Asymmetric Diels Research Articles

Chiral Polar Bifunctional Polyimide Enantiomers for Asymmetric Photo‐ and Piezo‐Catalysis

AbstractChiral catalysts for asymmetric catalysis represent a crucial research focus in chemistry and materials science. However, a few cases about chiral‐dependent photocatalysts primarily focus on plasmonic noble metals. Particularly, developing chiral nano‐catalysts that can be driven by mechanical energy remains in the blank stage. Herein, organic polymer‐based enantiomers, chiral polar polyimide (PI) microspheric nano‐assembly are synthesized as novel bifunctional catalysts for asymmetric photocatalysis and piezocatalysis. The PI catalyst enantiomers present enantioselectivity towards left‐ and right‐circularly polarized light, demonstrating chiral‐dependent H2O2 photoproduction. Interestingly, enantioselectivity of the catalyst reverses under irradiation of different bands, presenting tunability in the interaction between chiral catalysts and circularly polarized light. For the first time, enantioselective piezocatalytic behavior is demonstrated by the chiral polar PI catalysts. They show remarkable chiral preference for asymmetric Diels–Alder reaction and enantioselective conversion of tyrosine substrates under ultrasonic vibration. The findings provide a new perspective into exploring metal‐free chiral catalysts and their asymmetric catalysis applications across multiple energy forms.

Asymmetric Diels–Alder reaction of chalcone and isoprene mediated by titanium-based complexes

The asymmetric Diels–Alder reaction of chalcone and isoprene has been accomplished by use of chiral titanium complexes. Notably, an enantiomeric excess as high as 61% and a regioselectivity of 95% have been achieved. The preparation of the chiral titanium complexes is simple and does not require the pre-installation of a chiral auxiliary. This study represents the first example of asymmetric Diels–Alder reaction between chalcone and isoprene.

Highly Stereoselective Diels–Alder Reactions Catalyzed by Diboronate Complexes**

AbstractA highly enantioselective catalytic system for exo‐Diels–Alder reactions was developed based on the newly discovered bispyrrolidine diboronates (BPDB). Activated by various Lewis or Brønsted acids, BPDB can catalyze highly stereoselective asymmetric exo‐Diels–Alder reactions of monocarbonyl‐based dienophiles. When 1,2‐dicarbonyl‐based dienophiles are used, the catalyst can sterically distinguish between the two binding sites, which leads to highly regioselective asymmetric Diels–Alder reactions. BPDB can be prepared as crystalline solids on a large scale and are stable under ambient condition. Single‐crystal X‐ray analysis of the structure for acid‐activated BPDB indicated that its activation involves cleavage of a labile B←N bond.

Highly Stereoselective Diels-Alder Reactions Catalyzed by Diboronate Complexes.

A highly enantioselective catalytic system for exo-Diels-Alder reactions was developed based on the newly discovered bispyrrolidine diboronates (BPDBs). When activated various Lewis or Brønsted acids, BPDBs could catalyze highly stereoselective asymmetric exo-Diels-Alder reactions of monocarbonyl-based dienophiles. When 1,2-dicarbonyl-based dienophiles are used, the catalyst can sterically distinguish between the two binding sites, which leads to highly regioselective asymmetric Diels-Alder reactions. BPDBs can be prepared as crystalline solids on a large scale and are stable under ambient conditions. Single-crystal X-ray analysis of the structure for acid-activated BPDB indicated that activation involves breakage of a labile N→B bond.

Catalytic Asymmetric Diels-Alder Reaction of 2'-Hydroxychalcone as a Dienophile with a VANOL-Borate Ester Complex.

Numerous flavonoid Diels-Alder-type natural products have been isolated and received great attention from the synthetic community. Herein, we reported a catalytic strategy for an asymmetric Diels-Alder reaction of 2'-hydroxychalcone with a range of diene substrates using a chiral ligand-boron Lewis acid complex. This method enables the convenient synthesis of a wide range of cyclohexene skeletons in excellent yields with moderate to good enantioselectivities, which is critical to prepare natural product congeners for further biological studies.

Recent Advances in Asymmetric Synthesis of Pyrrolidine-Based Organocatalysts and Their Application: A 15-Year Update

In 1971, chemists from Hoffmann-La Roche and Schering AG independently discovered a new asymmetric intramolecular aldol reaction catalyzed by the natural amino acid proline, a transformation now known as the Hajos-Parrish-Eder-Sauer-Wiechert reaction. These remarkable results remained forgotten until List and Barbas reported in 2000 that L-proline was also able to catalyze intermolecular aldol reactions with non-negligible enantioselectivities. In the same year, MacMillan reported on asymmetric Diels-Alder cycloadditions which were efficiently catalyzed by imidazolidinones deriving from natural amino acids. These two seminal reports marked the birth of modern asymmetric organocatalysis. A further important breakthrough in this field happened in 2005, when Jørgensen and Hayashi independently proposed the use of diarylprolinol silyl ethers for the asymmetric functionalization of aldehydes. During the last 20 years, asymmetric organocatalysis has emerged as a very powerful tool for the facile construction of complex molecular architectures. Along the way, a deeper knowledge of organocatalytic reaction mechanisms has been acquired, allowing for the fine-tuning of the structures of privileged catalysts or proposing completely new molecular entities that are able to efficiently catalyze these transformations. This review highlights the most recent advances in the asymmetric synthesis of organocatalysts deriving from or related to proline, starting from 2008.

