Double cyclization nucleophilic addition

The initial step of olefin formation is a nucleophilic addition of the negatively polarized ylide carbon center (see the resonance structure 1 above) to the carbonyl carbon center of an aldehyde or ketone. A betain 8 is thus formed, which can cyclize to give the oxaphosphetane 9 as an intermediate. The latter decomposes to yield a trisubstituted phosphine oxide 4—e.g. triphenylphosphine oxide (with R = Ph) and an alkene 3. The driving force for that reaction is the formation of the strong double bond between phosphorus and oxygen ... 

The development of methods to effect nucleophilic addition to carbon-carbon double bonds by prior activation with metal cations has been applied, at least in a preliminary way, as a method of pyrrole ring closure. The conversion of butadienes to N-substituted pyrroles can be accomplished in two stages. In acetic add, 1,4-dienes react with PdnCl2 to give tr-allyl complexes with introduction of acetate at C-4. The ir-allyl complexes then react with amines to give a l-amino-4-acetoxy-2-butene (equation 70). When the addition of the amine is carried out in the presence of a silver salt and triphenylphosphine, a pyrrole is isolated, probably by cyclization of the amino-substituted allyl-Pd complex (equation 71) (81CC59). Although this procedure is attractive in terms of the simplicity of the... 

Isomerization of the double bond of geranyl pyrophosphate from to 7 produces neryl pyrophosphate. As shown in Figure 28.3, the carbocation that is formed from neryl pyrophosphate can cyclize to a new carbocation that contains a six-membered ring. Nucleophilic addition of water to this carbocation produces a-terpenol, whereas loss of a proton produces limonene, a monoterpene with a lemonlike odor that occurs in citrus fruits. Further transformations lead to other monoterpenes, such as menthol,... 

Terpene synthases, also known as terpene cyclases because most of their products are cyclic, utilize a carbocationic reaction mechanism very similar to that employed by the prenyltransferases. Numerous experiments with inhibitors, substrate analogues and chemical model systems (Croteau, 1987 Cane, 1990, 1998) have revealed that the reaction usually begins with the divalent metal ion-assisted cleavage of the diphosphate moiety (Fig. 5.6). The resulting allylic carbocation may then cyclize by addition of the resonance-stabilized cationic centre to one of the other carbon-carbon double bonds in the substrate. The cyclization is followed by a series of rearrangements that may include hydride shifts, alkyl shifts, deprotonation, reprotonation and additional cyclizations, all mediated through enzyme-bound carbocationic intermed iates. The reaction cascade terminates by deprotonation of the cation to an olefin or capture by a nucleophile, such as water. Since the native substrates of terpene synthases are all configured with trans (E) double bonds, they are unable to cyclize directly to many of the carbon skeletons found in nature. In such cases, the cyclization process is preceded by isomerization of the initial carbocation to an intermediate capable of cyclization. 

When cyclopropylideneamines 4 are formed under basic conditions by 1,3-dehydrochlorination of a-chloro ketimines 1 in the presence of cyanide ion, the stable hydrogen cyanide adducts 3 can be isolated. This cyclization to yield cyclopropanes only applies to tertiary a-chloro ketimines 1, which with cyanide also give rise to the formation of a a-cyanoaziridine 2, the latter being formed by nucleophilic addition of cyanide across the imino double bond followed by intramolecular nucleophilic substitution. ... 

Compounds with a carbonyl group conjugated to the double bond are conventionally called Michael acceptors. The Michael reaction is a route to a carbon-carbon bond. A nucleophile adds to a Michael acceptor. Together with nucleophilic addition at the carbonyl group, this is the first step of Robinson s cyclization, which is an excellent method for the preparation of medium-sized (and especially six-membered) rings. 

The chromium complexes of styrene and the related arenes can be susceptible to nucleophilic addition at the p-position of the double bond. The conjugate addition of nucleophiles at the p-position generates the tricarbonylchromium-stabilized benzylic carbanion and the generated benzylic carbanion could be further trapped with electrophiles. An intramolecular cyclization to the chromium complexed styrene double bond gave tricyclic compound (Eq. 4) [4]. 

Another Ilae pyrrole cyclization involves nucleophilic addition of amines to electrophilic 1 3-dienes. The reaction pattern has been realized with 2,3-diphenylsulfonyl-1,3-butadiene and with 2-acetyl-3-phenylsulfonyl-1,3-butadiene <88TL304l, 9lS17l>. Elimination of phenylsullinate, induced by base, introduces one double bond. The second can be introduced by ddq oxidation, as in Scheme 71. In Equation (53), oxidation is evidently the result of the exposure of the compound to the atmosphere. 

It is assumed that hydroxylamine condenses with chloral to give oxime, which then undergoes the nucleophilic substitution with aniline, and hydrolyzes to give oximino intermediate under basic conditions. In the presence of a strong acid, such as concentrated sulfuric acid, the oximino compound cyclizes via nucleophilic addition of aromatic ring to C=N double bond. An illustrative mechanism is provided below. 

This cyclization obviously does not proceed with an alkylation of a cr-alkenylpalla-dium complex but rather with a nucleophilic addition across the triple bond, which is activated by complexation with the arylpalladium halide intermediate. The ( )-configura-tion of the double bond clearly speaks in favor of this mechanism. More details of this reaction are described in Sect V.3.4. 

Diketone anions of 1-aryl-4,4,4-trifluorobutane-l,3-dione (85) undergo nucleophilic addition of sodium acetylide to give tertiary 1,4-alkynediols (86). Double cyclization gives a 2,2 -bifuran. While the mechanism of acetylide addition has not been proved, a likely first step is the formal reaction of two carbanions to give a C-C bond. °... 

As the final conclusion, the authors assumed that a mechanism involving nucleophilic addition of an allene double bond to a phosphinegold-complexed phos-phinegold acetylide to be more likely than an oxidative cyclization or simple nucleophilic addition to phosphinegold-complexed substrate. The corresponding catalytic cycle for the more probable pathway is shown in Scheme 4.9. 

In agreement with these analyses, it was found that conqiound S was unreactive toward base-catalyzed cyclization to 6, even though the double bond would be expected to be reactive toward nucleophilic conjugate addition. On the other hand the acetylene 7 is readily cyclized to 8 ... 

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