Oximes Diels-Alder reactions

Diels-Alder reaction of 2-bromoacrolein and 5-[(ben2yloxy)meth5i]cyclopentadiene in the presence of 5 mol % of the catalyst (35) afforded the adduct (36) in 83—85% yield, 95 5 exo/endo ratio, and greater than 96 4 enantioselectivity. Treatment of the aldehyde (36) with aqueous hydroxylamine, led to oxime formation and bromide solvolysis. Tosylation and elimination to the cyanohydrin followed by basic hydrolysis gave (24). 

The scope and efficiency of [4+2] cycloaddition reactions used for the synthesis of pyridines continue to improve. Recently, the collection of dienes participating in aza-Diels Alder reactions has expanded to include 3-phosphinyl-l-aza-l,3-butadienes, 3-azatrienes, and l,3-bis(trimethylsiloxy)buta-l, 3-dienes (1,3-bis silyl enol ethers), which form phosphorylated, vinyl-substituted, and 2-(arylsulfonyl)-4-hydroxypyridines, respectively <06T1095 06T7661 06S2551>. In addition, efforts to improve the synthetic efficiency have been notable, as illustrated with the use of microwave technology. As shown below, a synthesis of highly functionalized pyridine 14 from 3-siloxy-l-aza-1,3-butadiene 15 (conveniently prepared from p-keto oxime 16) and electron-deficient acetylenes utilizes microwave irradiation to reduce reaction times and improve yields <06T5454>. 

The analogous transformation of 125, also realized by flash vacuum pyrolysis, gave rise to allenic oximes 126 [165], which are not directly accessible by the classical route starting from allenyl ketones and hydroxylamine (see Section 7.3.2) [122], Because compounds 125 are prepared from allenyl ketones and furan by [4 + 2]-cycloaddition followed by treatment with hydroxylamine, the retro-Diels-Alder reaction 125 —> 126 is in principle the removal of a protecting group (see also Scheme 7.46). 

Particularly good yields of the cydoadduct 329 are obtained if R1 = R2 = H is valid for the allenyl ketone 328 [165]. The Diels-Alder products 329 can undergo many chemical transformations, for example to the oximes 330, which yield the modified allenes 331 after a subsequent flash vacuum pyrolysis. The oximes 331 generated by retro-Diels-Alder reaction are not available from ketones 328 and hydroxylamine hydrochloride directly [122] (see also Scheme 7.19). 

Conjugated oximes were converted to pyrazoles in a one-pot reaction by refluxing with hydrazine and iodine in ethanol. The process proceeds via an inverse electron-demand Diels-Alder reaction involving electron-deficient heterodienes and diimide species as dipolarophiles . ... 

A method was developed for preparation of the tetracyclic carboline alkaloids iso-canthine, isocanthin-6-one and l-methylisocanthin-3-one by an intramolecular hetero-Diels-Alder reaction. For example, oxime 317 in sulfolane at 285 °C afforded isocanthine 318 in 8% yield (equation 137) . 

As another application, treatment of bromotrifluoroacetone oxime with a base yields an interesting heterodiene. This molecule can be involved in hetero-Diels-Alder reactions with electron-rich olefins (Figure 2.56). In the presence of indole, it allows the introduction of the 2-aminotrifluoropropane motif (Figure 2.56). ... 

On the contrary, while working in the synthesis of the alkaloid ru-brolone, Bogerand Zhu (91TL7643) have found 0-alkyl a,/3-unsaturated oximes 98 to participate as effective 4ir components of an intramolecular Diels-Alder reaction with an electron-deficient dienophile. Thus, 98 was prepared from butane-1,4-diol and heated in triisopropylbenzene to furnish 2-pyrindine derivatives 99 by virtue of in situ elimination of alcohol (Scheme 25). 

Pyrrolidines and pyrrolidinones can be synthesized on insoluble supports by intramolecular carbometallation of alkenes (Entry 1, Table 15.4) and by Ugi reaction of support-bound isonitriles with amines and 4-oxo acids (Entry 4, Table 15.4). In Entry 5 in Table 15.4, the pyrrolidinone ring is formed by intramolecular Diels-Alder reaction of a furan with a fumaric acid derivative. 2-Pyrrolidinones have also been prepared by treatment of resin-bound O-mesitylenesulfonyl cyclobutanone oximes with... 

A new synthesis of isoxazoles is by successive treatment of a ketoxime with butyllithi-um, the ester of a carboxylic acid and sulfuric acid, e.g. 1 -> 2 (94S989). Hitrovinyl oximes 3 (R1, R3 = alkyl or aryl) undergo oxidative cyclization to isoxazoles 4 by the action of DDQ or iodine/potassium iodide (94JHC861). Flash-vacuum pyrolysis of the 1,3-dipolar cycloadduct 5 of acrylonitrile oxide to norbornadiene results in a retro-Diels-Alder reaction to give cyclopentadiene and 3-vinylisoxazole 6 (94CC2661). 

