Steric enhancement

Steric enhancement of reaction rate has been reported in cycloaddition of styrene to acridinium ion (74JOC1172) and of 2(lH)-pyridone to dimethyl butynedioate (79CC501) when methyl groups are either ortho or peri (Scheme 45). 

A stereogenic center on the tether (44a), composed of a relatively small hydroxyl substituent, results in the four possible product isomers shown in Figure 16. The designations anti and syn isomers refer to the orientation of the tether substituent and the adjacent carbonyl group in the product. Alcohol 44a yields all four possible products, and trans is preferred over cis by a factor of 2.5 or 4.2, depending on the solvent. The primary difference in the product ratios comes from the solvent-dependent synlanti ratio. In the protic solvent methanol, the anti isomers comprise 85% of the product whereas in the aprotic methylene chloride the syn isomers are 56% of the mixture. The syn selectivity may result from an intramolecular hydrogen bond of the alcohol to the nearby carbonyl (see pro-trans-syn conformation). Steric enhancement of the alcohol as a /-butyldimethylsilyl ether (44b) results in a solvent independent anti-selective photoreaction. The amount of syn isomers produced with a t-butyldimethylsilyloxy substituent is less than 1%. ... 

C now rises (from 14.9 with thiophenol) to 25.2 [20]. The steric enhancement of the isotope effect, to a magnitude giving strong evidence of tunnelling, is shown. Another possible case of steric contribution to the isotope effect in a hydrogen-atom transfer is reaction 10, where for various Ri values the tritium isotope effects are... 

C) ROTATIONAL EFFECTS STERIC HINDRANCE AND CENTRIFUGAL ENHANCEMENT... 

Table 15 shows that peroxyester stabiUty decreases for the alkyl groups in the following order tert — butyl > tert — amyl > tert — octyl > tert — cumyl > 3 — hydroxy — 1,1 dimethylbutyl. The order of activity of the R group in peroxyesters is also observed in other alkyl peroxides. Peroxyesters derived from benzoic acids and non-abranched carboxyUc acids are more stable than those derived from mono-a-branched acids which are more stable than those derived from di-a-branched acids (19,21,168). The size of the a-branch also is important, since steric acceleration of homolysis occurs with increasing branch size (236). Suitably substituted peroxyesters show rate enhancements because of anchimeric assistance (168,213,237). 

Both the equilibria and the enhancement of the coefficients can be improved by additives, of which sodium arsenite is the major one in use, but sodium hypochlorite and small amounts of amines also are effective. Sterically hindered amines as promoters are claimed by Say et al. (Chem. Eng. Prog., 80(10), 72-77 [1984]) to result in 50 percent more capacity than ordinary amine promoters of carbonate solutions. 

The stereoselectivity of organometallic additions with carbonyl compounds fits into the general pattern for nucleophilic attack discussed in Chapter 3. With 4-r-butylcyclohex-anone, there is a preference for equatorial approach but the selectivity is low. Enhanced steric factors promote stereoselective addition. 

---