RESUMO
We report herein an unprecedented enantioselective (4+4) cycloaddition of simple 1,3-dienes with azadienes for the construction of fused eight-membered N-heterocycles. In this transformation, the π-Lewis basic Pd(0) catalyst achieves activation of 1,3-dienes to induce nucleophilic addition to azadienes followed by ring cyclization via a selective terminal allylic substitution. Furthermore, highly efficient and diastereoselective derivatizations of the eight-membered rings provide a facile access to diverse enantiopure fused tetra- to hexacyclic compounds with potential application in medicinal chemistry.
RESUMO
Direct substitution of readily available alcohols is recognized as a key research area in green chemical synthesis. Starting from simple racemic secondary alcohols, the achievement of catalytic enantioconvergent transformations of the substrates will be highly desirable for efficient access to valuable enantiopure compounds. To accomplish such attractive yet challenging transformations, the strategy of the enantioconvergent borrowing hydrogen methodology has proven to be uniquely effective and versatile. This review aims to provide an overview of the impressive progress made on this topic of research that has only thrived in the past decade. In particular, the conversion of racemic secondary alcohols to enantioenriched chiral amines, N-heterocycles, higher-order alcohols and ketones will be discussed in detail.
RESUMO
We present herein a highly atroposelective indolization for the efficient synthesis of 1,1'-biheteroaryls bearing a chiral N-N axis. Under the cooperative catalysis of chiral phosphoric acid and InBr3, the reactions between 2,3-diketoesters and 1,3-dione-derived enamines resulted in a highly enantioselective construction of 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles in up to 92% ee. Derivatizations of these compounds to diverse functionalized N-N linked axially chiral biheteroaryls have also been demonstrated.
RESUMO
We present an enantioconvergent access to chiral N-heterocycles directly from simple racemic diols and primary amines, through a highly economical borrowing hydrogen annulation. The identification of a chiral amine-derived iridacycle catalyst was the key for achieving high efficiency and enantioselectivity in the one-step construction of two C-N bonds. This catalytic method enabled a rapid access to a wide range of diversely substituted enantioenriched pyrrolidines including key precursors to valuable drugs such as aticaprant and MSC 2530818.
RESUMO
We present herein a highly efficient atroposelective synthesis of axially chiral 1,1'-bipyrroles bearing an N-N linkage from simple hydrazine and 1,4-diones. Further product derivatizations led to axially chiral bifunctional compounds with high potential in asymmetric catalysis. For this chrial phosphoric acid (CPA)-catalyzed double Paal-Knorr reaction, an intriguing Fe(OTf)3 -induced enantiodivergence was also observed.
Assuntos
Ácidos de Lewis , Ácidos Fosfóricos , Catálise , EstereoisomerismoRESUMO
We report herein an unprecedented gold and oxidative NHC relay catalysis that enables highly enantioselective cascade annulation between readily available α-amino-ynones with enals. This method utilizes the in situ-generated pyrrolin-4-ones as a novel and versatile synthon, which engage with α,ß-unsaturated acylazolium intermediates generated from enals by oxidative NHC catalysis to produce pyrrole-fused lactones in high yield and excellent enantioselectivity. Synthetic utility of the lactone products is also demonstrated by facile conversion to densely functionalized pyrroles and pyrrolin-4-ones in high yields with excellent stereopurity.
Assuntos
Ouro , Metano , Catálise , Lactonas , Estresse Oxidativo , Pirróis , EstereoisomerismoRESUMO
We present herein an unprecedented diastereoconvergent synthesis of vicinal diamines from diols through an economical, redox-neutral process. Under cooperative ruthenium and Lewis acid catalysis, readily available anilines and 1,2-diols (as a mixture of diastereomers) couple to forge two C-N bonds in an efficient and diastereoselective fashion. By identifying an effective chiral iridium/phosphoric acid co-catalyzed procedure, the first enantioconvergent double amination of racemic 1,2-diols has also been achieved, resulting in a practical access to highly valuable enantioenriched vicinal diamines.
RESUMO
We present herein a highly diastereo- and enantioselective Pd-catalyzed [4 + 2] cycloaddition of benzofuran-derived azadienes with vinyl benzoxazinanones, which represents a rare highly stereoselective cycloaddition of this class of fused azadienes as a two-atom synthon. The use of a phosphoramidite ligand bearing a chiral secondary amine with a simple biphenyl backbone proved to be the key to construct the novel spirocyclic tetrahydroquinoline scaffold containing three contiguous stereocenters as a single diastereomer in high enantioselectivity.
