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Herein, we report the first enantioselective total synthesis of the highly complex hamigeran diterpenoid (-)-hamigeran F and its rearrangement product. The synthetic strategy features key steps of asymmetric hydrogenation, Horner-Wadsworth-Emmons olefination, and intramolecular Friedel-Crafts acylation to construct the [6,6,5]-tricyclic skeleton bearing three consecutive stereocenters, a sequence of steps involving Rosenmund reduction, Wittig reaction, dihydroxylation to assemble the α-acetoxy ketone group, and an intramolecular aldol reaction to build the tetracyclic core structure. more...

A DFT study was carried out to investigate a zirconium-catalyzed hydroaminoalkylation of alkenes with N-silylated benzylamine. A global reactivity index (GRI) analysis showed that that substrates act as electrophiles while the active zirconaaziridine behaves as a nucleophile. Furthermore, the distortion/interaction analysis unveiled the role of the distortion and interaction energies in controlling the regioselectivity and diastereoselectivity when different alkene substrates are used. These results provide an in-depth analysis on how the substrate type influences the product selectivity. more...

An enantioselective total synthesis of the alleged structure of (+)-fimbricalyxoid A is reported. The synthetic strategy features a pyridine

A three-step process for the enantioselective assembly of

An efficient asymmetric hydrogenation of racemic α-aryl-s-ethoxycarbonyl cyclopentanones via dynamic kinetic resolution is reported. Via catalysis by a chiral iridium Ir-SpiroPAP catalyst, a range of racemic α-aryl-s-ethoxycarbonyl cyclopentanones were hydrogenated to the corresponding ester-functionalized chiral 2-arylcyclopentanols with three contiguous stereocenters in high yields with excellent enantio- and diastereoselectivities. This method was successfully applied in the enantioselective synthesis of cyclopentane-based I³-amino ester/alcohol derivatives and phenylpropanoid (+)-burmaniol A. more...

A protocol for highly enantioselective hydrogenation of racemic α-arylamino lactones with catalysis by site-specifically modified chiral spiro iridium complexes has been developed. With the optimized catalyst, racemic α-arylamino-γ-lactones and α-arylamino-δ-lactones could be hydrogenated to the corresponding chiral 2-amino diols with good to excellent enantioselectivities. more...

A ligand-enabled nickel-catalyzed intramolecular hydroalkenylation of imines with unactivated alkenes has been developed. A variety of five- and six-membered cyclic allylic amines were synthesized in high yields. The use of both wide-bite-angle diphosphine ligand and Bronsted acid is crucial for realizing the reaction. Preliminary investigation of the asymmetric intramolecular hydroalkenylation of imines shows promising potential for the application of the method in the synthesis of enantio-enriched cyclic allylic amines. more...

An efficient asymmetric hydrogenation of racemic γ-substituted cyclic β-ketoesters via dynamic kinetic resolution to provide chiral cyclic β-hydroxy esters with three contiguous stereocenters is reported. Using a chiral spiro iridium catalyst (R)-5 (Ir-SpiroSAP), a series of racemic γ-aryl/alkyl substituted cyclic β-ketoesters were hydrogenated to the corresponding chiral cyclic β-hydroxy esters in high yields (84-97%) with good to excellent enantioselectivities (69->99% ee) and cis,cis-selectivities (up to >99:1). more...

A highly enantioselective and diastereoselective nickel-catalyzed desymmetrizing cyclization of 1,6-dienes was developed by using chiral spiro phosphoramidite ligands. The reaction provides a new atom- and step-economical approach to chiral spiro lactones and analogues bearing a quaternary stereocenter. more...

A protocol of iridium catalyzed asymmetric hydrogenation of 4-alkyl substituted 3-ethoxycarbonyl quinolin-2-ones and coumarins has been reported, providing a wide range of chiral dihydroquinolin-2-ones and dihydrocoumarins in high yields with excellent enantioselectivities (up to 99% ee) and high turnover numbers (up to 28 000). This efficient protocol was successfully applied for the synthesis of MPR3160 and the key chiral intermediate of R-106578. more...

A rhodium-catalyzed hydroformylation of alkynes with formic acid was developed. The method provides α,β-unsaturated aldehydes in high yield and E-selectivity without the need to handle toxic CO gas. more...

