A photochemical desulfonylation of sulfonamides has been discovered. Sulfonamides are abundant in medicinal-chemistry libraries. Strategies for their synthetic valorization remain relatively sparse, however, and their known reactions overwhelmingly retain the sulfonyl group, limiting the chemical space accessible from sulfonamides. Using this new method, an extensive array of aromatic sulfonamides bearing a selection of N-heteroaryl substituents was converted into the corresponding N-heteroaryl anilines, which are also medicinally important substructures. This reaction involves a unique photoinduced C-N reductive elimination from sulfur, which is proposed mainly to involve an excited-state, desulfonylative S-to-N aryl migration. An analogous polar aryl migration from a higher-energy, photogenerated sulfonamide tautomer was also identified, which likely serves as a minor pathway.

Significant improvements in the regioselectivity of Minisci alkylations have been enabled by adopting N-heteroaryl phosphonium salts as substrates for this textbook transformation. Minisci chemistry has been a workhorse synthetic protocol in industry and academia for decades since it generates more-complex N-heteroaryls such as pyridines by C–H alkylation of the latter species with abundant precursors like carboxylic acids. Its wide scope, robustness, and operational simplicity are also major advantages, but its regioselectivity is often poor and general solutions have been slow to emerge. This strategy draws on reliable regioselective methods to install phosphonium groups onto N-heteroarenes. We have demonstrated herein that C2-alkylation of easily accessible C4-PPh 3 +-containing pyridines and quinolines (and C4-alkylation of C2-PPh 3 +-containing quinolines) regiospecifically generates a range of alkylation patterns that have previously proven challenging for Minisci chemistry to access selectively – especially when using more-abundant alkyl sources. Moreover, the preliminary application of this strategy to further N-heteroarenes shows that sites less- or unreactive with alkyl radicals can be exclusively engaged by using the phosphonium group to block the preferred Minisci reaction site. Finally, after the alkylation, mild hydrolysis can tracelessly remove the PPh 3 + handle, or a suite of established substitutions can be used to enable regiospecific C–H/C–H difunctionalizations across the PPh 3 + installation/Minisci/PPh 3 + substitution sequence.

An original concept for catalytic electrochemical dehydration has enabled a suite of acid substitutions, including amidation, esterification, and thioesterification, through a linchpin anhydride formed in situ. By avoiding stoichiometric dehydrating agents, this method addresses a leading challenge in organic synthesis and green chemistry. It also proceeds without acid additives at room temperature, accesses a diverse range of product structures, is easily scaled, and enabled the first example of catalytic peptide coupling at room temperature.

An electrochemical coupling between carboxylic acids and pentafluorophenol (PFP-OH) to access synthetically versatile pentafluorophenyl (PFP) esters has been developed. Novel reactivity of PFP-OH was turned on by modulating its oxidation state, leveraging both its native O-nucleophilicity and its latent, oxidation-induced C-electrophilicity to promote a unique cascade of nucleophilic aromatic and acyl substitutions. Its esterification with acids was thus achieved for the first time without exogenous dehydrating agents. The acidity of PFP-OH and the oxidizability of its conjugate base enabled its mild and selective activation via deprotonation-oxidation, readily affording PFP esters that are useful in many applications (peptide synthesis, chemical biology, etc.) and that contain redox-sensitive functional groups. Finally, we verified in a unified forum that an amino-acid-derived PFP ester can be converted into a range of acyl-substitution products while retaining key stereochemical information, and we demonstrated that PFP esters have excellent stability to hydrolysis, comparing favorably even to N-hydroxysuccinimidyl (NHS) esters.

(Hetero)arylethylamines are privileged substructures in pharmaceuticals, agrochemicals, and other bioactive compounds. In principle, the amino-(hetero)arylation of olefins represents an ideal strategy for the rapid preparation of these pharmacophores, which could accelerate the discovery of valuable new products. Established amino-(hetero)arylation methods, however, do not accommodate several important classes of olefins and (hetero)aromatic structures, which precludes access to an appreciable range of molecular architectures. To address these limitations, we have developed a radical-mediated reaction that adds the amino and (hetero)aryl groups from a simple and stable (hetero)aryl sulfonamide across an alkene. The identification of a readily available triazine as an original N-protecting group was critical to the development of this transformation. The reaction features good regio- and stereoselectivity and succeeds with classes of olefins and medicinally valuable (hetero)aryl groups that are unproductive with alternate protocols. Lastly, we highlighted these advances by synthesizing TMP269, a class IIa histone deacetylase inhibitor that would otherwise be challenging to prepare by olefin amino-arylation.

The reliance on wasteful stoichiometric reagents to accomplish dehydration reactions such as esterification, amidation, and alcohol substitution is a longstanding challenge in synthetic chemistry. To address this problem, an electrochemical approach has been developed as a new conceptual platform for dehydration reactions. As a proof-of-concept demonstration, an electrochemical esterification protocol has been described that proceeds at room temperature, without acid or base additives, and without consuming stoichiometric reagents. This approach therefore overcomes key complications of esterification chemistry, and we envision that it will similarly enable improvements to a range of important, related transformations.

