Ni-Catalyzed Enantioconvergent Coupling of Epoxides with Alkenylboronic Acids:Construction of Oxindoles Bearing Quaternary Carbons

We have developed a nickel-nickel/bisphosphinecatalyzed stereoconvergent cross-coupling reaction of epoxides with alkenylboronic acids.Racemic spiroepoxyoxindoles were converted to chiral homoallylic alcohols bearing quaternary carbon stereogenic centers via a stereoablative enantioconvergent transformation.The subsequently fabricated oxindoles-carrying quaternary carbon products were obtained in good yields and enantioselectivity.A wide range of substrates and alkenylboronic acids was tolerated under the catalytic system.This reaction provided a rare example of a nickelcatalyzed enantioselective cross-coupling reaction of tertiary alkyl electrophiles and an enantioconvergent transformation of racemic epoxides,beneficial as a low-cost,sustainable,and efficient catalyst in the preparation of chiral oxindole-containing natural and pharmaceutical compounds.

Construction of Acyclic Quaternary Carbon Stereocenters via Enantioselective Nickel Catalysis

The construction of acyclic quaternary carbon stereocenters,which are ubiquitous in many bioactive compounds,pharmaceuticals and natural products,has been a long persuit in synthetic organic chemistry.Among numerous methods,enantioselective nickel-catalysis has attracted incremental attention in recent years.This review summarizes the recent development in the asymmetric strategies,research progress,mechanistic investigations for the generation of acyclic quaternary carbon stereocenters via enantioselective nickel catalysis.

I_(2)-DMSO-Mediated Multicomponent [2+1+1+1] Annulation Reaction via Ethyl Nitroacetate C-NO_(2), Bond Cleavage as a C1 Synthon: A Route to Multisubstituted 6-Pyrrolidinones Derivatives with a Quaternary Center

A[2+1+1+1]cyclization reaction has been developed for the synthesis of multisubstituted 6-pyrrolidinones from commercially available aryl methyl ketones,primary amines,and ethyl nitroacetate.In this I_(2)-DMSO-meditated process,the C-NO_(2) bond of ethyl nitroacetate is cleaved,affording a C1 synthon,and the formation of two C-C and two C-N bonds and a quaternary carbon center are constructed in one pot.This method has good substrate compatibility and permits the late-stage modification of pharmaceutical compounds.

Construction of remote cyano-substituted quaternary carbon centers via nickel-catalyzed migratory hydrocyanation of unconjugated dienes

The transition-metal-catalyzed migratory functionalization has emerged as a robust protocol for the building of C–C bonds remote from the“initiation”position.However,a similar strategy for the construction of quaternary carbon centers is still underdeveloped and only a limited number of reports exist.Herein,we report a nickel-catalyzed migratory hydrocyanation of unconjugated dienes to construct remote cyano-substituted quaternary carbon centers.This transformation features exceptional regioselectivity,mild reaction conditions,broad substrate scope and high yields.The synthetic utility of this method has been highlighted by a series of product derivatizations,and the potential of this transformation has been extended to synthesize TRPV1 antagonist and the key intermediate in the total synthesis of quebrachamine.Density functional theory(DFT)studies unveiled that the specific catalytic pocket assumed a significant role in the selective formation of cyano-substituted quaternary carbon centers.

Catalytic diastereoselective construction of multiple contiguous quaternary carbon stereocenters via [2+2] cycloaddition and mechanistic insight

Multiple contiguous quaternary carbon stereocenters(CQS) are highly challenging, yet important structural motifs in organic synthesis. Here, we describe a visible light induced catalytic [2 + 2] cycloaddition approach that constructed up to four CQS in a pentacyclic fused ring system diastereoselectively, from the readily accessible dienamides with pendent heteroaryls. Variously substituted dienamides have been cyclized with heteroaryls to provide a range of novel CQS-containing scaffolds(26 examples, up to 96%yield and >20:1 dr ratio). Mechanistic studies revealed that it may proceed through an uncommon β-C radical initiated 7-endo cyclization from the biradical intermediate.

Construction of highly congested quaternary carbon centers by NHC catalysis through dearomatization

A NHC-catalyzed hypervalent iodine reagents and transition-metal free redox-neutral dearomatization of phenols is reported.This protocol provides an efficient access for highly congested quaternatry carbon centers construction.It also features operationally simplicity,mild reaction conditions and good functional group tolerance.Moreover,the reported procedure can be easily emplified to 1 g scale.Mechanism study reveals the dearomative transformation possibly undergoes a single electron transfer process with NHC radical cation as a reactive intermediate.

Brønsted acid-catalyzed 1,6-hydrophosphination of propargylic para-quinone methides and aza-para-quinone methides for the rapid construction of phosphorus-substituted quaternary carbon centers

An intriguing Brønsted acid-catalyzed 1,6-hydrophosphination of in situ generated propargylic para-quinone methides(p-QMs)and aza-para-quinone methides(aza-p-QMs)with H-phosphorus oxides via dehydration/1,6-addition under ultrasonic irradiation is described.This methodology provides a rapid and green approach for the construction of diarylmethyl phosphorus oxides bearing phosphorus-substituted quaternary carbon centers in high yields(up to 98%yield)within merely 5min.This environmentally benign protocol represents a unique example of 1,6-conjugate additions of propargylic p-QMs and aza-p-QMs for site-selective C-P bond formation in an operationally simple and atom-economical manner.The use of readily available Brønsted acid catalyst,operationally simplicity,high yields,and high atom economy make this protocol very facile,practical,easily scaled-up and environmentally friendly.

