Product-development control

Since the equatorial substituents are more stable than axial substituent, the product development control gives mainly the equatorial alcohol unless the steric hindrance to the approach of the reagent is very severe. 

The additions of nucleophiles to ketones have been classified as governed either by product development control or by steric... 

Hydrides and complex hydrides tend to approach the molecule of a compound to be reduced from the less hindered side steric approach control). If a relatively uninhibited function is reduced the final stereochemistry is determined by the stability of the product (product development control). In addition, torsional strain in the transition state affects the steric outcomes of the reduction. 

PRODUCT-DETERMINING STEP PRODUCT DEVELOPMENT CONTROL Product formation,... 

If this interpretation is correct, then in any reaction with asymmetric induction, a search for antiperiplanarity between the incipient bond (Nu-Cl) and an adjacent sigma bond (C2-L) should lead to the most favourable transition states, all other things being equal. Let us apply this rule to the so-called product development control problem. Consider a conformationally fixed cyclohexanone, for example 14. 

Der von Berson diskutierte Reaktionsablauf tragt gewisse Ziige eines Modells mit product development control" (34). 

Preparation of trityl ethers, 415 Procedure for Birch reductions, 49 Product development control, 67 Product stability control, 69 Product stereochemistry in hydrogenation, 111, 112, 113... 

In homolytic substitution reactions, the 2-position of thiophene is the preferred site of attack. This is easily rationalized in terms of frontier orbital theory (B-76MI31401). Because of symmetry, both HOMO and LUMO of thiophene have the same absolute values for the coefficients (as shown in 216). Thus it is immaterial whether the [SOMO (radical)-HOMO (thiophene)] or the [SOMO (radical)-LUMO (thiophene)] interaction determines the site of attack only the 2-position is the point at which the radical would attack. The same conclusion is iso reached by consideration of product development control (74AHC(16)123). Attack at the 2-position would result in a transition state with an allylic radical, which would be stabilized to a greater extent than the one arising from attack at position 3 (Scheme 57). 

Consider now 4-fcrfbutylcyclohexanone, a configurationally rigid molecule. The carbonyl plane defines two half-spaces, the lower of which contains only the axial hydrogens at C2 and C6. Even so, the nucleophile generally arrives from above (90% in the reduction by LiAlH4). These results cannot be explained by Cram s model and other factors have been invoked. For instance, Dauben et al.56 suggested that equatorial attack is under steric approach control whereas axial attack is under product development control ... 

Axial attacks on cyclohexanones come from the more hindered side. This is the reason why Dauben et al.56 introduced the concepts of product development control and steric approach control and Schleyer the compression effect (Schleyer P. v. R.,/. Am. Chem. Soc., 1967, 89, 701 Laem-mle J., Ashby E. C., Rolling P. V., J. Org. Chem., 1973, 38, 2526). 

If the reactions leading to the alternative reaction products are one step, the most stable product is produced most rapidly, that is, more selectively. This type of selectivity is called product development control. 

The selectivity in all three cases is therefore due to product development control. ... 

A given molecular transformation, for example, the reaction C—H — C—Cl, is called regioselective when it takes place preferentially or exclusively at one place on a substrate. Resonance-stabilized radicals are produced regioselectively as a consequence of product development control in the radical-forming step. 

The bromination depicted in Figure 1.29 proceeds via an unsymmetrical allyl radical. This radical preferentially (80 20) reacts to yield the bromination product with the more highly substituted C=C double bond. As this reaction proceeds under kinetic control, the selectivity is based on product development control the more stable (since higher alkylated) alkene is formed more rapidly than the isomer. 

The bromination shown in Figure 1.30 also proceeds via an unsymmetrical allyl radical intermediate, and the bromination product with the aryl-substituted C=C double bond is formed exclusively. Since this process, too, is under kinetic control, the selectivity is again due to product development control the alkene isomer, which is strongly favored because of conjugation, is formed so much faster than the non-conjugated isomer that the latter is not observed at all. 

Side Note 1.2. The Rate of the Wohl-Ziegler Bromination Is More Dependent on a Polar Effect than on Product Development Control... 

So what have we learned here Both C and D lead to the same intermediate E upon hydrogen abstraction, but H is much higher in energy than I, allowing a new pathway to complete for C to the exclusion of H. Product development control does not work here and it should be known that, like many of our models in organic chemistry, it has its limits. 

All -eliminations from the benzyl derivative in Figure 4.5 exhibit -stereoselectivity. This is true regardless of whether the elimination is syn- or anti-selective or neither. The reason for the preferred formation of the E product is product development control. This comes about because there is a significant energy difference between the isomeric elimination prod-... 

The basis for the occurrence of product development control vanishes if there is only a marginal energy difference between //,Z-isomeric trisubstituted alkenes, as for those shown in Figure 4.6. Therefore, the corresponding / eliminations proceed without any stereocontrol. 

If the /1-elimination of H/Het from R —Het can, in principle, afford regioisomeric alkenes whose C=C double bonds (Figure 4.7) contain a different number of alkyl substituents, they are differentiated as Hofmann and Saytzeff products the Hofmann product is the alkene with the less alkylated double bond, and the Saytzeff product is the alkene with the more alkylated double bond. Because C=C double bonds are stabilized by alkyl substituents, a Hofmann product is, in general, less stable than its Saytzeff isomer. Accordingly, eliminations of H/Het from Rv(,f —Het, which exhibit product development control, furnish a Saytzeff product with some regioselectivity. 

Figure 4.21 shows how the bulkiness of the base influences the regioselectivity of the elimination of HBr from tert-amyl bromide. The stericahy undemanding base EtO can react with the H atoms in all -positions to the leaving group, irrespective of whether the H atom is bound to a primary or a secondary C atom. Thus, regioselectivity derives from product development control alone the thermodynamically more stable Saytzeff product is formed preferentially, though not exclusively. 

Fig. 4.21. Steric base effects on the Saytzeff/Hofmann selectivity of an E2 elimination. The small base EtO can attack the H atoms in both positions / to the leaving group, i.e., it does not matter whether the H atom is bound to a primary or secondary C atom. The regioselectivity therefore results only from product development control the thermodynamically more stable.

When the carbenium ion intermediate of an El elimination can be deprotonated to give two regioisomeric alkenes, generally both of them are produced. If these alkene isomers are Saytzeff and Hofmann products, the first one is produced preferentially because of product development control. This is illustrated in Figure 4.34 by the El elimination from ferf-amyl... 

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