Functionality-Directed Regio- and Enantio-Selective Olefinic C-H Functionalization of Aryl Alkenes.

Aryl alkenes represents one of the most widely occurring structural motif in countless drugs and natural products, and direct C-H functionalization of aryl alkenes provides atom- step efficient access toward valuable analogues. Among them, group-directed selective olefinic α- and ß-C-H functionalization, bearing a directing group on the aromatic ring, has attracted remarkable attentions, including alkynylation, alkenylation, amino-carbonylation, cyanation, domino cyclization and so on. These transformations proceed by endo- and exo-C-H cyclometallation and provide aryl alkene derivatives in excellent site- stereo-selectivity. Enantio-selective α- and ß- olefinic C-H functionalization were also covered to synthesis axially chiral styrenes.

Synthesis of 3-Oxo Quinolines by Cyclization Using Lignin Models and 2-Aminobenzyl Alcohols.

Phenoxy acetophenones were usually employed as ß-O-4' lignin models for chemical conversion. Herein, an iridium-catalyzed dehydrogenative annulation between 2-aminobenzylalcohols and phenoxy acetophenones was demonstrated to prepare valuable 3-oxo quinoline derivatives, which are hard to prepare using previous methods. This operationally simple reaction tolerated a wide scope of substrates and enabled successful gram-scale preparation.

Chelation-assisted iridium-catalyzed hydroalkenylation and hydroarylation/cyclization with conjugated trienes.

Iridium-catalyzed hydroalkenylation of conjugated trienes by chelation-assisted alkenyl C-H activation of acrylamides has been demonstrated to produce 1,4,6-trienes atom efficiently with excellent regio- and E/Z selectivities. In contrast, the reaction of benzamides and 1,3,5-trienes proceeds by a tandem hydroarylation of the trienes and cyclization via intramolecular 1,2-addition, providing valuable trans-tetrahydroisoquinolinone derivatives. A broad range of aromatic and aliphatic 1,3,5-trienes bearing various functionalities were compatible to deliver target products with high yields and E/Z selectivity. The successful gram-scale preparation and selective hydrogenation to give the alkylation product further demonstrates the practicability of this protocol to potential applications.

Recent advances in chelation-assisted site- and stereoselective alkenyl C-H functionalization.

Olefinic C-H functionalization represents an atom- and step economic approach to valuable olefin derivatives from simpler ones, but controlling the selectivity remains a challenge. Remarkable progress has been made in the site-selective C-H functionalization of arenes and alkanes, but there are still limited examples of selective C-H functionalization of olefins presumably due to the lability and easy decomposition of the alkenyl moiety. Chelation-assisted C-H activation represents an efficient protocol for site- and stereo-selective construction of carbon-carbon and carbon-heteroatom bonds. This review highlights recent advances in vicinal- and geminal-group-directed olefinic C-H functionalization, including alkenylation, arylation, alkynylation, alkylation, halogenation, silylation, cyanation and annulation by the formation of exo-/endo-metallocycles. In particular, geminal-group-directed C-H functionalization is covered for the first time, as well as distal-selective alkenyl C-H functionalization under palladium/norbornene cooperative catalysis, which provides novel disconnections in retrosynthetic analysis and represents the future trend in green chemistry.

Stereoselective and Atom-Economic Alkenyl C-H Allylation/Alkenylation in Aqueous Media by Iridium Catalysis.

A practical and atom-economic protocol for the stereoselective preparation of various 1,4- and 1,3-diene skeletons through iridium-catalyzed directed olefinic C-H allylation and alkenylation of NH-Ts acrylamides in water was developed. This reaction tolerated a wide scope of substrates under simple reaction conditions and enabled successful gram-scale preparation. Furthermore, an asymmetric variant of this reaction giving enantioenriched 1,4-dienes was achieved employing a chiral diene-iridium complex as the catalyst.

Ruthenium-Catalyzed Brook Rearrangement Involved Domino Sequence Enabled by Acylsilane-Aldehyde Corporation.

A ruthenium-catalyzed [1,2]-Brook rearrangement involved domino sequence is presented to prepare highly functionalized silyloxy indenes with atomic- and step-economy. This domino reaction is triggered by acylsilane-directed C-H activation, and the aldehyde controlled the subsequent enol cyclization/Brook Rearrangement other than ß-H elimination. The protocol tolerates a broad substitution pattern, and the further synthetic elaboration of silyloxy indenes allows access to a diverse range of interesting indene and indanone derivatives.

