Alkene acids, cyclization

Unsaturated acyliutn ions generated from alkenic acids or anhydrides react with alkenes to produce cy-clopentenones (equation 4i).88.i78-i8i with cycloheptene the major products arise from ring contraction. Again, it is unclear whether these reactions proceed via direct cyclization of (76) or a Nazarov cycliza-tion. 

Nazarov and Related Cationic Cyclizations 63.7A Alkenic Acid Chlorides and Bromides... 

Reaction of a divinyl alkyne such as 137 with aqueous acid generates a conjugated ketone (138), via hydration of an intermediate vinyl cation. Subsequent treatment with a mixture of phosphoric and formic acids leads to a new, oxygen-stabilized carbocation (139), which reacts with the adjacent alkene (a cyclization reaction) to form 140. Elimination led to the conjugated ketone (141). 3 This cationic ring-closing reaction... 

In addition to alkenes or alkanols, ketone 72, can be dehydrated as easily as an alcohol providing an alkene after cyclization (see compound 73). Other leaving groups, which can provide a cationic species would also be able to promote cyclization carboxylic acids could serve this role, epoxides or... 

Bromolactonization of alkenic acids has been the subject of extensive investigation.Cyclizations can be performed on the carboxylic acid salts as well as the free acids. Thallium(I) salts have proven to be especially efficacious. Treatment of the mercury(II) salts with bromine proceeds via a radical mechanism and provides the expected products in substrates where normal bromolactonization conditions lead to rearrangement (eq 10). Other sources of electrophilic bromine can also give different products (eq 11). ... 

Type B Syntheses (C—C—N + C—S).—Thiocyanation of oi -unsaturated jS-amino-ketones R3HNCRi=CHC(0)R2 (Ri = Me or Ph R= = Me, Ph, or OEt R = H, Me, or Ph) with cyanogen occurs at the olefinic H-atom, or gives a 2-imino-A -thiazoline, or its rearranged isomer (8), depending upon the structure of the starting material and reaction temperature. The thiocyanated alkenes are cyclized to mixtures of the cyclized products in acid or alkali, or else thermally. 

A interesting and useful reaetion is the intramolecular polycyclization reaction of polyalkenes by tandem or domino insertions of alkenes to give polycyclic compounds[l 38]. In the tandem cyclization. an intermediate in many cases is a neopentylpalladium formed by the insertion of 1,1-disubstituted alkenes, which has no possibility of /3-elimination. The key step in the total synthesis of scopadulcic acid is the Pd-catalyzed construction of the tricyclic system 202 containing the bicyclo[3.2. Ijoctane substructure. The single tricyclic product 202 was obtained in 82% yield from 201 [20,164). The benzyl chloride 203 undergoes oxidative addition and alkene insertion. Formation of the spiro compound 204 by the intramolecular double insertion of alkenes is an exam-ple[165]. 

Allylic carbonates are most reactive. Their carbonylation proceeds under mild conditions, namely at 50 C under 1-20 atm of CO. Facile exchange of CO2 with CO takes place[239]. The carbonylation of 2,7-octadienyl methyl carbonate (379) in MeOH affords the 3,8-nonadienoate 380 as expected, but carbonylation in AcOH produces the cyclized acid 381 and the bicyclic ketones 382 and 383 by the insertion of the internal alkene into Tr-allylpalladium before CO insertion[240] (see Section 2.11). The alkylidenesuccinate 385 is prepared in good yields by the carbonylation of the allylic carbonate 384 obtained by DABCO-mediated addition of aldehydes to acrylate. The E Z ratios are different depending on the substrates[241]. 

Alkanes, dipurin-8-yl-synthesis, 5, 574 Alkanes, poly-N-pyrazoIyl-synthesis, 5, 320 Alkanoic acids, tetrazolyl-anti-inflammatory activity, 5, 835 Alkanoic acids, 4-thienyi-cyclization, 4, 905-906 Alkene metathesis mechanism, 1, 668 Alkenes activated... 

An analogous Lewis acid catalyzed cyclization of the oi-acctoxy derivatives 3 gives rise to one pair of diastereomers of 4 in the case of the ( )-alkenc, while the (Z)-alkene affords a diastereomeric mixture of (2S, 3/J, 4/J )-4 (major product) and (2,S, 3,S, 4/ )-4 (minor product)90. 

Finally, in a study of Lewis-acid-catalysed intramolecular attack of acetals on vinylsilanes, to produce allylically unsaturated oxacyclics, it has been found (75) that the alkene stereochemistry can control the mode of cyclization in an exo- or endocyclic sense, as shown here ... 

Under certain conditions, amides can add directly to alkenes to form N-alkylated amides. 3-Pentenamide was cyclized to 5-methyl-2-pyrrolidinone by treatment with trifluorosulfonic acid. Acylbydrazine derivatives also cyclized in the presence of hypervalent iodine reagents to give lactams. When a carbamate was treated with Bu3SnH, and AIBN, addition to an alkene led to a bicyclic lactam. 

An important cyclization procedure involves acid-catalyzed addition of diene-ketones such as 58, where one conjugated alkene adds to the other conjugated alkene to form cyclopentenones (59). This is called the Nazarov cyclization Cyclization can also give the nonconjugated five-membered ring. ... 

The earliest reported Fxs were the result of the reaction of nitrous acid with naturally occurring alkenes being the identified intermediate a a-nitrooxime that suffers dehydration with cyclization. Apart from these conditions, the most recent Fxs synthesis descriptions have involved reactions between alkenes and dinitrogen trioxide (Fig. 3), nitroalkanes and aluminum trichlo-... 

Formation of chlorohydrins from alkenes Chlorination with solvent participation and cyclization Formation of chlorohydrins in acidic aqueous solution. 

Friedel-Crafts alkylation can occur intramolecularly to form a fused ring. Intramolecular Friedel-Crafts reactions provide an important method for constructing polycyclic hydrocarbon frameworks. It is somewhat easier to form six-membered than five-membered rings in such reactions. Thus, whereas 4-phenyl-1-butanol gives a 50% yield of a cyclized product in phosphoric acid, 3-phenyl-1-propanol is mainly dehydrated to alkenes.43... 

---