Hetero-Diels-Alder cycloaddition

Related reactions Diels-Alder cycloaddition Hetero Diels-Alder reaction ... 

Lewis-acid-catalyzed asymmetric hetero-Diels-Alder cycloaddition of a 1-thiabuta-1,3-diene with chiral A/-acryloyl and A/-crotonyl oxazolidinone dienophile [105]... 

Enhanced stereoselectivity in aqueous intramolecular hetero-Diels-Alder cycloaddition of chiral acyinitroso compounds [17c, d, 99]... 

Streith J., Defoin A. Aza Sugar Syntheses and Multi-Step Cascade Rearrangements Via Hetero Diels-Alder Cycloadditions With Nitroso Dienophiles Synlett 1996 189-200... 

Togni A., Pastor S. D. Cooperativity of Chirality in Homogeneous Catalysis The Gold(I)-Catalyzed Aldol Reaction and the Vanadium(IV)-Catalyzed Hetero-Diels-Alder Cycloaddition Chirality 1991 3 331-340... 

The first microwave-assisted hetero-Diels-Alder cycloaddition reaction was described by Diaz-Ortiz and co-workers in 1998 between 2-azadiene 198 and the same electron-poor dienophiles as for the preparation of pyrazolo[3,4-b]pyridines 200 (Scheme 72) [127]. These dienes reacted with... 

Shao reported the microwave-assisted hetero-Diels-Alder cycloaddition reaction of a series of acetylenic pyrimidines to introduce a fused lactone/lactam ring, with no degradation of either reactants or products typical for the harsh thermal conditions (150-190°C, 15-144h) [131]. In contrast to the results reported when conventional heating was applied, the Diels-Alder cycloaddition under microwave irradiation gave a high yield of the desired fused lactones or lactams [132]. This reaction provided a practical and general method for the preparation of fused bicyclic pyridines 205 (Scheme 74). 

Associated to copper(II) pre-catalysts, bis(oxazolines) also allowed the asymmetric Diels-Alder and hetero Diels-Alder transformations to be achieved in nearly quantitative yield and high diastereo- and enantioselectivities. Optically active sulfoximines, with their nitrogen-coordinating site located at close proximity to the stereogenic sulfur atom, have also proven their efficiency as copper ligands for these asymmetric cycloadditions. Other precursors for this Lewis acid-catalyzed transformation have been described (e.g., zinc salts, ruthenium derivatives, or rare earth complexes) which, when associated to bis(oxazolines), pyridine-oxazolines or pyridine-bis(oxazolines), led to efficient catalysts. 

The hetero-Diels-Alder reaction has also utilized dienophiles in which both reactive centers are heteroatoms. Kibayashi reported that the intramolecular hetero-Diels-Alder cycloaddition of chiral acylnitroso compounds, generated in situ from periodate oxidation of the precursor hydroxamic acid, showed a marked enhancement of the trans-selectivity in an aqueous medium compared with the selectivity in nonaqueous conditions (Eq. 12.55).125 The reaction was readily applied to the total synthesis of (—)-pumiliotoxin C (Figure 12.5).126... 

Ab initio Hartree-Fock and density functional theory (DFT) calculations were performed to study transition geometries in the intramolecular hetero-Diels-Alder cycloaddition reactions of azoalkenes 20 (LJ = CH2, NFI, O) (Equation 1). The order of the reactivities was predicted from frontier orbital energies. DFT calculations of the activation energies at the B3LYP level were in full agreement with the experimental results described in the literature <2001JST(535)165>. 

Many examples of asymmetric reactions catalyzed by copper complexes with chiral ligand systems have been reported. In particular, various copper-bis(oxazoline) catalysts (e.g., complexes (H) to (L), Scheme 48) are effective for carbon-carbon bond-forming reactions such as aldol,204 Mukaiyama-Michael, Diels-Alder,206 hetero Diels-Alder,207,208 dipolar cycloaddition,209,210... 

Hetero substituted 2-cyclopropylideneacetates are ring-strain activated acrylates, highly reactive dienophiles in Diels-Alder reactions, but also powerful Michael acceptors. The reactivity of these compounds is enhanced by the same strain release in the Diels-Alder cycloadditions as well as in the 1,4-additions, and indeed the borderline between tandem Michael-cyclization and Diels-Alder-type cycloaddition is not well defined in many cases. 

Cyclization reactions of pyrimidines were studied, for instance, the reactivity of tetrahydropyrido[4,3-fc]pyrimidines with DMAD leading to dihydropyrimidinylethylamines <05TL1975> and pyrimido[4,5-rf]pyrimidines obtained efficiently by hetero Diels-Alder cycloaddition of methyl 6-methyl-4-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-... 

Hong and coworkers have investigated the cycloaddition chemistry of fulvenes with a wide variety of alkenes and alkynes in great detail [191]. As one example, the reaction of 6,6-dimethylfulvene with benzoquinone is shown in Scheme 6.92. Under microwave conditions in dimethyl sulfoxide (DMSO) at 120 °C, an unusual hetero-[2+3] adduct was formed in 60% yield, the structure of which was determined by X-ray crystallography. The adduct is a structural analogue of the natural products aplysin and pannellin and differs completely from the reported thermal (benzene, 80 °C) Diels-Alder cycloaddition product of the fulvene and benzoquinone (Scheme 6.92) [191]. 