Herein, we report a practical method for efficient asymmetric hydrogenation of β-aryl alkylidene malonates. With a site-specifically tailored chiral spiro iridium catalyst, a series of β-aryl alkylidene malonate esters were hydrogenated to afford chiral malonate esters with good to excellent enantioselectivities (up to 99% ee) and high turnover numbers (up to 19000). The results showed that installing an ester group in α,β-unsaturated carboxylic esters significantly increased the efficiency of their asymmetric hydrogenation reactions. more...

A ruthenium-catalyzed asymmetric hydrogenation method for the synthesis of functionalized β-aryl cyclohexanols is described. With chiral spiro ruthenium catalyst (Ra,S,S)-5c, a series of racemic α-aryl cyclohexanones bearing a β-monoethylene ketal group were hydrogenated to the corresponding functionalized β-aryl cyclohexanols in high yields with enantioselectivity of up to 99% ee via a dynamic kinetic resolution. This protocol can be conducted on a decagram scale and provide potential approaches for the synthesis of optically active and densely functionalized aryl cyclohexanols. more...

Herein we report the first enantioselective total syntheses of pentacyclic homoproaporphine alkaloids by means of a route, which includes a tandem retro-oxa-Michael addition and nucleophilic substitution to generate the oxa-benzobicyclco[3.3.1]nonane core structure, a Pictet-Spengler cyclization to construct the fused B and C rings, and sequential Baeyer-Villiger oxidation and pinacol-type cyclization to install the hydroxyl-lactol moiety of D ring. With this unified route, six pentacyclic homoproaporphine alkaloids have been synthesized enantioselectively. more...

Density functional theory calculations were performed to investigate the catalyst-controlled selective functionalization of indoles with vinyl diazoacetates. The detailed reaction mechanism was established, and different roles of carboncation or carbene intermediates in defining an experimentally observed chemo- and regioselectivity were fully rationalized. more...

A green and efficient iridium-catalyzed asymmetric transfer hydrogenation of alkynyl ketones to chiral propargylic alcohols has been developed. By using sodium formate and ethanol as hydrogen sources, a series of alkynyl ketones were hydrogenated by chiral spiro iridium catalyst ( S)-1b to provide optically active chiral propargylic alcohols with up to 98% ee under base-free conditions. This protocol provides a practical and sustainable method for the preparation of optically active propargylic alcohols. more...

A highly efficient asymmetric hydrogenation of γ- and δ-ketoacids was developed by using a chiral spiro iridium catalyst (S)-1a, affording the optically active γ- and δ-hydroxy acids/lactones in high yields with excellent enantioselectivities (up to >99% ee) and turnover numbers (TON up to 100000). This protocol provides an efficient and practical method for enantioselective synthesis of Ezetimibe. more...

A highly efficient asymmetric Michael addition of thiols to exocyclic enones was achieved by using chiral spiro phosphoramide catalysts. The precisely chiral control in the protonation of the enol intermediate ensured high enantioselectivity. The reaction features high activity (yields up to 99%, turnover numbers up to 8400) and high enantioselectivity (up to 97% ee) with a broad substrate scope, and it has the potential for wide application in the synthesis of chiral sulfides. more...

An iterative protocol was developed for highly diastereo- and enantioselective construction of high-order 1,3-polyols via iridium-catalyzed asymmetric hydrogenation of β-alkyl-β-keto esters. The protocol involves four operations-asymmetric hydrogenation, hydroxy protection, ester hydrolysis, and C-acylation-and the catalyst loading can be as low as 0.005 mol %. The configurations of all stereogenic centers of 1,3-polyols are controlled by the catalyst. By the use of this protocol, a formal total synthesis of the polyketide cyanolide A was achieved with high diastereoselectivity and enantioselectivity. more...

A novel iterative protocol for the synthesis of polydeoxypropionates was developed based on iridium-catalyzed asymmetric hydrogenation of α-substituted acrylic acids. The catalyst loading can be as low as 0.01 mol %, and the overall yield for one iterative cycle is >76%. The reaction conditions are mild, and no organometallic reagents or chromatography steps are required. Using this protocol, (+)-phthioceranic acid and the polydeoxypropionate motifs of ionomycin and borrelidin were synthesized in high yield. more...

