An atom transfer radical [3+2] annulation (ATRAn) reaction involving alkenyl boronic esters and homoallylic iodides provides a rapid access to polysubstituted borylated cyclopentanes. A variety of α‐substituted vinylboronic esters are suitable substrates and offer unique opportunities for further modification of the formed 5‐membered ring. For instance, the oxidation of the boronic ester to an alcohol allows the preparation of products that corresponds to an annulation involving the enol form of acetone. Substitution of the iodide by a nucleophile such as lithium methoxide without modifying the boronic ester moiety is also feasible. Finally, by using a (3‐acetoxyprop‐1‐en‐2‐yl)boronic ester, a facile 1,2‐elimination reaction provided a methylenecyclopentane. In this case, the alkenylboronate radical trap acts as an equivalent to allene, a building block so far elusive for preparative radical reactions.

The preparation of polysubstituted bicyclo[3.1.0]hexanes starting from air-stable substituted pent-4-en-1-ylboronic acid esters has been investigated. The method involves a Matteson homologation with LiCHCl2, leading to 1-chlorohex-5-en-1-ylboronic acid ester intermediates. The subsequent intramolecular cyclopropanation step was performed in a one-pot process. With pinacol boronic esters, the cyclopropanation step was either performed thermally at 140 °C or at 70 °C after in situ transesterification to form a catechol boronic ester. This last approach is suitable for the preparation of enantioenriched bicyclo[3.1.0]hexanes using either chiral-auxiliary control or by taking advantage of the sparteine-controlled enantioselective boroalkylation of alcohols.

The direct hydroperfluoroalkylation of a wide range of unactivated alkenes has been achieved at room temperature with readily available iodoperfluoroalkanes using 4-tert-butylcatechol as a source of hydrogen atom and triethylborane. The hydrotrifluoromethylation could also be achieved under these conditions using gaseous trifluoromethyl iodide. An experimentally simple two-step, one-pot hydrotrifluoromethylation process using the easy-to-use trifluoromethanesulfonyl chloride as the source of trifluoromethyl radicals has also been developed. Using these two approaches, a broad range of substrates, including isoprenoid natural products, were efficiently derivatized.

Several types of Quantum Dots (QDs) (CdS, CdSe and InP, as well as core-shell QDs such as type I InP-ZnS, quasi type-II CdSe-CdS and inverted type-I CdS-CdSe) were considered for generating α-aminoalkyl free radicals. The feasibility of the oxidation of the N-aryl amines and the generation of the desired radical was evidenced experimentally by quenching of the photoluminescence of the QDs and by testing a vinylation reaction using an alkenylsulfone radical trap. The QDs were tested in a radical [3+3]-annulation reaction giving access to tropane skeletons and that requires the completion of two consecutive catalytic cycles. The scope of the [3+3]-annulation reaction was explored for the best performing QDs and isolated yields that compare well with classical iridium photocatalysis were obtained.

Tropanes and related bicyclic alkaloids are highly attractive compounds possessing a broad biological activity. Here we report a mild and simple protocol for the synthesis of N-arylated 8-azabicyclo[3.2.1]octane and 9-azabicyclo[3.3.1]nonane derivatives. It provides these valuable bicyclic alkaloid skeletons in good yields and high levels of diastereoselectivity from simple and readily available starting materials using visible-light photoredox catalysis. The success of this process relies on efficient electron transfer processes and highly selective deprotonation of aminium radical cations leading to the key α-amino radical intermediates.

Review article

The monoalkylation of N-methoxypyridinium salts with alkyl radicals generated from alkenes (via hydroboration with catecholborane), alkyl iodides (via iodine atom transfer) and xanthates is reported. The reaction proceeds under neutral conditions since no acid is needed to activate the heterocycle and does not require the use of an external oxidant. A rate constant for the addition of a primary radical to N-methoxylepidinium >10 7 M –1 s –1 was experimentally determined. This rate constant is more than one order of magnitude larger than the one measured for the addition of primary alkyl radicals to protonated lepidine demonstrating the remarkable reactivity of methoxypyridinium salts towards radicals. The reaction has been used for the preparation of unique pyridinylated terpenoids and was extended to a three component carbopyridinylation of electron rich alkenes including enol esters, enol ethers and enamides.

Review article

A convenient strategy for molecular editing of available ent-kauranic natural scaffolds has been developed based on radical mediated C–C bond formation. Iodine atom transfer radical addition (ATRA) followed by rapid ionic elimination and radical azidoalkylation were investigated. Both reactions involve radical addition to the exo-methylenic double bond of the parent substrate. Easy transformations of the obtained adducts lead to extended diterpenes of broad structural diversity and artificial diterpene-alkaloid hybrids possessing lactam and pyrrolidine pharmacophores. The cytotoxicity of selected diterpenic derivatives was examined by in vitro testing on several tumor cell lines. The terpene-alkaloid hybrids containing N-heterocycles with unprecedented spiro-junction have shown relevant cytotoxicity and promising selectivity indexes. These results represent a solid basis for following research on the synthesis of such derivatives based on available natural product templates.

Review article

Enantiomerically enriched azabicyclic compounds found in several important families of alkaloids can be prepared by a remarkably stereospecific and stereoselective intramolecular Schmidt reaction. The initial asymmetric alcohol center controls the whole process, leading to the formation of one out of up to four possible diastereoisomers with inversion of the configuration at the original asymmetric center.

