Reversal of chemoselectivity in Diels-Alder reaction with alpha,beta-unsaturated aldehydes and ketones catalyzed by Brønsted acid or Lewis acid

[reaction: see text] High chemoselectivity was observed in the Diels-Alder reaction of alpha,beta-unsaturated aldehyde and alpha,beta-unsaturated ketone with cyclopentadiene. Using Tf2NH as catalyst, the reaction gave Diels-Alder adduct derived from alpha,beta-unsaturated ketone as a major product. On the other hand, bulky Lewis acid, B(C6F5)3, gave mainly the cycloadduct of alpha,beta-unsaturated aldehyde and cyclopentadiene.     

Investigation of the asymmetric ionic Diels-Alder reaction for the synthesis of cis-decalins

The ionic Diels-Alder reaction, whereby an alpha,beta-unsaturated acetal in combination with a Lewis or Bronsted acid forms an equilibrium concentration of an activated dienophile, has been developed to provide an enantioselective synthesis of cis-decalins. Cyclohex-2-enone type chiral acetals of (2R,3R)-butane-2,3-diol have been screened against Lewis and Br?nsted acids with a variety of dienes and are efficient for the synthesis of a limited subset of cis-decalin structures. Diastereoselectivities of 73% and 82% have been found for the asymmetric ionic Diels-Alder reaction between the chiral acetal derivatives of cyclohex-2-enone (6) and 2-methylcyclohex-2-enone (18) with 2,3-dimethyl-1,3-butadiene (7). Terminal substituents on the diene partner in general render the system unreactive. However a synthetically useful cis-decalin 31, derived from the reaction of 2-methylcyclohex-2-enone and Z-3-t-butyldimethyl-silyloxypenta-1,3-diene has been prepared in enantiomerically pure form in 74% isolated yield using this asymmetric ionic Diels-Alder protocol.     

Asymmetric Induction of Chiral 1,1''''-Bis(oxazolinyl)ferrocenes as Ligands in Metal-Catalyzed Cyclopropanation and Diels-Alder Reactions

Bis(oxazoline) ligands1 have been successfully used in a variety of metal-catalyzed asymmetric reactions, such as cyclopropanation, allylic oxidation reactions, etc; Chiral ferrocene derivatives2 have also been proved as effective ligands in numerous asymmetric reactions, for example, chiral ferrocenylphosphines exhibited high enantioselectivity for the reduction of olefins, Heck reactions and Aldol reactions of aldehydes. These results stimulated us to study the behaviour the bis(oxazoline) …     

Enantioselective Diels-Alder reaction of α-(acylthio)acroleins: a new entry to sulfur-containing chiral quaternary carbons

A catalytic and enantioselective Diels-Alder reaction of α-(carbamoylthio)acroleins induced by an organoammonium salt of chiral triamine is described. α-(Carbamoylthio)acroleins are designed and synthesized as new sulfur-containing dienophiles for the first time. The Diels-Alder reaction affords chiral tertiary thiol precursors with up to 91% ee.     

Enantioselective copper catalyzed Diels-Alder reaction using chiral quinoline-phosphine ligand

A new chiral copper (II) catalyst was prepared from Cu(OTf)₂ and chiral pyridine-phosphine ligands 1–2 in dichloromethane and used in the Diels-Alder reaction of 3-acryloyl-1,3-oxazolidine-2-one with cyclopentadiene leading to enantioselectivities up to 99%.     

Design of an organocatalyst for the enantioselective Diels-Alder reaction with alpha-acyloxyacroleins

We have realized the first enantioselective organocatalytic Diels-Alder reaction between alpha-substituted acroleins, such as alpha-acyloxyacroleins, and not only cyclic but also acyclic dienes. alpha-Acyloxyacroleins are useful as synthetic equivalents of alpha-haloacroleins. The present catalyst could be prepared in situ from pentafluorobenzenesulfonic acid (2.5-3.0 equiv) and chiral triamine (1 equiv) derived from H-l-Phe-l-Leu-N(CH2CH2)2. The enantioselective Diels-Alder reaction of 5-(benzyloxymethyl)cyclopentadiene, cyclopentadiene, cyclohexadiene, 2,3-dimethylbutadiene, and isoprene with alpha-(p-methoxybenzoyloxy)acrolein catalyzed by the above chiral ammonium salt (2.5-20 mol %) at -20-22 degrees C gave the corresponding adducts with 83, 83, 91, 92, and 88% ee, respectively.     

