One-pot three-component tandem metathesis/Diels-Alder reaction

[reaction: see text] A tandem enyne, diene-ene metathesis reaction followed by Diels-Alder reaction accomplished a stereoselective three-component reaction protocol with four stereocenters.     

Tandem Diels-Alder/fragmentation approach to the synthesis of eleutherobin

[reaction: see text] A synthesis of 28, the carbon framework of the eleutherobin aglycone, is reported in a 15-step sequence from readily available starting materials. The tandem Diels-Alder reaction of 6 and 7 to produce 18, in which three new rings and six new stereocenters are formed, is a key step in the reaction sequence.     

Silyl-substituted 1,3-butadienes for Diels-Alder reaction, ene reaction and allylation reaction

Silyl-substituted 1,3-butadienes are useful building blocks and are readily applied in several types of reactions such as Diels-Alder reaction, ene reaction and allylation. They can also participate in different tandem reactions such as Diels-Alder/allylation, ene/allylation, ene/allylation/Diels-Alder reaction, ene/allylation/ene reaction and ene/allylation/Diels-Alder/allylation reaction. This feature article reviews the synthesis of silyl-substituted 1,3-butadienes, and their applications in the reaction types mentioned above, involving a tandem Diels-Alder/ene/allylation process. This article also introduces some reactions of alkenylsilanes and allylsilanes for comparison and discussion about the tandem reaction. The tandem reactions described in this article are a powerful tool to construct complicated multicyclic compounds with high selectivity and high efficiency.     

Tandem Pd-catalyzed carbonylation and intramolecular vinyl allene Diels-Alder reaction toward galiellalactone analogues

A novel route toward new galiellalactone analogues via a tandem palladium-catalyzed carbonylation and intramolecular Diels-Alder reaction of a dienyne carbonate is presented.     

Lewis acid-promoted hetero Diels-Alder cycloaddition of alpha-acetoxynitroso dienophiles

[reaction: see text] alpha-Acetoxynitroso compound 3 has been prepared as a new stable, isolable, and reactive dienophile in nitroso Diels-Alder reactions. The yield of the [4 + 2] cycloaddition of alpha-acetoxynitroso dienophile with 1,3-dienes could be enhanced in the presence of 20 mol % Lewis acid. An unexpected retro hetero-Michael reaction from 26 was observed, leading to the cleavage of the N-O bond of the cycloadduct. This tandem nitroso Diels-Alder/retro hetero-Michael sequence has been used with cyclic and acyclic 1,3-dienes.     

Oppolzer-type intramolecular Diels-Alder cycloadditions via isomerizations of allenamides

A new approach to Oppolzer's intramolecular Diels-Alder cycloaddition (IMDA) through γ-isomerization of readily available N-tethered allenamides is described. These IMDA reactions are carried out in tandem with the allenamide isomerization or 1,3-H shift, leading to complex nitrogen heterocycles in a highly stereoselective manner.     

Lewis acid-catalyzed tandem Diels-Alder reaction/retro-Claisen rearrangement as an equivalent of the inverse electron demand hetero Diels-Alder reaction

A highly stereoselective formal inverse electron demand hetero Diels-Alder reaction (HDA) occurs on reaction of 2-aryl-alpha,beta-unsaturated aldehydes with cyclopentadiene. The major pathway for this transformation is shown to be a Lewis acid-catalyzed tandem Diels-Alder reaction/retro-Claisen rearrangement.     

Tandem Diels-Alder/ene reactions

[reaction: see text] The reactions of unsaturated aldehydes and triene 3 afford adducts via a tandem Diels-Alder/ene reaction.     

