Olefin‐Directed Palladium‐Catalyzed Regio‐ and Stereoselective Oxidative Arylation of Allenes

An olefin‐directed palladium‐catalyzed oxidative regio‐ and stereoselective arylation of allenes to afford 1,3,6‐trienes has been established. A number of functionalized allenes, including 2,3‐ and 3,4‐dienoates and 3,4‐dienol derivatives, have been investigated and found to undergo the olefin‐directed allene arylation. The olefin moiety has been proven to be a crucial element for the arylating transformation.     

Cobalt‐Catalyzed Regio‐ and Stereoselective Hydroboration of Allenes

An efficient pincer‐ligand‐based cobalt‐complex‐catalyzed allene hydroboration affording Z‐allylic boronates is described. The reaction demonstrates an excellent regio‐ as well as Z‐stereoselectivity and a wide substrate scope that tolerates many functional groups. Based on solvent‐assisted electrospray ionization mass spectrometry (SAESI‐MS) studies, a rationale for the cobalt‐catalyzed hydroboration involving the highly selective insertion of an allene into the Co?H bond to form Z‐allylic cobalt intermediates is proposed.     

Highly Selective Copper‐Catalyzed Hydroboration of Allenes and 1,3‐Dienes

The highly selective copper‐catalyzed hydroboration of allenes has been developed. Allylboranes and alkenylboranes were selectively prepared by the judicious choice of catalytic species (copper hydride and boryl copper). Furthermore, two types of alkenylboranes could be selectively synthesized by the choice of an appropriate ligand. Mechanistic studies confirmed that the protonation of a (Z)‐σ‐allyl copper species, which was isolated and structurally characterized by single‐crystal X‐ray diffraction, was a key step in these reactions. Besides allenes, this method is also applicable to the selective hydroboration of 1,3‐diene derivatives to afford allylboranes and homoallylboranes.     

Palladium‐Catalyzed Intramolecular Hydroamination of Allenes Coupled to Aerobic Alcohol Oxidation

Taking the air! A Pd^II‐catalyzed intramolecular hydroamination of allenes coupled to alcohol oxidation has been developed. This reaction is performed by using a nitrogen‐based ligand under aerobic conditions, under which the molecular oxygen is used as the terminal oxidant for the reoxidation of Pd⁰ species to complete the catalytic cycle.

     

Stereodivergent Hydroboration of Allenes

Full details of a stereodivergent hydroboration of allenes are reported. While hydroboration of an allene with 9‐BBN provided a thermodynamically stable (E)‐allylic alcohol after oxidative work‐up, the reaction of an identical allene with HB(Sia)₂ (disiamylborane) formed a (Z)‐allylic alcohol as the kinetic product. The developed conditions allowed for the synthesis of trisubstituted olefins in a highly stereoselective fashion, which is known to be challenging. The method was also applied to the stereodivergent synthesis of structural motifs such as skipped dienes and allylbenzenes, which are often embedded in biologically active natural products.     

Palladium‐Catalyzed Regio‐ and Stereoselective Chlorothiolation of Terminal Alkynes with Sulfenyl Chlorides

Chlorothiolation of terminal alkynes with sulfenyl chlorides yields anti‐adducts without transition‐metal catalysts. In sharp contrast, transition‐metal‐catalyzed chlorothiolation has not been developed to date, possibly because organosulfur compounds can poison catalyst. Herein, the regio‐ and stereoselective palladium‐catalyzed chlorothiolation of terminal alkynes with sulfenyl chlorides is described. syn‐Chlorothiolation offers a complementary synthetic route to chloroalkenyl sulfides. 2‐Chloroalkenyl sulfides can easily be transformed into various sulfur‐containing products, most of which are often found in natural products and pharmaceuticals.     

Palladium‐Catalyzed CH Activation and Intermolecular Annulation with Allenes

A new and efficient Pd^II‐catalyzed intermolecular annulation of N‐benzoylsulfonamide with allenes for the synthesis of 3,4‐dihydroisoquinolin‐1(2H)‐ones is reported. This C?H functionalization is compatible with ambient air and moisture, and it can be applied to terminal or internal allenes with di?erent synthetically attractive functional groups. Control experiments and a kinetic isotope effect study are conducted and a plausible mechanism is proposed.     