Figure 4-7 shows a typical hetero Diels-Alder reaction of a nitrosoalkene. Upon in situ generation of the heterodiene 4-34 from the oxime 4-33, cycloaddition occurred in the presence of the silyl enol ether 4-35 to give the 5,6-dihydro-4H- 1,2-oxazine 4-36 in excellent yield [366]. Such conversions are very suitable for achieving kinetic resolutions of -/Z-isomeric silyl enol ethers since the Z-isomers are distinctly less reactive towards 4-34 [367]. 

Indoles may as well serve as dienophilic compounds for hetero Diels-Alder reactions with nitrosoalkenes. However, the resulting adducts are not stable and undergo further conversion to oximes which represent useful intermediates for the straightforward synthesis of tryptophane derivatives [376,377]. 

D. The use of chiral oxazaborolidines as enantioselective catalysts for the reduction of prochiral ketones, imines, and oximes, the reduction of 2-pyranones to afford chiral biaryls, the addition of diethylzinc to aldehydes, the asymmetric hydroboration, the Diels-Alder reaction, and the aldol reaction has recently been reviewed.15b d The yield and enantioselectivity of reductions using stoichiometric or catalytic amounts of the oxazaborolidine-borane complex are equal to or greater than those obtained using the free oxazaborolidine.13 The above procedure demonstrates the catalytic use of the oxazaborolidine-borane complex for the enantioselective reduction of 1-indanone. The enantiomeric purity of the crude product is 97.8%. A... 

The pyridyl azirine 97 was prepared from mesitylsulfonyloxy oxime 96. This is one of the first examples of heteroaromatic substituted azirines reported. This azirine undergoes a Diels-Alder reaction with isobenzofuran to provide the rwn-cycloadduct 98 in 54% yield <2005S555>. In addition to isobenzofuran, this azirine undergoes cycloaddition with a number of different dienes, including cyclopentadiene (82%), 1-methoxy-butadiene (58%), and Danishefsky s diene (67%). 

A clever approach to lysergic acid (78) has been described by Oppolzer and coworkers (equation 26). Their approach involved an initial retro Diels-Alder reaction of (75) to give diene (76). TTiis compound then underwent intramolecular cycloaddition with the oxime ether to afford adduct (77) as a 3 2 mixture of diastereomers (67% yield). This mixture could be converted to lysergic acid by a short sequence of reactions. 

J.D. White et al. reported the total synthesis of ( )-ibogamine via the catalytic asymmetric Diels-Alder reaction of benzoquinone. The azatricyclic framework of the molecule was established by converting the bicyclic ketone to the anti oxime and then subjecting it to a Beckmann rearrangement in the presence of p-toluenesulfonyl chloride to afford the 7-membered lactam. Elaboration of this lactam into the azatricyclic core of ibogamine and later to the natural product itself was accomplished in a few additional steps. 

Diels-Alder reactions of 1235 synthesis of 1228, 1231, 1250, 1335 Quinone oxime tautomers 251, 252 Quinones—see also Aminoquinones, Anthraquinones, Arenolquinones, Benzoquinones, CaUxquinones, Hydroquinones, Hydroxyquinones, Naphthoquinones, Perylenequinones, Scabequinone reduction of 1108 Quinone units 1396... 

Studies by Hudson and coworkers have demonstrated that both N-sulfonyl al-dimines and ketimines can be prepared from the corresponding aldoxime or ketoxime [18]. Thus, treatment of the oxime with a sulfinyl chloride initially affords the O-sulfinylated oxime 6 (Scheme 3). If 6 is warmed, it rearranges via a free radical process into an N-sulfonyl imine. This transformation appears to provide one of the best and most general routes to N-sulfonyl imines and has been extensively exploited recently by Boger and coworkers [19] in hetero Diels-Alder reactions (see Section 5.2). 

XIII). A thermal retro-Diels-Alder reaction of 39 liberating cyclopen-tadiene was used to afford a diene oxime ether which cyclized to give a tetracyclic indole as a 3 2 mixture of diastereomers. Three additional steps served to convert this adduct to ( )-lysergic acid (40). Of particular interest here is the fact that simple oximino compounds are not normally reactive dienophiles, and the intramolecularity of the conversion is apparently crucial to the success of this transformation. 

The use of the 4tt diene participation of vinylnitroso compounds in Diels-Alder reactions in the preparation of aryl pyruvate oximes,76a c e 8>h amino acids,76a,c 8 y-hydroxynitriles,76ad 8 y-lactones,76dg pyridine N-ox-ides,76f and pyrroles77 is summarized in Scheme 9-III. The intramolecular Diels-Alder reactions of in situ generated and unactivated vinylnitroso compounds have been shown to proceed readily employing electron-rich olefins, and the course of the reaction has been shown to proceed preferentially through an endo transition state [Eq. (36)].79... 

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