The direct carbonylation of C(sp3)& horbar;H bonds is a powerful strategy to transform readily available, unfunctionalized materials into diverse, value-added functionalities. However, these reactions often require forcing conditions, such as high temperatures and high CO gas pressures, in the presence of peroxide oxidants. In this study, we report a practical C(sp3)& horbar;H carbonylation method that operates under photoexcited conditions at room temperature with only 1 bar of CO gas, utilizing an aryl bromide as a pseudo-oxidant and a HAT precursor to bypass traditional exogenous oxidants. These mild conditions parameters enable the use of a simple vial-based setup, effectively obviating the need for cumbersome pressurized vessels during the photochemical process. The reaction proceeds smoothly with benzylic C-H and unactivated C(sp3)& horbar;H bonds, affording esters in good to excellent yields. Moreover, a one-pot procedure is also developed for the synthesis of amides, acids, thioesters, and an ester derivative of an indole alkaloid, directly from C-H bonds, further demonstrating the practical utility of this methodology.

Reported herein is the development of a solvent-controlled, regiodivergent oxidative cyclization for the preparation of N-containing heterocyclic N-oxides. By employing biaryl ketoximes as substrates in the presence of PIFA as an oxidant in HFIP, the reactions proceed to exclusively afford phenanthridine N-oxides. On the other hand, the use of nucleophilic solvents leads to a dearomative functionalization, generating solvent-incorporated spirocyclic isoindole N-oxides. An investigation of the substrate scope reveals that the 6-membered vs. 5-membered ring closure is partially dependent on the substitution pattern on the aryl ring that participates in the C-N bond formation. Finally, the synthetic utility of the developed method was demonstrated through a number of product transformations.

Dibenzopyranone is a privileged structure in natural products that exhibits multiple fascinating properties. Reported herein, is the synthesis of dibenzopyranone from o ‐bromo benzoic acids and aryl formates. The combination of a Pd‐catalyst and light irradiation allows the reaction to proceed under mild conditions at room temperature. Preliminary mechanistic studies suggested that the reaction undergoes an esterification process followed by a cyclization to form the dibenzopyranone ring structure. This method provides a complementary approach for the synthesis of substituted benzo[ c ]chromen‐6‐one from readily available materials.

Reported herein is the development of an intramolecular oxidative cyclization of ketoximes with alkenes for the preparation of isoquinoline N-oxides. The reaction, which utilizes phenyliodine bis(trifluoroacetate) (PIFA) as an oxidant and 2,2,2-trifluoroethanol (TFE) as a solvent, proceeds to afford various N-heterocyclic products, including aryl/heteroaryl-fused pyridine N-oxides, isoindole N-oxides, and 2-benzazepine derivatives. Preliminary experimental and computational mechanistic studies suggest that the ionic pathway is the primary mechanism. The synthetic utility of the developed method was highlighted via several product transformations.

The development of an oxa-Diels-Alder reaction between sultines and carbonyl compounds is reported. o-Quinodimethanes, generated from sultines, undergo a [4+2]-cycloaddition with activated aldehydes or ketones in the presence of Cu(OTf)(2) to provide a variety of functionalized isochromans, including spiroisochromans, in up to 99%yield. The developed protocol demonstrates broad functional-group compatibility and tolerates unprotected isatins bearing free NH-functionalities.

Described herein is the development of a visible-light-driven carbonylation of alkyl halides. The exploitation of visible light to activate Pd complexes and the use of formates to serve the dual role of a CO surrogate and a phenoxide source allow the preparation of esters in moderate to good yields. Its relatively mild reaction conditions and the ability to perform this transformation without direct handling of toxic CO gas provide a practical means to access esters from alkyl halides.

Reported herein is the development of a normal electron-demand, three-component aza-Diels-Alder reaction between sultines, aldehydes, and amines. In the presence of Cu(OTf)(2) as a Lewis acid catalyst, the use of sultines as o-quinodimethane precursors in conjunction with the in situ generation of imines enables the facile preparation of various polysubstituted tetrahydro-isoquinoline derivatives from readily available substrates. The synthetic utility of these products was further explored through a number of product transformations, including the syntheses of tricyclic N-heterocycles.

