Nucleophilic attack orbital overlap

The asymmetric induction that has been observed in this reaction can be explained in terms of the model shown in Scheme 9. In the most stable conformation the appropriately positioned phenyl group shields selectively the Re,Re face of the chromadiene by 7r,7r-orbital overlap forcing the nucleophile to attack preferentially on the opposite side. 

The amplitude of the frontier orbitals determines the selectivity. The most reactive atom in a molecule has the largest amplitude of the frontier orbitals. The frontier orbitals overlap each other to the greatest extent at the sites with the largest amphtudes. Reactions occur on the atoms in the electron donors and acceptors, where the HOMO and LUMO amplitudes are largest, respectively. Electrophiles prefer the a position of naphthalene, an electron donor, with the larger HOMO amplitude (Scheme 21). Nucleophiles attack the carbons of the carbonyl groups, an electron acceptor, with the larger LUMO amplitude (Scheme 7). 

Significantly less regioselectivity was observed for benzobicyclo[3.1.0]hexene (47). The isolated products, methanol adducts and NOCAS products of structures 48 and 49, suggest that nucleophilic attack occurs at C5 and C6. These results were explained by the orbital overlap between the benzene ring and the 3 °-3° versus 3 -2 cyclopropane orbitals. ... 

Front-side attack, corresponding to an attack on the big lobe of silicon, leads to retention. When unfavorable, out-of-phase overlap between the nucleophile and the orbitals of the leaving group predominates, nucleophilic attack occurs at the rear of the molecule, opposite X, leading to... 

There are four possible transition states in the reduction of 27 wherein maximum orbital overlap can be maintained with respect to the attacking hydride reagent and the developing electron pair on nitrogen. Two of these (cf. dotted arrow in 29 and 30) require boat-like transition states in order to satisfy the stereoelectronic requirements and are unfavorable kinetic-ally. Of the two possible chair-like transition states (cf solid arrow in 29 and 30) the latter suffers from a strong steric interaction between the nucleophile and the C-8 pseudo-axial hydrogen. The process 30 + 32 is thus disfavored by comparison with the process 29 31. 

Eisch, J. J. Kovacs, C. A. Chobe, P. Carbon-skeletal [1,2] anionic rearrangements and the ir-orbital overlap constraint the question of nucleophilic attack vs electron transfer. J. Org. Chem. 1989, 54, 1275-1284. 

The non-perpendicular Dunitz-Biirgi attack is due a negative frontier orbital overlap between the nucleophile and the oxygen. In the ate complex, the LUMO... 

Spiroacylal 2 was designed under the rationale that the constraint of the carbonyl groups into a conformation in which overlap of their 7r-orbitals with the bent bonds of the cyclopropane is assured should dramatically increase the vulnerability of the cyclopropane toward nucleophilic attack.8 Experimental support for this notion is abundant.8 Spiroacylal 2 is considerably more reactive than 1,1-dicarbethoxycyclopropane in such reactions. For instance, reaction of 2 with piperidine occurs at room temperature. The corresponding reaction in the case of the diester is conducted at 110°C.5 Reactions with enolates also occur under mild conditions.8 Compound 2 reacts with the weak nucleophile pyridine at room temperature to give a betaine.8 An illustrative mechanism for the reaction of the acylal 2 with aniline to afford 2-oxo-l-phenyl-3-pyrrolidinecarboxylic acid (3) is... 

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