Diels-Alder reactions naphthoquinone

Diels-Alder Reaction. In 1928, Diels and Alder discovered that 1,3-unsaturated organic compounds reacted with quinoid systems to give partially hydrogenated, cycHc compounds. In the course of their work, they found that 1 mol of 1,4-naphthoquinone [130-15-4] reacted readily with 1 mol of 1,3-butadiene [106-99-0] to give a partially hydrogenated anthraquinone (11) l,4,4a,9a-tetrahydro-9,10-anthracenedione [56136-14-2] which, on oxidation with chromic oxide, produced anthraquinone (43) ... 

Oxidation of thiophene with peracid under carefully controlled conditions gives a mixture of thiophene sulfoxide and 2-hydroxythiophene sulfoxide. These compounds are trapped by addition to benzoquinone to give ultimately naphthoquinone (225) and its 5-hydroxy derivative (226) (76ACS(B)353). The further oxidation of the sulfoxide yields the sulfone, which may function as a diene or dienophile in the Diels-Alder reaction (Scheme 88). An azulene synthesis involves the addition of 6-(A,A-dimethylamino)fulvene (227) to a thiophene sulfone (77TL639, 77JA4199). 

Studies of diastereoselectivity in Diels-Alder reactions of (S)S-4a,5,8,8a-tetrahydro-5,8-methane-2-(p-tolysulfinyl)-1,4-naphthoquinones with cyclopentadiene [147]... 

A broad study on the MW-assisted Diels Alder reactions of 2H-pyran-2-ones 50 and 51 with 1,4-naphthoquinone 52 and N-phenylmaleimide 53 (Equations 4.3) supported on silica-gel, K-10 montmorillonite, fitrol and alumina was carried out by Samant and colleagues [41]. 

The aqueous [4+2] cycloaddition reaction of 1,4-naphthoquinones 115 with methoxy cyclohexadiene performed in the presence of bovine serum albumin (BSA) is one of the first examples of protein-promoted Diels Alder reactions [79]. Some results are reported in Table 4.18. The globular protein does not affect the regioisomer ratio of adducts. The highest enantiomeric excess was obtained in the cycloaddition of juglone 115 (R = H) with 1-methoxy-1,3-cyclohexadiene 116. 

The Diels-Alder reaction of 2H-pyran-2-ones part IV - Microwave catalyzed Diels-Alder reaction of 4,6-disubstituted-2H-pyran-2-ones with 1,4-naphthoquinone and N-phenylmaleimide [41a]... 

An interesting phenomenon has been observed in the high pressure Diels-Alder reactions of the l-oxa[4.4.4]propella-5,7-diene (117) with 1,4-naphthoquinone, maleic anhydride and N-phenylmaleimide, where the diene 117 undergoes a rearrangement to the diene isomer 118 which, although thermodynamically less favored, exhibits a greater reactivity [40]. The reactivities of the three dienophiles differed since maleic anhydride and N-phenylmaleimide reacted only in the presence of diisopropylethylamine (DIEA) and camphorsulfonic acid (CSA), respectively (Scheme 5.15). The distribution of the adduct pairs shows that the oxygen atom does not exert a consistent oriental dominance on TT-facial selectivity. 

Typically, the synthesis of block B involves the Diels-Alder reaction of 1,4-naphthoquinone with cyclopentadiene, followed by reduction and OH methylation to give 92 (Scheme 33). The next step involves a Ru-catalysed [2+2] cycloaddition of 92 with dimethyl acetylenedicarboxylate (DMAD), followed by epoxidation (MeLi, BuOOH) to give 94 as block B. 

Brimble and McEwan (206) investigated the Diels-Alder reaction between naphthoquinones and cyclopentadiene using these catalysts. Acetylnaphthoqui-none reacts with cyclopentadiene in the presence of 67 Cu(OTf)2 to provide the cycloadduct in low selectivity (30% ee). Catalysts 269c and 269d afford lower selectivities. Improved selectivities are observed using 5-hydroxynaphthoquinone [50% ee with 67 Cu(OTf)2]. 

A wide variety of chiral sulfinyl substituents have been employed as chiral auxiliaries on both dienes162 and dienophiles163 in asymmetric Diels-Alder reactions. Carreno and colleagues164, for example, used Diels-Alder reactions of (Ss)-2-(p-tolylsulfinyl)-1,4-naphthoquinone (249) to separate racemic mixtures of a wide variety of diene ena-tiomers 250a and 250b via kinetic resolution and to obtain enantiomerically enriched... 

Brimble and coworkers176 studied the asymmetric Diels-Alder reactions of cyclopentadiene with chiral naphthoquinones 272 bearing different chiral auxiliaries. The highest endo and facial selectivities were obtained using zinc dichloride as the Lewis acid catalyst and (—)-pantolactone as the chiral auxiliary. Thus, the reaction between cyclopentadiene and 272 afforded a 98 2 mixture of 273 and 274 (equation 76). The chiral auxiliary was removed easily by lithium borohydride reduction. 

The regiochemistry of the Diels-Alder reaction of l-alkoxy-3-(rm-butyldimethylsilyl)oxy-2-azadienes and naphthoquinones, as a route to 2-azaanthraquinon-3-ones, has been investigated (91H915). 

