Dipolar frontier orbital approach

Calculations at several levels of theory (AMI, 6-31G, and MP2/6-31G ) find lower activation energies for the transition state leading to the observed product. The transition-state calculations presumably reflect the same structural features as the frontier orbital approach. The greatest transition-state stabilization should arise from the most favorable orbital interactions. As discussed earlier for Diels-Alder reactions, the-HSAB theory can also be applied to interpretation of the regiochemistry of 1,3-dipolar cycloaddi-... 

This chapter will try to cover some developments in the theoretical understanding of metal-catalyzed cycloaddition reactions. The reactions to be discussed below are related to the other chapters in this book in an attempt to obtain a coherent picture of the metal-catalyzed reactions discussed. The intention with this chapter is not to go into details of the theoretical methods used for the calculations - the reader must go to the original literature to obtain this information. The examples chosen are related to the different chapters, i.e. this chapter will cover carbo-Diels-Alder, hetero-Diels-Alder and 1,3-dipolar cycloaddition reactions. Each section will start with a description of the reactions considered, based on the frontier molecular orbital approach, in an attempt for the reader to understand the basis molecular orbital concepts for the reaction. 

The structural requirements of the mesomeric betaines described in Section III endow these molecules with reactive -electron systems whose orbital symmetries are suitable for participation in a variety of pericyclic reactions. In particular, many betaines undergo 1,3-dipolar cycloaddition reactions giving stable adducts. Since these reactions are moderately exothermic, the transition state can be expected to occur early in the reaction and the magnitude of the frontier orbital interactions, as 1,3-dipole and 1,3-dipolarophile approach, can be expected to influence the energy of the transition state—and therefore the reaction rate and the structure of the product. This is the essence of frontier molecular orbital (EMO) theory, several accounts of which have been published. 16.317 application of the FMO method to the pericyclic reactions of mesomeric betaines has met with considerable success. The following section describes how the reactivity, electroselectivity, and regioselectivity of these molecules have been rationalized. 

We are far from exhausting the subject of regioselectivity in dipolar cycloadditions with these few examples. Frontier orbital theory, for all its success in accounting for most of the otherwise bewildering trends in regioselectivity, is still fundamentally defective. We should keep in mind that the frontier orbitals used here must reflect some deeper forces than those that we are taking into account in this essentially superficial approach. Nevertheless, no other easily assimilated theory, whether based on polar or steric factors, or on the possibility of diradical intermediates, has had anything like such success. 

A cyclic transition state model, that differs from the Zimmerman-Traxler and the related cyclic models inasmuch as it does not incorporate the metal in a chelate, has been proposed by Mulzer and coworkers [78] It has been developed as a rationale for the observation that, in the aldol addition of the dianion of phenylacetic acid 152, the high ti-selectivity is reached with naked enolate anions (e.g., with the additive 18-crown-6). Thus, it was postulated that the approach of the enolate to the aldehyde is dominated by an interaction of the enolate HOMO and the n orbital of the aldehyde that functions as the LUMO (Scheme 4.31), the phenyl substituents of the enolate (phenyl) and the residue R of the aldehyde being oriented in anti position at the forming carbon bond, so that the steric repulsion in the transition state 153 is minimized. Mulzer s frontier molecular orbital-inspired approach reminds of a 1,3-dipolar cycloaddition. However, the corresponding cycloadduct 154 does not form, because of the weakness of the oxygen-oxygen bond. Instead, the doubly metallated aldol adduct 155 results. Anh and coworkers also emphasized the frontier orbital interactions as being essential for the stereochemical outcome of the aldol reaction [79]. 

Such cycloadditions involve the addition of a 2tt- electron system (alkene) to a 4ir- electron system (ylide) and have been predicted to occur in a concerted manner according to the Woodward-Hoffmann rules. The two most important factors involved in the cycloaddition reactions are (i) the energy and symmetry of the reacting orbitals and (ii) the thermodynamic stability of the cycloadduct. The reactivity of 1,3-dipolar systems has been successfully accounted for in terms of HOMO-LUMO interactions using frontier MO theory (71TL2717). This approach has been extended to explain the 1,3 reactivities of the nonclassical A,B-diheteropentalenes <77HC(30)317). 

One realizes that this frontier molecular orbital (FMO) approach for this [1 + 2] cycloaddition is analogous to that for 1,3-dipolar cycloadditions (Sect. 6.3). 

---