Peri-interaction

Model 25, invoking a preferential rotameric disposition of TFAE dictated by peri interactions, and solvate conformations resulting from CHB between the solute carbinyl proton and the anthryl ring, conectly predicts the senses of nonequivalence observed for 2-butanol (Fig. 4), and for 2-octanol as well. In these conformations, the substituent over the larger portion of the anthryl ring is the more shielded. 

This spectral nonequivalence for the diastereomeric solvates was originally rationalized in terms of conformers 28 (shown for TFPE as solute) where (/2)-NEA as its preferred rotamer (dictated by the peri interaction) interacts primarily with the carbinol hydroxyl and populates the conformers shown through an aryl-aryl attraction. Thus, in (5, )-28, the carbinyl proton is held more closely to the naphthyl ring, whereas in R,R)-28 its position is reversed. This situation results in the observed highfield sense of nonequivalence for the carbinyl proton of carbinols 27 and accounts for the opposite sense shown by the fluorine resonances. In one instance, aryl nonequivalence was also identified. AU three ring protons of trifluoromethyl-a-thienylcarbinol (13) show the same nonequivalence sense as the carbinyl proton (opposite to that of trifluoromethyl). Such also is expected from the proposed interactions 28, since the aryl substituent... 

Type A systems seem to behave as two separate aromatic rings, since there is a good deal of evidence for a lack of interaction between the two parts. Compounds with a central double bond (e.g., 482 and 483) are more stable than, for example, 484, at least when one of the heteroatoms (X and Y) is sulfur [compare 282b (Section IV,A,1) and 89 (Section V,B)]. Peri-interactions between free lone pairs can destabilize a system. 

Shifts toward the cis-fused conformation are shown by 183 184, 185 186, and 187 188. Axial phenyl at C-4 in the trans conformation 183 shifts the equilibrium toward the cis conformation 18436 as does the unfavorable peri interaction in trans-fused 185, which is relieved in the cis-fused conformation 186.215 The 1-hydroxyl-l-phenylquinolizidine 187 188 adopts an equilibrium containing 40% of the cis-fused conformation 188 in equilibrium with the trans-fused conformation 187.143... 

The acylation of a series of pyrazolo[3,4-c]pyridines has been studied.110 Acetic anhydride in refluxing benzene converted S-substituted derivatives to 1-acyl compounds (101 R2 = H), whereas the 7-methoxy derivative afforded the 2-substituted product 102 (R1 = H, R2 = OMe), attributed to peri interaction. In the absence of solvent, however, the latter reaction gave the 1-acyl isomer as the major product. Furthermore, benzoylation of the 5-chloro bicycle furnished a mixture of 101 and 102 (R1 = Cl, R2 = H). However, products benzoylated mainly at N-6 were obtained following introduction of a nitro group into the pyrazole ring. 

The JV-amino derivatives 269 underwent oxidative ring expansion to tri-azine 270. Analogous pyrazolo[3,4-c]pyridines, however, gave only intractable products. The latter system lacked the peri interaction necessary for repulsion of nucleophilic attack at the 4-position of the triazine ring.157... 

In the field of hydroxyindolizines the situation is more complicated. No ring carbonyl absorption occurs in the IR spectra of (21) and (22) (76AHC(S1)245), while an aromatic enol tautomer of (23) was excluded completely on the basis of IR and NMR arguments (80JOC5100). This may be due to peri interaction, since an equilibrium between (24) and (25) in DMSO has been deduced from NMR evidence. It was pointed out in Section 3.08.1 that indolizines show pyrroloid as well as pyridinoid properties. This dual character may be used to explain the relative stabilities of some hydroxyindolizines, for example (26) and (27), which have been shown to be the predominantly existing tautomers. 

Naphtho[6]furans are slightly known spectroscopically. An important one is furocadalene (118), obtained as a dehydrogenation product of certain sesquiterpenes <75jcs(Pl)478). A partial assignment for naphtho[l,2-6]furan (119) has been effected (69TL4479) the shift for 9-H is little more than would result from a peri interaction usual in naphthalenes and does not necessarily imply deshielding by an aromatic (furan) ring current. 

The increased stabilization upon thienoannulation as compared to benzo-annulation may be caused by the more effective stabilization of the positive charge, by diminished angular ring strain, and by limited peri interactions between hydrogen atoms (due to the heteroatoms) and hence by nearly perfect planarity. 

