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We developed a method for the enantioselective synthesis of germanium-stereogenic compounds by the desymmetric carbene insertion of dihydrogermanes. A chiral rhodium phosphate catalyst decomposes diaryldiazo-methanes to generate rhodium carbenes that insert enantioselectively into one of the two Ge–H bonds of dihydrogermanes to form germanium-stereogenic compounds under mild reaction conditions. By this method, a variety of chiral germanes with germanium-stereogenic centers were synthesized in high yields and excellent enantioselectivities. Kinetic studies of the reaction showed that the diazo decomposition process was the rate-determining step. The remaining Ge–H bond of the chiral germane products provides a possibility for preparing chiral tetra-substituted germanium-stereogenic compounds.

An efficient catalytic asymmetric dearomatizing amination of 2-naphthols and phenols catalyzed by N,N′-dioxide-copper(I) complex as a chiral catalyst was presented. A variety of optically active β-naphthalenone compounds with a nitrogen-containing quaternary carbon stereocenter were obtained with high yield and enantioselectivity under mild reaction conditions. Mechanistic studies indicated that this Csp2–N dearomatizing coupling proceeds via1,3-reductive elimination of phenolate-CuIII-amino intermediate in five-membered ring transition states. The origin of enantioselectivity has also been elucidated based on density functional theory calculations.

Cyclopamine is a teratogenic steroidal alkaloid, which inhibits the Hedgehog (Hh) signaling pathway by targeting the Smoothened (Smo) receptor. Suppression of Hh signaling with synthetic small molecules has been pursued as a therapeutic approach for the treatment of cancer. We report herein the asymmetric synthesis of cyclopamine based on a two-stage relay strategy. Stage-I: total synthesis of veratramine through a convergent approach, wherein a crucial photoinduced excited-state Nazarov reaction was applied to construct the basic [6–6–5–6] skeleton of C-nor-D-homo-steroid. Stage-II: conversion of veratramine to cyclopamine was achieved through a sequence of chemo-selective redox manipulations.

We present the first enantioselective nickel-catalyzed borylative coupling of 1,3-dienes with aldehydes, providing an efficient route to highly valuable homoallylic alcohols in a single step. The reaction involves the 1,4-carboboration of dienes, leading to the formation of C–C and C–B bonds accompanied by the construction of two continuous stereogenic centers. Enabled by a chiral spiro phosphine-oxazoline nickel complex, this transformation yields products with exceptional diastereoselectivity, E-selectivity, and enantioselectivity. The diastereoselectivity of the reaction can be controlled by employing either (Z)-1,3-dienes or (E)-1,3-dienes.

Catalytic asymmetric hydrogenation is one of the most reliable, powerful, and environmentally benign methods for the synthesis of chiral molecules with high atom economy and has been successfully applied in the industrial production of pharmaceuticals, agrochemicals, and fragrances. The key to achieving highly efficient and highly enantioselective hydrogenation reactions is the design and synthesis of chiral catalysts.

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.

An enantioselective total synthesis of the alleged structure of (+)-fimbricalyxoid A is reported. The synthetic strategy features a pyridine-N-oxidate-mediated SN2′ reaction to introduce an oxygen functionality at position C3 of the A-ring and a sequential three-step process via the cleavage of the C–O bonds and hemiketalization to form the 3,20-oxybridge. With this strategy, the target molecule was synthesized in 19% overall yield and 12 steps from our previously synthesized cis-fused octahydrophenanthrene (+)-6.

A three-step process for the enantioselective assembly of cis-fused octahydrophenanthrenes with a quaternary stereocenter is reported. This synthetic strategy relies on a regioselective γ-alkylation, a one-pot sequence of asymmetric hydrogenation and oxidation, and an intramolecular enolate arylation to facilitate the rapid and enantioselective construction of cis-fused octahydrophenanthrene scaffolds with an arylated all-carbon quaternary stereocenter concisely and efficiently.