The modification of highly oxygenated forskolin as well as manoyl and epi-manoyl oxide, two less functionalized model substrates sharing the same polycyclic skeleton, via intermolecular carbon-centered radical addition to the vinyl moiety has been investigated. Highly regio- and reasonably stereoselective iodine atom transfer radical addition (ATRA) reactions were developed. Unprotected forskolin afforded an unexpected cyclic ether derivative. Protection of the 1,3-diol as an acetonide led the formation of the iodine ATRA product. Interestingly, by changing the mode of initiation of the radical process, in situ protection of the forskolin 1,3-diol moiety as a cyclic boronic ester took place during the iodine ATRA process without disruption of the radical chain process. This very mild radical-mediated in situ protection of 1,3-diol is expected to be of interest for a broad range of radical and non-radical transformations. Finally, by using our recently developed tert-butyl­catechol-mediated hydroalkylation procedure, highly efficient preparation of forskolin derivatives bearing an extra ester or sulfone group was achieved.

A general method for the hydroalkylation of electron-rich terminal and non-terminal alkenes such as enol esters, alkenyl sulfides, enol ethers, silyl enol ethers, enamides and enecarbamates has been developed. The reactions are carried out at room temperature under air initiation in the presence of triethylborane acting as a chain transfer reagent and 4-tert-butylcatechol (TBC) as a source of hydrogen atom. The efficacy of the reaction is best explained by very favorable polar effects supporting the chain process and minimizing undesired polar reactions. The stereoselective hydroalkylation of chiral N-(alk-1-en-1-yl)oxazolidin-2-ones takes place with good to excellent diastereocontrol.

An improved procedure to run halogen atom and related chalcogen group transfer radical additions is reported. The procedure relies on the thermal decomposition of di-tert-butylhyponitrite (DTBHN), a safer alternative to the explosive diacetyl peroxide, to produce highly reactive methyl radicals that can initiate the chain process. This mode of initiation generates byproducts that are either gaseous (N2) or volatile (acetone and methyl halide) thereby facilitating greatly product purification by either flash column chromatography or distillation. In addition, remarkably simple and mild reaction conditions (refluxing EtOAc during 30 minutes under normal atmosphere) and a low excess of the radical precursor reagent (2 equivalents) make this protocol particularly attractive for preparative synthetic applications. This initiation procedure has been demonstrated with a broad scope since it works efficiently to add a range of electrophilic radicals generated from iodides, bromides, selenides and xanthates over a range of unactivated terminal alkenes. A diverse set of radical trap substrates exemplifies a broad functional group tolerance. Finally, di-tert-butyl peroxyoxalate (DTBPO) is also demonstrated as alternative source of tert-butoxyl radicals to initiate these reactions under identical conditions which gives gaseous by-products (CO2).

An efficient method for the thioalkylation of alkenes via radical desulfitative sulfur-group transfer is described. The reaction is based on the use of readily available thiosulfonates as starting materials and cheap radical initiators such as dilauroyl peroxide (DLP) and sun lamp irradiation. No transition metal catalyst is required, and the reaction takes place under mild conditions.

The generation of carbon‐centered radicals from air‐sensitive organoboron compounds through nucleohomolytic substitution at boron is a general method to generate non‐functionalized and functionalized radicals. Due to their reduced Lewis acidity, alkylboronic pinacol esters are not suitable substrates. We report their in situ conversion into alkylboronic catechol esters by boron‐transesterification with a substoichiometric amount of catechol methyl borate combined with an array of radical chain processes. This simple one‐pot radical‐chain deboronative method enables the conversion of pinacol boronic esters into iodides, bromides, chlorides, and thioethers. The process is also suitable the formation of nitriles and allylated compounds through C−C bond formation using sulfonyl radical traps. The power of combining radical and classical boron chemistry is illustrated with a modular 5‐membered ring formation using a combination of three‐component coupling and protodeboronative cyclization.

Recently there has been an explosion of interest in the synthetic community for the addition of radicals into unsaturated organoboron-ate complexes. This review will give a concise outline for radical processes involving boron-ate complexes which trigger a subsequent anionotropic rearrangement.

The radical azidoalkylation of alkenes that was initially developed with α-iodoesters and α-iodoketones was extended to other activated iodomethyl derivatives. By using iodomethyl aryl sulfones, the preparation of γ-azidosulfones was easily achieved. Facile conversion of these azidosulfones to homoallylic azides using a Julia–Kocienski olefination reaction is reported, making the whole process equivalent to the azidoalkenylation of terminal alkenes.

A concise route for the preparation of two simple optically pure indolizidin-5-ones has been developed. The key chain elongation process was achieved using a triethylborane/catechol mediated hydroalkylation of Boc-protected 2-vinylpyrrolidines. By using complementary strategies, these two bicyclic lactams can be alkylated with complete control of the stereochemistry at C(5) and their conversion to a variety of indolizidine alkaloids such as coniceine, indolizidine 209D and 167B, 5-epi-indolizidine 249A and monomorine has been reported in the literature.

A very concise total synthesis of (+)-brefeldin C starting from 2-furanylcyclopentene is described. This approach is based on an unprecedented enantioselective radical hydroalkynylation process to introduce the two cyclopentane stereocenters in a single step. The use of a furan substituent allows a high trans diastereoselectivity to be achieved during the radical process and it contains the four carbon atoms C1–C4 of the natural product in an oxidation state closely related to the one of the target molecule. The eight-step synthesis requires six product purifications and it provides (+)-brefeldin C in 18 % overall yield.