Bicyclic p,y-unsaturated

The secondary marine metabolite (+)-acetoxycrenulide has unprecedented structural features which prompted L.A. Paquette et al. to embark on its total synthesis. The eight-membered carbocycle of the target was constructed via a Claisen rearrangement. The bicyclic p,y-unsaturated lactone was subjected to Simmons-Smith conditions, that delivered the cyclopropyl ring exclusively from the p-face of the molecule as a result of the predominant ground-state conformation. 

Finally, the presence of a ) -ether or amine group in certain bicyclic P, y-unsaturated ketones alters the course of rearrangement of the latter group. This has been discussed by Cargill 0 al ... 

Eckersley, T.J. and Rogers, N.A.J., Photochemical studies on bicyclic P.y-unsaturated ketones. II. 

Here too there is an enol that tautomerizes to the product. The mechanism is illustrated for the case of p-keto acids,475 but it is likely that malonic acids, a-cyano acids, a-nitro acids, and p,y-unsaturated acids476 behave similarly, since similar six-membered transition states can be written for them. Some a,p-unsaturated acids are also decarboxylated by this mechanism by isomerizing to the p,7-isomers before they actually decarboxylate.477 Evidence is that 36 and similar bicyclic p-keto acids resist decarboxylation.47" In such compounds the... 

Maximally unsaturated azepines feature during the period under review. Cyclisation of the P,y-unsaturated aldehyde (1) by treatment with trifluoroacetic acid, followed by treatment with base (DABCO or DMAP) affords 2//-azepine <95AG(E)I469>. The compound itself is difficult to isolate but it is remarkably stable in solution, no trace of the thermodynamically favoured 3/f-azepine being observed after 48h at room temperature. In addition, the bicyclic adduct (2) is formed, probably arising from [2 + 4] cycloaddition of isobutene formed in situ and the intermediate immonium ion (3). 

Oxidative ring-opening with pyridinium chlorochromate (PCC) gives p, y-unsaturated ketones (equation 24). Formation of chlorinated byproducts could be suppressed by employing certain additives (AgNOj, H20). However, bicyclic cyclopropanes afford only moderate yields. 

The enantioselective hetero-Diels-Alder reactions of a,p-unsaturated acylphosphonates with enol ethers catalyzed by Cu(II)bzT(oxazoline) complexes have been investigated in depth. It was found that Cu(II)bA(oxazoline) complexes activate a,p-unsaturated acylphosphonates to the extent that they undergo facile cycloaddition reactions at low temperature with electron-rich alkenes. For example, dimethyl ( )-l-oxo-2-butenylphosphonate reacts with ethyl vinyl ether in the presence of Cu[(S,5)-t-Bu-box] (OTf)2 complex (10 mol% catalyst) to generate the cycloadduct in 89% yield (Scheme 7.86) with exceptional stereoselectivity (endo/exo = 99/1, 99% ee). Cyclic enol ethers also undergo stereoselective reactions with dimethyl ( )-l-oxo-2-butenylphosphonate. It specifically reacts with 2,3-dihydrofuran in the presence of Cu[(5,5)-t-Bu-box] (OTf)2 to deliver the bicyclic enolphosphonate. Of particular merit is the fact that a large variety of p.y-unsaturated acylphosphonates may be tolerated with no loss in selectivity for the derived cycloadducts. ... 

High quantum and chemical yields of ODPM rearrangements are obtained with substrates in which the P.y-enone chromophore is part of a conformationally rigid molecular assembly which at the same time guarantees adequate orbital overlap of the C=C and G—0 ir-bonds. Whereas in bicyclic and bridged P,-y-unsaturated ketones these prerequisites are widely met, acyclic 3,-y-unsaturated ketones usually rearrange inefficiently since other channels of energy dissipation from the triplet state predominate. Exceptions to this rule are substrates in which the C=C ir-lrand is part of a styrene or an a,3-enone moiety (Section 2.6.3.1). In this context it should also be noted that 3.7 unsaturated aldehydes, except for one case, are ODPM unreactive (Section 2.6.3.2). 

