Steric strain control

The structure of the cyclic ketone is of utmost importance. Reduction of cyclic ketone by complex hydrides is started by a nucleophilic attack at the carbonyl function by a complex hydride anion. The approach of the nucleophile takes place from the less crowded side of the molecule (steric approach or steric strain control) leading usually to the less stable alcohol. In ketones with no steric hindrance (no substituents flanking the carbonyl group or bound in position 3 of the ring) usually the more stable (equatorial) hydroxyl is generated (product development or product stability control) [850, 851, 852, 555]. The contribution of the latter effect to the stereochemical outcome of... 

Steric approach control, 67 Steric strains, 71 Steric strain control, 69 Steroid hydrogenation, 111 5/3-Stigmast-22-en-3-one, 130 Stigmasterol, 266 Sulfur dichloride, 459 Sulfur tetrafluoride, 459, 472 Sulfur tetrafluoride fluorination, 471 Surface catalysts, 157... 

The terms steric strain control and product stability control are preferred by H. C. Brown and H. R. Deck, J. Amer. Chem. Soc., 87, 5620 (1965). 

The relation of rates of reduction with NaBH4 to variations in structure in a wide variety of monocyclic and bridged bicyclic compounds has also been discussed for example, a methyl a to a ketone slows the rate of reduction. Brown ° stated that reactions should not be discussed in terms of axial and equatorial attack, since the rates simply reflect differences in the energies of the possible transition states and not enough is known about the transition state to analyze it. He accepted th concepts of SAC and PDC, but preferred to call them steric strain contrpl and product stability control. ... 

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. 

Oxidation of the Cu02 layer removes electrons from the x2-y2 bands which have antibonding character in the in-plane Cu-O bonds. Therefore, as the number of holes (nH) increases, the in-plane Cu-O bond length (rCu 0) is shortened. In addition to this electronic factor, the in-plane rCu 0 is also controlled by a nonelectronic factor (i.e., steric strain) associated with the cations located at the 9-coordinate sites adjacent to the Cu02 layers (e.g., La, Sr, Ba) (40). With the increasing size of the 9-coordinate site cations, the in-plane Cu-O bond is lengthened to reduce the extent of the resulting steric strain. 

Thermodynamic product it has less steric strain and is more stable than the kinetic-controlled isomer having a bulky (-butyl group ortho to a CH,. 

In most cases, steric effects control the axial-equatorial equilibrium and favor the equatorial position of the substituents. Indeed, an axial substituent experiences gauche interactions with C-3 and C-5, while the equatorial substituent is trans to C-3 and C-5 and thus relieves the strain of these gauche, interactions. Furthermore, the two axial hydrogens on C-3 and C-5 experience steric interactions with the hydrogen atom (LXXXa) or the substituent (LXXXb) occupying the C-1 axial position. These diaxial 1 /3 interactions are larger with a substituent than with H. 

The stereochemical characteristics of lithium trimethoxyaluminohydride and lithium aluminum hydride in the reduction of cyclic ketones were analyzed by a linear combination of steric strain and product stability control. Qualitative and quantitative explanation of the experimental observations was possible using this approach. ... 

The effect of steric strain in the imine anion assures good regiochemical control for alkylation. ... 

These results are consistent with the chelated transition states depicted in Scheme 18. Steric interactions between the substituent and the carboxamide favor (AC) for ( )-allylic ethers. The R -substi-tuent of a (Z)-allylic ether, though less affected by this interaction, still experiences a certain degree of steric strain in the anti transition state (AB) thus diminishing anti selectivity. Enantioselectivity is controlled by the substituents R and R on the pyrrolidine ring. As pictured in Scheme 18, bonding occurs preferentially on the face of the enolate anti to R. For the diastereomeric secondary allylic ethers (Table 21, entries 8) transition state (AB) represents the matched arrangement for R = H and R = alkyl, whereas (AC) is matched for R = alkyl and R = H. The former arrangement would lead to an ( )-pro-duct and the latter to a (Z)-product. 

---