A free-radical approach featuring an intramolecular aryl migration has significantly expanded the scope for the alkyl–(hetero)arylation of simple olefins. It was also leveraged as the key step in a new synthesis of a recently approved pharmaceutical.

An electrochemical approach has been leveraged to underpin a new conceptual platform for dehydration reactions, which has been demonstrated in the context of esterification. Esters were prepared from the corresponding acid and alcohol partners at room temperature without acid or base additives and without consuming stoichiometric reagents. This methodology therefore addresses key complications that plague esterification and dehydration reactions more broadly and that represent a leading challenge in synthetic chemistry.

A free-radical cascade approach has enabled the develop-ment of a synthetically versatile alkyl–arylation of olefins. This transformation engages an excellent range of olefins, from mono- to tetrasubstituted, without requiring directing or electronically activating groups. Further synthetic advantages, such as the facile generation of quaternary cen-ters and the introduction of heteroaryl groups with Lewis basic nitrogen atoms, also complement transition-metal-catalyzed alkyl–arylation. Vicinal stereoarrays were gener-ated with high levels of diastereoselectivity. The synthetic potential of this transformation was demonstrated by serving as the key step in a concise synthesis of oliceridine, a new painkiller that received FDA approval in 2020.

Nature routinely engages alcohols as leaving groups, as DNA biosynthesis relies on the removal of water from ribonucleoside diphosphates by a radical-mediated "spin-center shift" (SCS) mechanism. Alcohols, however, remain underused as alkylating agents in synthetic chemistry due to their low reactivity in two-electron pathways. We report herein an enantioselective α-benzylation of aldehydes using alcohols as alkylating agents based on the mechanistic principle of spin-center shift. This strategy harnesses the dual activation modes of photoredox and organocatalysis, engaging the alcohol by SCS and capturing the resulting benzylic radical with a catalytically generated enamine. Mechanistic studies provide evidence for SCS as a key elementary step, identify the origins of competing reactions, and enable improvements in chemoselectivity by rational photocatalyst design.

The intramolecular cross-coupling of sulfonic acid derivatives occurs in the presence of tris(trimethylsilyl)silane (TTMSS) at room temperature and in air to form biaryl compounds. A photoredox-catalyzed procedure is also described. These protocols provide mild and convenient alternatives to standard tin-mediated reactions.

Huanfeng Jiang at the South China University of Technology developed (J. Am. Chem. Soc. 2013, 135, 5286) the palladium-catalyzed dehydrogenative aminohalogenation of methyl acrylate with aniline 1. A 1,3-hydrogen shift/ chlorination catalyzed by an iridium complex was reported (Angew. Chem. Int. Ed. 2013, 52, 6273) by Belén Martín- Matute at Stockholm University. Robert M. Waymouth discovered (J. Am. Chem. Soc. 2013, 135, 7593) the chemoselective oxidation of polyol 5 by a cationic palladium species. A ruthenium(II) hydride was found to catalyze the conversion of alcohols such as 7 to carboxylic acids using water as the oxygen source as disclosed (Nature Chem. 2013, 5, 122) by David Milstein at the Weizmann Institute of Science in Israel. Susan K. Hanson at the Los Alamos National Laboratory in New Mexico reported (Org. Lett. 2013, 15, 650) the acceptorless dehydrogenation of alcohols catalyzed by cobalt complex 12 to form imines such as 13 upon reaction with an amine. A collabo­ration led by Pedro J. Pérez at the University of Huelva in Spain studied (J. Am. Chem. Soc. 2013, 135, 3887) the oxidation of alkanes under catalysis with copper complex 15, primarily yielding alcohols and ketones, such as in the conversion of cyclohexane (14) to cyclohexanol (16) and cyclohexanone (17). A remarkable symmetry-breaking Wacker oxidation of diene 18 to produce 19 was the key step in the total synthesis of (+)-obolactone reported (Org. Lett. 2013, 15, 1294) by Reinhard Brückner at the University of Freiburg in Germany. Kiyotomi Kaneda at the University of Osaka found (Angew. Chem. Int. Ed. 2013, 52, 5961) that a palladium salt catalyzes the conversion of electron-deficient internal olefin 20 to ketone 21. As part of a program to develop environmentally sustainable procedures, Caterina Fusco at the University of Bari in Italy described (Tetrahedron Lett. 2013, 54, 515) the oxidative cleavage of lactam 22 by methyl(trifluoromethyl)dioxirane in water to pro­duce ω-nitro acid 24. Motomu Kanai at the University of Tokyo reported (Org. Lett. 2013, 15, 1918) the β-functionalization of tertiary aromatic amine 25 with nitroolefin 26 to produce 27 by iron catalysis.

