Steric preference

The relative stability of the intermediates determines the position of substitution under kinetically controlled conditions. For naphthalene, the preferred site for electrophilic attack is the 1-position. Two factors can result in substitution at the 2-position. If the electrophile is very bulky, the hydrogen on the adjacent ring may cause a steric preference for attack at C-2. Under conditions of reversible substitution, where relative thermodynamic stability is the controlling factor, 2-substitution is frequently preferred. An example of this behavior is in sulfonation, where low-temperature reaction gives the 1-isomer but at elevated temperatures the 2-isomer is formed. ... 

With some ketones there is a sufficient difference in the rate of loss of various a-hydrogens at the enolization step and a steric preference for the incoming deuterium during ketonization to facilitate selective exchange of certain a-hydrogens. Typical examples are the steroids. 

The cycloaddition of sulfene to bicyclo[2.2.1]heptyl enamines is stereospecific, addition coming from the exo side (156). However, the steric preference of cis and trans isomers relative to the four-membered ring generated does not seem as strong, at least in the case of the addition of chlorosulfene (CICH = SOj) to bicyclic enamines, where a mixture of stereoisomers is obtained (157). 

Thus the observed orientation in both kinds of HBr addition (Markovnikov electrophilic and anti-Markovnikov free radical) is caused by formation of the secondary intermediate. In the electrophilic case, it forms because it is more stable than the primary in the free-radical case because it is sterically preferred. The stability order of the free-radical intermediates is also usually in the same direction 3°>2°>1° (p. 241), but this factor is apparently less important than the steric factor. Internal alkenes with no groups present to stabilize the radical usually give an approximately 1 1 mixture. 

These examples illustrate the issues that must be considered in analyzing the stereoselectivity of enolate alkylation. The major factors are the conformation of the enolate, the stereoelectronic requirement for an approximately perpendicular trajectory, the steric preference for the least hindered path of approach, and minimization of torsional strain. In cyclic systems the ring geometry and positioning of substituents are often the dominant factors. For acyclic enolates, the conformation and the degree of steric discrimination govern the stereoselectivity. 

This result can be explained in terms of a steric preference for conformation A over B. The approach of the mercuric ion is directed by the hydroxy group. The selectivity increases with the size of the substituent R.25... 

We propose that there is in fact a substantial electronic preference, not reflected in the Mechanics calculations, for the ester carbonyl and the C=Rh bond to be syn at the point of commitment to cychzation. This preference is strong enough to overcome the calculated steric preference (3.37 kcal moh ) for the anti transition state. The competition then, is between the syn transition state leading to (R,R)-29, and the syn transition state leading to (S,S)-29. The relative energies of these two transition states differ by slightly less than 1 kcal moh, so we predict, and observe, low diastereoselectivity. 

The terms axo and ondb are often used to indicate the relative positions of the bridging unit (in this case an oxygen atom) and the residue of the dienophiie. When these are on the same lace the adduct is referred to as the exo form, and when the bridge and the residue are on opposite faces it called the endo form. For many pairs of adducts, formed between dienophiles and cyclic dienes, the exo product has fewer steric interactions and IS the more stable. In some cases, however, secondary electronic effects may overcome steric preferences so that the endo (kinetic product) is favoured. 

The NIH shift in the hydroxylation of Trp by TPH is known to occur from carbon 5 to carbon 4 exclusively (70,140). However, the NIH shift for indole in the H0-FeIV=0 and [H20-FeIV=0]+ models showed no preference for migration of the hydride to carbon 4 over carbon 6, which was claimed to be caused by the lack of steric preference exerted by the active site models compared to that of the actual enzymes (117). 

Indeed, there is apparently no selectivity in the reactions of fluorine with hydrocarbons at room temperature. However, at room temperature the reaction of fluorine with a molecule such as benzene initially may show a slight steric preference for reactions with the it system due only to the higher probability of a collision occurring there in preference to a proton site. 

The epoxidation of cis- and trans-1-hydroxy-3,7-dimethylocta-2,6-diene with H202 and TS-1 is chemoselective at the 2-position and stereoselective no epoxidation takes place at the 6-position, and reactant molecules retain their structure in the products. The interesting results have been described as hydroxy-assisted epoxidation. The role of the OH group in the reaction is confirmed by the fact that in the epoxidation of cyclopent-2-en-l-ol, the product with the O cis to the OH group is favored over the one in trans by a factor of 9 1. The same steric preference was found in the epoxidation of cyclo-hex-2-en-l-ol (Kumar et al., 1995). 

Scheme 1. Proposed mechanism of migratory insertion/addition of the coordinated alkyne ligand to the /i-CSiMe3 ligand generating the W2(/r-CRCR CSiMe3)moiety. The steric preference for R = H relative to alkyl or aryl is implied in the proposed transition state, B.

Scheme 3. Proposed reaction pathway for the formation of the Wj-jr-allyl,

If one subscribes to the oxocarbenium-centric theory of glycosidic bond formation [20, 21], it is apparent from Scheme 5.2 that the grounds for stereoselective bond formation are slim. This is because neither of the two possible interconverting halfchair conformers of the oxocarbenium ion (4H5 and 5H4) appear to exhibit any overwhelming steric preference for one face of the system over the other [22],... 

How can force constants for these functions be obtained that correctly model the balance between the metal ion preference (e.g. square planar) and the steric preferences of the ligand (e.g., tetrahedral) ... 

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