Introduction: Enhanced recovery after surgery (ERAS) protocols are a series of perioperative care to optimize preoperative preparation, prevent postoperative complications, minimize stress, and speedup recovery. Tympanoplasty and mastoidectomy are common surgical procedures for chronic suppurative otitis media.Objective: To compare the efficacy and safety between ERAS and conventional recovery after surgery in the perioperative period of chronic suppurative otitis media.Methods: From April 2018 to February 2019, a total of 84 patients scheduled for tympanoplasty and/or mastoidectomy due to chronic suppurative otitis media were involved and randomly divided into the ERAS group and the control group. The patients’ preoperative anxiety, postoperative pain, and comfort level were determined by comparing the results of Self-Rating Anxiety Scale (SAS), Visual Analog Scale (VAS) and General Comfort Questionnaire (GCQ). The postoperative complications, postoperative hospital stay, and hospitalization cost were calculated.Results: The ERAS group showed a lower SAS score (30 [28-31.5] vs 35 [30-43], P< .05], a higher GCQ score (88 [84-100] vs 83 [78.25-92.25], P< .05), and a lower VAS score (0 [0-0] vs 1 [0-2], P< .05] after surgery. No significant difference (P> .05) was observed between the ERAS group and the control group in postoperative complications, postoperative hospitalization time, and hospitalization cost, respectively.Conclusion: Enhanced recovery after surgery can reduce pain and improve comfort in the perioperative period of chronic suppurative otitis media.

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 Brønsted 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.

A highly enantioselective Si–H bond insertion reaction of α-aryldiazoacetates catalyzed by chiral spiro dirhodium tetraphosphate was developed. Various chiral α-silyl esters were prepared with high yield (up to 92%) and excellent enantioselectivity (up to >99% ee) through this protocol. It is noteworthy that the 2-substituted aryl diazoacetates, which are challenging substrates for other chiral dirhodium catalysts, also exhibited good results in this reaction. This work represents one of the few successful applications of chiral dirhodium phosphates in asymmetric catalysis.

Transfer functionalization has emerged as an efficient strategy for the synthesis of organic functional compounds. This article reports a new cleavage model of functional radicals, which enables transfer hydrocyanation of alkenes, dienes, and alkynes. By introducing readily available, low-toxic azobisisobutyronitrile (AIBN) as a hydrocyanation reagent, we have developed a practical and economic method for the preparation of nitrile compounds. Mechanistic studies showed that the hydrocyanation proceeds through a relay transfer of the cyano group and the hydrogen atom of cyanoisopropyl radicals generated by pyrolysis of AIBN. The reaction represents the first example of group transfer of α-functional radicals.

The Nazarov electrocyclization reaction is a convenient, widely used method for construction of cyclopentenones. In the past few decades, catalytic asymmetric versions of the reaction have been extensively studied, but the strategies used to control the position of the double bond limit the substituent pattern of the products and thus the synthetic applications of the reaction. Herein, we report highly enantioselective silicon-directed Nazarov reactions which were cooperatively catalyzed by a Lewis acid and a chiral Brønsted acid. The chiral cyclopentenones we synthesized using this method generally cannot be obtained by means of other catalytic enantioselective reactions, including previously reported methods for enantioselective Nazarov cyclization. The silicon group in the dienone substrate stabilized the β-carbocation of the intermediate, thereby determining the position of the double bond in the product. Mechanistic studies suggested that the combination of Lewis and Brønsted acids synergistically activated the dienone substrate and that the enantioselectivity of the reaction originated from a chiral Brønsted acid promoted proton transfer reaction of the enol intermediate.

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.

Chiral propargylsilanes and chiral allenylsilanes have emerged as versatile building blocks for organic synthesis. However, efficient methods for preparing these organosilicon compounds are lacking. We herein report a highly enantioselective method for synthesis of chiral propargylsilanes and chiral allenylsilanes from readily available alkynyl sulfonylhydrazones. Specifically, chiral spiro phosphate dirhodium complexes were used to catalyze asymmetric insertion of alkynyl carbenes into the Si–H bonds of silanes to afford a variety of chiral propargylsilanes with excellent enantioselectivity. Subsequently, a platinum catalyst was used for stereospecific isomerization of the chiral propargylsilanes to the corresponding chiral allenylsilanes.