呋喃类化合物在离子液体和硅胶负载离子液体中的Diels-Alder反应研

以1-丁基3-甲基咪唑盐作为离子液体阳离子,与三种不同阴离子BF4、PF6、Tf2N组成性质不同的三种离子液体,催化呋喃类和丁炔二羧酸酯之间发生的Diels-Alder反应,合成了一系列化合物,研究了离子液体的催化效果。研究表明,呋喃类化合物的极性越低, Diels-Alder 反应的活性越高。在含硫的呋喃类化合物的反应中,当以 [Bmim]PF6 作为离子液体时,Diels-Alder 反应的产率可达到53%。另外,当 [Bmim]PF6 离子液体被吸附在硅胶表面上时,Diels-Alder的反应产率有所提高。     

Triflimide activation of a chiral oxazaborolidine leads to a more general catalytic system for enantioselective Diels-Alder addition

The strong acid triflimide ((CF3SO2)2NH) protonates chiral oxazaborolidines to form superactive, stable, chiral Lewis acids which are highly effective catalysts for a wide variety of enantioselective Diels-Alder reactions, documented herein by more than 20 examples.     

An efficient synthetic methodology of chiral isoquinuclidines by the enantioselective Diels-Alder reaction of 1,2-dihydropyridines using chiral cationic palladium-phosphinooxazolidine catalyst

High purity chiral isoquinuclidines (97% ee) were obtained from the enantioselective Diels-Alder reaction of 1-phenoxycarbonyl-1,2-dihydropyridine with 1-benzyl-2-acryloylpyrazolidin-3-one using chiral cationic palladium-phosphinooxazolidine (Pd-POZ) catalyst. The obtained DA adduct was easily converted to the chiral piperidine derivative bearing three stereogenetic centers in the structure.     

Organocatalytic enantioselective Diels-Alder reaction of dienes with alpha-(N,N-Diacylamino)acroleins

Catalytic and highly enantioselective Diels-Alder reaction of cyclic and acyclic dienes with alpha-phthalimidoacroleins provides cyclic alpha-quaternary alpha-amino acid precursors. The conformationally flexible chiral ammonium salt of H-L-Phe-L-Leu-N(CH(2)CH(2)) 2-reduced triamine with pentafluorobenzensulfonic acid is very effective as an asymmetric catalyst for the Diels-Alder reaction.     

Single and double asymmetric induction in Diels-Alder cycloadditions with chiral acylnitroso dienophiles

Diels-Alder reaction of the achiral 1-silyloxybutadiene 1a with the chiral acyinitroso dienophile 2a gave cycloadduct 4 in high diastereomeric excess (d.e. > 98 %), a result which is undoubtedly due to the C-2 symmetrical chiral dimethylpyrrolidine inductor. Excellent d.e. was also observed when the (R)-prolinol dienophile 2d was reacted with the chiral diene 1b (d.e. = 96 %), whereas cycloaddition of the (S) enantiomer 2e with 1b gave only poor asymmetric induction (d.e. = 4 %). These two latter examples nicely illustrate the influence of “matched pair” (1b/2d) versus “mismatched pair” (1b/2e) upon double asymmetric induction. All herein reported Diels-Alder cycloadditions were regiospecific.     

Catalytic imino Diels-Alder reaction by triflic imide and its application to one-pot synthesis from three components

An imino Diels-Alder reaction of 2-siloxydienes with aldimines catalyzed by triflic imide (Tf₂NH; 0.1∼10 mol % amount) has been developed leading to substituted piperidin-4-ones. Tf₂NH catalyst is compatible with basic functions, such as pyridine and indole rings in the imino Diels-Alder reaction. Furthermore, X-ray crystallographic analysis indicates that trans-2,6-diphenyl-4-piperidinone 4a obtained by this reaction has a unique conformation in the solid state.     

Pseudo-C3-symmetric trisoxazolines as ligands in copper catalyzed enantioselective Diels-Alder reaction

Air- and water-stable chiral catalyst trisoxazolines4-6 /Cu(ClO(4))(2)[middle dot]6H(2)O have been used in the Diels-Alder reaction of cyclopentadiene with acryloyl-2-oxazolidinones or ketoesters. The reaction is carried out in air and up to 82% ee was achieved.     