AbstractA higher‐order superbase incorporating a cyclopropenimine functionality catalyzes conjugate addition reactions of α‐aryl ester pro‐nucleophiles.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

ChemInformVolume 47, Issue 3 Natural Products ChemInform Abstract: Direct, Biomimetic Synthesis of (+)-Artemone (I) via a Stereoselective, Organocatalytic Cyclization. Eric D. Nacsa, Eric D. Nacsa Dep. Chem., Harvey Mudd Coll., Claremont, CA 91711, USASearch for more papers by this authorBrian C. Fielder, Brian C. Fielder Dep. Chem., Harvey Mudd Coll., Claremont, CA 91711, USASearch for more papers by this authorShannon P. Wetzler, Shannon P. Wetzler Dep. Chem., Harvey Mudd Coll., Claremont, CA 91711, USASearch for more papers by this authorVeerasak Srisuknimit, Veerasak Srisuknimit Dep. Chem., Harvey Mudd Coll., Claremont, CA 91711, USASearch for more papers by this authorJonathan P. Litz, Jonathan P. Litz Dep. Chem., Harvey Mudd Coll., Claremont, CA 91711, USASearch for more papers by this authorMary J. Van Vleet, Mary J. Van Vleet Dep. Chem., Harvey Mudd Coll., Claremont, CA 91711, USASearch for more papers by this authorKim Quach, Kim Quach Dep. Chem., Harvey Mudd Coll., Claremont, CA 91711, USASearch for more papers by this authorDavid A. Vosburg, David A. Vosburg Dep. Chem., Harvey Mudd Coll., Claremont, CA 91711, USASearch for more papers by this author Eric D. Nacsa, Eric D. Nacsa Dep. Chem., Harvey Mudd Coll., Claremont, CA 91711, USASearch for more papers by this authorBrian C. Fielder, Brian C. Fielder Dep. Chem., Harvey Mudd Coll., Claremont, CA 91711, USASearch for more papers by this authorShannon P. Wetzler, Shannon P. Wetzler Dep. Chem., Harvey Mudd Coll., Claremont, CA 91711, USASearch for more papers by this authorVeerasak Srisuknimit, Veerasak Srisuknimit Dep. Chem., Harvey Mudd Coll., Claremont, CA 91711, USASearch for more papers by this authorJonathan P. Litz, Jonathan P. Litz Dep. Chem., Harvey Mudd Coll., Claremont, CA 91711, USASearch for more papers by this authorMary J. Van Vleet, Mary J. Van Vleet Dep. Chem., Harvey Mudd Coll., Claremont, CA 91711, USASearch for more papers by this authorKim Quach, Kim Quach Dep. Chem., Harvey Mudd Coll., Claremont, CA 91711, USASearch for more papers by this authorDavid A. Vosburg, David A. Vosburg Dep. Chem., Harvey Mudd Coll., Claremont, CA 91711, USASearch for more papers by this author First published: 14 July 2016 https://doi.org/10.1002/chin.201603173Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume47, Issue3December 29, 2015 RelatedInformation

We present a four-step synthesis of (+)-artemone from (-)-linalool, featuring iminium organocatalysis of a doubly diastereoselective conjugate addition reaction. The strategy follows a proposed biosynthetic pathway, rapidly generates stereochemical complexity, uses no protecting groups, and minimizes redox manipulations.

The synthesis and characterization of six new classes of higher-order superbases, including five that incorporate cyclopropenimine functionality, has been achieved. We propose a nomenclature that designates these as the CG2, GC2, PC3, PC1, C3, and GP2 classes of superbases. The pK(BH+) values were measured to be between 29.0 and 35.6 in acetonitrile. Linear correlations of ten superbase basicities vs that of their substituents demonstrated the insulating effect of the cyclopropenimine core. The molecular structures of several of these materials were obtained by single-crystal X-ray analysis, revealing interesting aspects of conformational bias and noncovalent organization. The types of superbasic cores and substituents were each reliably shown to affect selectivity for deprotonation over alkylation. Higher-order cyclopropenimine and guanidine superbase stability to hydrolysis was found to correlate to basicity. Finally, a GC2 base was found to catalyze conjugate additions of α-aryl ester pronucleophiles, representing the first report of a neutral Brønsted base to catalyze such reactions.

Bimolecular nucleophilic substitution reactions of alcohols are fundamentally important transformations in organic chemistry yet, to date, they are relatively underdeveloped with respect to catalysis. This Article describes the emerging area of catalytic SN2 reactions with specific emphasis on the design and development of phosphorus(V) and cyclopropenone-based catalytic SN2 reactions of alcohols.

AbstractThe presented method applies iBu3N as a base and diphenyl‐ (DPC) and dianisylcyclopropenones (DAC) as promoters and proceeds with high stereoselectivity and inversion of configuration.