Palladium‐Catalyzed Decarboxylative γ‐Arylation for the Synthesis of Tetrasubstituted Chiral Allenes

An enantiospecific palladium‐catalyzed decarboxylative coupling of acyclic β,γ‐alkynoic acids with various aryl iodides to chiral tetrasubstituted allenes is described. The coupling reaction comprises a decarboxylative γ‐palladation of α,α‐disubstituted carboxylic acids to provide the tetrasubstituted allenes with complete point‐to‐axial chirality transfer in excellent yields.     

Palladium‐Catalyzed Asymmetric Amination of Allenyl Phosphates: Enantioselective Synthesis of Allenes with an Additional Unsaturated Unit

A highly enantioselective Pd‐catalyzed amination of allenyl phosphates generating 2,3‐allenyl amines with central chirality has been developed. Under the optimized conditions, chiral 2,3‐allenyl amines with or without (an) additional C? C double or triple bond(s) have been prepared at 0 °C with up to 90 % yield and 94 % ee by identifying (R)‐3,4,5‐(MeO)₃‐MeOBIPHEP as the ligand.     

Synthesis and Functionalization of Allenes by Direct Pd‐Catalyzed Organolithium Cross‐Coupling

A palladium‐catalyzed cross‐coupling between in situ generated allenyl/propargyl‐lithium species and aryl bromides to yield highly functionalized allenes is reported. The direct and selective formation of allenic products preventing the corresponding isomeric propargylic product is accomplished by the choice of SPhos or XPhos based Pd catalysts. The methodology avoids the prior transmetalation to other transition metals or reverse approaches that required prefunctionalization of substrates with leaving groups, resulting in a fast and efficient approach for the synthesis of tri‐ and tetrasubstituted allenes. Experimental and theoretical studies on the mechanism show catalyst control of selectivity in this allene formation.     

A Versatile Synthesis of β‐Lactam‐Fused Oxacycles through the Palladium‐Catalyzed Chemo‐, Regio‐, and Diastereoselective Cyclization of Allenic Diols

Chemo‐, regio‐ and stereocontrolled palladium‐catalyzed preparations of enantiopure morpholines, oxocines, and dioxonines have been developed starting from 2‐azetidinone‐tethered γ,δ‐, δ,ε‐, and ε,ζ‐allendiols. The palladium‐catalyzed cyclizative coupling reaction of γ,δ‐allendiols 2 with allyl bromide or lithium bromide was effective as 8‐endo cyclization by attack of the primary hydroxy group to the terminal allene carbon to afford enantiopure functionalized oxocines; whereas the palladium‐catalyzed cyclizative coupling reaction of 2‐azetidinone‐tethered ε,ζ‐allendiols 4 furnished dioxonines 16 through a totally chemo‐ and regioselective 9‐endo oxycyclization. By contrast, the palladium‐catalyzed cyclizative coupling reaction of 2‐azetidinone‐tethered δ,ε‐allendiols 3 with aryl and alkenyl halides exclusively generated six‐membered‐ring compounds 14 a and 15 a . These results could be explained through a 6‐exo cyclization by chemo‐ and regiospecific attack of the secondary hydroxy group to the internal allene carbon. Chemo‐ and regiocontrol issues are mainly influenced by the length of the tether rather than by the nature of the metal catalysts and substituents. This reactivity can be rationalized by means of density functional theory calculations.     

Palladium‐Catalyzed Oxidative Carbocyclization–Borylation of Enallenes to Cyclobutenes

A highly efficient palladium‐catalyzed oxidative borylation of enallenes was developed for the selective formation of cyclobutene derivatives and fully‐substituted alkenylboron compounds. Cyclobutenes are formed as the exclusive products in MeOH in the presence of H₂O and Et₃N, whereas the use of AcOH leads to alkenylboron compounds. Both reactions showed a broad substrate scope and good tolerance for various functional groups, including carboxylic acid ester, free hydroxy, imide, and alkyl groups. Furthermore, transformations of the borylated products were conducted to show their potential applications.     

Regio‐ and Enantioselective Synthesis of N‐Substituted Pyrazoles by Rhodium‐Catalyzed Asymmetric Addition to Allenes

The rhodium‐catalyzed asymmetric N‐selective coupling of pyrazole derivatives with terminal allenes gives access to enantioenriched secondary and tertiary allylic pyrazoles, which can be employed for the synthesis of medicinally important targets. The reaction tolerates a large variety of functional groups and labelling experiments gave insights into the reaction mechanism. This new methodology was further applied in a highly efficient synthesis of JAK 1/2 inhibitor (R)‐ruxolitinib.