Diels-Alder reactions continued

The hetero-Diels-Alder reaction continues to be a popular method of producing the tetrahydroquinoline ring structure. The generation of o-azaxylylene allows for the subsequent cycloaddition with dienophiles to produce the corresponding quinoline ring structure (Scheme 73) <1998H(48)1103, 1998JHC467>. 

The transformation of compound 145 to 146 involves a cascade of reactions and the two intermediates can be isolated. Thus, treatment of compound 145 with ammonia causes almost instantaneous transformation of the nonpolar dialdehyde to a complex mixture of polar materials, from which the dihydropyridine 147 can be isolated in about 45 % yield. This compound reacts rapidly on being treated with ammonium acetate in acetic acid at room temperature to give compound 148, as the result of a formal intramolecular Diels-Alder reaction. Continued treatment... 

The classic Diels-Alder reaction continues to be applied to steroidal dienes and has been used to prepare benzene-fused compounds (277) (from 6-methylene testosterone ), and (278) and (279) [from the furano-steroid (217) ] and adducts between A -dienes and methyl acrylate, hexafluorobut-2-yne, dimethylacetylene dicarboxylate, and methyl propiolate have been obtained. In this last reaction the mono-adduct (280) was accompanied by a diadduct, assigned the structure (281), which arises from homo-conjugate Diels-Alder addition and which appears to be the first example of homo-conjugate addition to a substituted bicyclo[2,2,l]heptadiene. The diadduct was also obtained in good yield by treatment of the mono-adduct with more methyl propiolate. 

Diels-Alder Cycloadditions.—The range of functionalized diene systems, displaying regioselective behaviour in the Diels-Alder reaction, continues to expand. Notable new additions include l-phenylseleno-2-trimethylsilyloxy-4-methoxybuta-l,3-diene (82) and the isomers 1- and 2-methyl-l,3-bis(trimethylsilyloxy)buta-l,3-dienes (84) and (85). The diene (82) is readily derived from l-methoxy-3-trimethylsilyloxybuta-1,3-diene (81) and provides a direct route to the synthetically valuable 4-acylcyclohexa-2,5-dienones (83), whereas dienes (84) and (85) react with activated dienophiles (e.g. RCH=CHC02Et) in good yield, leading to keto-esters of the type (86) on hydrolysis. 

SCHEME 4.16 Regioselectivity in Diels—Alder reaction continued. 

The intramolecular Diels-Alder reaction continues to dominate the... 

The hetero-Diels-Alder reaction continues to be the reaction of choice for the synthesis of sugars from non-carbohydrate precursors. This year Weinreb and his group have applied their sulphinyl dienophile approach to the synthesis of 3-deoxy-3-methylaminoarabinopyranoside (210), a component of both the... 

Diels-Alder reactions continue to be of value for the interception of highly reactive dienes or dienophiles. Thus, irradiation of 2-cyclo-octen-l-one or of 2-cyclohepten-l-one in the presence of excess cyclopentadiene affords the norbornene derivatives (173 n = 5 or 4 respectively), which undergo retro-[4 -I- 2] addition on distillation. Presumably the trans-2-cycloalken-l-ones are reactive intermediates in these processes. Elimination of acetic acid from bis(trifluoromethyl)cyclopentadienylcarbinyl acetate yields the reactive 6,6-bis(trifluoromethyl)fulvene, which rapidly dimerizes by [4 + 2] cycloaddition the fulvene intermediate can be intercepted by similar addition to cyclopentadiene. The adduct (174) is formed on reaction of cyclopentadiene with the imine produced by iodine-catalysed rearrangement of NN-... 

The synthetic scope of the Diels-Alder reaction continues to be widened as a result of the studies of Corey s group. A brief note this year describes the use of 3-hydroxy-2-pyrone (195) as a vinylketene equivalent for the synthesis of dihydrophenols and cyclohexenones. These compounds are the result of the loss of CO2 from the initially formed adducts in a reverse [4 + 2]reaction, but in the reaction of (195) with maleic anhydride the adduct (196) is stable. 

Catalysed Diels-Alder reactions continue to provide interesting results. The reactions of methylcyclopentadiene (which has an equilibrium concentration consisting of 45 %, 54%, and 1 % of the 1-, 2-, and 5-methyl isomers respectively) with vinyl acetate (uncatalysed) and with a a-chloroacrylonitrile (cupric fluoroborate catalysed) have been examined. Conversion of the initial adducts so obtained to the corresponding methylnorborn-5-en-2-ones (211)—(214) revealed a remarkable difference in regio-selectivity in the initial [4 + 2] reactions the uncatalysed (catalysed) reaction product percentages being 13.5 (57), 16(9), 38 (32), and 32.5 (2) respectively. The usual ortho/para orientation is increased by the catalysis, (211) -t- (213) accounting for 89% rather than 57.5 % of the reaction mixture, and the much lower proportion of (213) -t- (214) in the catalysed process (34 % vs. 70.5 %) indicates much less isomerization of 1-methyl-... 

Annulations based on the Diels-Alder reaction continue to be reported. A doubly convergent route utilizes the two conjugated diene moieties of (177) in separate Diels-Alder reactions [(177)- (178) and (179)- (180)]. Another... 

Intramolecular Diels-Alder reactions continue to be of value in carbocycle synthesis. Thermolysis (200OC, PhMe) of 23, prepared from D-galactose, gave octahydronaphthalene 24, 5... 

Anthracyclines.—Diels-Alder reactions continue to be a dominant feature in many approaches to the anthracycline antibiotics. The rather unreactive dienophile (194) takes part in such reactions with o-quinodimethanes to provide... 

New approaches to the intramolecular Diels-Alder reaction continue to be introduced. Mathias Christmann, now at the TU Dortmund, showed (Angew. Chem. Int. Ed. 2008, 47, 1450) that a secondary amine organocatalyst converted the prochiral dialdehyde 19 into the hicycHc diene 20 with high de and ee. Martin G. Banwell of the Australian National University prepared Organic Lett. 2008,10,4465) the triene 21 in high ee by microbiological oxidation of iodobenzene. On warming, 21 was converted smoothly into 22, which was carried on in a formal synthesis of platencin. 

Right from the discovery of the Diels-Alder reaction in 1928, its importance in the synthesis of natural products was recognized. From early syntheses (such as cortisone) to more contemporary examples highlighted previously, the Diels-Alder reaction continues to play a prominent role in the synthesis of complex natural products. 

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