Fenestranes

The reaction of the allylic acetate with a diene system 784 affords the poly-fused ring system 785 by three repeated alkene insertions[487]. An even more strained molecule of the [5.5.5.5] fenestrane 788 has been constructed by a one-pot reaction in a satisfactory yield by the Pd-catalyzed carbonylation-cycliza-tion of 786 without undergoing elimination of /3-hydrogen in the cr-alkylpalla-dium intermediate 787 owing to unfavorable stereochemistry for syn elimination[488]. 

An example for the synthetic potential is the formation of a fenestrane skeleton 11 from the open-chain compound 10 by a cascade of two consecutive intramolecular Pauson-Khand reactions, the yield in this case is however only 9% J... 

An illustrative example for the usefulness of the Weiss reaction for the construction of complex cyclopentanoid carbon skeletons is the synthesis of the all -cis [5.5.5.5]fenestrane 7 after Cook et al., starting from the a-diketone ... 

It is interesting to note that all previous attempts to utilize the Claisen rearrangement within the carbon framework of the fenestrane system as well as all efforts to prepare a fenestrane in which one of the ring fusions is trans, had not been successful. In Eq. 12.74, a facile rearrangement of fenestrene took place in aqueous pyridine to form a... 

Another elegant fenestrane synthesis, discovered by Keese, is described in Chapter 6. 

Scheme 3.77. Domino radical cyclization for the synthesis of fenestranes.

The Pauson-Khand reaction is the Co-induced formation of cyclopentenones from ene-ynes and CO. One impressive example of a domino Pauson-Khand process is the synthesis of fenestrane 6/4-15, as reported by Keese and colleagues [278]. The transformation is initiated by a double Grignard reaction of 4-pentynoic acid 6/4-12, followed by protection of the formed tertiary hydroxyl group to give 6/4-13. The Co-induced polycyclization of 6/4-13 led directly to the fenestrane 6/4-15... 

Chung and coworkers [280] combined a [2+2+1] with a [2+2+2] cycloaddihon for the synthesis of multi-ring skeletons, angular triquinanes, and fenestranes. For the preparation of tetracyclic compounds such a 6/4-17, these authors used diynes as 6/4-16 and CO as substrates (Scheme 6/4.5). Fully substituted alkynes gave low yields, and 1,5- as well as 1,7-dialkynes, did not react... 

The first claimed synthesis of a fenestrane precursor follows a similar route460a) (4.48). In general such intramolecular cycloadditions represent an efficient way of synthesizing centropolycyclanes 460b). 

A domino Pauson-Khand-Reaction was developed by Keese et al. starting from enediyne 155 leading to the shortest synthesis of a fenestrane 157 (scheme 31).1791... 

The process is initiated by a double Grignard reaction of 4-pentynoic acid 153, first with 3-butenyl magnesium bromide and subsequently magnesium acetylide followed by silylation of the formed ter-tiaiy hydroxyl function. The cobalt induced polycy-clization leads directly to the fenestrane 157 interestingly, the reaction halts at the stage of 156 when employing the unprotected alcohol. 

Scheme 31. Synthesis of fenestranes by domino Pauson-Khand reaction...

The synthesis of [4.4.4.4]fenestrane or windowpane has become an active area of research due to the aesthetic appeal of the hydrocarbon and the nature of its central quaternary carbon atom which is expected to be distorted from normal tetrahedral geometry . Ongoing investigations have generated a number of ring-expanded triquinane and tetraquinane ([5.5.5.5]fenestrane) homologs. These molecules form the subject matter of the discussion which follows. 

The Dauben-Walker approach has yielded the smallest and most strained fenestrane known to date Following the intramolecular Wadsworth-Enunons cyclization of 443 which also epimerizes the butenyl sidechain to the more stable exo configuration, intramolecular photocycloaddition was smoothly accomplished to provide 444. Wolff-ELishner reduction of this ketone afforded the Cj-symmetric hydrocarbon 445. Application of the photochemical Wolff rearrangement to a-diazo ketone 446 p,ve 447. 