The development of an intermolecular aza-Diels-Alder (DA) cycloaddition of sultines and imines is reported. By exploiting sultines as o-quinodimethane precursors and aryl imines as dienophiles in the presence of Cu(OTf)2, an aza-DA reaction proceeds to provide a wide variety of 3-aryl tetrahydroisoquionlines in moderate to excellent yield (up to 89%). The synthetic utility of these products was demonstrated in the preparation of tetracyclic N-heterocycles, including a tetrahydroprotoberberine skeleton.

Axial chirality features prominently in molecules of biological interest as well as chiral catalyst designs, and atropisomeric 2,2'-biphenols are particularly prevalent. Atroposelective metal-catalyzed cross-coupling is an attractive and modular approach to access enantioenriched biphenols, and yet existing protocols cannot achieve this directly. We address this challenge through the use of enantiopure, sulfonated SPhos (sSPhos), an existing ligand that has until now been used only in racemic form and that derives its chirality from an atropisomeric axis that is introduced through sulfonation. We believe that attractive noncovalent interactions involving the ligand sulfonate group are responsible for the high levels of asymmetric induction that we obtain in the 2,2'-biphenol products of Suzuki-Miyaura coupling, and we have developed a highly practical resolution of sSPhos via diastereomeric salt recrystallization.

Minisci-type reactions constitute one of the most powerful methods for building up complexity around basic heteroarenes. The most desirable variants involve formal oxidative coupling of a C-H bond on each partner, leading back to the simplest possible starting materials. We herein disclose a method that enables such a coupling of linear amides and heteroarenes with full control of enantioselectivity at the newly formed stereocenter as well as site selectivity on both the heteroarene and the amide. This is achieved by the use of a chiral phosphoric acid catalyst in conjunction with diacetyl as a combined hydrogen atom transfer reagent and oxidant. Diacetyl is directly photoexcitable, and thus, no extraneous photocatalyst is required: an added feature that contributes to the simplicity and practicality of the protocol.

Enantioselective transition metal catalysis is an area very much at the forefront of contemporary synthetic research. The development of processes that enable the efficient synthesis of enantiopure compounds is of unquestionable importance to chemists working within the many diverse fields of the central science. Traditional approaches to solving this challenge have typically relied on leveraging repulsive steric interactions between chiral ligands and substrates in order to raise the energy of one of the diastereomeric transition states over the other. By contrast, this Review examines an alternative tactic in which a set of attractive noncovalent interactions operating between transition metal ligands and substrates are used to control enantioselectivity. Examples where this creative approach has been successfully applied to render fundamental synthetic processes enantioselective are presented and discussed. In many of the cases examined, the ligand scaffold has been carefully designed to accommodate these attractive interactions, while in others, the importance of the critical interactions was only elucidated in subsequent computational and mechanistic studies. Through an exploration and discussion of recent reports encompassing a wide range of reaction classes, we hope to inspire synthetic chemists to continue to develop asymmetric transformations based on this powerful concept.

Palladium catalysis induced by visible light is an emerging field of catalysis. In contrast to classical reactions catalyzed by Pd complexes in the ground state, which mostly proceed through two-electron redox processes, the mechanisms of these new methods based on photoexcited Pd complexes usually operate through transfer of a single electron. Such processes lead to putative hybrid Pd/radical species, which exhibit both radical and classical Pd-type reactivity. This Minireview highlights the recent progress in this rapidly growing area.

The Heck reaction is one of the most reliable and useful strategies for the construction of C-C bonds in organic synthesis. However, in contrast to the well-established aryl Heck reaction, the analogous reaction employing alkyl electrophiles is much less developed. Significant progress in this area was recently achieved by merging radical-mediated and transition-metal-catalyzed approaches. This review summarizes the advances in alkyl Heck-type reactions from its discovery early in the 1970s up until the end of 2018.