Total synthesis of natural (+)- [corrected] and ent-(-)-4-desacetoxy-6,7-dihydrovindorosine [corrected] and natural and ent-minovine: oxadiazole tandem intramolecular Diels-Alder/1,3-dipolar cycloaddition reaction

Efficient and unusually concise total syntheses of both enantiomers of the Aspidosperma alkaloids 4-desacetoxy-6,7-dihydrovindorosine (12) and minovine (1) are detailed. A tandem intramolecular Diels-Alder/1,3-dipolar cycloaddition reaction of the 1,3,4-oxadiazole 8, in which three new rings, four new C-C bonds, and five stereocenters are formed, is a key step in the sequence. The availability of optically active material permitted an assessment of the enantiomeric integrity of minovine and the source of its reported unusual optical rotation. [Reaction: see text]     

Simultaneous accumulation of both skeletal and appendage-based diversities on tandem Ugi/Diels-Alder products

Diversity-oriented organic synthesis (DOS) is a key concept for construction of skeletally diverse small molecule libraries to discover drug-like small molecules. Here, we describe a DOS class to transform a complex 7-oxanorbornene skeleton, which is readily accessible by a tandem Ugi/Diels-Alder reaction, into two heterotricycle skeletons selectively by using tandem ROM/CM/RCM reaction. In the present study, the mode of cyclization is pre-encoded by building blocks used in the complexity-generating tandem Ugi/Diels-Alder reaction. Since variable alkenes can be used in the CM reaction, our approach can be extended to construct both skeleton- and appendage-diverse small molecule libraries.     

Trienamines in asymmetric organocatalysis: Diels-Alder and tandem reactions

The discovery of a novel activation mode provided by organocatalysis is presented. It is demonstrated that the merger of optically active secondary amines and polyenals generates reactive trienamine intermediates, which readily participate in Diels-Alder reactions with different classes of dienophiles, hence, providing a facile entry to highly complex molecular frameworks with excellent stereocontrol. For the Diels-Alder reactions with 3-olefinic oxindoles, spirocyclic oxidoles are formed in high yields, and with enantioselectivities in the range of 94-98% ee. It is demonstrated, that some of these products can be transformed into the hexahydrofuro[2,3-b]indole fragment. The organocatalytic trienamine concept has been extended to also include Diels-Alder reactions of olefins substituted with cyanoacetates providing multifunctional cyclohexenes with three contiguous stereocenters in high yield and good stereocontrol. The novelty of this activation strategy lies within the perfect chirality relay over a distance of up to eight bonds. Moreover, we also present the first trienamine tandem reaction by combining trienamine catalysis with enamine activation. In addition to the experimental results, a detailed mechanistic survey is also provided including NMR spectroscopic studies and calculations of the reactive trienamine intermediates, rationalizing the origin of stereochemistry.     

Accurate prediction of rate constants of Diels-Alder reactions and application to design of Diels-Alder ligation

Bioorthogonal reactions are useful tools to gain insights into the structure, dynamics, and function of biomolecules in the field of chemical biology. Recently, the Diels-Alder reaction has become a promising and attractive procedure for ligation in bioorthogonal chemistry because of its higher rate and selectivity in water. However, a drawback of the previous Diels-Alder ligation is that the widely used maleimide moiety as a typical Michael acceptor can readily undergo Michael addition with nucleophiles in living systems. Thus, it is important to develop a nucleophile-tolerant Diels-Alder system in order to extend the scope of the application of Diels-Alder ligation. To solve this problem, we found that the theoretical protocol M06-2X/6-31+G(d)//B3LYP/6-31G(d) can accurately predict the activation free energies of Diels-Alder reactions with a precision of 1.4 kcal mol(-1) by benchmarking the calculations against the 72 available experimental data. Subsequently, the electronic effect and ring-strain effect on the Diels-Alder reaction were studied to guide the design of the new dienophiles. The criteria of the design is that the designed Diels-Alder reaction should have a lower barrier than the Michael addition, while at the same time it should show a similar (or even higher) reactivity as compared to the maleimide-involving Diels-Alder ligation. Among the designed dienophiles, three substituted cyclopropenes (i.e. 1,2-bis(trifluoromethyl)-, 1,2-bis(hydroxylmethyl)- and 1,2-bis(hydroxylmethyl)-3-carboxylcyclopropenes) meet our requirements. These substituted cyclopropene analogs could be synthesized and they are thermodynamically stable. As a result, we propose that 1,2-bis(trifluoromethyl)-, 1,2-bis(hydroxylmethyl)- and 1,2-bis(hydroxylmethyl)-3-carboxylcyclopropenes may be potential candidates for efficient and selective Diels-Alder ligation in living systems.     

