Internal dienes

As in the case of the steroids, introduction of additional nuclear substituents yields morphine analogs of increased potency. The more important of these are derived from one of the minor alkaloids that occur in opium. Thebaine (14), present in crude opium in about one-tenth the amount of morphine, exhibits a reactive internal diene system that is well known to undergo various addition reactions in a 1,4 manner (e.g., bromination). Thus, reaction with hydrogen peroxide in acid may be visualized to afford first the 14-hydroxy-6-hemiketal (15). Hydrolysis yields the isolated unsaturated ketone (16). Catalytic reduction... 

The synthetic utility and generality of the reaction is demonstrated by an intramolecular/intermolecular double allylation using an oo-dienyl aldehyde 38 as a probe. The internal diene terminus selectively undergoes nucleophilic allylation intramolecularly to form a cyclopentanol structure. The terminal... 

Terminal dienes such as butadiene, isoprene and 2,3-dimethylbutadienereactregiospeci-fically with I(Py)2BF4, in the presence of a nucleophile, to give 1,2-iodofunctionalization (equation 58)87. In contrast, internal dienes such as (Z, )-2,4-hexadiene and 1,3-cyclooctadiene yield the 1,4-addition products under similar conditions (equation 59). 

Reactions of pcrfluoroalkadienes with antimony(V) fluoride are similar to those of per-fluoroalkenes. Terminal dienes 1 rearrange with antimony(V) fluoride at 0-20 C selectively to internal dienes 2, in which the terminal trifluoromethyl groups are predominantly in the configuration.3,37,38 Higher temperatures and a threefold excess of catalyst lead to cyclo-pentenes (see Section 5.3.3.1.). 

The result of acid-catalyzed isomerisation of F-dienes depends on several factors structure of substrate, catalyst, and temperature. Action of SbF5 on terminal dienes under mild conditions causes a 1,3 fluorine shift occurring stereoselectively to give trans-, frans-, and cis-, trans- isomers of the corresponding internal dienes [160] ... 

Internal dienes, RCH=CH—(CH2)X—CH=CHR, can also undergo metathesis polycondensation, currently forming poly(l-alkenylene) and the appropriate alkene small molecule [scheme (19)] but at the expense of reduced activity and rate [1] ... 

Other internal dienes are not reactive towards carbolithiation, but enynes are. Although the yields are variable, the products are valuable allenyllithiums such as 13.16... 

Two major classes of intramolecular Diels-Alder (IMDA) reactions may be identified based on the point of connection of the diene to the dienophile (Figure 1). Type I reactions involve trienes with the connecting chain attached to the diene terminus, while type 11 substrates have the dienophile tethered via one of the internal diene positions. 

There are two types of IMDA reactions Type-I and Type-II. Type-I reactions are those in which the diene is attached to the dienophile by a tether from its terminus while in Type-II reactions, the tether is attached to an internal diene position (Figure 4.18). In general, both Type-1 and Type-11 IMDA reactions only occur if the tether contains three or more atoms. This is due to the high level of strain involved in the transition states of reactions of precursors with one or two atoms in the connecting chains. 

Unfortunately, the reaction fails with most a,o>-dienes. One reason for this is that the Ru catalyst isomerizes terminal a,co-dienes such as 1,7-heptadiene to internal dienes which are not reactive. Conjugated dienes such as 1,3-butadiene or 2,3-di-methyl-1,3-butadiene are also unreactive. Further C-C double bonds substituted with electron withdrawing groups such those of methyl acrylate, acrylonitrile, or methyl vinyl ketones do not react. So why are the C-C double bonds of vinylsilanes, vinyl-siloxanes and styrenes reactive Perhaps the simplest explanation is that silicon and... 

Aryl nitroso-compounds make good dienophiles but are somewhat unstable. Keck and his co-workers have shown that they can be masked as the anthracene adduct and then smoothly released and transferred to an internal diene [e.g. (44) - (45)]. ° Further elaboration of (45) yielded the alkaloids ( )-heliotridine (46) and ( )-retronecine (47). 

In 1991, Billups etal. reported the DA reactivity 2,5-cyclo [4] dendralene 138, a compound that closely resembles the radialenes (see Chapter 4), both in structure and reactivity (Scheme 12.29) [37]. Unsurprisingly, when treated with an excess of l-bromo-2-chlorocyclopropene, a preference for addition at the more electronically activated internal diene site was observed, and a mixture of the mono and bis-adducts 140 and 141 was isolated in 65% overall yield. 

An orbital representation (Figure 14-9) clearly shows bond formation by overlap of the p orbitals of the dienophile with the terminal p orbitals of the diene. While these four carbons rehybridize to sp, the remaining two internal diene p orbitals give rise to the new TT bond. 

Stirring a solution of acetonide 256 in a 1 1 mixture of dichloromethane and trifluoroacetic acid for 15 min at room temperature resulted in the stereoselective formation of cycloadduct 260 as a single stereoisomer in approximately 60% yield. The product contains the 5,7-bicyclic carbon skeleton of rameswaralide 255. Presumably, the reaction proceeded by hydrolysis of the acetonide to give diol 257, which then underwent ionization to afford the furfurylic cation 258. This cation can then undergo [4-1-3] cycloaddition, either in a concerted or stepwise manner, with the internal diene, resulting in cation 259. Lastly, rearoma-tization followed by proton loss would afford cycloadduct 260. This is a unique and rare example in which a furfuryl cation participates in [4-1-3] cycloaddition processes and is also completely stereoselective [126]. 

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