Lewis Acid Catalyzed Diels-Alder Reactions Research Articles

Selectivities in Chiral Lewis Acid Catalyzed Diels–Alder Reactions of Acetylenic Ketones: Explanation for Differences of Selectivities between Acylic and Cyclic Dienes

Huey Lewis (acid) and the News: Crystallographic and computational studies on the cationic-oxazaborolidine-catalyzed Diels–Alder reaction of acetylenic ketones indicated that the reaction proceeds through a favored syn, exo transition state. These results provide a basis for understanding why acyclic dienes give higher enantioselectivities than cyclic dienes. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

A Straightforward Route to Functionalized trans-Diels−Alder Motifs

A sequence consisting of a Lewis acid-catalyzed Diels-Alder reaction on a 2-halocyclohexenone, followed by reductive alkylation, provides a route to trans-fused octalinones bearing angular methyl groups with functionality corresponding to that which would have been possible from a trans-directed Diels-Alder reaction.

ChemInform Abstract: (S)-(+)-Carvone as Chiral Starting Material. Part 2. Lewis Acid Catalyzed Diels-Alder Reactions of (S)-(+)-Carvone with Silyloxy Dienes. Total Synthesis of (+)-α-Cyperone.

ChemInform Abstract: (S)-(+)-Carvone as Chiral Starting Material. Part 2. Lewis Acid Catalyzed Diels-Alder Reactions of (S)-(+)-Carvone with Silyloxy Dienes. Total Synthesis of (+)-α-Cyperone.

ChemInform Abstract: A Stereoselective Synthesis of 2,6-Dideoxy-6,6,6-trifluoro-arabino-hexoses via an Asymmetric Diels-Alder Strategy.

The enantioselective syntheses of each enantiomer of ethyl 2,6-dideoxy-6,6,6-trifluoro-β-arabino-hexopyranoside (3) and of 2,6-dideoxy-6,6,6-trifluoro-arabino-hexose (4) are described. The key step in the approach is the inverse electron demand Lewis acid catalysed Diels–Alder reaction of the heterodiene (E)-1,1,1-trifluoro-4-[(1R)-1- phenylethoxy]but-3-en-2-one (5) and either ethyl vinyl ether (7a) or benzyl vinyl ether (7b). The titanium(IV) chloride catalysed cycloadditions at low temperature displayed high endo-selectivity and modest diastereofacial selectivity. Hydroboration of the mixture of the cis-cycloadducts (8a) afforded the separable diastereoisomers (9a) and (10a). Hydrogenolysis of (9a) gave ethyl 2,6-dideoxy-6,6,6-trifluoro-β-L-arabino-hexopyranoside (+)-(3), and of (10a) gave the corresponding D-glycoside (−)-(3). Similarly, hydroboration of the cis-cycloadducts (8b) gave the protected benzyl glycosides (9b) and (10b). Hydrogenolysis of each gave 2,6-dideoxy-6,6,6-trifluoro-L-arabino-hexopyranose (−)-(4) and the corresponding D-sugar (+)-(4) respectively. The absolute configurations of fluorinated carbohydrates (+)- and (−)-(3) were determined by comparison of their molar rotations with those of the parent glycosides. These assignments were confirmed by an X-ray crystallographic structure determination of the glycoside (9a).

ChemInform Abstract: Diastereoselective Addition Reactions of Racemic Chiral Vinyl Sulfimides.

S-Aryl S-vinyl sulfimides are prepared by a new method via Horner–Wadsworth–Emmons reagents generated in situ. Lewis acid-catalysed Diels–Alder reaction of S-ethenyl-S-phenyl-N-tosylsulfimide with cyclopentadiene leads to the endo anti product with good diastereofacial and endo–exo selectivities. A range of alcohols and amines, with the limitation that they be practically usable in large excess, add to β-aryl vinyl sulfimides with modest diastereoselectivity. The major products of both the cycloaddition and the nucleophilic additions are rationalised by a model invoking addition to the least-hindered face of the s-cisconformation of the vinyl sulfimide.

Synthesis of Grandisine A

Grandisine A is an indolizidine alkaloid isolated from Elaeocarpus grandis. It selectively (but weakly) binds to the δ-opioid receptor. The key step in the synthesis is a Lewis acid catalyzed Diels-Alder reaction that creates the stereogenic centers at C7 and C12 with the correct relative configuration.

Synthesis of Precursors of the Agalacto (Exo) Fragment of the Quartromicins via an Auxiliary-Controlled Exo-Selective Diels−Alder Reaction

[reaction: see text] A direct synthesis of the alpha-hydroxyaldehyde exo-5, a precursor of the exo-spirotetronate subunit of the quartromicins, was achieved through an exo-selective Lewis acid-catalyzed Diels-Alder reaction of dienophile 12a and diene 1.

Small-Molecule Diversity Using a Skeletal Transformation Strategy

[reaction: see text] We describe a short synthetic sequence resulting in >4000 skeletally diverse small molecules that have three distinct skeletal frameworks among other unique structural features. The sequence entails skeletal transformations pioneered by Winterfeldt and co-workers. We use epoxide ring openings and subsequent functionalizations that provide, e.g., spirocyclic oxazolidines, Lewis acid catalyzed Diels-Alder reactions of a steroid-derived diene that afford stable and isolable ring B adducts, and subsequent retro-Diels-Alder fragmentations that yield 14-membered paracyclophanes.

The modulation of face–face π–π interactions in Lewis acid catalysis

The enantiomeric excess observed for the exo-adduct from the Lewis acid catalysed Diels–Alder reaction between cyclopentadiene and methacrolein can be increased up to 21% by simple modification of the electronics of the aromatic ring in a series of stilbene-derived diol ligands, suggesting that the proposed face–face π–π interaction between the catalyst and the dienophile can be modulated by altering the electron density on the aromatic ring.