Asymmetric Total Synthesis of Senepodine F.

The first asymmetric total synthesis of the Lycopodium alkaloid senepodine F, which contains a decahydroquinoline ring (AB-ring) and a quinolizidine ring (CD-ring) connected by a methylene tether, has been achieved. The key steps of this synthesis include an organocatalytic asymmetric Diels-Alder reaction, a diastereoselective intramolecular aza-Michael reaction, and an intramolecular SN2 cyclization to construct multisubstituted nitrogen-containing heterocycles. In addition, our total synthesis led to the stereochemical reassignment on the decahydroquinoline ring of senepodine F.

One-step assembly of a MacMillan catalyst-based phenolic-type polymer.

We report herein a "bottom-up" approach for the one-step assembly of a MacMillan catalyst-based phenolic-type polymer (Mac-CP). The resulting self-supported polymeric organocatalyst possesses homogeneously distributed and highly concentrated catalytic sites. Furthermore, Mac-CP is soluble in CH3CN but insoluble in hexane. This unique property can be used to employ the polymer as an efficient catalyst in homogeneous organocatalysis and heterogeneous recycling. As a result, Mac-CP possesses comparable catalytic activity and enantioselectivity to its homogeneous counterpart in the asymmetric Diels-Alder reaction (95% yield, 93% enantiomeric excess (ee) for endo and 92% ee for exo).

Charge‐activated TADDOLs: Recyclable organocatalysts for asymmetric (hetero‐)Diels–Alder reactions

AbstractSeveral charge‐containing TADDOL salts were synthesized and used as organocatalysts in asymmetric Diels–Alder and hetero‐Diels–Alder reactions. Their catalytic activity was found to exceed that of a noncharged analog while maintaining or improving upon the enantioselectivity. The enhanced activities of the TADDOL salts enabled them to act as presumed hydrogen bond donor catalysts in the Diels–Alder and hetero‐Diels–Alder reactions of 1,3‐cyclohexadiene with methyl vinyl ketone at 40°C and 2‐phenoxy‐1,3‐butadiene with ethyl glyoxylate at room temperature, respectively. Given the ionic nature of these charge‐activated catalysts, it also proved possible to recycle and reuse the TADDOL without chromatography or the need for a recrystallization.

Divergent Total Synthesis of Four Kopsane Alkaloids: N‐Carbomethoxy‐10,22‐dioxokopsane, Epikopsanol‐10‐lactam, 10,22‐Dioxokopsane, and N‐Methylkopsanone

AbstractWe have achieved the divergent total synthesis of four kopsane alkaloids which share a complex heptacyclic caged ring system. Key transformations include an asymmetric Diels–Alder reaction to assemble the central bicyclo[2.2.2]octane moiety and the quaternary stereocenter at C20, a SmI2‐mediated cascade reduction/aldol reaction to construct the five‐membered ring and the quaternary stereocenter at C7, and a late‐stage cascade reductive amination/cyclization to establish the highly strained caged ring system.

Divergent Total Synthesis of Four Kopsane Alkaloids: N-Carbomethoxy-10,22-dioxokopsane, Epikopsanol-10-lactam, 10,22-Dioxokopsane, and N-Methylkopsanone.

We have achieved the divergent total synthesis of four kopsane alkaloids which share a complex heptacyclic caged ring system. Key transformations include an asymmetric Diels-Alder reaction to assemble the central bicyclo[2.2.2]octane moiety and the quaternary stereocenter at C20, a SmI2 -mediated cascade reduction/aldol reaction to construct the five-membered ring and the quaternary stereocenter at C7, and a late-stage cascade reductive amination/cyclization to establish the highly strained caged ring system.

Application of Proline-Derived (Thio)squaramide Organocatalysts in Asymmetric Diels–Alder and Conjugate Addition Reactions

AbstractThe synthesis of chiral proline-derived squaramide and thiosquaramide organocatalysts, which are capable of the dual activation in asymmetric reactions is reported. The (thio)squaramide moiety can form hydrogen bonds to activate the substrates and to stereocontrol the reaction, while the pyrrolidine unit can form enamines to activate carbonyl compounds via aminocatalysis. Comparing the performance of thiosquaramide to squaramide, the Diels–Alder reaction of (anthracen-9-yl)acetaldehyde and trans-β-nitrostyrene was examined, which has been investigated in the literature using quantum chemical calculations. Both squaramide and thiosquaramide gave excellent yields (up to 99%) and enantiomeric excess values (up to 98%). Moreover, their catalytic performance was compared in conjugate addition of lawsone to β,γ-unsaturated α-keto ester.

Synthesis of chiral-at-metal rhodium complexes from achiral tripodal tetradentate ligands: resolution and application to enantioselective Diels-Alder and 1,3-dipolar cycloadditions.

