Dienes oxygen-substituted

Whereas tropones usually act as dienes in cycloaddition reactions (Section 5.4), tricarbonyl (tropone) iron 59 displays a reactivity that is almost identical to that of a normal enone. High pressure cycloadditions of 59 with 1-oxygen substituted dienes 60 gave the desired cycloadducts 61 in good to excellent yields (Equation 5.9). The subsequent decomplexation of the cycloadducts has been accomplished by treatment with CAN [20]. 

Fallis and coworkers studied Jt-facial selectivity in the reactions of series of 5-substituted 1,2,3,4,5-pentamethylcyclopentadienes Cp -X. They reported that the diene 5 (Cp -X X = SCH3) with maleic anhydride proceeded more slowly than that of the 5-oxygen substituted cyclopentadienes 6 and 7 (Cp -X X = OH, OCH3), where the HOMO of the diene 5 lies higher than those of 6 and 7 [7, 8] (Table 2). These results seemed to suggest that in the case of the reaction of 5 the NHOMO considerably contributed to the reactions. 

In a synthesis of gibberellic acid, a diene and quinone, both with oxygen-substituted side chains, gave the initial intermediate. Later in the synthesis, an intramolecular D-A reaction was used to construct the A-ring. 

The zirconocene catalysts described above are very oxophilic, which provides several synthetically useful transformations. Oxygen substitution at the al-lylic or homoallylic position of an olefin substrate allows for excellent regio-and diastereocontrol in the ethyl magnesiation reactions of a-olefins and dienes [21]. When 29 is substituted with a hydroxyl group (29a), syn 30a is favored over anti in a 95 5 ratio, while substitution with OCH3 (29b) reversed the diastereoselectivity to 11 89 (Eq. 6). Use of THF in place of diethyl ether as the reaction solvent for the reaction of 29a lowered the overall diastereo-... 

The most common procedure is ozonolysis at -78 °C (P.S. Bailey, 1978) in methanol or methylene chloride in the presence of dimethyl sulfide or pyridine, which reduce the intermediate ozonides to aldehydes. Unsubstituted cydohexene derivatives give 1,6-dialdehydes, enol ethers or esters yield carboxylic acid derivatives. Oxygen-substituted C—C bonds in cyclohexene derivatives, which may also be obtained by Birch reduction of alkoxyarenes (see p. 103f.), are often more rapidly oxidized than non-substituted bonds (E.J. Corey, 1968 D G. Stork, 1968 A,B). Catechol derivatives may also be directly cleaved to afford conjugated hexa-dienedioic acid derivatives (R.B. Woodward, 1963). Highly regioselective cleavage of the more electron-rich double bond is achieved in the ozonization of dienes (W. KnOll, 1975). 

Scheme 52 and Table 6 emphasize the beneficial influence of high pressure on the Diels-Alder reactions of (Lewis acid sensitive) nitrogen- or oxygen-substituted dienes (221) to acrylates (222) cf. entries 1/2 and 3/4). ... 

Alkoxy-1,3-dienes and 2-alkoxy-l,3-dienes undergo addition of dichlorocarbene to the more remote double bond or to the oxygen-substituted double bond, respectively. For example, 1 -alkoxy-1,3-diene 5 gives cyclopropane 6, and 2-alkoxy-l, 3-diene 7 gives cyclopropane 8. ... 

Oxygen-substituted Dienes 4.1.3.2 Nitrogen-substituted Dienes 4.133 Sulfur-substituted Dienes... 

Oxygen-substituted dienes generally afford highly regioselective Diels-Alder eyeloadditions. This is a hallmark of the Danishefsky dienes [14] (Seheme 6.4). 

Carbohydrate Dienophiles. The most popular carbohydrate dienophiles to date have been pyranoid enones. Examples of Diels-Alder reactions involving carbohydrate 2,3-enones, 3,4-enones, and enolone esters are described below. In landmark studies reported by Fraser-Reid and co-workers, carbohydrate-derived 2,3-enones were shown to react with dienes to give cyclohexopyranosides (7- 3), Derivatives of methyl and ethyl 2,3-dideoxy- a D-g/ycero-hex-2-enopyranosid-4-ulose 1 underwent cycloaddition with butadiene in the presence of aluminum chloride, and with oxygen -substituted dienes in the absence of any catalyst. Annulated pyranosides 2 and 3 were obtained... 

Luckily, both products end up at N-oxide 579 on treatment with methyl iodide and CsF. A subsequent 2,3-sigmatropic reaction led to the oxygen-substituted diene 578 as a useful building block in terpene synthesis. 

Danishefsky found that alkoxy- and silyloxy-substituted dienes such as 47 (Danishefsky s diene see Scheme 17.10) sei-ve as excellent 4jr-components in cycloaddition reactions with aldehydes catalyzed by a broad range of Lewis acids [43, 44, 106, 107]. The cycloaddition between 47 and the ribose-derived aldehyde 200 in the presence of the NMR shift reagent Eu(fod)3 (201) as a mild, Lewis acidic catalyst [108] furnished 202 as the only observed product in 85 % yield (Equation 23) [109]. Danishefsky utilized this family of oxygen-substituted dienes to access natural and unnatural hexoses [44, 106, 110]. As a demonstration of the general synthetic strategy, diene 203, bearing a 1-phenmenthyl auxiliary, was utilized in combination with Eu(hfc)3 (204) to prepare L-glucose (206, Scheme 17.28). 

Hetero-Diels-Alder cycloadditions of oxygen-substituted dienes have also been used for the construction of polyketide-derived natural products. This is exemplified in Danishefsky s synthesis of the zinc-sequestering ionophore zincophorin (213, Scheme 17.29) [111]. The MgBr2-mediated, chelate-con-... 

A great advantage of catalyst 24b compared with other chiral Lewis acids is that it tolerates the presence of ester, amine, and thioether functionalities. Dienes substituted at the 1-position by alkyl, aryl, oxygen, nitrogen, or sulfur all participate effectively in the present asymmetric Diels-Alder reaction, giving adducts in over 90% ee. The reaction of l-acetoxy-3-methylbutadiene and acryloyloxazolidinone catalyzed by copper reagent 24b, affords the cycloadduct in 98% ee. The first total synthesis of ewt-J -tetrahydrocannabinol was achieved using the functionalized cycloadduct obtained [23, 33e] (Scheme 1.39). 

Thiophene 1,1-dioxide (61) is too unstable to isolate and dimerizes with loss of S02 to give 3a, 7a-dihydrobenzothiophene 1,1-dioxide (172) in 34%113. However, alkyl-substituted thiophene 1,1-dioxides can serve as dienes in the Diels-Alder reaction, since the aromatic properties of the thiophene nucleus are lost completely and the n-electrons of the sulfur atom are used for forming the bond with oxygen. The sulfones 173-178 are found to react with two moles of maleic anhydride at elevated temperature to give bicyclic anhydrides114. Thus, at high reaction temperature, S02 is split off to give cyclohexadiene... 

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