Frontier molecular orbital theory synthesis

The period 1930-1980s may be the golden age for the growth of qualitative theories and conceptual models. As is well known, the frontier molecular orbital theory [1-3], Woodward-Hoffmann rules [4, 5], and the resonance theory [6] have equipped chemists well for rationalizing and predicting pericyclic reaction mechanisms or molecular properties with fundamental concepts such as orbital symmetry and hybridization. Remarkable advances in aeative synthesis and fine characterization during recent years appeal for new conceptual models. 

This alternation of chemical behavior, 67t-system versus 47t-system, thermal versus photochemical, has at its core the quantum effeas that dictate the symmetries of molecular orbitals. In 1964, Roald Hoffmann (1937- ) was 27, had completed his Ph.D. at Harvard two years earlier, and was in the second year of an appointment as a Harvard junior fellow. The renowned Woodward (who would win the Nobel Prize in chemistry in 1965) discussed his observations on electrocyclic reactions with Hoffmann. Although Kenichi Fukui had developed frontier molecular orbital theory more than a decade earlier and many related theoretical ideas were percolating in the chemical community, it was Woodward and Hoffmann who published, in 1965, their intellectual synthesis as a book titled The Conservation of Orbital Symmetry. Their theory explained a broad spectrum of concerted reactions and made bold predictions that were later verified. 

The "principle of microscopic reversibility", which indicates that the forward and the reverse reactions must proceed through the same pathway, assures us that we can use the same reaction mechanism for generating the intermediate precursors of the "synthesis tree", that we use for the synthesis in the laboratory. In other words, according to the "principle of microscopic reversibility", [26] two reciprocal reactions from the point of view of stoichiometry are also such from the point of view of their mechanism, provided that the reaction conditions are the same or at least very similar. A corollary is that the knowledge of synthetic methods and reaction mechanisms itself -according to the electronic theory of valence and the theory of frontier molecular orbitals- must be applied in order to generate the intermediate precursors of the "synthesis tree" and which will determine the correctness of a synthesis design and, ultimately, the success of it. 

Roald Hoffmann, a former coworker of R.B. Woodward and Nobel Prize as well for his contribution to the frontier orbital theory (the famous Woodward-Hoffmann rules concerning the conservation of molecular orbital symmetry), has also emphasised the artistic aspects of organic synthesis "The making of molecules puts chemistry very close to the arts. We create the objects that we or others then study or appreciate. That s exactly what writers, visual artists and composers do" [15a]. Nevertheless, Hoffmann also recognises the logic content of synthesis that "has inspired people to write computer programs to emulate the mind of a synthetic chemist, to suggest new syntheses". 

Theoretical studies are also done to interpret the synthesis reactions and mechanism of reactions. The regioselectivity of 1,3-dipolar cycloaddition reaction between substituted trimethylstannyl-ethynes and nitrile oxides yielding isoxazoles, was interpreted by the application of frontier electron theory <93CPB478>. By the combination of experimental and molecular orbital (ab initio) studies, a multistep mechanism is proposed for unimolecular radical chemistry of isoxazoles in the gas phase <920MS(27)317>. 

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