Synlett 2013; 24(5): 535-549
DOI: 10.1055/s-0032-1318217
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© Georg Thieme Verlag Stuttgart · New York

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

Ana Arrieta
a   Departamento de Química Orgánica I – Kimika Organiko I Saila, Facultad de Química – Kimika Fakultatea, Universidad del País Vasco – Euskal Herriko Unibertsitatea (UPV/EHU), P° Manuel de Lardizabal 3, 20018 San Sebastián-Donostia, Spain   Fax: +34(943)015270   Email: fp.cossio@ehu.es
,
María C. de la Torre
b   Instituto de Química Orgánica General (IQOG), CSIC, Juan de la Cierva 3, 28006 Madrid, Spain
,
Abel de Cózar
a   Departamento de Química Orgánica I – Kimika Organiko I Saila, Facultad de Química – Kimika Fakultatea, Universidad del País Vasco – Euskal Herriko Unibertsitatea (UPV/EHU), P° Manuel de Lardizabal 3, 20018 San Sebastián-Donostia, Spain   Fax: +34(943)015270   Email: fp.cossio@ehu.es
c   Ikerbasque, Basque Foundation for Science, 48011 Bilbao, Spain
,
Miguel A. Sierra
d   Facultad de Ciencias Químicas, Universidad Complutense de Madrid, Avda. Complutense s/n, 28040 Madrid, Spain
,
Fernando P. Cossío*
a   Departamento de Química Orgánica I – Kimika Organiko I Saila, Facultad de Química – Kimika Fakultatea, Universidad del País Vasco – Euskal Herriko Unibertsitatea (UPV/EHU), P° Manuel de Lardizabal 3, 20018 San Sebastián-Donostia, Spain   Fax: +34(943)015270   Email: fp.cossio@ehu.es
› Author Affiliations
Further Information

Publication History

Received: 17 December 2012

Accepted after revision: 22 January 2013

Publication Date:
12 February 2013 (online)


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

 
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