Palladium-Catalyzed -Allylic Alkylation of Pyrazoles and Unactivated Vinylcyclopropanes.

An efficient palladium-catalyzed -allylic alkylation of pyrazoles and unactivated vinylcyclopropanes is demonstrated, affording various -alkyl pyrazoles in ≤99% yield. This protocol displays high atom economy, a broad range of substrates, and excellent regioselectivity and stereoselectivity. Late-stage modification of bioactive molecules, scaled-up reaction, and divergent derivatization documented the practicability of this methodology.

Palladium-Catalyzed Isomerization/Hydrocarbonylation of Electron-Deficient Alkenes for the Construction of Lactones and Lactams.

An efficient palladium-catalyzed isomerization/hydrocarbonylation of electron-deficient alkenes was developed, affording a variety of benzofuran-2(3)-ones, dihydrofuran-2(3)-ones, indolin-2-ones, and isochroman-3-ones in high yields. The reaction exhibits excellent regioselectivity, high atom economy, and a broad range of substrates. The late-stage modification of bioactive molecules and scaled-up reaction demonstrated the practicability of this methodology.

Palladium-Catalyzed Asymmetric Larock Isoquinoline Synthesis to Access Axially Chiral 3,4-Disubstituted Isoquinolines.

Larock isoquinoline synthesis is one of the most efficient and straightforward approaches to the construction of 3,4-disubstituted isoquinolines. However, there have been no asymmetric versions for the synthesis of axially chiral isoquinolines since their initial report in 2001. Herein, we documented the first example of an asymmetric Larock isoquinoline synthesis by employing Pd(OAc)/Walphos SL-W002-1 as the catalyst, affording the axially chiral 3,4-disubstituted isoquinolines with up to 97.

Rhodium-Catalyzed Selective Nucleophilic Cyclization/Cross-Coupling of Two -Alkynylanilines Bearing Differential -Substituents.

Herein, we reported an effective selective nucleophilic cyclization/cross-coupling cascade reaction of -tosyl -alkynylanilines and -acyl -alkynylanilines using Rh(COD)BF/BuXantPhos as a catalyst. The present protocol features excellent chemo- and regioselectivity, high atom-economy, and a broad range of substrates. The mechanism studies indicated that the key to the success of this reaction is the powerful capacity of the rhodium catalyst to recognize the -substituent group in the selective nucleophilic cyclization and selective alkyne insertion.

Bifunctional Lewis Base Catalyzed Asymmetric -Allylic Alkylation of 2-Hydroxypyridines.

A chiral Lewis base catalyzed enantioselective -allylic alkylation of 2-hydroxypyridines and MBH carbonates is documented, affording a convenient access to -alkylated 2-pyridones with up to 99% ee and 99% yield. Experimental and computational studies have revealed that the strong hydrogen bond interaction between the chiral Lewis base catalyst and 2-hydroxypyridines plays a crucial role in this reaction for the reactivity, chemoselectivity, and enantioselectivity.

Palladium-catalyzed nucleomethylation of alkynes for synthesis of methylated heteroaromatic compounds.

Herein, we disclosed a novel and efficient palladium-catalyzed nucleomethylation of alkynes for the simultaneous construction of the heteroaromatic ring and methyl group. The 3-methylindoles, 3-methylbenzofurans and 4-methylisoquinolines were obtained in moderate to excellent yields. Notably, this methodology was employed as a key step for synthesis of a pregnane X receptor antagonist, zindoxifene, bazedoxifene and AFN-1252.

C-C Bond Activation of Cyclopropanes Enabled by Phosphine-Catalyzed Formation of High-Strain Methylenecycopropane Intermediate.

An effective strategy for the ring-opening/elaboration of cyclopropanes by phosphine catalyst is documented, providing the 2,4-pentadiene sulfonamides and isoindolines in moderate to good yields. The key to the success of this reaction is phosphine-catalyzed introduction of a trigonal center into cyclopropanes, which results in the formation of higher ring strain cyclopropylidenemethyl phosphonium salt. Moreover, this methodology is employed as the key step for the synthesis of bioactive molecules.

Palladium-Catalyzed α-Amino C-H Functionalization via Isomerization of α,β-Unsaturated Carbonyls.

Palladium-catalyzed regioselective α-amino C-H functionalization via the isomerization of α,β-unsaturated carbonyls including esters, ketones, and amides has been established, providing an easy access to a wide array of tricyclic 1,2,3,4-tetrahydro--carbolines, azepinoindoles, 2,3,4,5-tetrahydro-1-pyrido[4,3-]indoles, 4,5,6,7-tetrahydro-1-pyrrolo[2,3-]pyridines, 1,2,3,4-tetrahydropyrazino-[1,2-]indoles, pyran-fused indoles, and tetrahydroisoquinolines in good to excellent yields. This transformation showed high regioselectivity, excellent functional group tolerance, and scalability. Moreover, this methodology was also employed as the key step for the total synthesis of desbromoarborescidines A, B, and C.

