Cyclization intermolecular reactions, enol ethers

In the prostaglandin synthesis shown, silyl enol ether 216, after transmetaJ-lation with Pd(II), undergoes tandem intramolecular and intermolecular alkene insertions to yield 217[205], It should be noted that a different mechanism (palladation of the alkene, rather than palladium enolate formation) has been proposed for this reaction, because the corresponding alkyl enol ethers, instead of the silyl ethers, undergo a similar cyclization[20I],... 

Intermolecular coupling of a vinyl ether with styrene at a carbon anode in methanol is successful, giving a mixture of the cross coupled product and the two homocoupled products [49], Intramolecular coupling between an enol ether and an alkene centre, as in 24 and 25, proceeds to give the cyclized product in good yield [50], Five and six membered rings can be constructed in this way. An easily oxidised vinyl ether group is necessary to initiate the reaction and the second alkene... 

In intermolecular PET processes, radical ions are formed either as close pairs or as free species from neutral molecules (Sch. 1) [2,6]. Most commonly, carbonyl compounds or related derivatives as for example enol ethers, cyclopropyl ketones, and siloxycyclopropanes are used for intramolecular cyclization reactions. With the exception of cycloadditions the ring-building key step is always an intramolecular bond formation. In PET... 

Cycloadditions only proceeding after electron transfer activation via the radical cation of one partner are illustrated by the final examples. According to K. Mizono various bis-enolethers tethered by long chains (polyether or alkyl) can be cyclisized to bicyclic cyclobutanes using electron transfer sensitizer like dicyanonaphthalene or dicyano-anthracene. Note that this type of dimerization starting from enol ethers are not possible under triplet sensitization or by direct irradiation. Only the intramolecular cyclization ci the silane-bridged 2>. s-styrene can be carried out under direct photolysis. E. Steckhan made use of this procedure to perform an intermolecular [4+2] cycloaddition of indole to a chiral 1,3-cyclohexadiene. He has used successfully the sensitizer triphenylpyrylium salt in many examples. Here, the reaction follows a general course which has been developed Bauld and which may be called "hole catalyzed Diels-Alder reaction". 

The ene and Prins reactions are not mechanistically distinct. Coverage will therefore be organized by the nature of the carbonyl compound, with intermolecular reactions presented first, followed by intramolecular reactions. The emphasis will be on material published since the field has been reviewed " and on examples demonstrating the stereo-, regio- and chemo-selectivity of these reactions. Coverage is restricted to the addition of carbonyl and thiocarbonyl compounds to simple alkenes. Addition of carbonyl compounds to vinylsilanes, allylsilanes and enol ethers is covered in the following chapters. Addition of imines and iminium compounds to alkenes is presented in Part 4 of this volume. Ene reactions with alkenes and alkynes as enophiles are covered in Volume 5, Chapter 1.1. Use of aldehydes and acetals as initiators for polyene cyclizations is covered in Volume 3, Chapter 1.6. 

The tropane alkaloid skeleton can be accessed in one pot via domino ene-type reactions of acetone silyl enol ether, the first one of them being intermolecular, with catalytic use of TMSOTf (eq 79). Alternatively, as)mmetric tropinones can be reached by cyclization of 1,3-bis-silyl enol ethers with acyl-iminium triflates. ... 

Tyrrell demonstrated a three step tandem sequence involving an intermolecular Nicholas reaction, intramolecular Nicholas reaction, and a cationic cyclization. Treatment of silyl enol ether 55 with hexacarbonyl(propiolaldehyde diethyl acetal) dicobalt and boron trifluoride provides cobalt-alkyne complex 56. Exposure of this material to tetrafluoroboric acid promotes an intramolecular Nicholas reaction to form the second six-membered ring. Alkyne decomplexation with ceric ammonium nitrate enables the final cyclization step to yield the target tricycle 57." ... 

Since enol silyl ethers are readily accessible by a number of methods in a regioselective manner and since the trialkylsilyl moiety as a potential cationic leaving group facilitates the termination of a cyclization sequence, unsaturated 1-trialkylsilyloxy-1-alkenes represent very promising substrates for radical-cation cyclization reactions. Several methods have been reported on the synthesis of 1,4-diketones by intermolecular oxidative coupling of enol silyl ethers with Cu(II) [76, 77], Ce(IV) [78], Pb(IV) [79], Ag(I) [80] V(V) [81] or iodosoben-zene/BFa-etherate [82] as oxidants without further oxidation of the products. 

Alkylation of the enolate of (138) with methallyliodide gave the product (149) whose stereochemistry was assigned on the basis of equilibration experiment. It was converted to the dione (150) by oxidation with osmium tetrooxide and sodiumperiodate. The aldol cyclization of (150) effected with sodium hydride and trace of t-amyl alcohol in refluxing benzene afforded the enone (151) in 88% yield. Normal protic conditions (sodium hydroxide, ethanol) were not effective in this transformation. All attempts for its conversion to aphidicolin (148) by intermolecular additions proved fruitless and therefore were turned to intramolecular methods. Molecular models show clearly that the top face of the carbonyl group is less hindered to nucleophilic attack than is the bottom face. Thus the reduction of (151) with lithium aluminium hydride afforded the alcohol (152) whose vinyl ether (153) was subjected to pyrolysis for 2 hr at 360 C in toluene solution containing a small amount of sodium t-pentoxide to obtain the aldehyde (154) in 69% yield. Reduction and then tosylation afforded the alcohol (155) and tosylate (156) respectively. Treatment of this tosylate with Collman s reagent [67] (a reaction that failed in the model system) afforded the already reported ketoacetonide (145) whose conversion to aphidicolin (148) has been described in "Fig (12)". 

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