Ketones, hydroxy Diels-Alder reactions

Fluoboric acid is also an efficacious promoter of cyclic oxo-carbenium ions (Scheme 4.24) bearing an activated double bond which, in the presence of open-chain and cyclic dienes, rapidly undergo a Diels-Alder reaction [91]. Chiral a, -unsaturated ketones bearing a -hydroxy substituents, protected as acetals, react with various dienes in the presence of HBF4, affording Diels-Alder adducts that were isolated as alcohols by hydrolysis of the acetal group by TsOH. Some examples of reactions with isoprene are reported in Table 4.23. The enantios-electivity of the reaction is dependent on the size of the substituent R on the of-carbon high levels of asymmetric induction were observed with R = z-Pr (90 1) and R = t-Bu (150 1) and low levels with R = Me (2.7 1) and R = Ph (3.0 1). Scheme 4.24 shows the postulated reaction mechanism. 

The high enantioselectivity shown in the above reactions can be attributed to two important factors. First, coordination of the Lewis acid with the a-hydroxy ketone moiety of dienophile 17 or 19 leads to the formation of a rigid five-membered chelate 21. This chelate causes the differentiation of the two dia-stereotopic faces of the enone system. Second, arising from the established absolute configuration of 17 and 19, within 21, the Diels-Alder reaction proceeds with the enone fragment at its cisoid position (yyu-planar). 

Okamura and Nakatani [65] revealed that the cycloaddition of 3-hydroxy-2-py-rone 107 with electron deficient dienophiles such as simple a,p-unsaturated aldehydes form the endo adduct under base catalysis. The reaction proceeds under NEtj, but demonstrates superior selectivity with Cinchona alkaloids. More recently, Deng et al. [66], through use of modified Cinchona alkaloids, expanded the dienophile pool in the Diels-Alder reaction of 3-hydroxy-2-pyrone 107 with a,p-unsaturated ketones. The mechanistic insight reveals that the bifunctional Cinchona alkaloid catalyst, via multiple hydrogen bonding, raises the HOMO of the 2-pyrone while lowering the LUMO of the dienophile with simultaneous stereocontrol over the substrates (Scheme 22). 

Linders, J.T.M., Kokje, J.P., Overhand, M., Lie, T.S. and Maat, L., Chemistry of opium alkaloids, Part XXV Diels-Alder reaction of 6-demethoxy-p-dihydrothebaine with methyl vinyl ketone using microwave heating preparation and pharmacology of 3-hydroxy-a, a, 17-trimethyl-6 3, 14 3-ethenomorphinan-7 3-methanol, a novel deoxygenated diprenorphine analog, Rec. des Trav. Chim. des Pays-Bas, 1988,107, 449. 

The thermal Diels-Alder reaction ([4 + 2] cycloaddition) is widespread in the synthesis of fullerene derivatives. In contrast, only a few examples of the photochemical Diels-Alder reaction in solution or in the solid state are known. The first example is described by Tomioka and coworkers [249], Irradiation of ketone 73 and C6o at 10°C with a high pressure mercury lamp through a Pyrex filter led to the formation of 61-hydroxy-61-phenyl-l,9-(methano[l,2]benzenomethano) fullerene 75 (Scheme 29). This compound is unusually unstable and yields the monoalky 1-1,2-dihydrofullerene 76 either by silica gel chromatography or upon heating. 

Table 18 Diels-Alder Reactions of a,p-Unsaturated Hydroxy Ketones with Cyclopentadiene (Scheme 83)...

Several of the seminal routes to the lactone, as devised by Corey, are summarized in Fig. 5. Diels-Alder reaction of (methoxymethyl)cyclo-pentadiene [15] with chloroacrylonitiile and then basic hydrolysis gave the bicydic ketone [16] (20). Ring expansion in a selective Baeyer-Villiger reaction led to lactone [17] that was then hydrolyzed to hydroxy add [18],... 

Fascinating rearrangements of aziridines have been applied to the synthesis of diterpene alkaloids by Wiesner and co-workers (Scheme 40). For example, the ester 217, prepared from cyclopentadiene carboxylate (215) and the benzyne precursor 216 by a Diels-Alder reaction, was converted to the aziridine 218 by treatment with benzenesulfonyl azide in 83% yield. When the aziridine 218 was heated with water for 24 h, the hydroxy ester 219 was obtained in 97% yield subsequent oxidation with the Jones reagent afforded the ketone 220. This rearrangement is analogous to that of the benzenesulfonylaziridine of norbomene. ... 

The total synthesis of the antitumor antibiotic FR901464 was accomplished by E.N. Jacobsen et al. The preparation of the central six-membered fragment was achieved via a highly enantioseiective hetero Diels-Alder reaction between a diene and an aldehyde. The resulting silyl end ether was subjected to a modified Rubottom oxidation condition (buffer and nonpolar solvent) with mCPBA to afford the desired a-hydroxy ketone with compiete diastereoseiectivity. 

Pyrazolo[3,4-Z)]pyridines, the 7-chloro-6-fluoro-2,4-dimethylquinoline and its mercapto-thiadiazolyl or oxadiazolyl quinolines 21 were prepared via Diels-Alder reaction conversion of methyl 2-(3-oxo-3-phenylpropenylamino)benzoate into 3-benzoyl-l.S -quinolin-4-one 22 . A mixture of aniline derivatives and malonic ester gave a variety of 3-aryl-4-hydroxyquinolin-2(l//)-ones 23. Condensation of isatins with ketones afforded quinoline-4-carboxylic acids. 2-Aryl-l,2,3,4-tetrahydro-4-quinolinones 22 and carbazolylquinolone were also prepared. The substitution of 2-chloroquinoline gave the 2-substituted quinolines. Basic alumina has catalyzed the C-C bond formation between 2-hydroxy-1,4-naphthoquinone and 2-chloroquinoline derivative to give 21. Reaction of organic halides with 8-hydroxyquinolines gave the respective ethers. The azodye derivatives of 21 were prepared in the absence of solvent. Silica gel catalyzed the formation of 2-ketomethylquinolines from reaction of 2-methylquinolines with acyl chlorides. 

Scheme 9.1 Diels-Alder reaction of a-hydroxy vinyl ketone and cyclopentadiene...

The synthesis starts from thebeine, which is subjected to a Diels-Alder reaction with methyl vinyl ketone and then reacted with n-butylmagnesium chloride. Finally, in a nucleophilic substitution, the methoxy-group is replaced by hydroxy. 

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