Bidentate auxiliary-directed alkenyl C-H allylation via exo-palladacycles: synthesis of branched 1,4-dienes.

An alkenyl C-H allylation by an exo-palladacycle intermediate is demonstrated, employing unactivated (Z)-alkenes and allyl carbonates. With the use of an 8-aminoquinoline (AQ) derived amide as the directing group, the N,N-bidentate-chelation-assisted C-H activation protocol proceeded under mild and oxidant-free conditions with excellent selectivity. The utility of this approach is demonstrated by the preparative scale, selective conversion of inseparable Z/E alkenes and ready removal of the amide auxiliary to provide the corresponding ester.

Iridium-Catalyzed Cross-Coupling Reactions of Alkenes by Hydrogen Transfer.

A range of Ru-, Rh-, or Pd-catalyzed vinylic C-H/C-H cross-coupling reactions of olefins have been demonstrated to provide 1,3-dienes, using a quantitative amount of metal oxidants. Although transfer hydrogenation and C-H alkenylation are two important areas that evolved independently, we herein report the first iridium-catalyzed cross-coupling reactions of alkenes by integration of directed C(alkenyl)-H alkenylation and transfer hydrogenation to obviate the usage of a metal oxidant, employing a hydrogen acceptor such as inexpensive chloranil.

NHC-catalyzed [4+2] cycloaddition reactions for the synthesis of 3'-spirocyclic oxindoles via a C-F bond cleavage protocol.

A chiral NHC-catalyzed cycloaddition of γ-fluoroenals is developed. The nucleophilic γ-carbon generated via C-F bond cleavage undergoes highly enantioselective cycloaddition (up to >99% ee) to isatins and provides 3'-spirocyclic oxindoles in good yields (up to 91%).

Facile Preparation of (2Z,4E)-Dienamides by the Olefination of Electron-deficient Alkenes with Allyl Acetate.

Direct cross-coupling between two alkenes via vinylic C-H bond activation represents an efficient strategy for the synthesis of butadienes with high atomic and step economy. However, this functionality-directed cross-coupling reaction has not been developed, as there are still limited directing groups in practical use. In particular, a stoichiometric amount of oxidant is usually required, producing a large amount of waste. Due to our interest in novel 1,3-butadiene synthesis, we describe the ruthenium-catalyzed olefination of electron-deficient alkenes using allyl acetate and without external oxidant. The reaction of 2-phenyl acrylamide and allyl acetate was chosen as a model reaction, and the desired diene product was obtained in 80% isolated yield with good stereoselectivity (Z,E/Z,Z = 88:12) under optimal conditions: [Ru(p-cymene) Cl2]2 (3 mol %) and AgSbF6 (20 mol %) in DCE at 110 ºC for 16 h. With the optimized catalytic conditions in hand, representative α- and/or ß-substituted acrylamides were investigated, and all reacted smoothly, regardless of aliphatic or aromatic groups. Also, differently N-substituted acrylamides have proven to be good substrates. Moreover, we examined the reactivity of different allyl derivatives, suggesting that the chelation of acetate oxygen to the metal is crucial for the catalytic process. Deuterium-labeled experiments were also conducted to investigate the reaction mechanism. Only Z-selective H/D exchanges on acrylamide were observed, indicating a reversible cyclometalation event. In addition, a kinetic isotope effect (KIE) of 3.2 was observed in the intermolecular isotopic study, suggesting that the olefinic C-H metalation step is probably involved in the rate-determining step.

Triflic acid catalyzed formal [3 + 2] cycloaddition of donor-acceptor oxiranes and nitriles: a facile access to 3-oxazolines.

A TfOH-catalyzed chemoselective [3 + 2] cycloaddition of donor-acceptor oxiranes and nitriles is described. This reaction provides an efficient and practical method for the preparation of useful 3-oxazolines in good to excellent yields (up to 99%).

N-Heterocyclic Carbene-Catalyzed Activation of Esters of N-Hydroxyphthalimide: A Highly Enantioselective Route to Chiral Dihydropyridinones Bearing an All Carbon Quaternary Stereogenic Center.

An N-heterocyclic carbene-catalyzed highly enantioselective [3 + 3] annulation reaction of N-hydroxyphthalimide (NHPI) 3,3-disubstituted acrylates and N-Ts ketimines was developed. In most cases, the desired chiral dihydropyridinone products bearing an all carbon quaternary stereogenic center could be obtained in good yields with excellent enantioselectivities (>99% ee's), which demonstrated the NHPI acrylates as a kind of excellent substrate in NHC-catalysis.