Regioselectivity Diels-Alder additions

Vinyl sulfones are the most versatile and widely used sulfur substituted dienophiles. They may serve as both activated ethylene and terminal alkene equivalents in highly regioselective Diels-Alder additions to classical , i.e. electron-rich, 1,3-dienes. The sulfonyl moiety facilitates the introduction of further functionality into the cycloadducts and can be easily removed by mild reduction (Scheme 16). These features have been exploited in a synthesis of the terpenoid zingiberenol (56) (Scheme 17). ... 

On the other hand. Table 6.2 predicts the regioselectivity considering the frontier orbital contributions, [24] and is very useful in designing syntheses in which the key step involves a Diels-Alder addition. 

A review of Claisen rearrangements in aqueous solution has appeared. The synthesis of natural products utilizing tandem Diels-Alder additions with sigmatropic rearrangement processes has been reviewed, and a brief review of the regioselective synthesis of coumarins, quinolones and thiocoumarins with 3,4-fused pyran or furan ring systems by the Claisen rearrangement has been presented. ... 

Scheme 10.26 Regioselective tethered double Diels-Alder-additions to Q,...

Another highlight of the period under review is the report of the total synthesis of the tricyclic alkaloid fawcettimine (22) (Scheme 2).9 Lewis-acid-catalysed Diels-Alder addition of butadiene to 2-allyl-5-methylcyclohex-2-enone provided the ds-octalone (23), which was modified as indicated to give the dialdehyde (24). After considerable experimentation, conditions were defined which led to regioselective ring-closure in the desired direction. The unsaturated aldehyde was treated directly with the Wadsworth-Emmons reagent to provide... 

The oxadiazinone (50), obtained from the pyrimidine (49), undergoes a hetero Diels-Alder addition with carbon dioxide elimination on heating with enamines to yield the 6-alkylated lumazine derivatives regioselectively (Scheme 21) [95JHC807],... 

Fig. 15.28. RegioseLective Diels—Alder reactions with a 2-substituted diene II selectivity increase by way of addition of a Lewis acid.

Wiberg and coworkers published relative rate constants and the products of reaction of silene 6 with a number of alkenes and dienes in ether solution at 100 °C6 106-108. These data are listed in Table 2 along with an indication of the type of product formed in each case. As is the norm in Diels-Alder additions by more conventional dienophiles, the rate of [2 + 4]-cycloaddition of 6 to dienes increases with sequential methyl substitution in the 2- and 3-positions of the diene, as is illustrated by the data for 2,3-dimethyl-1,3-butadiene (DMB), isoprene and 1,3-butadiene. The well-known effects of methyl substitution at the 1- and 4-positions of the diene in conventional Diels-Alder chemistry are also reflected with 6 as the dienophile. For example, lruns-1,3-pen tadiene reacts significantly faster than the f/.v-isorrier, an effect that has been attributed to steric destabilization of the transition state for [2 + 4]-cycloaddition. In fact, the reaction of c/s-l,3-pentadiene with 6 yields silacyclobutane adducts, while the trans-diene reacts by [2 + 4]-cycloaddition108. No detectable reaction occurs with 2,5-dimethyl-2,4-hexadiene. The reaction of 6 with isoprene occurs regioselectively to yield adducts 65a and 65b in the ratio 65a 65b = 8.5 (equation 50)106,107. 

The reaction of 3-phenyl-1,2,4,5-tetrazine (166) with phenylalkyne (276) corresponds to the Diels-Alder addition of a 1-substituted diene with a monosubstituted alkyne, and the ortho adduct is expected. Scheme 50 shows that the addition is highly regioselective, leading to the ortho product... 

Nishimura and co-workers used bis(o-quinodimethanes) connected by a.n+dioxa-methylene tethers for the regioselective bis-functionalization by double Diels-Alder addition (Scheme 7-14) [93]. The tethered bis(o-quinodimethanes) were intermediately formed by heating the bis(bromomethyl) derivatives 72a-d together with C, in toluene in the presence of KI and [18]crown-6 [90]. With an 0-(CH2)2-0 tether (72a), the cis-2 and cw-3 bis-adducts 73a and ( )-74a were isolated in 10% and 8% yield, respec-... 

Scheme 7-14 Regioselective bis-functionalizations by double Diels-Alder addition of tethered bis(o-quinodimethanes) to Cgo [93, 94].

The first case was detected by Diederich and coworkers in the context of a regioselectivity investigation of the Diels-Alder addition of 4,5-dimethoxy-... 

Dewar [147,183,184] include zwitterionic forms together with the diradicals (model of the diradicaloids (Fig. 2), which considers the fact that most Diels-Alder additions, although being concerted, form the two new a bonds in a non-synchronous fashion in their transition states). Applied to 51 (and 43), this model predicts a para regioselectivity (52) for the Diels-Alder addition of methyl vinyl ketone due to favorable homoconjugative participation of the non-conjugated alkene moiety [185-189], as shown with the zwitterionic form 52. ... 

The two successive Diels-Alder additions (tandem cycloadditions) of the C2v-symmetrical tetraene 11 are not regioselective, i.e., mixtures of all the possible regioisomeric bis-adducts are obtained when utilizing non-symmetrical dienophiles. There is no control of the monoadduct on the regio-selectivity of the second cyclo addition. As we have seen with the synthesis of daunomycinone, control of the substitution pattern of the two remote rings A and D of the anthracyclinones can be achieved provided a number of adequate manipulations are carried out with the benzoquinone monoadduct of 11. A more efficient and more versatile way to control the regioselectivity of the tandem cycloadditions is through appropriate and stereoselective double substitutions of tetraene 11. 

The reagents (468), (469), and (470) are keten equivalents since they undergo Diels-Alder addition to dienes and the disguised carbonyl group may be subsequently exposed. (Keten itself usually prefers [2 + 2] addition.) A comparison between (468), (469), and (470) for regioselective synthesis of bicyclo[2,2,2]octenenones (471) shows that 2-chloroacrylonitrile is superior in this respect and is also the most reactive. ... 

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