Organogermanium compounds have shown potential as pharmaceuticals and functional materials and have been used as coupling partners in transition metal-catalyzed cross-coupling reactions. Methods for the synthesis of organic germanium compounds, including catalytic C−Ge coupling reactions and hydrogermylations of alkenes or alkynes, have been developed. However, the development of an efficient method for enantioselective C−Ge bond formation and synthesis of chiral organogermanium compounds remains a challenge, impeding the exploration of their functionalities. We herein report a highly enantioselective reaction for the formation of C−Ge bond catalyzed by chiral dirhodium phosphate catalysts, providing an efficient method for the synthesis of chiral organogermanes. The method features a broad substrate scope, good functional group tolerance, and mild reaction conditions. The mechanism of the C−Ge bond formation reaction was studied computationally and experimentally.

Ligand modulation of transition-metal catalysts to achieve optimal reactivity and selectivity in alkene hydrofunctionalization is a fundamental challenge in synthetic organic chemistry. Hydroaminoalkylation, an atom-economical approach for alkylating amines using alkenes, is particularly significant for amine synthesis in the pharmaceutical, agrochemical, and fine chemical industries. However, the existing methods usually require specific substrate combinations to achieve precise regio- and stereoselectivity, which limits their practical utility. Protocols allowing for regiodivergent hydroaminoalkylation from the same starting materials, controlling both regiochemical and stereochemical outcomes, are currently absent. Herein, we report a ligand-controlled, regiodivergent nickel-catalyzed hydroaminoalkylation of unactivated alkenes with N-sulfonyl amines. The reaction initiates with amine dehydrogenation and involves aza-nickelacycle intermediates. Tritert-butylphosphine promotes branched regioselectivity and syndiastereoselectivity, whereas ethyldiphenylphosphine enables linear selectivity, yielding regioisomers with inverse orientation. Systematic evaluation of diverse monodentate phosphine ligands reveals distinct regioselectivity cliffs, and % Vbur(min), a ligand steric descriptor, was established as a predictive parameter correlating ligand structure to regioselectivity. Computational investigations supported experimental findings, offering mechanistic insights into the origins of regioselectivity. Our method provides an efficient and predictable route for amine synthesis, demonstrating broad substrate scope, excellent tolerance toward various functional groups, and practical advantages. These include the use of readily available starting materials and cost-effective nickel(II) salts as precatalysts.

Stereoconvergent reactions enable the transformation of mixed stereoisomers into well-defined, chiral products─a crucial strategy for handling Z/E-mixed olefins, which are common but challenging substrates in organic synthesis. Herein, we report a stereoconvergent and highly enantioselective method for synthesizing Z-homoallylic alcohols via the nickel-catalyzed reductive coupling of Z/E-mixed 1,3-dienes with aldehydes. This process is enabled by an N-heterocyclic carbene ligand characterized by C2-symmetric backbone chirality and bulky 2,6-diisopropyl N-aryl substituents. Our method achieves excellent stereocontrol over both enantioselectivity and Z-selectivity in a single step, producing chiral Z-homoallylic alcohols that are valuable in natural products and pharmaceuticals.

Unactivated aliphatic alkenes are particularly desirable as starting materials because they are readily accessible in large quantities, but the enantioselective intermolecular reductive coupling of unactivated alkenes with imines is challenging. In this paper, we report a method for nickel-catalyzed intermolecular reductive coupling reactions between aliphatic alkenes and imines to yield chiral amines with excellent enantioselectivities and good linear selectivities. The reaction conditions are compatible with a broad range of aliphatic alkenes, including those derived from bioactive molecules. The success of this method can be attributed to the use of newly developed monodentate chiral spiro phosphine ligands.

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.

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.