An improved synthesis of the racemic rhodium compound [RhCl2(κ4 C,N,N',P-L1)] (1) containing an achiral tripodal tetradentate ligand is reported. Their derived solvate complexes [Rh(κ4 C,N,N',P-L1)(Solv)2][SbF6]2 (Solv = NCMe, 2; H2O, 3) are resolved into their two enantiomers. Complexes 2 and 3 catalyze the Diels-Alder (DA) reaction between methacrolein and cyclopentadiene and the 1,3-dipolar cycloaddition reaction between methacrolein and the nitrone N-benzylidenphenylamine-N-oxide. When enantiopure (A Rh,R N)-2 was employed as the catalyst, enantiomeric ratios >99/1, in the R at C2 adduct, and up to 94/6, in the 3,5-endo isomer, were achieved in the DA reaction and in the 1,3-dipolar cycloaddition reaction, respectively. A plausible catalytic cycle that accounts for the origin of the observed enantioselectivity is proposed.

DABCO-based chiral ionic liquids as recoverable and reusable organocatalyst for asymmetric Diels-Alder reaction.

New DABCO-based chiral ionic liquids were synthesized and evaluated in asymmetric Diels-Alder reaction of cyclopentadiene with α,β-unsaturated aldehydes or 4-phenyl-3-buten-2-one. Chiral ionic liquid of modified MacMillan catalyst having a DABCO cation and hexafluorophosphate anion acts as organocatalyst (5mol%) for the Diels-Alder reaction of crotonaldehyde and cyclopentadiene producing 98% of the product and 87% ee (endo) in CH3 CN/H2 O (95/5) at 25°C in 2h. The scope and limitations of the catalysis were also studied by using cyclopentadiene and α,β-unsaturated aldehydes, and the Diels-Alder products were obtained in 18%-92% yields with 68%-93% ee. The catalyst was recycled and reused up to 6 cycles with a slight drop in ee and conversion of the product.

SuFEx-Click Approach for the Synthesis of Soluble Polymer-Bound MacMillan Catalysts for the Asymmetric Diels–Alder Reaction

Novel polymeric MacMillan catalysts were prepared from modified chiral imidazolidin-4-one monomers via sulfur(VI) fluoride exchange chemistry. The resulting polysulfates containing chiral imidazolidin-4-one units could be employed as polymeric organocatalysts for the asymmetric Diels–Alder reaction. With the use of these polysulfate catalysts, sufficient catalytic activity and enantioselectivity were obtained, which were similar to those obtained by monomeric catalysts in a homogeneous catalytic reaction. In addition, the polysulfate catalysts could be recovered and reused five times without a considerable loss of activity and selectivity.

Asymmetric Copper-Catalyzed Diels–Alder/Retro-Diels–Alder Reaction of 2-Pyrones with Alkynes

Key words copper catalysis - Diels–Alder reaction - axial chirality - 2-pyrones

Simple amino silyl ether organocatalyst for asymmetric hetero Diels–Alder reaction of isatins with enones

New two catalysts component system comprising of a primary β-amino silyl ethers as an organocatalyst and N-protected amino acids as a co-catalyst put together worked as an efficient organocatalyst system in the hetero Diels-Alder reaction of isatins with enones affording the chiral spirooxindole-tetrahydropyranones in good chemical yields and stereoselectivities (up to 94%, up to dr 78:22., up to 85% ee).

Asymmetric Diels–Alder reaction between furans and propiolates

We report the first asymmetric Diels–Alder reaction between furan and propiolates. Propiolate, a dienophile, was equipped with an Evans’ auxiliary and a sulfonyl group to control and facilitate diastereoselective cycloaddition. Treatment with furan as a diene and aluminium Lewis acid afforded a 7-oxabicyclo[2.2.1]heptadiene skeleton diastereoselectively. The origin of diastereoselectivity can be explained by chelation of aluminium center to carbonyl groups and oxygen of furan. Friedel–Crafts-type products were obtained when pyrrole was used as diene.

Mono‐Gold(I)‐Catalyzed Enantioselective Intermolecular Reaction of Ynones with Styrenes: Tandem Diels–Alder and Ene Sequence

AbstractGold‐catalyzed intermolecular reaction leading to dihydronaphthalene derivatives in one pot from two equivalents of ynones with respect to styrene is uncovered. The [4+2] Diels–Alder cycloaddition of ynones and styrenes is catalyzed by a mono‐gold(I) complex and the conjugated acid to provide an unstable 3,8a‐dihydronaphthalene to subsequently undergo an intermolecular ene‐type reaction with the π‐activated ynone to afford multi‐component coupling dihydronaphthalene products. Linear relationships between chiral ligand‐gold complexes and chiral dihydronaphthalene products proves mono‐gold catalysis that triggers an asymmetric tandem Diels–Alder and ene reaction sequence.

Fe-BPsalan complex catalyzed highly enantioselective Diels–Alder reaction of alkylidene β-ketoesters

A practical Fe-BPsalan-catalyzed asymmetric Diels–Alder reaction of various alkylidene β-ketoesters and dienes was developed to afford estrone analogues in excellent yields, good to high diastereoselectivities and excellent enantioselectivities.