Steric limitations

Similar conformational analyses were performed for inactive compounds, and inactive compounds in pharmacophoric conformations were superimposed with the active compounds to determine steric limitations in the active site. Where appropriate, the geometry of each inactive molecule was obtained by modifying the chemical strucmre of the relevant active analogs followed by the energy minimization of the resulting structure. 

Since the coordination number of tantalum or niobium in fluoride and oxyfluoride compounds cannot be lower than 6 due to steric limitations, further decrease of the X Me ratio (lower than 6) leads to linkage between complex ions in order to achieve coordination saturation by sharing of ligands between different central atoms of the complexes. The resulting compounds have X Me ratios between 6 and 4, and form crystals with a chain-type structure. 

The unique properties of the proton have been attributed by some authors to the fact that it has no electronic or geometric structure. The absence of any electron shell implies that it will have a radius that is about 105 times smaller than any other cation and that there will be no repulsive interactions between electron clouds as a proton approaches another reactant species. The lack of any geometric or electronic structure also implies that there will not be any steric limitations with regard to orientation of the proton. However, it still must attack the other reactant molecule at the appropriate site. 

Thiolation is restricted by more effective nitrogen donors or steric limitations. The bis(aminothiolate) complexes are obtained from bismuth nitrate or chloride and the hydrogen chloride adduct of the thiol and essentially independent of stoichiometry. The nitrogen-bismuth interactions in these complexes [e.g., Bi(SCH2CH2NH2)2(N03)(H20) 54,... 

Because of the large number of carbonyl groups required to satisfy the noble gas rule and the relatively small metallic radius, serious steric limitations are present for manganese tetranuclear closed clusters12). The only known tetranuclear compounds are some mixed clusters, MnOs3(CO)16H and MnOs3(CO)13H3 (see later), which have been prepared from Os3(CO)12 and [Mn(CO)s] 161). 

Short PS macromonmers (DP = 4 or 9) polymerized completely under ROMP conditions. Macromonomers with DP = 14 to 46 invariably led to incomplete polymerization, suggesting that the dense polymacromonomer imposes steric limitations on the polymerization. Heroguez et al. studied the ROMP of polyethylene oxide) macromonomers [111, 112], The macromonomers are prepared from a norbornene derivative according to the following sequence ... 

Spatioselectivity or Transition State Selectivity. TSS occurs when the formation of reaction intermediates (and/or transition states) is sterically limited by the space available near the active sites. Contrary to molecular sieving, TSS does not depend on the size of pore openings, but depends on the size and shape... 

The stereospecific substitution produces a sterically less strained product when a more bulky p-nitrophenyl substituent occupies the equatorial position and the less bulky phenylthiyl substituent occupies the axial position. Steric limitations of the nucleophile attack caused by strains in the final product are thus removed. And therefore, ion-radical addition ofp-nitrobenzyl radical to the lithium salts of 5-nitro-l,3-dioxanes proceeds stereospecifically (Zorin et al. 1983 Scheme 6.3). 

In a study which was conducted simultaneously to the work in the Mehta group and which also aimed to prove the absolute configuration of natural kelsoene (1), Schulz et al. used a stereoselective approach starting from the enantiomerically pure chiral pool material (i )-pulegone 17 [9, 10] (see above). The final steps of their synthesis of the unnatural enantiomer of kelsoene (ent-l) were similar to the above-described first total synthesis of natural kelsoene (1) (Scheme 8). Taking into account the steric limitations of the system as communicated by Srinivas and Mehta, diquinane enone ent-6... 

The photochemical conversion of 3-phenylazirine into benzonitrilio methylide in a nitrogen matrix at 12 K was found to be a completely reversible process (4). In contrast, however, it is reported that acetonitrilio fluorenylide 85 (R=Me) is photostable at 77 K and does not convert into the corresponding azirine (55). This stability was attributed to a steric limitation on bond rotation. 