AbstractDurch sichtbares Licht induzierte Palladiumkatalyse ist ein aufstrebendes Teilgebiet der Katalyse. Im Unterschied zu klassischen, durch Pd‐Komplexe im Grundzustand katalysierten Reaktionen, die vornehmlich durch Zweielektronen‐Redoxprozesse voranschreiten, laufen die Mechanismen der neuartigen Reaktionen auf Basis photoangeregter Pd‐Komplexe meist durch die Übertragung eines einzelnen Elektrons ab. Diese Prozesse führen mutmaßlich zu hybriden Pd/Radikal‐Spezies, die sowohl die Reaktivität von Radikalen als auch die von klassischen Pd‐Spezies aufweisen. Dieser Kurzaufsatz beleuchtet aktuelle Fortschritte auf diesem schnell wachsenden Gebiet.

Due to the great value of amino alcohols, new methods for their synthesis are in high demand. Abundant aliphatic alcohols represent the ideal feedstock for the method development toward this important motif. To date, transition-metal-catalyzed approaches for the directed remote amination of alcohols have been well established. Yet, they have certain disadvantages such as the use of expensive catalysts and limited scope. Very recently, transition-metal-free visible-light-induced radical approaches have emerged as new powerful tools for directed remote amination of alcohols. Relying on 1,5-HAT reactivity, these methods are limited to β - or δ-amination only. Herein, we report a novel transition-metal- and visible-light-free room-temperature radical approach for remote β -, γ-, and δ-C(sp3)-N bond formation in aliphatic alcohols using mild basic conditions and readily available diazonium salt reagents.

The Mizoroki−Heck reaction is one of the most efficient methods for alkenylation ofaryl, vinyl, and alkyl halides. Due to its innate nature, this protocol requires the employment of compounds possessing a halogen atom at the site of functionalization. However, the accessibility of organic molecules possessing a halogen atom at a particular site in aliphatic systems is extremely limited. Thus, a protocol that would allow a Heck reaction to occur at a specific non-functionalized C(sp3)−H site would be highly desirable.Here, we report a radical relay Heck reaction which allows for a selective remotealkenylation of aliphatic alcohols at unactivated β-, γ- and δ-C(sp3 20 )–H sites. The use of easily installable/removable Si-based auxiliary enables selective I-atom/radical translocation events at remote C−H sites followed by the Heck reaction. Notably, the reaction proceeds smoothly under mild visible light-mediated conditions at room temperature, producing highly modifiable and valuable alkenol products from readily available alcohols feedstocks.

An efficient Pd-catalyzed cyclization of o-picolylbromoarenes into pyridoindoles has been developed. This novel transformation, which proceeds through a not common for Pd catalysis L-to X-type pyridine ligand swap, provides an efficient route to aryl-, as well as to cyanopyrido[1,2-a]indoles, not easily accessible by existing cyclization methods.

A novel method for desaturation of aliphatic amines into enamines as well as allylic and homoallylic amines has been developed. This general protocol operates via putative aryl hybrid Pd-radical intermediates, which combine the signature features of radical chemistry, a hydrogen atom transfer (HAT) process, and transition metal chemistry, a selective fihydride elimination step, to achieve efficient and selective desaturation of amines. These hybrid Pd-radical intermediates are efficiently generated under mild photo induced conditions and are capable of a 1,n-HAT (n = S-7) event at C(sp(3)) H sites. The selectivity of HAT is tunable by varying different auxiliaries, which highlight the generality of this method. Remarkably, this desaturation method, which operates under mild conditions and does not require employment of exogenous photosensitizers or oxidants, can be performed in a practical scalable fashion from simple amines.

A general, efficient, and site-selective visible light-induced Pd-catalyzed remote desaturation of aliphatic alcohols into valuable allylic, homoallylic, and bis-homoallylic alcohols has been developed. This transformation operates via a hybrid Pd-radical mechanism, which synergistically combines the favorable features of radical approaches, such as a facile remote CH-HAT step, with that of transition-metal-catalyzed chemistry (selective beta-hydrogen elimination step). This allows achieving superior degrees of regioselectivity and yields in the desaturation of alcohols compared to those obtained by the state-of-the-art desaturation methods. The HAT at unactivated C(sp(3))-H sites is enabled by the easily installable/removable Si-auxiliaries. Formation of the key hybrid alkyl Pd-radical intermediates is efficiently induced by visible light from alkyl iodides and Pd(0) complexes. Notably, this method requires no exogenous photo-sensitizers or external oxidants.

An unprecedented hydrogen atom transfer event for hybrid Pd-radical species is reported.