We have developed a protocol for insertion of alkylidene carbenes into the B–H bonds of amine–borane adducts, enabling, for the first time, the construction of C(sp2)–B bonds by means of carbene-insertion reactions. Various acyclic and cyclic alkenyl borane–amine adducts were prepared from readily accessible starting materials in good to high yields and were subsequently subjected to a diverse array of functional group transformations. The unprecedented spiro B–N heterocycles prepared in this study have potential utility as building blocks for the synthesis of pharmaceuticals. Preliminary mechanistic studies suggest that insertion of the alkylidene carbenes into the B–H bonds of the amine–borane adducts proceeds via a concerted process involving a three-membered-ring transition state.

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.

Catalytic enantioselection usually depends on differences in steric interactions between prochiral substrates and a chiral catalyst. We have discovered a carbene Si–H insertion in which the enantioselectivity depends primarily on the electronic characteristics of the carbene substrate, and the log(er) values are linearly related to Hammett parameters. A new class of chiral tetraphosphate dirhodium catalysts was developed; it shows excellent activity and enantioselectivity for the insertion of diarylcarbenes into the Si–H bond of silanes. Computational and mechanistic studies show how the electronic differences between the two aryls of the carbene lead to differences in energies of the diastereomeric transition states. This study provides a new strategy for asymmetric catalysis exploiting the electronic properties of the substrates.

Catalytic asymmetric reactions in which water is a substrate are rare. Enantioselective transition-metal-catalyzed insertion of carbenes into the O–H bond of water can be used to incorporate water into the stereogenic center, but the reported chiral catalysts give good results only when α-aryl-α-diazoesters are used as the carbene precursors. Herein we report the first highly enantioselective O–H bond insertion reactions between water and α-alkyl- and α-alkenyl-α-diazoesters as carbene precursors, with catalysis by a combination of achiral dirhodium complexes and chiral phosphoric acids or chiral phosphoramides. Participation of the phosphoric acids or phosphoramides in the carbene transfer reaction markedly suppressed competing side reactions, such as β-H migration, carbene dimerization, and olefin isomerization, and thus ensured good yields of the desired products. Fine-tuning of the ester moiety facilitated enantiocontrol of the proton transfer reactions of the enol intermediates and resulted in excellent enantioselectivity. This protocol represents an efficient new method for preparation of multifunctionalized chiral α-alkyl and α-alkenyl hydroxyl esters, which readily undergo various transformations and can thus be used for the synthesis of bioactive compounds. Mechanistic studies revealed that the phosphoric acids and phosphoramides promoted highly enantioselective [1,2]- and [1,3]-proton transfer reactions of the enol intermediates. Maximization of molecular orbital overlap in the transition states of the proton transfer reactions was the original driving force to involve the proton shuttle catalysts in this process.

This study was designed to determine whether plasma CXCL12 levels in postmenopausal osteoporosis (PMOP) patients are related to disease severity. A total of 91 PMOP females were recruited, and 88 postmenopausal non-osteoporotic (PMNOP) women and 90 healthy females were incorporated as controls. Dual-energy X-ray absorptiometry was utilised to explore bone-mineral density (BMD). The Genant semi-quantitative grading scale was used for vertebral fractures, and plasma CXCL12/SDF-1 levels were investigated by ELISA. Plasma TNF-α and C-telopeptide cross-linked collagen type 1 (CTX-1) were also tested. The Oswestry Disability Index (ODI) and a visual analogue scale (VAS) were completed in order to assess clinical severity. Plasma CXCL12 levels were considerably elevated in PMOP females compared to PMNOP women and healthy controls. Plasma CXCL12 concentrations were positively correlated with the Genant grading system. We observed significant and negative correlations of plasma CXCL12 levels with lumbar spine, femoral neck and total hip BMD. Moreover, plasma CXCL12 concentrations were positively correlated to VAS and ODI, as well as plasma TNF-α and CTX-1 levels. In conclusion, elevated plasma CXCL12 levels are correlated with disease severity in PMOP females.

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.

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.