Substituent placement

Placing an individual substituent consists of setting the atom s coordinates relative to the seed atom. The distance from the seed atom is the standard bond length. The angle used is the seed atom s CFS/. Algorithm 11 has the details. 

This algorithm places an atom a, which is adjacent to the seed atom, at a standard distance from the seed atom, at an angle equal to the CFS/q of the seed atom. 

If the seed atom is the head atom, initialize its CFS. Both CFS/,- and CFS are set to the same angle, found as follows  

For the bond length I, use the standard bond length unless is in a PFU. In that case, use its local distance in the PFU. ° 

Smooth the CFS,q of the seed atom, i.e., apply individual bond alignment. 

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As was the case when one added a (3-fluorine substituent, placement of an ether or alcohol functionality (3 to a fluorine substituent leads to modest shielding (Scheme 3.21). 

Substrates for which the rate of the 5-exo-trig cyclization is greatly reduced, such as 470, underwent a 6-endo-trig cyclization to give pyran 471 in 68% yield, although with poor (2.5 1) diastereoselectivity. Other alkyl halides that were examined produced related pyrans but in better yield (70-85%) and with similar (1.2-6 1) diastereoselectivities. Using similar substituent placement to control relative rates, 7- and 8-membered rings were also constructed in 50-86% yields. 

KHMDS). While the tricyclic core of 125 corresponds to that desired, the substituent-placement is incorrect. 

His research interests have included almost all aspects of water-soluble polymers kinetics and synthesis by free-radical processes, controlled substituent placement in the derivati-zation of carbohydrate polymers, solution and interfacial adsorption and viscosity behavior of both polymer types, and meaningful extrapolation of such fundamental data to the performance of water-soluble polymers in application formulations. He has published more than 70 technical papers and received several patents in these areas of study. 

For KS, in common with many other carbohydrate polymers of the GAG family (e.g. the heparan sulphate/heparin systems) and elsewhere, the anticipated molecular structures are not unique. They are present as distributions, both in terms of molecular size and in the nature of substituents and their placements placements. Thus they differ greatly from the ordered world of peptides and proteins and are more akin to synthetic polymers in their nature, their chromatographic and spectroscopic behaviour and in the resultant analytical problems. It is apt to consider substituent placements along the repeat unit backbone as exhibiting microstructural patterns within diad, triad or larger groups of monomer units, for which statistical data can be elicited, e.g. in terms of sulfation and its distribution. The spectroscopic route to KS structure can also be similar to that used for synthetic macromolecules. 

Effect of Substituent Placement Changes in Optical Properties... 

A less obvious example in which the success of a synthesis depends on the order of substituent placement on the ring is illustrated by the preparation of m-nitroacetophenone. Although both substituents are meta-directing, the only practical synthesis involves nitration of acetophenone (disconnection a). 

Algorithm 8 Substituent Placement When Seed Atom Is in a Ring... 

Substituent placement is random Copoly(alkyl + aralkylisocyanates)... 

Nucleophilic substitution by ammonia on a halo acids (Section 19 16) The a halo acids obtained by halogenation of car boxylic acids under conditions of the Hell-Volhard-Zelinsky reaction are reac tive substrates in nucleophilic substitu tion processes A standard method for the preparation of a ammo acids is dis placement of halide from a halo acids by nucleophilic substitution using excess aqueous ammonia... 

The effect of the substituents on chain mobility and chain packing has been related to the gas transport properties [209]. Role of symmetry of methyl group placement on bisphenol rings in PES shows the permeability coefficients in the following order ... 

These reactions occur, presumably, via cyclic transition states with preferential placement of the allylic diisopropylcarbamate substituent in an equatorial position. The ( )-.vi -diastcreomer is available with much greater stereoselectivity by using the corresponding 1-diisopropyl-aminocarbonyl-2-propenyltitanium reagent (see Section D.1.3.3.3.8.)fi. 

Cyclic acetals formed by the reaction of saccharides or saccharide derivatives with aldehydes or ketones are named in accordance with 2-Carb-24.1, bivalent substituent names (formed by general organic nomenclature principles) being used as prefixes. In indicating more than one cyclic acetal grouping of the same kind, the appropriate pairs of locants are separated typographically when the exact placement of the acetal groups is known. 