Tandem Diels-Alder cyclization/aromatization reactions of 5-vinyl-1-acyl-2-aryl-2,3-dihydro-4-pyridones

A tandem Diels-Alder cyclization/aromatization of 5-vinyl-2,3-dihydro-4-pyridones and various dienophiles is reported. The intermediate Diels-Alder cycloadduct undergoes an elimination/aromatization to provide β-amino-ketones, β-amino-alcohols, and unnatural amino acids containing useful functionality.     

Tandem Diels-Alder reaction/radical cyclizations for the rapid construction of bridged ring systems

Bridged tricyclic ring systems can be prepared in a one-pot reaction using a tandem Diels-Alder reaction/radical cyclization strategy. The regiochemistry of the radical addition is unexpected.     

Tandem Pauson-Khand reaction and Diels-Alder reaction for access to polycycles in a one-pot reaction

Starting from easily available cyclic alkenes, enynes, and dienophiles, a tandem intermolecular Pauson-Khand reaction and Diels-Alder reaction yields polycyclic compounds in high yields.     

Rhodium catalyzed tandem Diels-Alder/hydrolysis reactions of 2-boron-substituted 1,3-dienes

2-Boron substituted 1,3-dienes have been prepared and used in preliminary experiments to demonstrate that it is possible to effect rhodium catalyzed Diels-Alder/hydrolysis tandem reactions.     

Laccase-generated quinones in naphthoquinone synthesis via Diels-Alder reaction

The tandem synthesis of naphthoquinones was conducted from the reaction of laccase-generated quinones and acyclic dienes via Diels-Alder reaction. This reaction was carried out under mild condition in aqueous medium and yielded naphthoquinones up to 80%. In addition, the effect of solvent was also investigated and water was shown to be optimal for this reaction.     

Progress toward the total synthesis of bacchopetiolone: application of a tandem aromatic oxidation/Diels-Alder reaction

A stereoselective synthesis of the bacchopetiolone (1) carbocyclic core using a tandem phenolic oxidation/Diels-Alder reaction is described. [reaction: see text].     

Tandem Wittig-intramolecular Diels-Alder cycloaddition of ester-tethered 1,3,9-decatrienes under microwave heating

Intramolecular Diels-Alder (IMDA) cycloaddition of the ester-tethered 1,3,9,-decatrienes possessing a carbonyl substituent at C10 has been investigated under controlled microwave heating (MeCN, 180 °C) to afford a variety of 3,4,4a,7,8,8a-hexahydroisochromen-1-ones in 53-89% yields and in 64:36-79:21 ratios for the cis and trans isomers. Under the same microwave heating conditions, a tandem Wittig-IMDA cycloaddition, starting from the α-bromoacetates of 3,5-hexadien-1-ols and glyoxalate/phenylglyoxal hydrates in the presence of PPh₃ and 2,6-lutidine, has been demonstrated, furnishing 3,4,4a,7,8,8a-hexahydroisochromen-1-one adducts in 73-91% yields in favor of the cis isomers. During this tandem process, three consecutive carbon-carbon bonds in the end products were efficiently formed with the aid of microwave irradiation within short reaction times.     

Decomplexation-nitroso Diels-Alder (NDA) approach to C,D-ring functionalisation for hippeastrine

A tandem decomplexation-nitroso Diels-Alder (decomplexation-NDA) procedure has been shown to give the regiocontrol and stereocontrol needed for application in an organoiron-mediated synthesis of the alkaloid hippeastrine, using a selection of nitrosoarenes with functionality present to facilitate removal of the arene after the NDA step.