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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 no external oxidant is required. A rate constant for the addition of a primary radical to N-methoxylepidinium >107 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., N-Methoxypyridinium salts are exceptionally reactive radical traps that can be used in efficient radical chain reactions with organoboranes.

Due to the wide spectrum of biological activities of steroids, the detection and quantification of steroidal residues in various biological materials are crucial for drug development, doping prevention, and environmental protection. In addition, the analytical technique of stable isotopic dilution (SID) by Liquid Chromatography-Mass Spectrometry (LC-MS) requires 13C-labeled steroids as standards to provide accurate and reproducible steroid quantification. In this context, the synthesis of 13C-labeled steroids is reviewed. The approaches based on partial synthesis starting from commercially available steroids have been, by far, the most commonly employed strategy.1 Introduction2 Hemisynthesis of 13C3-Labeled Steroids via Partial Degradation of the A Ring2.1 Degradation of the A Ring to an Enol Lactone2.1.1 Introduction of 13C Atom(s) via Claisen Condensation: Turner’s Strategy2.1.2 Introduction of 13C Atom(s) with 13C-Labeled 5-(Diethylphosphono)pentan-2-one Ethylene Ketal Based on the Fujimoto–Belleau Reaction2.2 Degradation of the A Ring and Introduction of 13C Atom(s) with [13C3]-1-(Triphenylphosphoranylidene)propan-2-one3 Construction of the A Ring from an α,β-Unsaturated Ketone with 13C-Labeled 1-Iodo-3,3-(ethylenedioxy)butane as Electrophile4 Construction of the A and B rings: Stork’s Strategy5 Hemisynthesis with Introduction of 13C Atom(s) in the C17 Side Chain6 Conclusion

In this contribution, we describe two simple and efficient routes for the preparation of keto-aldehyde 1, a key intermediate for the synthesis of

We developed a new approach to γ-lactols and methylene-γ-lactols based upon the radical cyclization of aluminium acetals obtained by reduction of α-bromoesters with DIBAL-H. The cyclic aluminium acetals resulting from the cyclization process could engage in situ in further functionalization, as illustrated by the Oppenauer-type oxidation to give the corresponding lactones and γ-butenolides. The preparation of butenolides using this strategy compared favourably with the direct, tin-mediated cyclization of α-bromoesters, for which side reactions such as epimerization via [1,5]-HAT processes have been observed.

The rapid and regioselective synthesis of a series of 2,6-disubstituted dihydropyranic building-blocks bearing an oxygenated side chain is described. The corresponding 4-iodo tetrahydropyran precursors, easily prepared by Prins cyclization, underwent regioselective elimination in the presence of an In(OAc)(3)/LiI system to provide the title compounds. The one-pot Prins cyclization-elimination process was also studied and could be achieved with the TMSBr/Lil/In(OAc)(3) system. (C) 2015 Elsevier Ltd. All rights reserved.

Aluminum acetals are easily obtained from esters and lactones by reduction with aluminum hydrides. These thermally unstable tetrahedral intermediates have found applications in organic synthesis, with various methodologies taking advantage both of the stabilities of these aluminum species at low temperatures and of their tendencies to undergo rearrangement into the corresponding aldehydes. Efficient one-pot transformations can be achieved from aluminum acetals under ionic and radical conditions. A comprehensive overview of the reactivity of these species, including the most recent advances in this field, is presented in this microreview.

Cognac in the jar! An efficient one-pot sequence for the preparation of γ-lactones is described. Following reduction of α-bromo ester precursors with DIBAL-H and radical cyclization of the resulting O-aluminum acetals, a preparative in-situ Oppenauer-type oxidation of the cyclic O-aluminum acetal using simple aldehydes or ketones gives access to γ-lactones in high yields.

An efficient preparation of gamma-lactols and methylene-gamma-lactols is described. Highly acid-sensitive lactols are prepared in a concise manner by using a radical cyclization of aluminum acetals. The precursors for the radical reactions are readily prepared from allyl or propargyl alcohols and alpha-bromo acids. Functionalization of the resulting gamma-lactols and methylene-gamma-lactols can be achieved following isolation, leading to synthetically useful building blocks, such as 1,4-diols, 1,4-dienes, gamma-lactones, and polysubstituted tetrahydrofurans.

Vinyl radicals have a propensity to rearrange via intramolccular 1,5-hydrogen transfer to the more-stable alkyl radicals, which themselves possess a suitable structure to undergo rapid 5-exo-trig cyclizations. This tandem radical translocation-cyclization process represents a useful tool for the preparation of a wide range of five-membered rings. Moreover, this reaction is highly selective and, due to its radical nature, tolerates a variety of functional groups. During the last decade, tin-free procedures have emerged, rendering this process very attractive for the synthesis of natural products and their analogues. Selected examples of this strategy illustrating the scope of the method are described. 1 Introduction 2 Vinyl Radicals from Vinyl Halides 3 Vinyl Radicals Generated by Addition to Alkynes and Allenes 3.1 Addition of Carbon-Centered Radicals 3.1.1 Intermolecular Addition of Carbon-Centered Radicals 3.1.2 Intramolecular Addition of Carbon-Centered Radicals 3.2 Addition of Tin-Centered Radicals 3.3 Addition of Oxygen-Centered Radicals 3.4 Addition of Nitrogen-Centered Radicals 3.5 Addition of Sulfur-Centered Radicals 3.6 Addition of Phosphorus-Centered Radicals 4 Translocation-Cyclization Processes Involving a Stereoselective Hydrogen Atom Transfer 5 Conclusion

International audience; The formation of the CC bond using radical cyclization of haloacetals (Ueno-Stork reaction) has proven to be an extremely efficient method to access g-lactones and related compounds. This reaction is also highly attractive for the regio-and stereoselective introduction of side chains to cyclic and acyclic allylic alcohols. It has been used as a key step in many natural product syntheses and has proven to be particularly efficient for the stereoselective generation of quaternary carbon centers. This review focuses on the different methods available to carry out this radical cyclization, as well as on the stereochemical aspect of the reaction and its applications in total synthesis.

Due to their stability, availability and reactivity, sulfides are particularly attractive sources of carbon-centered radicals. However, their reactivity in homolytic substitution processes is strongly reduced when compared with the corresponding selenides or halides. Despite this, sulfur-containing compounds can be engineered so that they become effective agents in radical chain reactions. A detailed description of the reactivity of organo-sulfur compounds is reported here with the aim of providing clear guidance on the scope and limitation of their use as radical precursors in chain reactions.

The efficient preparation of 1-azabicyclic alkanes is described. Highly functionalized skeletons are prepared in a concise manner using a radical tin-free 1,5-hydrogen transfer−cyclization process. The precursors for the radical reactions are readily assembled either from pyrrolidine/piperidine/hexahydro-1H-azepine or via condensation of a properly designed N-alkylimine with an allenylzinc species.