Over the past decade, the most significant, conceptual advances in the field of fluorination were enabled most prominently by organo- and transition-metal catalysis. The most challenging transformation remains the formation of the parent C-F bond, primarily as a consequence of the high hydration energy of fluoride, strong metal-fluorine bonds, and highly polarized bonds to fluorine. Most fluorination reactions still lack generality, predictability, and cost-efficiency. Despite all current limitations, modern fluorination methods have made fluorinated molecules more readily available than ever before and have begun to have an impact on research areas that do not require large amounts of material, such as drug discovery and positron emission tomography. This Review gives a brief summary of conventional fluorination reactions, including those reactions that introduce fluorinated functional groups, and focuses on modern developments in the field.

/pdf/introduction-of-fluorine-and-fluorine-containing-functional-1i8kwiad20.pdf

Introduction of Fluorine and Fluorine-Containing Functional Groups

Metal-catalyzed carbon-sulfur bond formation.

In recent years, the use of essential oils (EOs) derived from aromatic plants as low-risk insecticides has increased considerably owing to their popularity with organic growers and environmentally conscious consumers. EOs are easily produced by steam distillation of plant material and contain many volatile, low-molecular-weight terpenes and phenolics. The major plant families from which EOs are extracted include Myrtaceae, Lauraceae, Lamiaceae, and Asteraceae. EOs have repellent, insecticidal, and growth-reducing effects on a variety of insects. They have been used effectively to control preharvest and postharvest phytophagous insects and as insect repellents for biting flies and for home and garden insects. The compounds exert their activities on insects through neurotoxic effects involving several mechanisms, notably through GABA, octopamine synapses, and the inhibition of acetylcholinesterase. With a few exceptions, their mammalian toxicity is low and environmental persistence is short. Registration has been the main bottleneck in putting new products on the market, but more EOs have been approved for use in the United States than elsewhere owing to reduced-risk processes for these materials.

Essential oils in insect control: low-risk products in a high-stakes world.

https://chemistry.mdma.ch/hiveboard/rhodium/pdf/piper.phytochemistry.pdf

Phytochemistry of the genus Piper

The long term use of many insecticides is continually threatened by the ability of insects to evolve resistance mechanisms that render the chemicals ineffective. Such resistance poses a serious threat to insect pest control both in the UK and worldwide. Resistance may result from either an increase in the ability of the insect to detoxify the insecticide or by changes in the target protein with which the insecticide interacts. DDT, the pyrethrins and the synthetic pyrethroids (the latter currently accounting for around 17% of the world insecticide market), act on the voltage-gated sodium channel proteins found in insect nerve cell membranes. The correct functioning of these channels is essential for normal transmission of nerve impulses and this process is disrupted by binding of the insecticides, leading to paralysis and eventual death. Some insect pest populations have evolved modifications of the sodium channel protein which prevent the binding of the insecticide and result in the insect developing resistance. Here we review some of the work (done at Rothamsted Research and elsewhere) that has led to the identification of specific residues on the sodium channel that may constitute the DDT and pyrethroid binding sites.

https://iubmb.onlinelibrary.wiley.com/doi/epdf/10.1080/15216540701352042

DDT, pyrethrins, pyrethroids and insect sodium channels.

A number of stereoisomers of recent pyrethroids having an α-cyano-3-phenoxybenzyl moiety, i.e., fenvalerate, Cypermethrin and fenpropanate could be optionally synthesized from (+)- or (-)-3-phenoxy-mandelic acid and their absolute configurations were determined to be S to the benzylic asymmetric carbon atoms of the most active isomers. Toxicity ratios of the S-isomers to the R-isomers to house fly were generally larger than those to mosquito larva. Relative toxicity of fenvalerate As (S-acid, R-alcohol) to Aα was enhanced in accordance with exposure period of mosquito larva on dipping or tobacco cutworm on dry leaf residue. The late emerging toxicity of the As appears to result from in vivo activation as evidenced by biological assays involving hemolymph exchange and ligature on larvae of cabbage armyworm. Feeding deterrent nature of As was also discussed.

Chemistry, Absolute Structures and Biological Aspect of the Most Active Isomers of Fenvalerate and Other Recent Pyrethroids

Chihauhuin, a New Germacranolide from Ambrosia confertiflora DC. (Compositae)

In connection with disclosure of a new class of insecticides, the modified phenylacetates, six new optically active α-isopropy-4-substituted phenylacetic acids whose substituents are respectively 4-methyl,4-methoxy, 4-fluoro, 4-chloro, 4-bromo and 3,4-methylenedioxy group were prepared by optical resolution and their absolute configurations were determined by comparative ORD with α-isopropylphenylacetic acid derivatives whose absolute configuration is known as (S)-(²). Esters of the (S)-(²)-acids with 5-benzyl-3-furylmethanol were nearly twice toxic to Musca domestica than those of the racemic esters. Optical purities of the resolved acids were determined by GLC and NMR (with Eu-FOD) as (−)-methyl esters.

Optical Resolution and Determination of Absolute Configurations of α-Isopropyl-4-substituted Phenylacetic Acids and Insecticidal Activities of Their 5-Benzyl-3-furylmethyl Esters

The potent antifungal constituent against Pyricularia oryzae Cav. obtained from Podophyllum peltatum L. has been disclosed to be a mixture of three new 3-acyl-4-hydroxy-5,6-dihydropyrones (podiblastin A, B and C). The absolute configuration at C-6 of podoblastins was determined to be (R).

Podoblastin a, b and c. new antifungal 3-acyl-4-hydroxy-5,6-dihydro-2-pyrones obtained from podophyllum peltatum l

Treatment of cyclopropanemethanols with pyridinium poly(hydrogen fluoride) in the presence of diisopropylamine and KHF2 gave selectively homoallylic fluorides or fluorocyclobutanes according to the mode of substitution of the starting cyclopropanemethanols. Cyclopropanemethanols with no substitution at 1-position of the cyclopropane ring gave homoallylic fluorides in a stereoselective manner. While, 1-methylcyclopropanemethanol gave the fluorocyclobutane in high stereoselectivity. Fluorocyclobutanes containing hydroxy methyl group were also prepared from 2-(1-methylcyclopropyl)oxiranes. The amine and the metal fluoride were necessary as additives for the best results. Influencing factors involving solvents and temperature for the reactions are also described.

Hirosuke Yoshioka

Papers

Chemistry, Absolute Structures and Biological Aspect of the Most Active Isomers of Fenvalerate and Other Recent Pyrethroids

Chihauhuin, a New Germacranolide from Ambrosia confertiflora DC. (Compositae)

Optical Resolution and Determination of Absolute Configurations of α-Isopropyl-4-substituted Phenylacetic Acids and Insecticidal Activities of Their 5-Benzyl-3-furylmethyl Esters

Podoblastin a, b and c. new antifungal 3-acyl-4-hydroxy-5,6-dihydro-2-pyrones obtained from podophyllum peltatum l

Ring-Opening Fluorination and Ring-Expansion Fluorination of Cyclopropanemethanols with Amine/Metal Fluoride/Poly(hydrogen fluoride)–Pyridine Complex