A new strategy featuring an iridium-catalyzed asymmetric hydrogenation of a racemic ketone via dynamic kinetic resolution to generate a cyclopentanol with three contiguous stereocenters and a SmI2-promoted pinacol coupling to install the six-membered ring with correct stereochemistry has been described for the enantioselective total synthesis of (-)-hamigeran B (19 steps, 10.6% overall yield) and (-)-4-bromohamigeran B (19 steps, 12.3% overall yield). more...

An enantioselective synthesis of pharmaceutically important spirobarbiturates has been achieved via spirocyclic chiral phosphine-catalyzed asymmetric [4 + 2] annulation of barbiturate-derived alkenes with allenoates. With the use of this tool, various spirobarbiturate-cyclohexenes are obtained in good to excellent yields with excellent diastereo- and enantioselectivities. A wide range of α-substituted allenoates and barbiturate-derived alkenes were tolerated. more...

(+)-Gracilamine, a biologically attractive and structurally unique pentacyclic Amaryllidaceae alkaloid, was biomimetically synthesized in 11 linear steps in 9.9% overall yield from the known racemic oxocrinine. The synthesis features an asymmetric hydrogenation, a ring-opening/benzylic oxidation/cyclization sequence, and a biomimetic intramolecular cycloaddition. This total synthesis not only allows the assignment of its absolute configuration, but also provides experimental support for the hypothesis that naturally occurring (+)-gracilamine is biogenetically derived from the crinine-type alkaloid (+)-epivittatine. more...

While the phosphine catalysis is a powerful tool for the construction of N-heterocycles, the phosphine-catalyzed annulations toward lactam motif are still extremely scarce. Here, we report the asymmetric (3 + 2) annulations of δ-acetoxy allenoates with β-carbonyl amides by using the (R)-SITCP catalyst. The δC and γC of allenoate respectively engage in annulation with the αC and N of the amide, forging a γ-lactam with good to excellent stereoselectivity. more...

A highly efficient iridium-catalyzed asymmetric hydrogenation of tetrasubstituted cyclic enones has been developed for the enantioselective synthesis of chiral cycloalkanols with three contiguous stereocenters. The C═O and C═C bonds of the enone substrates were hydrogenated sequentially in one pot with excellent enantioselectivity (92 to >99% ee) and diastereoselectivity (dr 95:5 to >99:1). The reaction provided a practical approach to all of the stereoisomers of the antiulcer drug rosaprostol. more...

A highly efficient asymmetric hydrogenation of α,β-unsaturated carboxylic acids with tetrasubstituted olefin catalyzed by chiral spiro iridium complexes has been developed for the preparation of chiral α-substituted carboxylic acids in excellent enantioselectivities (up to 99% ee). more...

A highly efficient Ir-catalyzed asymmetric hydrogenation of racemic β-keto lactams via dynamic kinetic resolution (DKR) for the synthesis of optically active β-hydroxyl lactams has been described. With the Ir-SpiroSAP catalyst, a series of racemic β-keto lactams including β-keto γ-, δ-, and e-lactams were hydrogenated to chiral β-hydroxy lactams in high yields (87–99%) with excellent enantio- and diastereoselectivity (83–99.9% ee, syn/anti: 97:3–>99:1) at low catalyst loading under mild reaction conditions. This efficient method has been successfully applied in the synthesis of the chiral intermediate of fluoroquinolone antibiotic premafloxacine. more...

A highly efficient asymmetric hydrogenation of α-substituted α,β-unsaturated acyclic ketones catalyzed by chiral spiro iridium complexes for the preparation of chiral 2-substituted allylic alcohols has been developed (ee up to 99.7%). This method provides a concise route to (-)-mesembrine (34% yield, 12 steps). more...

A synthetic strategy featuring efficient ruthenium-catalyzed asymmetric hydrogenation of racemic α-aryloxy cyclic ketone via dynamic kinetic resolution and palladium-catalyzed intramolecular reductive Heck cyclization has been developed for the asymmetric total synthesis of (-)-galanthamine (20.1%, 12 steps) and (-)-lycoramine (40.2%, 10 steps). more...