By using monomers with different substituents, multiple functionalities could be introduced into the phenylacetylene oligomer at any desired position along the sequence backbone, resulting in macrocycles with a wide variety of symmetries (e.g. 47-53). In principle, this versatile synthetic method should allow construction of PAMs in which anyparticular group couldbe placed at any particular site. Judicious choice of the type and placement of functionalities has... 

The relative insensitivity of Sp to changes in electronegativity of substituents which is observed for P fluoro-compounds is also evident for penta-arylphosphoranes. Thus the placement of />ara-substituents on the phenyl rings of pentaphenylphosphorane has very little effect and Sp is -f 88 1 p.p.m. for (16 Y = H, Me, or Cl). The effect on Sp of the introduction of an amino-group in the bis-biphenylenephosphorane system (17) is similar to that of an alkyl group (see Table 3). ... 

Nevertheless, the placement of two Cl atoms on the C and C carbon atoms of the NHC skeleton, the presence of the strong SO Ar electron-withdrawing group on the aryl A-substituents, or the modification of the NHC skeleton from an imidazol-to a triazol-type, have allowed to fill the gap between the TEP of phosphines and NHCs, see Pig. 1.14. 

The stereoselectivity is enhanced if there is an alkyl substituent at C(l). The factors operating in this case are similar to those described for 4-r-butylcyclohexanone. The tnms-decalone framework is conformationally rigid. Axial attack from the lower face leads directly to the chair conformation of the product. The 1-alkyl group enhances this stereoselectivity because a steric interaction with the solvated enolate oxygen distorts the enolate to favor the axial attack.57 The placement of an axial methyl group at C(10) in a 2(l)-decalone enolate introduces a 1,3-diaxial interaction with the approaching electrophile. The preferred alkylation product results from approach on the opposite side of the enolate. 

Owing to the concerted mechanism, chirality at C(3) [or C(4)] leads to enantiospecific formation of new stereogenic centers formed at C(l) [or C(6)].203 These relationships are illustrated in the example below. Both the configuration of the new stereocenter and the new double bond are those expected on the basis of a chairlike TS. Since there are two stereogenic centers, the double bond and the asymmetric carbon, there are four possible stereoisomers of the product. Only two are formed. The Zs-double bond isomer has the 5-con figuration at C(4) and the Z-isomer has the -configuration. These are the products expected for a chair TS. The stereochemistry of the new double bond is determined by the relative stability of the two chair TSs. TS B is less favorable than A because of the axial placement of the larger phenyl substituent. 

The stereochemistry of acyclic anionic oxy-Cope rearrangements is consistent with a chair TS having a conformation that favors equatorial placement of both alkyl and oxy substituents and minimizes the number of 1,3-diaxial interactions.214 For the reactions shown below, the double-bond configuration is correctly predicted on the basis of the most stable TS available in the first three reactions. In the fourth reaction, the TSs are of comparable energy and a 2 1 mixture of E- and Z-isomers is formed. 

In fact there is substantial structural variability among the five instances of the helical tubuland structure described above, in the form of variable placements of the diol hosts along the twofold axes, and variable a dimensions of the lattice, both of which have marked influence on the size and shape of the canals. Full analysis of these effects is provided elsewhere 8) and the major results only are reported here. As a consequence of steric repulsions between the bridge on the syn face and methyl substituents R on adjacent molecules presenting an anti face to the canal, as shown in Fig. 8, the molecules presenting the anti face are moved along the twofold axes, farther... 

An interesting stereochemical profile of this cyclization is that in the five-membered product structures, substituents PhS and OH groups are placed cis to each other, whereas in six-membered products the placement is trans (Table 6, entry 7). The cis selectivity in the five-membered ring systems is not affected by a and fi-substituents of the alkoxides (entries 2, 3 and 4), indicating that the steric effect is not the dominant factor. Instead, interaction between the oxido and carbene center composes a five- (or seven-) membered transition state 28, which allows the carbene to abstract the nearest quasi axial hydrogen as a hydride to produce a carbonyl intermediate 29, leading to the cyclization products 27 and 30 (Scheme 13, Eq. 1). Similarly, the stereoselective stepwise cyclization of cis- and rra s-2-(3,3-dithiopropyl)cyclohexanol to 2-phenylthio-... 

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