Since the reaction is subject to severe steric limitations, the nature of the R and R" is very important. The reaction proceeds readily with primary alcohols, less readily with secondary, and hardly at all with tertiary alcohols. 

A phenol synthesis reaction induced by gold catalysts without steric limitations for the substituents was also reported [169]. These results provided a very helpful tool for organic synthesis of a large variety of derivatives such as biaryls, iso-chromanes, benzofurans, tetrahydroisoquinolines and other natural products [133, 170, 171]. 

Sterically Limited Access Due to Substitution Anoxic (Micro)Environment... 

As all of the direct extraction rates were low relative to the hydrogenative HDS rates, even at low conversions, the fully saturated compound dimethyl-cyclohexylcyclohexane was observed in the product mixture. As discussed in later sections, this fact indicates that the major cause of rate reduction by adjoining alkyl substituents may not be due to lowering adsorption constants but could well be due to steric limitations in the oxidative addition of the C-S bond to the catalytic site, as discussed later. A more subtle explanation could be adsorption-disguised kinetics whereby the intermediate is not released from the catalyst surface but remains adsorbed so that further conversion proceeds. This was not observed for unsubstituted diben-zothiophenes, however. 

Pathway III of Fig. 26 has been demonstrated for thiophene and benzo-thiophene with Ir complexes (4) and for all thiophenes, including dibenzo-thiophene, with Rh complexes (94, 95). These oxidative additions appear to be influenced by substituents present on the carbon atoms adjacent to the sulfur atom. Insertion between sulfur and the unsubstituted carbon is highly preferred. For 2-methylthiophene the exclusive product is the 1-5 bond insertion product, whereas for 3-methylthiophene, no preference for insertion was observed (1-2 and 1-5 bond insertion products were equal). In competitive studies, thiophene was found to be about twice as reactive as 2,5-dimethylthiophene. This behavior is similar to that observed for relative reaction rates of substituted thiophenes observed with conventional HDS catalysts. Thus steric limitations can occur, even with monomeric, homogeneous catalysts. 

There are no real thermodynamic limits in the removal of sulfur from any organic sulfur compound by reaction with hydrogen (1, 2, 5). There are, however, limits on the overall rates of conversion that may be achieved by increasing the temperature of the reaction. A classic limitation in rates is the result of the inverse relationship between adsorption on a catalytic surface and temperature. This may be a problem with dialkyldibenzothio-phenes, which have steric limitations for adsorption. 

Following similar logic, if the mechanistic route follows the pathway in which an adsorbed molecule is first attacked by a hydride ion and then a proton (Fig. 25, pathways I, II, and IV), the rate-limiting step could depend on the availability of either a hydride ion or a proton in the vicinity of the adsorbed intermediate. The lability of the molecule toward hydride attack would also be a function of the degree of electron donation from the n system to the metal to which it is adsorbed and to steric limitations imposed by alkyl substituents on the aromatic ring systems. In these pathways, two or three bonding orbitals must be available on the Co for the mechanisms to proceed. Occupation of these orbitals by some nonreacting molecules would result in inhibition. 

The structures of fibrous proteins are determined by the amino acid sequence, by the principle of forming the maximum number of hydrogen bonds, and by the steric limitations of the polypeptide chain, in which the peptide grouping is in a planar conformation. 

This value of N is solved by considering steric limitations of adsorbed molecules in the volume of the cavity as saturation is approached. The total x/m becomes... 

Parallel experiments carried out with cyclo[6]pyrroles showed that only the hexa-iV-methyl derivative could be efficiently obtained, most likely because of steric limitations [169], Interestingly, however, cyclo[6]pyrrole 54a was found to coordinate the uranyl cation [U02]2+ with a concomitant two-electron oxidation of the macrocycle to a [20]annulenoid structure 55a [170], As expected, this system is strongly paratropic, as evidenced by the shielding of peripheral ethyl substituents in the II NMR spectra (-1.42 ppm for CH2 and -1.12 ppm for CH3). Additionally, electronic absorptions of 55a are much less intense that those of the free base 54a. 

---