Acylation polyenes

Other, removable cation-stabilizing auxiliaries have been investigated for polyene cyclizations. For example, a sdyl-assisted carbocation cyclization has been used in an efficient total synthesis of lanosterol. The key step, treatment of (257) with methyl aluminum chloride in methylene chloride at —78° C, followed by acylation and chromatographic separation, affords (258) in 55% yield (two steps). When this cyclization was attempted on similar compounds that did not contain the C7P-silicon substituent, no tetracycHc products were observed. Steroid (258) is converted to lanosterol (77) in three additional chemical steps (225). 

Acyl radicals can be generated and they cyclize in the usual manner. A polyene-cyclization reaction generated four rings, initiating the sequence by treatment of a phenylseleno ester with Bu3SnH/AIBN to form the acyl radical, which added to the first alkene unit. The newly formed carbon radical added to the next alkene, and so on. Acyl radicals generated firom Ts(R)NCOSePh derivatives cyclize to form lactams. ... 

Some excellent examples of cationic polycyclizations, especially in the field of steroid synthesis, were described in Chapter 1. However, these polycyclizations can also be performed using a radical as initiator. Such reactions can be divided into those based on serial 6-mdo-trig cyclizations from polyene acyl precursors [92], radi-... 

We have previously emphasized the activation of organic molecule via coordination. The converse may also be true, such that transition metals may be used as protecting groups for reactive unsaturated functional groups. Thus t 4-metal coordination of a butadiene system deactivates it pjgure 6.27 Butadiene towards Diels-Alder reactions. Friedel-Crafts acylation of free polyenes coordination modes... 

The reaction of iodine azide in acetonitrile with cyclic conjugated dienes and polyenes afforded cis-1,2- or cis- 1,4-diazides80 81 in 80-90% yield, via SN2 reaction of the azide ion with the intermediate trans-/)-iodo azides (Section 1.2.2.2). These diazides were not purified, due to their explosive nature, and their stereochemistry was deduced from the H-NMR spectrum of the cycloadducts obtained with dimethyl acetylenedicarboxylate80,81. Instead, the addition of iodine azide to. V-acyl and 7V-sulfonylindole82-83 and benzofuran83 gave mixtures of trans- and cis-2,3-diazides. 

V.Z. Lankin, A.K. Tikhase and Yu.G. Osis, Simulation of the enzymic reactions sequence in liposomes including free radical peroxidation, reduction and hydrolysis of polyenic acyls of phospholipids for investigation of this processes influence on the membrane structure. Biochemistry (Moscow) 2001(in press). 

Zhang, J., and Xu, X., Total synthesis of 6-ep/-sarsolilide A, Tetrahedron Lett., 41, 941, 2000. Boehm, H.M.. I landa, S., Pattenden, G., Roberts. L.. Blake, A.J., and Li, W.-S., Cascade radical cyclizations leading lo steroid ring constructions. Regio- and stereo-chemical studies using ester- and fluoroalkene substituted polyene acyl radical intermediates.,/. Chem. Soc., Perkin Trans. 1, 3522, 2000. Hampton, A.. Sasaki, T, and Paul, B., Synthesis of 6 -cyano-6 -deoxyhomoadenosine-6 -phosphonic acid and its phosphoryl and pyrophosphoryl anhydrides and studies of their interactions with adenine nucleotide utilizing enzymes, J. Am. Chem. Soc.. 95. 4404, 1973. 

There are many synthetic examples that use radical cyclization as a key step, and the radical precursor is not limited to iodides or bromides. In Pattenden s synthesis of pentalenene, conjugated selenyl ester 156 was treated with Bu3SnH and AIBN to give a 45% yield of tricyclic ketone 159. Loss of PhSe generated the acyl radical 157, which exists in equilibrium with the ketene radical 156. Radical cyclization via the latter intermediate leads to 159. Cyclization via aryl radicals is also possible. In Schultz s synthesis of hexahydro-phenanthren-2-one derivatives, " aryl bromide 160 was cyclized to 161 in 78% yield under standard conditions. Radical cascade reactions have become quite popular for the synthesis of polycyclic ring systems. In these reaction, polyenes are subjected to radical cyclization, generating tricyclic or even tetracyclic ring systems. 5 Chiral auxiliaries have been used effectively in radical cyclization reactions. ... 

Direct electrophilic attack on the exo side of a coordinated diene is also possible, even to complexes of modestly electron-rich metal centers. For example, Friedel-Crafts acetylation of (cyclohexa-l,3-diene)Fe(CO)3 gives principally the exo isomer. However, such direct exo attack occurs more commoiJy on the uncoordinated portion of a partially coordinated polyene or polyenyl ligand (recall that uncoordinated olefins and dienes are generally more nucleophilic than coordinated ones). An example of such exo attack on the uncoordinated portion of a pentadienyl ligand is shown in Equation 12.74. In ttiis case, coordination of a CO ligand is thought to displace one or more carbons of the dienyl ir-system from the iron center to trigger exo acylation. Similar results have been reported for electrophilic attack on the uncoordinated portion of the polyene system in [(C )Fe(CO)3]". ... 

Acylation of phenols Cyclization of polyenes Hydrolysis of amides COOH = Terminal thiohydantoin hydrolysis... 

Topological resonance energies are Dewar resonance energies comparing cyclic systems to acyclic polyenes within the Hiickel scheme and have been reported for 1-10 as shown in Table 2. " Negative values (in units) indicate reduced conjugative stability relative to acylic models, and this criterion indicates destabilization in all these species. These values are not normalized for different numbers of electrons. 

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