Periselectivity substituent effects

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. 

Figure 4 shows the main geometric features of the transition structures associated with the [n4c] and [n6d] steps in the reaction between ketene and prop-2-en-l-imine. Experimental and computational studies [42, 43] showed that the periselectivity of this reaction is very sensitive to substituent effects. Thus, in general disubstituted ketenes and/or imines possessing bulky substituents at the (3-position favor the formation of [2+2] cycloadducts because of severe steric... 

SCHEME 4.11 Acyclic diene substituent effects on periselectivity. 

A surprising steric sensitivity is frequently observed for these radical cation reactions. As was shown previously during the discussion of chemoselectivity, the variable positioning of bulky substituents has effects on periselectivity as well. DFT calculations on the influence of diene substitutions for the neutral reaction have demonstrated a behavior similar to that of the radical cation reaction. Although... 

Keywords Spiroconjugation Periselectivity Carbenes Ketenes Torquoselectivity Ambident nucleophiles and electrophiles a-effect Hammett s substituent constants Hammond postulate Curtin-Hammett principle Diastereotopic Homotopic Enantiotopic substituents... 

---