In the last decades, hypervalent iodine reagents have raised from chemical curiosities to mainstream reagents in organic synthesis. The use of benziodoxole-derived reagents has been especially successful in oxidation methods, whereas non-cyclic iodinanes have been used both for oxidation and atom-transfer reactions. On the other hand, the exceptional properties of 10 benziodoxole reagents for atom-transfer reactions have only started to attract the attention of the synthetic community more recently. In this review, progress in the use of these compounds for C-X and C-C bond formations will be presented. In particular, recent breakthroughs in trifluoromethylation and alkynylation reactions have been realized since 2006 bas ed on benziodoxole-derived reagents and these results are the main focus of this article.

Fine-tuned organic photoredox catalysts are introduced for the metal-free alkynylation of alkylnitrile radicals generated via oxidative ring opening of cyclic alkylketone oxime ethers.

The first example of intramolecular oxyalkynylation of non-activated alkenes using oxidative Pd chemistry is reported. Both phenol and aromatic or aliphatic acid derivatives could be used under operator friendly conditions (room temperature, technical solvents, under air). The discovery of the superiority of benziodoxolone-derived hypervalent iodine reagent 3d as alkyne transfer reagent further expands the rapidly increasing utility of hypervalent iodine reagents in catalysis and is expected to have important implications for other similar processes.Cyclic structures are ubiquitous in natural products and other bioactive substances. 1 Consequently, the efficient synthesis of carbo-and hetero-cycles is an important field of research in organic chemistry. Metal-catalyzed cyclization reactions, especially when involving multiple C-C or C-X bond formations, constitute an efficient pathway to heterocycles. 2 One such method is the Wacker cyclization, which is the Pd catalyzed cyclization of nucleophiles on double bonds (Scheme 1, A). 2c,3 In place of -hydride elimination, further C-C, 2c,4 C-O, 5 C-N 6 and C-Cl 7 bond formation together with cyclization have been reported. 8 In particular, C-O and C-N bond formations have profited tremendously from the use of hypervalent iodine reagents as oxidants. 5,6 In contrast, C-C bond formation has been limited to SP 2 hybridized vinyl, carbonyl and aryl groups; none of these methods reported the use of hypervalent iodine reagents. 2c,4 It was recently demonstrated that oxidation of Pd(II) intermediates with aryliodonium salts was much slower than with PhI(OAc)2, which would make C-C bond formation unable to compete with other side reactions. 8b Herein, we report a Pd-catalyzed Wacker cyclization-alkynylation domino process using a benziodoxolone-derived reagent 3d (Scheme 1, B).Acetylenes have broad utility in organic chemistry, biological chemistry and material sciences. 9 Furthermore, the direct addition of acetylenes to non-activated olefins is challenging, and has been successful only for strained olefins 10 or using radical methods. 11 The Pd-catalyzed C-C bond formation between a SP 3 and a SP center is also a difficult process, which was successful only in rare cases. 12 Our report constitutes the first example of intramolecular oxyalkynylation of non-activated alkenes, which represents an important breakthrough in the area of oxidative Pd chemistry. The discovery of the unique This document is the Accepted Manuscript version of a Published Work that appeared in final form in Organic Letters, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/ ol9027286. superiority of benziodoxolone derived reagents 3c-3e for alkynyl transfer when compared with established alkynyliodonium salts (3a, 3b) constitutes an important advance in the burgeoning field of hypervalent iodine chemistry 13 and opens new perspective for the development of ...

Sweet cyclizations: The synthesis of pyrrolizidines and indolizidines has been achieved. Olefins were subjected to an intramolecular palladium‐catalyzed aminoalkynylation with the hypervalent iodine reagent TIPS‐EBX. After removal of the protecting group, a two‐step cyclization sequence and subsequent reduction led to the natural product (±)‐trachelanthamidine (see scheme; TIPS‐EBX=triisopropylsilyl ethynylbenziodoxolone).

Azides are building blocks of increasing importance in synthetic chemistry, chemical biology, and materials science. Azidobenziodoxolone (ABX, Zhdankin reagent) is a valuable azide source, but its safety profile has not been thoroughly established. Herein, we report a safety study of ABX, which shows its hazardous nature. We introduce two derivatives, tBu-ABX and ABZ (azidobenziodazolone), with a better safety profile, and use them in established photoredox- and metal-mediated azidations, and in a new ring-expansion of silylated cyclobutanols to give azidated cyclopentanones.

