Computational Chemistry; A Useful Tool for the Chemical Synthesis of Complex Molecules, Heterocycles and Catalysts

Abstract

This Account describes our recent studies on the chemical synthesis of cyclic, densely substituted molecules by means of a hybrid approach consisting of the synergistic interaction between computational and experimental chemistry. In addition, two related total syntheses of complex molecules (±)-Scopadulin and (–)-­Exiguolide are presented as case studies in which computational chemistry can be used to detect and, eventually, avoid potential failures involving key transformations of advanced intermediates.

1 Introduction

2 Computational Treatment of Molecules

3 Computational Characterization of Reactants, Reaction ­Intermediates, Products and Transition Structures

4 Computational–Experimental Analysis of the Stereocontrol in Thermal Pericyclic Reactions

4.1 Concerted and Stepwise [3+2] Cycloadditions

4.2 Concerted and Stepwise [8+2] Cycloadditions

5 Total Synthesis of Complex Molecules; Two Case Studies

5.1 Total Synthesis of (±)-Scopadulin

5.2 Total Synthesis of (–)-Exiguolide

6 Conclusions and Outlook

Key words

pericyclic reactions - cycloaddition - asymmetric ­catalysis - antitumor agents - metathesis - Michael addition - ring ­closure - ylides

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