RESUMO
We present herein an unprecedented desymmetrization of meso 1,3-diones by enantioselective intermolecular condensation. Under the catalysis by a chiral phosphoric acid, a range of readily available 1,3-diones undergo reaction with hydrazines to produce cyclic and acyclic keto-hydrazones bearing an all-carbon quaternary center in high efficiency and enantioselectivity. These compounds are also highly versatile for the preparation of multifunctional building blocks and heterocycles in excellent stereoselectivity.
RESUMO
Medium-sized rings, including those embedded in bridged and fused bicyclic scaffolds, are common core structures of myriad bioactive molecules. Among various synthetic strategies towards their synthesis, intermolecular higher-order cycloaddition provides great potential to build complex medium-sized rings from simple building blocks. Unfortunately, such transformations are often plagued with competitive reaction pathways and low levels of site- and stereoselectivity. Herein, we report catalyst-controlled divergent access to three classes of medium-sized bicyclic compounds in high efficiency and stereoselectivity, by palladium-catalysed cycloadditions of tropones with γ-methylidene-δ-valerolactones. Mechanistic studies and density functional theory calculations disclosed that the divergent reactions stem from the different reaction profiles of the diastereomeric intermediates. While one undergoes either O- or C-allylation to provide [5.5.0] or [4.4.1] bicyclic compounds, the unique conformation of the other diastereomer allows an unconventional alkene isomerization to deliver bridgehead alkene-containing bicyclo[4.4.1] compounds. The conversion of these products to diverse complex polycyclic scaffolds has also been demonstrated.
RESUMO
Chiral phosphoric acid-catalyzed biomimetic asymmetric [4 + 2] cycloaddition of ortho-alkenyl naphthols/phenols and ortho-quinone methides (o-QMs) has been demonstrated to afford various important 2,3,4-trisubstituted chromans in high yields with excellent enantio- and diastereoselectivities (up to 99% yield, 99% ee, >20:1 dr). Notably, this methodology not only enabled access to the trans-cis chiral trisubstituted chromans from 1-alkenyl 2-naphthols but also is compatible with 2-alkenyl 1-naphthols and phenols to deliver trans-trans chiral trisubstituted chromans.
RESUMO
The first metal/organo cooperatively catalyzed asymmetric reaction of C-alkynyl N-Boc-protected N,O-acetals with in situ generated oxonium ylides has been developed. This new type of propargylation allows for the efficient synthesis of structurally diverse unreported chiral propargylamines bearing oxa-quaternary stereocenters. The reaction features unprecedented substrate scope and high diastereo- and enantioselectivity. Theoretical studies suggest a novel cooperative catalysis model and the unique transfer of R2OH.
RESUMO
The first highly stereoselective intermolecular catalytic asymmetric dearomatization (CADA) of α-naphthols through C-C formation and the first asymmetric allylic dearomatization of naphthols by chiral organocatalysis have been achieved. These new and complete atom-economic reactions provide enantioriched α- and ß-naphthalenones bearing an all-carbon quaternary center.
RESUMO
A novel organocatalytic asymmetric tandem Nazarov cyclization/semipinacol rearrangement reaction using "unactivated" substrates has been developed, generating a series of chiral spiro[4.4]nonane-1,6-diones in up to 96% yield and 97% enantiomeric excess. Significantly, it is the first direct example for asymmetric synthesis of cyclopentanones with four stereocenters using Nazarov cyclization. DFT calculations have been applied to understand the reaction mechanism, stereochemistry, and substituent effects.
RESUMO
A six-membered N-heterocyclic carbene fused with a spiro-scaffold is designed. The new NHC shows stronger σ-donation ability than typical 5-membered NHCs. This property leads to interesting reactivities of this spiro-fused six-membered NHC. For example, the NHC-BF3 Lewis pair complex can be readily prepared by using LiBF4 as the BF3 source, or through a direct bond-reconstruction of the tetrafluoroborate salt NHC·HBF4.
Assuntos
Cobre/química , Cicloexenos/química , Flúor/química , Propanóis/química , Catálise , MetilaçãoRESUMO
An asymmetric fluorination/semipinacol rearrangement of 2-oxa allylic alcohols, as catalyzed by cinchona-alkaloid derivatives, gives chiral ß-fluoro ketones with moderate to high levels of enantioselectivity (see scheme). Both enantiomers of the product could be obtained by using the appropriate catalyst.