The first Pd(0)-catalyzed intramolecular oxy-and amino-alkynylation of non-activated olefins is reported. The reaction gives access to important tetrahydrofuran and pyrrolidine heterocycles with high diastereoselectivity. The unique synthetic potential of acetylenes is further exploited to access key building blocks for the synthesis of bioactive natural products.Heterocycles are essential structural elements for the bioactivity of natural and synthetic molecules. Among them, tetrahydrofurans and pyrrolidines are particularly important in natural products, such as the antitumoral annonaceous acetogenins gigantecin (1) and squamostatin C (2), 1 or the antibiotic alkaloid preussin (3) (Figure 1). 2 Consequently, the stereoselective synthesis of tetrahydrofurans and pyrrolidines has been extensively investigated. 3 Particularly interesting are methods using cyclization of alcohols or amines onto non-activated olefins combined with a further bond forming event. Iodoetherification or amination reactions have been often used in the synthesis of heterocycles. 4 Recently, the power of metal catalysis has been harnessed to achieve multiple functionalizations of olefins 5 for the synthesis of tetrahydrofurans and pyrrolidines together with further C-N, 6 C-O 7 or C-C bond formation. 8 Impressive progress has been realized in Pd-catalyzed domino reactions involving cyclization on olefins to form a tetrahydrofuran or a pyrrolidine followed by carbonylation, 8a-c vinylation 8d-e or arylation. 8f-j Despite these recent breakthroughs, there are currently no examples of an oxy-or amino-alkynylation reaction for the synthesis of tetrahydrofurans or pyrrolidines. 9 Such a process would be highly useful, as the functionalization of alkynes through cross-coupling, reduction, addition, cyclization, cycloisomerization or cycloaddition gives access to important building blocks used in synthetic chemistry, chemical biology and material sciences. 10 Our group has developed the Pd(II)-catalyzed oxy-and amino-alkynylation of olefins with EBX (ethynyl benziodoxolone) reagent 4 for the synthesis of lactones and lactams (Scheme 1). 11 However, the developed This document is the Accepted Manuscript version of a Published Work that appeared in final form in Organic Letters, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/ol2029383. methods could not be used to access tetrahydrofurans or pyrrolidines and C-C bond formation was limited to primary positions. Herein, we report a different approach for the oxy-and amino-alkynylation of olefins using Pd(0) catalysis and triisopropylsilyl ethynyl bromide (5a), which allowed us to override both limitations (Scheme 1). To the best of our knowledge, this is the first example of Pd(0) catalysis for the oxy-and amino-alkynylation of olefins or for any C-X/C(SP 3 )-C(SP) domino sequence on alkenes. Tetrahydrofurans and pyrrolidines were obtained in good yields an...

A versatile synthesis of azidolactones through azidation and cyclization of carboxylic acids onto alkenes has been developed. Based on either photoredox or palladium catalysis, (1,1) and (1,2) azido lactones can be selectively synthesized. The choice of catalyst and benziodoxol(on)e reagent serving as azide source was essential to initiate either a radical or Lewis acid mediated process with divergent outcome. These transformations were carried out under mild conditions using a low catalyst loading and gave access to a large scope of azido lactones.

Tetrahydrofurans and pyrrolidines are among the most important heterocycles found in bioactive compounds. Cyclization-functionalization domino reactions of alcohols or amines onto olefins constitute one of the most efficient methods to access them. In this context, oxy-and aminoalkynylation are especially important reactions, due to the numerous transformations possible with the triple bond of acetylenes, yet these methods have been limited to the use of silyl protected acetylenes. Herein, we report the first palladium-catalyzed oxy-and aminoalkynylation using aliphatic bromoalkynes, which proceeded with high diastereoselectivity and functional group tolerance. A one-pot hydrogenation of the triple bond gave then access to alkyl-substituted tetrahydrofurans and pyrroldines. Finally, a detailed study of the side products formed during the reaction gave a first insight into the reaction mechanism.