Combined use of three forms of chiroptical spectroscopies in the study of the absolute configuration and conformational properties of 3-phenylcyclopentanone, 3-phenylcyclohexanone, and 3-phenylcycloheptanone Patrizia Scafato a , Francesca Caprioli a, y , Laura Pisani a , Daniele Padula b , Fabrizio Santoro c , Giuseppe Mazzeo d , Sergio Abbate d, * , France Lebon d , Giovanna Longhi d a Dipartimento di Scienze, Universit a della Basilicata, Via dell’Ateneo Lucano, 85100 Potenza, Italy b Institute of Organic Chemistry and Biochemistry, Academy of Sciences, Flemingovo n amĕstí 2, 16610 Prague, Czech Republic c CNR, Consiglio Nazionale delle Ricerche, Istituto di Chimica dei Composti Organometallici (ICCOM-CNR), UOS di Pisa, Area della Ricerca, via G. Moruzzi 1, 56124 Pisa, Italy d Dipartimento di Medicina Molecolare e Traslazionale, Universit a di Brescia, Viale Europa 11, 25123 Brescia, Italy article info Article history: Received 26 July 2013 Received in revised form 23 September 2013 Accepted 7 October 2013 Available online 21 October 2013 We dedicate this work to the memory of Carlo Rosini, who suggested undertaking this study before his premature death Keywords: ORD ECD VCD Vibronic features Absolute configuration Conformations Phenyl hindered rotation abstract Three forms of chiroptical spectroscopies, electronic circular dichroism (ECD), vibrational circular di- chroism (VCD), and optical rotatory dispersion (ORD) have been employed to study the configuration and conformational properties of the three molecules: (S)-3-phenylcyclopentanone, (S)-3- phenylcyclohexanone, and (S)-3-phenylcycloheptanone (including (S)-3-phenylcyclopentanone-2,2,5,5- d 4 and (S)-3-phenylcyclohexanone-2,2,6,6-d 4 ). ECD and VCD spectra in the mid-IR for the three mo- lecular systems are marginally dependent on fine conformational details, as interpreted in terms of standard DFT computational methods, with common spectroscopic features to the three systems clearly identified. Accounting for vibronic coupling mechanisms reproduces the structuring of ECD n/p* band. The ORD curves are quite similar for the three types of molecules, but their interpretation highlights a crucial role played by conformations of the cycloalkanone ring in the case of (S)-3- phenylcycloheptanone. The same conclusions are reached by considering the VCD spectra in the CH- stretching region. Ó 2013 Elsevier Ltd. All rights reserved. 1. Introduction In the last 15e20 years, the increased availability of quantum- mechanical and computational methods, coded in easy-to-use and largely available packages, has enabled more and more scien- tists to better understand chiral molecules by predicting and comparing several experimental properties with computational analyses, disclosing new opportunities in the research field of chirality. Through the investigation of chiroptical properties, 1 like optical rotation (OR), optical rotatory dispersion (ORD), electronic circular dichroism (ECD) and vibrational circular dichroism (VCD), 2 it is possible nowadays to perform accurate structural analyses and to arrive at the safe determination of the molecular absolute con- figuration (AC). In many studies, chiroptical data of molecules having either known or unknown AC were correctly predicted. More recently the absolute configuration has been assigned mainly by the concerted use of these techniques. 3 The combined use of all these powerful chiroptical tools allows the AC determination of organic molecules to receive a safer solution. However, in spite of such significant progress, some relevant problems still remain: in particular, the treatment of molecules endowed with high confor- mational flexibility requires accurate calculation of the relative * Corresponding author. E-mail address: abbate@med.unibs.it (S. Abbate). y Present address: Stratingh Institute for Chemistry, Faculty of Mathematics and Natural Sciences, University of Groningen, Nijenborgh 4, 9747AG Groningen, The Netherlands. Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet 0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tet.2013.10.016 Tetrahedron 69 (2013) 10752e10762