Through-bond interaction substituent effects

A study of conformationally rigid halogeno-ketones shows that a- or y-fluoro-substituents produce a red shift in the n-% band, and P- or 5-fluorines a zero or blue shift, while an iodo-group produces red shifts when a, p, or 6 but blue when y. Explanations are tentatively offered in terms of alternating charge effects and conjugative through-bond interaction. Details have appeared of the preparation and circular dichroism of the almost symmetrical a-dione (15). 

As suggested by Roberts and Moreland many years ago (1953), the acidity constants of 4-substituted bicyclooctane-l-carboxylic acids provide a very suitable system for defining a field/induction parameter. In this rigid system the substituent X is held firmly in place and there is little possibility for mesomeric delocalization or polarization interactions between X and COOH (or COO-). Therefore, it can be assumed that X influences the deprotonation of COOH only through space (the field effect) and through intervening o-bonds. On this basis Taft (1956, p. 595) and Swain and Lupton (1968) were able to calculate values for o and crR. 

Fig. 15 Predicted cooperative effects on activation energies (in kcal/mol) at the B3LYP/ 6-31G level for model enediynes ( push and pull denote through-space repulsive (steric) and attractive (H-bonding) interactions of ort/zo-substituents with in-plane 71-orbitals of an adjacent acetylene moeity).

On the other hand, 7-azabenzonorbornadiene bearing a tert-but-oxycarbonyl substituent in the 7-position, in spite of the bulky 7-substituent, exhibits exo selectivity in the addition of ethoxycarbonyl azide.129 Benzenesulfonyl and tosyl azides, however, give rise to a complex mixture from which no products could be characterized.129 The phenyl azide adduct has been obtained in 88% yield, but the stereochemistry is not known.1498 An orbital model for the effect of the 7-substituent, as a through-space interaction between the substituent and the syn double bond, has been suggested,150 and generalizations that may help to predict the syn-anti selectivity in these compounds have been developed.99,149,150... 

The face-selectivity of hydride reductions of the conformationally-rigid ketone series (100) has been examined for pure axial and equatorial isomers with four different R groups, viz. Me, Cl, OMe, and SMe.162 The reactivities show Taft correlations with the inductive effects of the substituents. Only through-bond and -space electrostatic interactions are used to explain the results neither Cieplak nor Anh antiperiplanar effects are invoked. 

Abstract The main computational studies on the formation of (3-lactams through [2+2] cycloadditions published during 1992-2008 are reported with special emphasis on the mechanistic and selectivity aspects of these reactions. Disconnection of the N1-C2 and C3-C4 bonds of the azetidin-2-one ring leads to the reaction between ketenes and imines. Computational and experimental results point to a stepwise mechanism for this reaction. The first step consists of a nucleophilic attack of the iminic nitrogen on the sp-hybridized carbon atom of the ketene. The zwitterionic intermediate thus formed yields the corresponding (3-1 actant by means of a four-electron conrotatoty electrocyclization. The steroecontrol and the periselectivity of the reaction support this two-step mechanism. The [2+2] cycloaddition between isocyanates and alkenes takes place via a concerted (but asynchronous) mechanism that can be interpreted in terms of a [n2s + (n2s + n2s)] interaction between both reactants. Both the regio and the stereochemistry observed are compatible with this computational model. However, the combination of solvent and substituent effects can result in a stepwise mechanism. 

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