If the released electrophile HSOs+ is not intercepted during the protodesulfonylation as in Figure 5.7, it reacts with the defunctionalized aromatic compound again. In this way an isomer of the original sulfonic acid may be obtained. The best-known example of such an isomerization is the conversion of naphthalene-1-sulfonic acid into naphthalene-2-sulfonic acid (Figure 5.8). Naphthalene-1-sulfonic acid is destabilized by the so-called peri-interaction, that is, the steric interaction between the Cs—H bond of the naphthalene and the substituent on Cl. The peri-interaction is thus a cis-alkene strain. Because naphthalene-2-sulfonic acid does not... 

Apart from the construction of phenanthrenes, carbene complexes have also been used for the synthesis of more extended polycyclic arenes. An unusual dimerization of chromium coordinated ortbo-ethynyl aryl carbenes results in the formation of chrysenes (Scheme 37) [81]. This unusual reaction course is presumably due to the rigid C2 bridge that links the carbene and alkyne moieties, and thus prevents a subsequent intramolecular alkyne insertion into the metal-carbene bond. Instead, a double intermolecular alkyne insertion favored by the weak chromium-alkyne bond is believed to occur forming a central ten-membered ring that may then rearrange to the fused arene system. For example, under typical benzannulation conditions, carbene complex 97 affords an equimolar mixture of chrysene 98a and its monochromium complex 98b. The peri-interactions between the former alkyne substituent (in the 5- and 11-positions) and the aryl hydrogen induce helicity in the chrysene skeleton. 

Azine approach. The parent cation and substituted derivatives are available by acid-catalyzed cyclization of 2-/3-oxoalkylthiopyridines (401) using an acid such as sulfuric, phosphoric or PPA. Chloro or nitro substituents in the pyridine ring do not seriously interfere (66JHC27). The cyclization of 3-hydroxypyridine analogues (402) is also at the nitrogen to yield the thiazole derivatives. The cyclization, however, is sensitive to the peri interaction between 3- and 5-substituents. In 3,5-dimethyl derivatives (403 R2 = R3 = Me) the steric repulsion is apparent by the unusually low field signals for the methyl protons <81H(15)1349>. 

Naphthalene undergoes electrophilic aromatic substitution at C-1 more easily than at C-2. There is a smaller loss of resonance energy in forming the intermediate for reaction at C-1 and reaction takes place more rapidly at this centre. However, the products of aromatic substitution at C-1 suffer interactions with C-8 (peri interactions) and are less stable than the corresponding products of substitution at C-2. Hence those aromatic substitution reactions that are carried out under conditions that allow equilibration between isomers (thermodynamic control) lead to substitution ai C-2, but reactions that are carried out under conditions... 

Correct reagent selection allowed reduction of steroidal enone (74) to either diastereoisomeric allylic alcohol, uncontaminated by its isomer. Sodium borohydride/cerium chloride in methanol-THF gave the equatorial alcohol (73), while L-selectride produced the axial isomer (75) via equatorial attack (Scheme 12). Unexpected axial attack on diketone (76) to give equatorial alcohol (77 equation 19) led to the proposition that for hydride additions to decalones two 1,3-diaxial interactions override one peri interaction which in turn takes precedence over a single 1,3-diaxial interaction. ... 

In certain cases, exceptions to these rules are observed. In one of the two independent anions (B) of Ca ascorbate dihydrate, 05 (Figure 6) adopts a rare, unfavorable (peri) interaction (16) with 03. In addition, 06 is rotated about C5-C6 to permit the three oxygen atoms 03, 05 and 06 to form an interesting tridentate complex with Ca Mole-... 

Stoik et al. have shown that heteroannular extended dienolates such as (73), which contain substituents at both the a- and y-positions, undergo predominantly equatorial alkylation (Scheme 35). The dienolate (73) was product by lithium-ammonia reduction of the tricyclic dienone (72) and the product of its alkylation wiA I-bromo-3-chloro-2-butene and hydrolysis of the resulting enol ether, i.e. (74), was a key intermediate in a short, highly stereoselective synthesis of ( )-adrenosterone. It was pointed out that equatorial alkylation is obtained with dienolates such as (73) and related compounds brcause a peri interaction (Me OMe) of the a- and y-substituents forces the ring a to adopt a half-boat conformation in which the a-face of the ir-system is accessible to attack. 

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