enabling the adoption of this C-H oxidation strategy in large-scale industrial settings without substantial environmental impact.

http://europepmc.org/articles/PMC4860034?pdf=render

Scalable and sustainable electrochemical allylic C–H oxidation

Thiolato-complexes of the transition metals

Metal-catalyzed cross-coupling reactions belong to the most important transformations in organic synthesis Copper catalysis has received great attention owing to the low toxicity and low cost of copper However, traditional Ullmann-type couplings suffer from limited substrate scopes and harsh reaction conditions The introduction of several bidentate ligands, such as amino acids, diamines, 1,3-diketones, and oxalic diamides, over the past two decades has totally changed this situation as these ligands enable the copper-catalyzed coupling of aryl halides and nucleophiles at both low reaction temperatures and catalyst loadings The reaction scope has also been greatly expanded, rendering this copper-based cross-coupling attractive for both academia and industry In this Review, we have summarized the latest progress in the development of useful reaction conditions for the coupling of (hetero)aryl halides with different nucleophiles Additionally, recent advances in copper-catalyzed coupling reactions with aryl boronates and the copper-based trifluoromethylation of aromatic electrophiles will be discussed

Selected Copper-Based Reactions for C-N, C-O, C-S and C-C Bond Formation

reactions constituted an important breakthrough in the application of radical chemistry in organic synthesis.2 An important and very attractive feature of these reactions is their high degree of functional group tolerance. Since radicals are usually stable under protic conditions, alcohols or even water can, in principle, be used as solvents in radical chemistry. Consequently, protic functional groups do not need protection. As soon as the underlying principles of the kinetic and thermodynamic behavior of free radicals were firmly established, efficient synthetic applications became feasible.3 The use of chain reactions has resulted in a number of very impressive total syntheses of natural products. An example is shown in eq 1.4 The characteristic features of free radicals can by now be deduced from ESR data.5 The course of some radical reactions can be understood by theoretical means.6

Reagent-Controlled Transition-Metal-Catalyzed Radical Reactions

The article discusses the mechanisms and the applications in organic synthesis, materials, supramolecular, and polymer synthesis of most organic reactions mediated by single electron transfer. Each reaction or class of reactions will be discussed by starting with the original discovery publication, followed by a summary of all or most review articles published in the field, and a discussion of the mechanism(s) and of the most important methodologic and synthetic developments since the most recent review was published. The mechanisms of most organic reactions are considered to proceed by two-electron transfer pathways, even though both biology and radical chemistry rely extensively on one-electron transfer processes. Radicals generated by homolytic cleavage at high temperature were traditionally employed in the industrial production of polymers and to a lesser extent in the synthesis of organic molecules.

Single electron transfer in radical ion and radical-mediated organic, materials and polymer synthesis.

Epoxides are reductively cleaved by means of lithium 4,4'-di-tert-butylbiphenylide. Ethylene oxide itself cleaves to lithium 2-lithioethoxide in less than 5 min at −95 o C. Epoxides possessing one unsubstituted carbon atom reduce in a matter of minutes at −78°C

Synthetically useful .beta.-lithioalkoxides from reductive lithiation of epoxides by aromatic radical anions

Synthetically useful dianions via reductive lithiation of tetrahydrofurans by aromatic radical anions

A very general preparative method for homoallyllithiums consists of reductive lithiation of homoallyl phenyl sulfides by lithium 4,4'-di-tert-butylbiphenylide. The sulfides can be prepared by a variety of methods including (1) the triethylamine-catalyzed addition of thiophenol to a conjugated enal or enone followed by a Wittig or Peterson olefination, (2) the reaction of a silyl enol ether with a diphenyl dithioacetal catalyzed by stannic chloride, followed by a Peterson olefination, or (3) the treatment of the lithio derivatives of phenyl thioethers or thioacetals or the corresponding cuprates with allyl halides

Generation, some synthetic uses, and 1,2-vinyl rearrangements of secondary and tertiary homoallyllithiums, including ring contractions and A ring expansion. Remarkable acceleration of the rearrangement by an oxyanionic group

Les γ-lithioalcoolates de lithium sont prepares par reaction du di-t-butyl-4,4' biphenylure de lithium avec les oxetannes

.gamma.-Lithioalkoxides via reductive lithiation of oxetanes by aromatic radical-anions

A novel process and intermediates thereof for making 4,5-dihydro-pyrazolo[3,4-c]pyrid-2-ones of the type shown below from appropriate phenyl hydrazines is described. These compounds can be useful as factor Xa inhibitors.

Boguslaw Mudryk

Papers

Synthetically useful .beta.-lithioalkoxides from reductive lithiation of epoxides by aromatic radical anions

Synthetically useful dianions via reductive lithiation of tetrahydrofurans by aromatic radical anions

Generation, some synthetic uses, and 1,2-vinyl rearrangements of secondary and tertiary homoallyllithiums, including ring contractions and A ring expansion. Remarkable acceleration of the rearrangement by an oxyanionic group

.gamma.-Lithioalkoxides via reductive lithiation of oxetanes by aromatic radical-anions

Process for preparing 4,5-dihydro-pyrazolo [3,4-c]pyrid-2-ones