Absolute stereochemistry assignment of N‐phosphorylimine‐derived aza‐Diels‐Alder adducts with TDDFT CD calculations

N-phosphorylimines undergo Lewis acid-catalyzed Diels-Alder reactions with Danishefsky's diene. Application of the chiral catalyst zinc(II)-(S)-BINOL results in good-to-low asymmetric induction but poor chemical conversion. However, the absolute stereochemistry of novel aza-Diels-Alder cycloadducts, such as diethyl 4-oxo-2-phenyl-3,4-dihydropyridin-1(2H)-ylphosphonate, can be determined using circular dichroism (CD). Comparison between experimental and TDDFT-calculated CD spectrum shows that use of the (S)-catalyst results in predominant formation of the (6R) cycloadducts.

Asymmetric Lewis Acid Catalyzed Diels—Alder Reactions of α,β‐Unsaturated Ketones and α,β‐Unsaturated Acid Chlorides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Asymmetric Lewis acid-catalyzed Diels-Alder reactions of alpha,beta-unsaturated ketones and alpha,beta-unsaturated acid chlorides.

[reaction: see text] Conformational analysis, van der Waals attractions, and transition structure calculations are combined to design an asymmetric Lewis acid-catalyzed Diels-Alder reaction for simple acyclic alpha,beta-unsaturated ketones and alpha,beta-unsaturated acid chlorides, giving up to 83 and 92% ee, respectively. The two-point-binding chiral recognition mechanism, Lewis acid-Lewis base coordination with boron and a van der Waals attraction with the naphthyl group, uses the inherent enone unit of simple alpha,beta-unsaturated carbonyl compounds, ending the need for auxiliary oxygen binding sites on the dienophile.

Diels—Alder Reaction. Effect of Internal and External Factors on the Reactivity of Diene—Dienophile Systems

AbstractFor Abstract see ChemInform Abstract in Full Text.

The Influence of Ligand Side Chain on the Enantioselectivity of Lewis Acid Catalyzed Diels—Alder Reactions.

AbstractFor Abstract see ChemInform Abstract in Full Text.

The effect of solvent on a Lewis acid catalyzed Diels-Alder reaction, using computed and experimental kinetic isotope effects.

A new transition structure for the Diels-Alder reaction between isoprene and acrolein catalyzed by Et(2)AlCl is found to reconcile reported discrepancies between computed and observed secondary kinetic isotope effects (KIEs). Including the effect of solvent realigns the computed results with experiment demonstrating the importance of nonbond interactions at transition structures. Comparison of experimental and newly predicted KIE data reaffirms the ability of theory and experiment to probe the mechanism and transition structure geometry of organic reactions.

Stereocontrolled photo-reaction pathways of endo/exo-2-benzoyl-substituted bicyclo[2.2.2]oct-5-en-2-ol: Paternò–Büchi reaction versusα-cleavage

Two stereoisomeric ketones, endo- and exo-(2-hydroxy-[2.2.2]bicyclo-5-en-1-yl)-phenyl methanone (endo-2 and exo-2) were synthesized via a Lewis acid catalyzed Diels–Alder reaction. Both compounds were tested in terms of their efficiency as photoinitiators for radical polymerization. Whereas the exo isomer serves as a good photoinitiator, the curing efficiency is poor in the case of the endo derivative. CIDNP investigations and product analysis by NMR and GC-MS together with density functional calculations reveal the distinctly different reaction pathways of the two isomers. On one hand, exo-2 undergoes α-cleavage from the triplet excited state forming a radical pair that is able to induce polymerizations. On the other hand, endo-2 cyclizes in a Paternò–Büchi reaction yielding a tetracyclic product 11 and no formation of radicals is observed.

Diels—Alder reaction. Effect of internal and external factors on the reactivity of diene—dienophile systems

The key factors influencing the Diels—Alder reaction rate at ambient and elevated pressures were elucidated using data on the reactivity of various diene—dienophile systems in usual and Lewis acid-catalyzed Diels—Alder reactions, the reaction enthalpy, complex formation, dissolution, and solvation, and the donor-acceptor properties of the reactants. It was found that taking account of both the orbital interaction energy and the balance of bond rupture and formation energies allows correct prediction of the reaction rate in the absence or in the presence of Lewis acids.

Molecular Signal Transductionby Conformational Transmission

2,3,6,7-Tetrasubstituted cis-anti-cis perhydroanthracenes and cis-decalines are suitable transducers for molecular signals via conformational transmission. Repeated use of a Lewis-acid catalyzed Diels-Alder reaction led to the stereoselective construction of the perhydroanthracene and decalin target molecules. A covalently induced triple ring flip of the perhydroanthacene system was achieved by the formation of a bisacetal. A chelation induced conformational switch was possible with bipyridine receptor groups in positions 6 and 7 and Zn(II) as the incoming signal. By attaching pyrene effectors in positions 2 and 3 the ability of the device to transduce a molecular signal from the receptor via the biconformational transducer to the effector leading to an outcoming photosignal was proven.

Efficient synthesis of a tricyclic BCD analogue of ouabain: Lewis acid catalyzed Diels-Alder reactions of sterically hindered systems.

Efficient synthesis of a tricyclic BCD analogue of ouabain: Lewis acid catalyzed Diels-Alder reactions of sterically hindered systems.

Asymmetric Synthesis and Applications of Chiral 3‐Phenylsulfinyl‐3‐sulfolenes.

AbstractFor Abstract see ChemInform Abstract in Full Text.