Furo[3,4-J]pyridazines have also been used in Diels-Alder reactions (331a with maleic anhydride, acrylic acid, 1,4-naphthoquinone, dibenzoyl-ethylene, 1,4-benzoquinone, benzo[c]furandione ° 331c with maleic anhydride) 331a has been shown to be more reactive than 331c. 1,3-Diphenylfuro[3,4-b]quinoxaline (335) has been obtained from phthalide 334 (Eq. 17) as a green crystalline, quite stable solid (mp 244-246°C). In DMSO (deep blue solution), 335 reacts instantaneously with such dienophiles... 

Chiral bis(oxazoline)/Copper(II) complexes are evaluated for asymmetric Diels-Alder reaction of naphthoquinone derivatives, and moderate levels of enantiomeric excess are observed in certain cases [56] (Eq. 8A.33). 

Ab initio and density functional theoretical studies of the 4 + 2-cycloaddition of 2-azabutadiene with formaldehyde predict a concerted reaction that agrees well with experimental evidence.184 The azadiene A-plienyl-l-aza-2-cyanobuta-l,3-diene reacts with electron-rich, electron-poor, and neutral dipolarophiles under mild thermal conditions.185 5,6-Diliydro-4//-1,2-oxazines have been shown to be usefiil as synthon equivalents of 2-cyano-l-azabuta-1,3-dienes.186 The intramolecular Diels-Alder reaction of 1-aza-l,3-butadienes (106) can be activated by a 2-cyano substituent (Scheme 37).187 Stereoselectivity in the hetero-Diels-Alder reactions of heterobutadienes, nitrosoalkenes, and heterodienophiles has been extensively reviewed.188 The azadiene l-(f-butyldimethylsilyloxy)-l-azabuta-1,3 -diene (107) reacts with halobenzo-quinones, naphthoquinones, and A-phcnylmalcimidc to yield low to good yields of various pyridine heterocycles (108) (Scheme 38).189 The 4 + 2-cycloaddition of homophthalic anhydride with A-(cinnamylidcnc)tritylaminc produces the 3,4-adduct whereas with A -(cinnamylidcnc)bcnzylidinc the 1,2-adduct is produced.190... 

Diels-Alder reactions of a,fi-unsaturatedN,N-dimethylhydrazones.1 These readily available hydrazones can function as 1-amino-l-aza-l,3-dienes in Diels-Alder reactions. Thus, 1 undergoes regioselective cycloaddition with various electrophilic dienophiles to give tetrahydropyridines such as 2 and 3. Unfortunately, removal of the dimethylamino group with zinc and acetic acid (or other reagents) also effects reduction of the double bond. The initial adduct from cycloaddition of 1 with naphthoquinone is unstable and undergoes spontaneous elimination of the elements of dimethylamine to give the aromatic adduct 4. 

Molecular electrostatic potentials have been used to explain the regioselectivity exhibited in the Diels-Alder cycloaddition reactions between 1-trimethylsilyloxy-butadiene and the quinones 5-formyl-8-methyl-1,4-naphthoquinone, 5-methoxy-7-methyl-1,4-phenanthrenequinone, and 5,6,7-trimethyl-1,4-phenanthrenequinone.128 The intramolecular Diels-Alder reaction of masked o-benzoquinones (123) with a variety of dienes provides adducts (124) which rearrange to functionalized ris-decal ins (125) with complete stereocontrol of up to five stereocentres. This methodology ... 

The ready evolution of the adducts into aromatic quinones by spontaneous sulfinyl elimination and further aromatization prompted the use of sulfinyl naphthoquinones as a synthetic equivalent of the unknown compound naph-thynoquinone [103]. For this purpose, sulfinyl quinones represent a convenient synthetic alternative to haloquinones. The highly regioselective course of the Diels-Alder reactions of 2-phenylsulfinyl-1,4-naphthoquinones (as well as their corresponding thioethers and sulfones) unsymmetrically substituted by... 

Thus, Ghosez et al. were successful in showing that A,iV-dimethyl hydrazones prepared from a,/3-unsaturated aldehydes react smoothly in normal electron demand Diels-Alder reactions with electron-deficient dienophiles [218, 219]. Most of the more recent applications of such 1-aza-l,3-butadienes are directed towards the synthesis of biologically active aromatic alkaloids and azaanthra-quinones [220-224] a current example is the preparation of eupomatidine alkaloids recently published by Kubo and his coworkers. The tricyclic adduct 3-19 resulting from cycloaddition of naphthoquinone 3-17 and hydrazone 3-18 was easily transformed to eupomatidine-2 3-20 (Fig. 3-6) [225]. 

Diels-Alder reactions. This diene reacts with 2-chloro-1,4-quinones to give adducts that undergo aromatiz tion when heated. Yields tend to be low in reactions with benzo-quinones, but are usuajlly satisfactory with naphthoquinones. The reagent was developed to provide a synthesis pf the trimethyl ether (2) of erythrolaccin. 

Diel -AldeT catalyst. Kelly and Montury have examined the effect of three Lewis acids on the Diels-Alder reaction of perf-hydroxylated naphthoquinones with l-methoxy-3-methyl-l,3-butadiene magnesium iodide, boron trifluoride etherate, and boron triacetate. All three increase regioselectivity. BF, etherate and B(OAc)3... 

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