[reaction: see text] The enantioselective copper(II)-catalyzed Friedel-Crafts addition of indoles to N-sulfonyl aldimines was developed using chiral bisoxazoline as ligands, and high enantioselectivities (up to 96% ee) were achieved. more...

A kinetic resolution of racemic 2-substituted cyclopentanones via highly regio- and enantioselective Baeyer-Villiger oxidation has been successfully developed. The reaction could afford the normal 6-substituted δ-lactones in up to 98% ee and >19/1 regioselectivity. Meanwhile, the unreacted ketones were recovered in excellent ee values (up to 98%). It represents the best results of the kinetic resolution of racemic 2-substituted cyclopentanones via nonenzymic asymmetric BV oxidation. more...

The asymmetric arylation of N-tosylarylimines with arylboronic acids was realized by using rhodium/(S)-ShiP as catalyst. The reaction proceeded in aqueous toluene to give diarylmethylamines in good yields with up to 96% ee. [reaction: see text] more...

The highly efficient asymmetric total syntheses of (-)-Δ(8)-tetrahydrocannabinol ((-)-Δ(8)-THC) (13 steps, 35%) and (-)-Δ(9)-tetrahydrocannabinol ((-)-Δ(9)-THC) (14 steps, 30%) have been developed by using ruthenium-catalyzed asymmetric hydrogenation of racemic α-aryl cyclic ketones via dynamic kinetic resolution and intramolecular S(N)Ar cyclization. more...

A highly efficient one-pot process via a tandem reaction of catalytic asymmetric hydrogenation and oxa-Michael cyclization for the synthesis of 2,6-cis-disubstituted tetrahydropyrans has been developed (ee up to 99.9%, cis/trans-selectivity up to 99:1). This method provides a concise route to (−)-centrolobine (68.8% yield, three steps). more...

A catalytic hydrovinylation of N-acetylenamines with ethylene is reported. This new hydrovinylation reaction is catalyzed by a ruthenium hydride complex, RuHCl(CO)(PCy(3))(2), providing a series of N-acetylamines with a quaternary carbon center with up to 99% yield. more...

A direct highly diastereo- and enantioselective asymmetric vinylogous Mannich-type (AVM) reaction of aldimines with nonactivated natural α-angelica lactone has been successfully developed. It was demonstrated that the nonactivated natural α-angelica lactone is a useful vinylogous nucleophile to give the chiral δ-amino γ,γ-disubstituted butenolide carbonyl derivatives. The N,N'-dioxide L2-Sc(III) complex is efficient toward the obtention of a range of corresponding products with adjacent quaternary and tertiary stereocenters in excellent dr and ee values. more...

A highly efficient enantio- and diastereoselective synthesis of chiral cis-beta-N-alkyl/arylamino cyclic alcohols has been realized by asymmetric hydrogenation of racemic alpha-amino cyclic ketones via DKR catalyzed by [RuCl(2)((S)-Xyl-SDP)((R,R)-DPEN)]. The enantioselectivities of the reaction were up to 99.9% ee with 99:1 cis-selectivities. A practical catalytic asymmetric synthesis of all four isomers of conhydrine was also developed. more...

[reaction: see text] A novel chiral monodentate spiro phenylphospholane ligand 4 was prepared from a readily accessible, enantiomerically pure 1,1'-spirobiindane-7,7'-diol in high yield. This ligand has proven to be efficient for Pd-catalyzed enantioselective allylation of aldehydes with allylic alcohols. Aromatic, heteroaromatic, and aliphatic aldehydes gave homoallylic alcohols in good enantioselectivities (up to 83% ee) and excellent anti diastereoselectivities (up to 99:1 dr). more...

[reaction: see text] 9,9'-Spirobifluorene-1,1'-diol (SBIFOL) was conveniently synthesized from 1,2-dibromobenzene and 3-bromoanisole in high yield. Both enantiomers of SBIFOL were obtained in 99% ee by inclusion resolution with 2,3-dimethoxy-N,N,N',N'-tetracyclohexylsuccinamide. The absolute configurations were determined by X-ray analysis of a single crystal of molecular complex. more...