Flash thermolysis of a series of methylated bicyclo[3,2,0]hept-2-ene-7-ones gave dihydrotolualdehydes and tolualdehydes as the major products. The suggested reaction path involved recyclization of a heptatrienal formed from the p,y-unsaturated bicyclic ketones by sequential [2 + 2]cycloreversion to the acyclic ketene and 1,5-hydride shift. 

The photochemical reactions of P,y-unsaturated enones have stimulated intense interest due to their spectroscopic properties, interesting mechanistic implications, and apphcation in organic synthesis. The interest in P,y-enone photochemistry was initiated due to the spectroscopic properties of these enones, which indicated interaction between the two chromophores, which was further enhanced significantly after a novel observation by Buchi and Burgess, who noted that irradiation of the bicyclic compound la leads to the formation of lb (Scheme 1). 

Other classes of nickel-catalyzed [3+2] cycloadditions include the addition of 2-haloacetophenone derivatives to alkynes to produce indenol derivatives (Scheme 3-36). This process likely involves initial oxidative addition to the haloaromatic, followed by alkyne insertion and carbonyl addition. In this case, zinc powder serves as reducing agent to regenerate the active nickel(0) catalyst. A mechanistically intriguing cycloaddition that proceeds without the action of reducing agents is the direct formation of bicyclic products from the addition of unsaturated ketones with alkynes. This process likely involves initial metallacycle formation followed by unusual rearrangement steps unique to the requisite doubly unsaturated carbonyl component. 

The Ir(lll) complex also funchoned as a catalyst in a tandem Nazarov cyclization-Michael addition. The reaction of monocyclic a-alkylidene-P-keto-y.b-unsaturated ester with nitroalkene gave bicyclic cyclopentenones which possessed an alkyl side chain, with high yield and diastereoselectivity (Scheme 11.36) [47]. 

Carretero and co-workers reported that the a-sulfonyl radicals resulting from such radical additions to y-oxygenated-a,P-unsaturated sulfones are useful intermediates for the generation of a second carbon-carbon bond via intramolecular addition to a suitably located carbon-carbon double bond.46,47 The highly functionalized acyclic y-hydroxy vinyl sulfone 68 underwent a novel cascade process, based on two sequential radical cyclizations, affording the bicyclic compounds 69 and 70 in good yield (Scheme 18). 

The results can be rationalized as follows the first cyclization of substrate 68 gave a mixture of a-sulfonyl radical intermediates 71 and 72 (Scheme 19). These then underwent a second fully stereoselective cyclization to give the cis- and franr-fused bicyclic products 69 and 70, respectively, as single isomers. Such sequential transformations, in which two carbon-carbon bonds are formed in a single step, are attractive methods for enhancing the efficiency of organic synthesis. As y-hydroxy-a,P-unsaturated phenyl sulfones can be prepared in enantiomerically pure form,48 this procedure should be readily applied to the synthesis of enantiomerically pure bicyclic products. 

Polycyclic y-lactones. An intramolecular version of the formation of y-lactones by reaction of an alkene with acetic acid and manganese(HI) acetate (1) (6, 355-356) provides a general route to polycyclic y-lactones. Thus the unsaturated p-keto acid 2 cyclizes to the ds-bicyclic y-lactone 3 when warmed in acetic acid with 1 (1.3 equiv.)2... 

It is interesting that upon illumination, the complex RhCl(CO)(PMc3)2 catalyzes carbonylation of liquified propane at room temperature to yield butanal with high regioselectivity [48], The reaction of some C-H compounds with carbon monoxide and ethylene or other olefins in the presence of metal carbonyls results in carbonylation at a C-H bond [49] (Scheme IV-25). The carbonyl Ru3(CO)i2 catalyzes the cyclocarbonylation of yne-aldehydes to bicyclic a,p-unsaturated y-butyrolactones [49d],... 

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