Inter- and intramolecular hetero-Diels-Alder cycloaddition reactions in a series of functionalized 2-(lH)-pyrazinones have been studied in detail by the groups of Van der Eycken and Kappe (Scheme 6.95) [195-197]. In the intramolecular series, cycloaddition of alkenyl-tethered 2-(lH)-pyrazinones required 1-2 days under conventional thermal conditions involving chlorobenzene as solvent under reflux conditions (132 °C). Switching to 1,2-dichloroethane doped with the ionic liquid l-butyl-3-methylimidazolium hexafluorophosphate (bmimPF6) and sealed-vessel microwave technology, the same transformations were completed within 8-18 min at a reaction temperature of 190 °C (Scheme 6.95 a) [195]. Without isolating the primary imidoyl chloride cycloadducts, rapid hydrolysis was achieved by the addition of small amounts of water and subjecting the reaction mixture to further microwave irradia-... 

Scheme 6.95 Hetero-Diels-Alder cycloaddition reactions of 2(1 H)-pyrazinones.

A general hetero-Diels-Alder cycloaddition of fulvenes with azadienes to furnish tetrahydro-[l]pyrindines has been described by Hong and coworkers (Scheme 6.241 see also Scheme 6.92) [424]. A solution of the azadiene and fulvene (1.2 equivalents) precursors in chlorobenzene was heated under open-vessel microwave irradiation for 30 min at 125 °C to provide the target compounds in excellent yields and with exclusive regio- and diastereoselectivity. Performing the reactions under conventional conditions or under microwave irradiation in different solvents provided significantly reduced yields. 

The ene reaction, an electronic relative of the Diels-Alder cycloaddition, is a six-electron process involving the reaction of the n and allylic reactions these reactions are reviewed in detail (for reviews of the Alder-ene reaction and related chemistry, see Refs 1,1a, and lb). Recent developments in the area of hetero-ene chemistry (X1 = H, X2 = N,0) are also surveyed. 

This chapter focuses on some typical examples, starting with the usual cycloaddition reactions and then the catalytic asymmetric Diels-Alder reactions, hetero Diels-Alder reactions, retro Diels-Alder reactions, and intramolecular... 

Bis(oxazoline)-type complexes, which have been found useful for asymmetric aldol reactions, Diels-Alder, and hetero Diels-Alder reactions can also be used for inducing 1,3-dipolar reactions. Chiral nickel complex 180, which can be prepared by reacting equimolar amounts of Ni(C10)4 6H20 and the corresponding (J ,J )-4,6-dibenzofurandiyl-2,2 -bis(4-phenyloxazoline) (DBFOX/Ph) in dichloromethane, can be used for highly endo-selective and enantioselective asymmetric nitrone cycloaddition. The presence of 4 A molecular sieves is essential to attain high selectivities.88 In the absence of molecular sieves, both the diastereoselectivity and enantioselectivity will be lower. Representative results are shown in Scheme 5-55. 

In an attempt to further elucidate the mechanism of this process, these workers monitored the reaction between propiophenone enolsilane and fumaroylimide by in situ infrared (IR) spectroscopy, Scheme 25 (240). In the absence of alcoholic additives, the accumulation of an intermediate is observed prior to appearance of product. When i-PrOH is introduced, immediate decomposition of the intermediate occurs with concomitant formation of product. Evans suggests that the intermediate observed in this reaction is dihydropyran (374). Indeed, this reaction may be viewed as a hetero-Diels-Alder cycloaddition followed by alcohol induced decomposition to the desired Michael adduct. That 374 may be acting as a competent inhibitor was suggested by an observed rate reduction when this reaction was conducted in the presence of IV-methyloxazolidinone. 

Another example, in which the piperidine cycle is generated de novo, exploits a hetero Diels-Alder cycloaddition of 1 -/r-tolylsulfinyl-1,3-penta-diene 91 with benzylnitrosoformate, that generates an oxazine 92 with complete regioselectivity and 7i-facial diastereoselectivity.69 Osmilation of the double bond inserts stereoselectively two hydroxyl groups on the oxazine skeleton, protection and catalytic hydrogenation finally afforded the enantiomerically pure imino sugars 94 (Fig. 38). 

Another example is the synthesis of carpanone (23), which takes place by a two-step dimerisation of two identical moieties (22). the second step proceeding via a hetero-Diels-Alder cycloaddition [19] (Scheme 4.5). 

Scheme 11 Regio- and stereoselectivity issues of the model hetero-Diels-Alder cycloaddition...

In analogy to olefins, Cjq undergoes a broad variety of cycloadditions (see Chapter 4 and Scheme 14.3). In many cases cycloadducts of Cjq exhibit the same stability as the corresponding non-fullerene based adducts. These reactions are very useful for the introduction of fimctionat groups. Among the most important cycloadditions are [4-1-2] cycloadditions such as Diels-Alder and hetero-Diels-Alder reactions, where Cjq reacts always as dienophile, [3-1-2] cycloadditions with 1,3 dipoles, thermal or photochemical [2-1-2] cycloadditions, [2-t-l] cycloadditions and others, for example, [8-1-2] cycloadditions. Among these general reactions several examples deserve special attention, since they reflect characteristic chemical properties of Cjq [36] ... 

Diels-Alder and hetero [4 -I- 2] cycloadditions of l-(l,3-butadien-l-yl)benzotriazole (638) with N-phenylmaleimide, maleic anhydride, ethyl acrylate, Eschenmoser salt, and nitrosobenzene give a... 

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