Endocyclic anions

Calculation of EM. The reference intramolecular reaction is nucleophilic attack by the anion of a carboxylic acid of pK, 3.15 on 2-phenoxy-l,3,2-dioxaphosphorinan-2-oxide. The rate constant for this reaction can be calculated as 7.67 x 10-10 dm3 mol 1 s-1 at 39° using the formula derived by Khan and Kirby (1970), and allows the direct calculation of the EM for the corresponding intramolecular reaction (COO-—P3—6n of A.5.5). The EM is assumed to be the same for the corresponding endocyclic reaction of the diphenyl ester anion (A.5.6), and has been shown not to differ significantly for endocyclic and exocyclic displacements (Bromilow etal., 1972)... 

Apart from PET-reductive cyclization, chemical reduction has also been applied to the total synthesis of natural products such as capnellenediol 186 [184]. Naphthalene sodium is shown to be a suitable oxidant for generating ketyl radical anions which cyclize efficiently in a 5-exo-dig mode. In contrast, electroreductive cyclization of 184 does not lead to 185, but exclusively to the thermodynamically preferred 5-exo isomer with a remaining double bond in the endocyclic position [185] (Scheme 35). The steroid precursor 4.5-secocholes-tan-5-one 187, in which the lOa-side chain is varied, has been cyclized under the same conditions [186-188] (Scheme 36). Reduction with naphthalene sodium or sodium in ether exclusively produces the A B-cis steroid 188 with an exo double... 

Nucleophilic attack by the amide anion can occur at either the exocyclic or endocyclic carbonyl. The former regenerates the lactamate anion, whereas the latter results in polymerization. Although the locus of nucleophilic attack has no major effects in a homopolymerization, it can exert considerable control over the copolymerizations and on copolymer structure. 

The nature of the ligands on the palladium in ir-allyl complexes can influence the regioselectivity exhibited by soft carbon nucleophiles. ir-Allylpalladium complexes generated from methylenecycloalkanes provide an example of the effect of ligands on regiochemistry. The complexes derived from methylene-cyclopentane and methylenecycloheptane both exhibit exclusive exocyclic addition by the anion of methyl(methylsulfonyl) acetate with triphenylphosphine ligands on the Pd (equation 223). In contrast, the complex derived from methylenecyclohexane yields a 62 38 ratio of exocyclic endocyclic addition (equation 226). 

Stereoselective allylic alkylations have been carried out with the aid of palladium catalysts. The 17-(Z)-ethylidene groups of steroids (obtained from the ketones by Wittig olefination) form n-allyl palladium complexes in the presence of copper(n) salts (B.M. Trost, 1974, 1976). Their alkylation with dimethyl malonate anions in the presence of 1,2-ethane-diylbis[diphenylphosphine] (— diphos) gives a reaction exclusively at the side chain and only the (20S) products. If one starts with the endocyclic 16,17 double bond and replaces an (S)-20-acetoxy group by using tetrakis(triphenylphospbine)palladium,the substitution occurs with complete retention of configuration, resulting from two complete inversions (B.M. Trost, 1976). 

With alkylating agents, 4-ethoxycarbonyl-2-A/-methylaminothiazines appear to be ambident substrates. It seems the thiazines cannot be directly alkylated, and alkylations are made in the anionic form (216) (65JOC2290). In dioxan, alkylation occurs at the exocyclic nitrogen, in water, alkylation concerns the endocyclic nitrogen (Scheme 89). It has been noted that there is no methylation of NH by diazomethane. 

The six-membered ring B can be lithiated at two different positions. Endocyclic lithiation yields structure B, which is 6.1 kcal/mol above the eight-membered anion A, comparable to the neutral system. The Si-N-Si angle at the anionic center measures 130.4° it is more than 23° smaller than in A because of the smaller ring... 

The non-symmetrical four-membered ring species of OMCTS, D, can be lithiated in three different positions. Removal of the proton at the endocyclic NH unit results in a structure DE that is 24.4 kcal/mol above A. The transannular Si Si distance is calculated to be 241.2 pm and the Si-N-Si angle at the anionic site is 90.4°. 

Thus it is possible to conclude that in the 13C NMR spectra of tetrazolate anions, 2//-tctrazolcs, and 1,3-tetrazolium ions the signal of the endocyclic carbon atom is considerably shifted downfield compared to the corresponding signal in the spectra of 1-substituted neutral tetrazoles and 1,4-disubstituted tetrazolium ions, and also of the fuzed tetrazolo-azines. It is just in the tetrazolate anions and tetrazole derivatives with a substituent at position 2 that a lesser variation in the bond distances in the ring and stronger aromaticity are observed (cf. Sections 6.07.3.1 and 6.07.4.1). 

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