Asymmetric induction in Diels-Alder reactions of o-quinodimethanes

Asymmetric inductive effects have been measured on the Diels-Alder reaction of dimethyl fumarate with o-quinodimethane bearing a chiral α-alkoxy group. The chiral substituents used were 1-phenylethoxy, 2-(1-phenyl)propoxy, 1-(2-phenyl)propoxy, 2-(4-phenyl)-butoxy and 1-cyclohexylethoxy. The greatest asymmetric induction was found with the first of these chiral substituents (47% ee). A π-stacking effect, previously suggested as the rationale for asymmetric induction in a similar system, is shown to be inconsistent with the results from this study.     

A new cationic,chiral catalyst for highly enantioselective Diels-Alder reactions

[reaction: see text] The Diels-Alder reaction of cyclopentadiene and 2-methacrolein is catalyzed by a chiral Lewis acid to form the exo adduct in 96% yield and 96% ee.     

Stereoselective pinacol coupling of chiral formylferrocene using divalent samarium triflate: preparation of a new chiral bisferrocenyl oxazoline ligand and its application to asymmetric Diels-Alder reactions

[reaction: see text] The pinacol coupling reaction of planar chiral ortho-oxazoline-substituted formylferrocene was smoothly mediated by SmI2 or Sm(OTf)3 to give the (R,R) isomer selectivity (up to 76% diastereomeric excess). The combination of Yb(OTf)3 and the (R,R)-ferrocenyl diol was revealed to be a good catalyst for the asymmetric Diels-Alder reaction of 3-acyloxazolidinone with cyclopentadiene, and the endo adduct was produced in up to 80% enantiomeric excess.     

Catalytic enantioselective Diels-Alder reaction via a chiral indium(III) complex

[reaction: see text] A chiral indium complex has been developed to effect high enantioselectivities in catalyzing enantioselective Diels-Alder reaction. The cycloaddition of a variety of cyclic and open-chained dienes to 2-methacrolein and 2-bromoacrolein resulted in good yields and excellent enantioselectivities (up to 98% ee).     

N-heterocyclic carbene (NHC)-catalyzed highly diastereo- and enantioselective oxo-Diels-Alder reactions for synthesis of fused pyrano[2,3-b]indoles

A chiral N-heterocyclic carbene (NHC)-catalyzed Diels-Alder reaction of 2-oxoindolin-3-ylidenes and α-chloroaldehydes was developed for the synthesis of fused pyrano[2,3-b]indoles in good to excellent yields (up to 99%) with high cis-diastereoselectivities (>99:1 dr) and enantioselectivities (up to >99% ee).     

Highly enantioselective Diels-Alder reactions of Danishefsky type dienes with electron-deficient alkenes catalyzed by Yb(III)-BINAMIDE complexes

1-Methoxy-3-trimethylsiloxy-1,3-butadiene (Danishefsky's diene) is recognized as a synthetically useful diene due to its high reactivity in the Diels-Alder reaction with electron-deficient alkenes to give oxygen-functionalyzed cyclohexenes and substituted cyclohexenones, which are important building blocks for the total synthesis of natural products. However, the development of catalytic enantioselective versions of Diels-Alder reactions using Danishefsky type dienes with electron-deficient alkenes has been difficult because of the instability of the dienes under Lewis acidic conditions. Only highly reactive CO and CN double bonds are employed in a hetero-Diels-Alder reaction which proceeds under catalysis of chiral Lewis acids. We have developed a new chiral ligand, BINAMIDE, which is easily prepared from 1,1'-binaphtyl-2,2'-diamine by acylation. The highly diastereo- and enantioselective Diels-Alder reaction of Danishefsky type dienes with electron-deficient alkenes in the presence of an Yb(III)-BINAMIDE complex has been developed. The reaction proceeded in an exoselective mode and gave chiral highly functionalized cyclohexene derivatives in good yields.     

Tandem intramolecular Diels–Alder/retro-Diels–Alder cycloaddition of 2H-chromen-2-one as dienes with the expulsion of CO_2

To study the intramolecular Diels-Alder cycloadditon of 2H-chromen-2-one as a diene, a series of chiral N-allyl-N-benzylamides that contain a 2H-chromen-2-one moiety were designed for the synthesis of benzo[f]isoindol-1-ones via an intramolecular Diels-Alder and a subsequent retro-Diels-Alder cycloaddition with the expulsion of CO₂. Both the yield (80%-89%) and absolute stereocontrol of the tandem reaction were high when an electron-withdrawing group was attached to the dienophile. The double bond in the styrene substructure remained in the products could be further derivatized by dihydroxylation.