Synthesis of 1-Substituted Cyclopropylamines via Formal Tertiary C-H Amination of Cyclopropanes.

A novel and facile approach to synthesis of 1-substituted cyclopropylamines via phosphine-catalyzed formal tertiary C-H amination of cyclopropanes was described. The indoles, pyrroles, imidazoles, uracils, 2-pyridone, pyrimidin-4(3)-one, and phthalimide had been proven as good aminating partners. The present protocol features transition-metal-free, excellent regioselectivity, high-atom-economy, and mild reaction conditions and a broad range of substrates.

Enantioselective Synthesis of Indole-Fused Bicyclo[3.2.1]octanes via Palladium(II)-Catalyzed Cascade Reaction.

Indole-fused bicyclo[3.2.1]octanes are highly important structural units in natural products and biologically active compounds.

An efficient route to chiral N-heterocycles bearing a C-F stereogenic center via asymmetric hydrogenation of fluorinated isoquinolines.

An efficient iridium-catalyzed asymmetric hydrogenation of the fluorinated isoquinoline derivatives has been successfully developed for the synthesis of chiral fluorinated tetrahydroisoquinoline derivatives with up to 93% ee. This methodology features the use of a hydrochloride salt as well as a catalytic amount of halogenated hydantoin which were vital for the reactivity, enantioselectivity, and inhibition of the hydrodefluorination pathway.

Asymmetric transfer hydrogenation of 3-nitroquinolines: facile access to cyclic nitro compounds with two contiguous stereocenters.

Hi, neighbor! The first organocatalyzed asymmetric transfer hydrogenation of aromatic nitro compounds was successfully developed with up to 99 % ee. The new methodology provides a direct and facile access to enantiopure cyclic nitro compounds with two contiguous stereocenters.

A mild method for generation of o-quinone methides under basic conditions. The facile synthesis of trans-2,3-dihydrobenzofurans.

A novel and efficient method for the generation of o-quinone methide intermediates was developed from the readily available 2-tosylalkylphenols under the mild basic conditions, and their reactions with sulfur ylides were investigated for the stereoselective synthesis of trans-2,3-dihydrobenzofurans.

Homogeneous palladium-catalyzed asymmetric hydrogenation.

The transition metal catalyzed asymmetric hydrogenation of unsaturated compounds arguably presents one of the most attractive methods for the synthesis of chiral compounds. Over the last few decades, Pd has gradually grown up as a new and popular metal catalyst in homogeneous asymmetric hydrogenation the same as traditional Ru, Rh and Ir catalysts. Much progress has been successfully achieved in the asymmetric reduction of imines, enamines, olefins, ketones and heteroarenes.

Iridium catalyzed asymmetric hydrogenation of cyclic imines of benzodiazepinones and benzodiazepines.

Highly enantioselective Ir-catalyzed hydrogenation of seven-membered cyclic imines of benzodiazepinones and benzodiazepines was achieved with up to 96% ee. This method provides a direct access to synthesize a range of chiral cyclic amines existing in numerous important natural products and clinical drugs.

Dihydrophenanthridine: a new and easily regenerable NAD(P)H model for biomimetic asymmetric hydrogenation.

A new and easily regenerable NAD(P)H model 9,10-dihydrophenanthridine (DHPD) has been designed for biomimetic asymmetric hydrogenation of imines and aromatic compounds. This reaction features the use of hydrogen gas as terminal reductant for the regeneration of the DHPD under the mild condition. Therefore, the substrate scope is not limited in benzoxazinones; the biomimetic asymmetric hydrogenation of benzoxazines, quinoxalines, and quinolines also gives excellent activities and enantioselectivities.

Asymmetric hydrogenolysis of racemic tertiary alcohols, 3-substituted 3-hydroxyisoindolin-1-ones.

Asymmetric hydrogenolysis of racemic tertiary alcohols, 3-substituted 3-hydroxyisoindolin-1-ones, was developed using chiral phosphoric acid as catalyst and a Hantzsch ester as the hydrogen source with up to 95% ee. The reaction process of this asymmetric transfer hydrogenation may occur directly through the acyliminium ion intermediate.

Highly enantioselective partial hydrogenation of simple pyrroles: a facile access to chiral 1-pyrrolines.

A highly enantioselective Pd-catalyzed partial hydrogenation of simple 2,5-disubstituted pyrroles with a Brønsted acid as an activator has been successfully developed, providing chiral 2,5-disubstituted 1-pyrrolines with up to 92% ee.