Unsaturated acids cyclization

The few exceptions to this general rule arise when the a-carbon carries a substituent that can stabilize carbonium-ion development well, such as oxygen or sulphur. For example, 1-trimethylsilyl trimethylsilyl enol ethers give products (72) derived from electrophilic attack at the /J-carbon, and the vinylsilane (1) reacts with a/3-unsaturated acid chlorides in a Nazarov cyclization (13) to give cyclopentenones such as (2) the isomeric vinylsilane (3), in which the directing effects are additive, gives the cyclopentenone (4) ... 

On the other hand, y, 8-unsaturated acids give lactones that involve cyclization without decarboxylation. 

As in the case of linear peroxidation products, the initiation step of the formation of isoprostanes is the abstraction of a hydrogen atom from unsaturated acids by a radical of initiator. Initiation is followed by the addition of oxygen to allylic radicals and the cyclization of peroxyl radicals into bicyclic endoperoxide radicals, which form hydroperoxides reacting with hydrogen donors. 

Scheme 28 Cathodic cyclization of unsaturated acids in the presence of triphenyl phosphine alkyl, H, aryl, R H, aryl, yields 11 -49%.

When p-arylserines rather than glycine are used as the starting amino acid, cyclization occurs concomitant with dehydration to afford the corresponding unsaturated 5(4//)-oxazolone." ... 

Two papers describing the intramolecular ene cyclization for the preparation of C6 functionalized pteridines has appeared. Thus 4-amino-5-nitrosopyrimidines such as 249 reacted with a,/3-unsaturated acid chlorides acylating at the 6-amino group group to afford nitrosoamides 250 which on thermolysis in toluene underwent the pericyclic cyclization and subsequent loss of water to afford a mixture of the E- and Z-isomers of the 6-oxopteridine 251 in good yield <2006HCA1140, 2007HCA521>. 

Oxetanones can be generally prepared by displacement processes on various /3-substituted carboxylic acids or by halolactonization of /3,y-unsaturated acids. A very general and reliable method consists of treatment of a /8-hydroxy acid with benzenesulfonyl chloride and pyridine at 0°C (equation 91). The yields of /3-lactones are usually in excess of 80% (79JOC356, 74JOC1322). An alternative method involves cyclization of the benzenethiol ester of a /3-hydroxy carboxylic acid by means of mercury(II) methanesulfonate in acetonitrile (equation 92). The yields were excellent in the two cases reported (76JA7874). 

Synthesis according to the first approach requires quinazoline precursors with an appropriate subtituent on position 2 or 3 which, upon cyclization, forms the terminal pyrimidine ring. Thus, 2-aminoquinazolin-4(3//)-one (505) underwent cyclization with a,j8-unsaturated acids (78KGS105 80MI1) or their chlorides (87KGS1527) to the pyrimido... 

Alkene acylation may be used in the synthesis of cyclic products by appropriately selecting the alkene and the acid derivative. When a,P-unsaturated acid halides react with cycloalkenes, the intermediate undergoes cyclization to yield octalones and indanones 112... 

Both diethyl acetylenedicarboxylate and chlorofumarate have found frequent application as the second component, but other unsaturated acid derivatives are acceptable. The initially formed aryloxyalkenoic acids or their esters (471) are readily cyclized with acid or acetyl chloride. 

Anisole and many of its derivatives react with an unsaturated acid chloride in the presence of aluminum chloride to yield a chromanone (20LA(42l)l). The two most widely used acid halides are but-2-enoyl (crotonyl) and 3-methylbut-2-enoyl (3,3-dimethylacryloyl) chlorides. In cases where the uncyclized intermediate, an acrylophenone, is isolated, cyclization may be achieved under acidic or basic conditions, or even simply by distillation (Scheme 220) (52G155). 

A similar coupling with a,p-unsaturated acid chlorides provides p-silyl divinyl ketones (Nazarov reagents). These ketones cyclize in the presence of a Lewis acid, particularly BF3 etherate, to cyclopentenones, generally with retention of the silyl group. 

The cyclization of a,/J-unsaturated amides to lactams has recently been reported by Chapman.388 Irradiation of cis-a-phenylcinnamide in benzene in the absence of oxygen leads to the formation of cis- and bww-3,4-diphenylazetidin-2-one [Eq. (99)] in low yield, with the former predominating. a,/J-Unsaturated acids are similarly converted into the corresponding / -lactones. 

Acylation of alkynes, cyclopentenones. Acylation of alkynes with a,a-disubsti-llllotE/f, y-unsaturated acid chlorides, catalyzed with A1C13> results in 5,5-disubstituted-2-cyclopentenones by an unexpected intramolecular cyclization-rearrangement.2 Example ... 

Cyclopentenone annelation (cf. 10,444). The reagent undergoes a Nazarov-type cyclization with an a,/S-unsaturated acid chloride to give an annelated 3-phenylthio-cyclopentenone. This reaction was used to prepare the bicyclic cyclopentenone 3, a useful intermediate in synthesis of cyclopentenoid natural products, such as hirsutene (4).3... 

The mechanism of selenocyclization of yS,y-unsaturated acids and their derivatives has been studied. The reactions of ( )-4-phenylbut-3-enoic acid and its silyl and alkyl esters (15 R = H, SiMe3, alkyl) with benzeneselenenyl halide PhSeX (X = Cl, Br) have been examined by VT-NMR and in situ IR spectroscopic methods. Whereas the reactions of the acid in the presence of a base were irreproducible and complicated, reactions of the silyl esters were clean and spontaneously and quantitatively afforded the corresponding chloroselenylation adduct at -70 °C as a single (Markovnikov) isomer. This adduct underwent three processes as the temperature was raised (1) reversal to the starting materials, (2) isomerization to the anti-Markovnikov product, and (3) cyclization to the selenolactone (16). All of these processes are believed to proceed via a seleniranium ion, the intermediacy of which was established by independent synthesis and spectroscopic identification. The reversible formation of chloroselenide adducts was unambiguously established by crossover experiments. The reaction of (15) with PhSeBr was found to be rapid but thermodynamically unfavourable at room temperature.29... 

The second method of preparation (shown in Scheme 2) depends on treating dehydroepiandrosterone (prepared from cholestrol or sitosterol) with acetylene to form the 17a-ethnyl-17p-hydroxy derivative, which is carbonated to the 17a-propionic acid. Reduction of the unsaturated acid in alkaline solution yields the saturated acid, which cyclizes to the lactone on acidification. Bromination to the 5,6-dibromo-compound, followed by oxidation of the hydroxyl group to the ketone, and then dehydro-bromination to the 7a-hydroxyl derivative, produces spironolactone when esterified with thiolacetic acid. 

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