Extensive Studies on the AlEt3/THF-Promoted Diastereoselec-tive Tandem Rearrangement/Reduction of a-Hydroxy (Amino) Heterocyclopropane: An Efficient Approach to 2-Quaternary 1,3-Diheteroatom Units

A facile and highly diastereoselective method for the construction of 2-quaternary 1,3-amino alcohols and 1,3-diols has been developed on the basis of the AlEt3/THF-promoted tandem rearrangement/reductive reaction of a-hydroxy (amino) aziridines (epoxides). The progressive achievement in this article included that both 2-epimers of the units could be constructed from the initially same substrate. Also a stereochemistry assignment we reported previously was corrected.

Synthesis of tetraarylmethanes:1897–2022

Tetraarylmethanes(TAMs)contain a carbon atom bound to four aryl groups.They have found diverse applications in chemistry,materials science,chemical biology and medicinal chemistry because of their unique 3-dimensional structures.As a reflection of the high demand for TAMs,over 32,000 unique TAMs have been prepared.The distinct structures of TAMs and the crowded nature of the central carbon atom require different strategies for their syntheses.Herein we present the first review on the synthesis of TAMs,from classical approaches to modern methods,including enantioselective syntheses of TAMs.We provide a critical evaluation of methods and highlight important directions for future research into the synthesis of this aesthetically pleasing and very useful class of spherical structures.

Construction of three stereocenters via hydrogenative desymmetrization of 2,2,5-trisubstituted cyclohexane-1,3-diones

A Ru-catalyzed hydrogenative desymmetrization of 2,2,5-trisubstituted cyclohexane-1,3-diones was developed for construction of three stereocenters including two coherent and discontiguous chiral centers and a chiral quaternary carbon with excellent enantio-and diastereoselectivities.Stereodivergent synthesis of four stereoisomers could be conducted with high enantioselectivities.The desymmetrization could be achieved at gram scale without loss of reactivity and optical purity,and a formal synthesis of bioactive molecule(-)-isocelorbicol was completed.

Organophosphine bearing multiple hydrogen-bond donors for asymmetric Michael addition reaction of 1-oxoindane-2-carboxylic acid ester via dual-reagent catalysis

Multiple hydrogen bonds containing nucleophilic phosphines derived from dipeptide dual-reagents catalyzed asymmetric Michael addition reactions between indene esters and activated olefins in high yields and good to excellent enantioselectivities under mild reaction conditions.The success of current highly selective reactions should provide inspiration for expansion to other reactions and would open up new paradigms for the synthesis of indanone derivatives bearing chiral quaternary carbon centers.

Synthesis of (±)-Bakuchiol via a Pot-Economy Approach

A rapid synthetic route toward(±)-Bakuchiol is presented in 29%overall yield.After the sole all-carbon quaternary carbon center is created via allylboration of 2-aryl acetaldehyde,a“Pot-Economy”approach including mesylation,elimination,and desilylation was realized in the presence of ^(t)BuOK under ambient temperature to provide(±)-Bakuchiol.

Asymmetric Alkynylation of Tertiary Carbon-Centered Radical via Copper-Catalyzed Radical Relay

Alkynes are frequently found in a high proportion of natural products and bioactive moleculars,as well as a common synthon in organic synthesis,which can be easily transformed to an alkenyl,alkyl,heteroaryl,or carboxylic acid group.The enantioselective construction of alkyne substituted all carbon quaternary stereocenters is rarely reported and still a big challenge.As part of our continuous effort on developing asymmetric radical transformations,we found introducing an amidyl group(CONHAr)adjacent to the tertiary carbon radical could enable the asymmetric radical coupling with alkyne reagents.The amidyl group may stabilize the tertiary carbon radical or coordination with the chiral copper catalyst.Herein,we communicate a copper-catalyzed asymmetric trifluoromethyl-alkynylation ofα-aryl substituted acrylamides,which provides a straightforward and efficient access to chiral quaternary all-carbon centers bearing alkynyl groups in good yields and enantioselectivities.This reaction was also applied for the synthesis of chiral functionalized dipeptide.

A Novel Strategy for the Key Fully Substituted Cyclopentenedione Moiety of Madindolines via AIEt3-promoted Tandem Reductive Rearrangement of α-Hydroxy Epoxides

The fully substituted cyclopentenedione core of madindoline A （1） and B （2） as potent and selective inhibitor of IL-6 has been synthesized efficiently. The quaternary carbon center C-2＇ was constructed on the basis of a newly developed AIEt3-promoted tandem reductive rearrangement of α-hydroxy epoxides.

Palladium-catalyzed asymmetric carbamoyl-carbonylation of alkenes

An unprecedented palladium-catalyzed asymmetric carbamoyl-carbonylation of tethered alkenes with CO and alcohols has been developed.This reaction provided an efficient route to access oxindoles andγ-lactams bearingβ-carbonyl substituted quaternary carbons in good yields with excellent chemo-,regio-and enantioselectivity.Gram-scale synthetic capability and facile transformations of the products to chiral spirooxindole and other functional molecules further illustrated the practicability of this reaction.

Michael Addition Reaction of Fluorinated Nitro Compounds

The Michael addition reactions of fluorinated nitro compounds with electron deficient olefins to give γ-fiuoro-γ-nitro-esters, nitriles and ketones which bear a fluorinated quaternary carbon center were reported. The reactions were promoted by TMG, affording the desired adducts in acceptable to good yields.

A Formal Synthesis of (+)-Cassiol Exploiting Meyers' Bicyclic Lactam Methodology

A formal synthesis of (+)-cassiol using (1S,2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediol as chiral auxiliary is reported. The quaternary chiral center in the molecule was constructed by sequential alkylation of a bicyclic lactam (prepared from the aforementioned auxiliary and 5-oxo-heptanoic acid) with methyl iodide and benzyloxymethyl chloride.