This strategy has been successfully employed for the construction of [5,5,5,5]-fenestranes (Equation (36)), as well as for the synthesis of complex natural products such as terpenoids, for example, hirsutene (Equation (37)). ... 

Most importantly, condensed and polycyclic cyclobutane bridgehead derivatives have been synthesized using the photochemical method (Houben-Weyl, Vol. 4/5 b, p 1185). Derivatives of the hitherto smallest and most highly strained [4.4.4.5]fenestrane, methyl 1-methyl-all-ra-[4.4,4.5]fenestrane-7-carboxylate (3a), were formed by irradiation of (la,3/8,6a,9/ )-5-diazo-l-methy][4.4.4.5]fenestran-4-one in methanol.37 Other fenestranes 3b38 and 439 were also formed by irradiation of the corresponding diazocarbonyl precursors. 

FA techniques, see Flowing afterglow techniques /-block metallaboranes future research, 3, 257 overview, 3, 133-174 /-block metallacarboranes characteristics, 3, 246 overview, 3, 175-264 FBS, see Fluorous biphasic system [5,5,5,5]-Fenestranes, via carbonylative carbocyclization,... 

Keese and co-workers [162,163] have constructed molecules with the intention of producing [5.5.5.5]fenestranes via intramolecular meta photocy-... 

These intramolecular meta-addition processes were utilized in the key steps for the total synthesis of a-cedrene [245], isocomene [246], hirsutene [247], coriolin [248], silphinene [249], rudmollin [250], laurenene [251], and fenestranes [252-254], which were synthesized by Wender s and Keese s groups (Scheme 58). 

Therefore only some (subjectively) representant examples will be mentioned. The syntheses of both cubane (88) and [ 4,4 A A ]-fenestrane (89) include an (intramolecular) photocycloisomerization step of an appropriate alkenyl-cycloalkenone (Sch. 24) [6,84]. 

Fenestranes represent particular targets. Like steroids, they are con-formationally rigid, strained, and chemically robust molecules. These properties make them interesting for application in various fields [78]. Fenestranes 103 [79], 104 [80], and 105 [78] (Sch. 20) were synthesized via met a photocycloadditions as photochemical key step. 

Another example of geometrical consequences of intramolecular interactions can be demonstrated by the structure of a few carbon-cage molecules. Whereas the adamantane molecule [57] has only one kind of C-C distance, due to its high symmetry, there is a distribution of C-C distances in, for example, heptacy-clotetradecane (Figure 12(a)) [67] and fenestrane (Figure 12(b)) [68] due to intramolecular nonbonded interactions. 

These allylpalladation-acylpalladation cascade bicyclization reactions have been applied mainly by Oppolzer to the synthesis of various natural products including (zb)-pentalenolactone E methyl ester [152], 3-isorauniti-cine [153], ( )-coriolin [154], and ( )-hirsutene [155]. Their application to the syntheses of [5.5.5.5]fenestrane derivatives by Keese [156,157] (Scheme 63) is also noteworthy. 

A spectacular application allowed the synthesis of fenestranes by a three-step sequential action of cobalt nanoparticles and a palladium catalyst [131]. The cascade reaction started with a PKR of enyne 105, accomplished by the cobalt catalyst giving 106, followed by the formation of allyl-7r3 palladium complex 107 which reacted with a nucleophile derived from diethyl malonate, to give enyne 108. The final step was a second PKR that gave 109 in good yield. They used cobalt nanoparticles as with Co/charcoal the third step did not take place, apparently due to damage in this catalyst after the allylation step (Scheme 31). 

Scheme 31 Three-step one pot synthesis of fenestranes from an enyne and an alkyne...

Several groups have developed the combination two or more PKR or PK-type reactions in the same reaction step. The multiplication of the synthetic power of this transformation has found immediate application for the synthesis of natural [S.5.5.5] systems called fenestranes. Starting materials have been enediynes that give two [2 + 2 + 1] cycloadditions. The extension of the reaction to triynes has led to interesting tandem processes that may include [2 + 2 + 2] cyclizations. Other cycloadditions like the Diels-Alder have also been combined with the PK. 

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