Steric Size

In terms of its steric impact, fluorine is the smallest substituent that can replace a hydrogen in a molecule, other than an isotope of hydrogen. Table 1.1 provides insight into the comparative steric impact of various fluorinated substituents on the equilibrium between axial and equatorial substitution in cyclohexane.24 

Guide to Fluorine NMRfor Organic Chemists, Second Edition. William R. Dolbier, Jr. 2016 John Wiley Sons, Inc. Published 2016 by John Wiley Sons, Inc. 

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Conversely, when A-alkyl tryptophan methyl esters were condensed with aldehydes, the trans diastereomers were observed as the major products." X-ray-crystal structures of 1,2,3-trisubstituted tetrahydro-P-carbolines revealed that the Cl substituent preferentially adopted a pseudo-axial position, forcing the C3 substituent into a pseudo-equatorial orientation to give the kinetically and thermodynamically preferred trans isomer." As the steric size of the Cl and N2 substituents increased, the selectivity for the trans isomer became greater. A-alkyl-L-tryptophan methyl ester 42 was condensed with various aliphatic aldehydes in the presence of trifluoroacetic acid to give predominantly the trans isomers. ... 

The regioselectivity is governed by the steric size of the substituent but not by the degree of substitution. When the substituent is sterically bulky (e.g., i-butyl or silyl), the preferred regioisomer formed has the substituent away (at the y-position) from the carbon-carbon bond being created. 

The type I situation usually gives an antidiastereoselectivity that is independent of the stereochemistry of the double bond in the allyl bromide moiety. The diastereoselectivity (anti/syn ratio) is governed by the steric size of the substituent on the aldehydes. Anti/syn ratio increases as the size of the aldehyde R group or the substituent on the allyl bromide increases (Scheme 8.14). 

As observed in runs 3-5 (Table 6) the reaction shows poor diastereofa-cial selectivity. For example, the reaction with 4-substituted cyclohexanone provides a mixture of an equatorial approach product 52eq and an axial approach product 52ax in a ration of ca. 6 1, irrespective of the steric size of the substituents... 

When the steric size of the substituents increases, no adducts with bulky (Et3N) or less basic (EtzO) donors are formed with (Me3C)2Si= NSi(CMe3)3.14 The structure of the benzophenone adduct is quite remarkable.16 Instead of the expected cycloaddition product, the carbonyl oxygen atom is coordinated to the undersaturated silicon atom. 

Recently, Porter et al. (1986b, 1988) have reported the synthesis of both meso- and ( )-forms of a series of two-chain carbonyl diacids made by joining two pentadecanoic acid units by a carbonyl group at the 3,3, 6,6, 9,9 and 12,12 positions, 3,5-didodecyl-4-oxoheptanedioic acid (C-15 3,3 ), 6,8-dinonyl-7-oxotridecanedioic acid (C-15 6,6 ), 9,11-dihexyl-10-oxononadecanedioic acid (C-15 9,9 ) and 12,14-dipropyl-13-oxopentacosanedioic acid (C-15 12,12 ), respectively. The diacids were used to probe further the question of stereochemical preference in two-chain amphiphiles. The method used for examining the diastereomeric preference was equilibration by base-catalyzed epimerization in homogeneous, bilayer and micellar media. This method allows for stereoselection based on hydrophobic/hydrophilic considerations rather than classic steric size effects. 

It is interesting to note that the reaction of trans-henzal-acetophenone with ylide 162a affords (15, 25 )-phenylcyclopropane with 35.3% optical purity, whereas its enantiomer having the (li ,2/ )-configuration is formed when tranj-benzalacetophenone is reacted with ylide 162b. Studies on the relationship between the steric requirements of the substituents attached to the chiral ylide sulfur atom and the optical purity of the cyclopropane rings formed have shown that increases in the steric size of the iV,iV-dialkylamino... 

Based simply on steric effects, this proportion appears somewhat low, whereas in view of the anomeric effect just described the proportion now seems rather high. Anomeric effects are observed to be solvent dependent, and hydroxy componnds experience considerable solvation with water throngh hydrogen bonding. This significantly increases the steric size of the substituent, and reinforces the steric effects. 

Although the degree of selectivity between a and P-sulphonation varies with acidity, the selectivity for P-sulphonation in benzocycloalkenes (1, 2, 38, 39) generally follows the order predicted by steric hindrance to electrophilic attack (Table 6). The selectivity for P-sulphonation in 85% H2SO4 increases in the order tetralin < indan < o-xylene < cycloheptabenzene < o-diethylbenzene. The increased P-selectivity in o-xylene, cyclohq>tabenzene, and o-diethylbenzene over indan and tetralin supports the important role played by stoic effects. In the comparison of indan versus tetralin, where the difference in steric size is minimized, the traditional increase in P-selectivity in indan is observed. Thus, if cyclobutaben-zene could tolo ate strongly acidic conditions, one would expect the strain effect would dictate a yet greater p/a product ratio. 

Allylboronates of type 103 react with equivalent amounts of aldoximes 102 (equation 73) giving allylhydroxylamines 104 in good yields. Similar reactions of aldoximes and glyoxylate oxime ethers with allyl bromide and indium also provide hydroxylamines. Additions of substituted allyl boronates to oximes produce mixtures of stereoisomers with ratio highly dependent on the steric size of substituents in both molecules. Addition of allyltri-n-butyltin to aldoxime ether 105 (equation 74) was found to proceed with a considerable diastereoselectivity. 

The isomer ratio can be controlled by the steric size of the hydride donor silanes, and the highest selectivity is achieved when 9(10)-octalin itself is the hydride donor. None of the catalytic hydrogenations can produce such a high amount of the less stable cis isomer. 

The ability of the cations [M(CNR)4]+ (M = Rh, Ir) to self-associate is a function of steric crowding in the molecule, and for bulky R groups monomeric species predominate. An estimate has been made of the steric size of isocyanides in terms of fan-shaped angles and as part of this study the structure of RhCl(CNC6H2Bu -2,4,6)3 has been elucidated (126). The structural determinations of a series of dimeric rhodium(I) isocyanide salts have been completed. An eclipsed configuration was found for [Rh2 CN (CH2)3NC)4](BPh4)2 NCMe (42)2 (287), whereas [Rh2(CNPh)8]-... 

A different way to determine the steric size of various silyl groups is to use the values of cone angle 6>100, which are listed in equation 817. It illustrates the mechanism of addition of the (p-anisyl)phenyl methyl ion (11) to allylsilanes101. The rate of addition depends on the size of the silyl groups. Bulky silyl groups, the size of which is reflected by their 0 values can accelerate the addition process. Given the 0 values, the size of the silyl groups follows the order shown in entry 6 of Table 1. 

A pronounced rate-retardation of 1.65 x 104-fold by an a-McsSi group relative to Me in the solvolysis of benzylic p-toluenesulfonates is due to a steric effect66. The rate increment in ethanol decreases with increasing steric size of the a-silyl group attached to the benzylic position and follow the order listed in entry 54 of Table 1. 

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