ELSEVIER THEO CHEM Journal of Molecular Structure (Theochem) 395-396 (1997) 123- I55 Steric and stereoelectronic effects in saturated heterocycles I. Small molecular fragment constituents. Theory vs. experiment’ Hanoch Senderowitz, Benzion Fuchs* School zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA of Chemistry,’ Tel-Aviv University, Ramat-Aviv, 69978 Tel-Aviv, Israel Received 4 October 1996; accepted 29 October 1996 Abstract Structural and energetic consequences of replacing one or more carbon atoms in small, cyclic and acyclic hydrocarbons with electronegative atoms or groups are reviewed. In this first part, the conformation-dependent steric and stereoelectronic effects on the properties (energies, structural parameters, etc.) of small molecular building blocks are scrutinized and these molecules are then zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA use d in a “fragment analysis” of larger molecules, such as carbohydrates or other mono- and polyheterocycles. Satisfactory results were obtained for molecules with single and multiple instances of anomeric and gauche effects involving 0 and N heteroatoms. 0 1997 Elsevier Science B.V. 1. Introduction This review is an outcome of a combined research effort of the “theory vs. experiment” kind, and describes the approach to and results of developing tools for reproducing (and later predicting) experi- mental observations on saturated polyheterocycles exhibiting stereoelectronic, i.e., anomeric [l-4] or gauche [ 1,5,6] effects, in X-C-Y and X-C-C-Y moieties (X, Y are electronegative hetero atoms/ groups), respectively. We aim at a better understand- ing of the nature, origin, manifestations and conse- quences of these effects, since there has been considerable controversy, despite extensive existing documentation on this subject [ 1- 141, and see below. * Corresponding author. ’ This is the first in a series of two review articles on “Steric and Stereoelectronic Effects in Saturated Heterocycles”. *Part of the Raymond and Beverly Sackler Faculty of Exact Sciences. In our approach, we analyse in detail the small molecules which constitute the building blocks of the saturated (poly)heterocycles for which structural and energetical information is sought. This extra- polation from small fragments to larger systems is a known, successful approach in conformational analysis. For example, the conformational energies and structures of butane are applied to substituted cyclohexanes and decalin [l] and those of dimethox- ymethane to 2-methoxytetrahydropyran [3]a, carbo- hydrates, etc. [8,9,13,15]. Our practice is to: (i) seek experimental informa- tion on relevant heterocyclic systems, (ii) analyse the systems in terms of their constituent fragments, i.e. of the small molecular units they are built of and for which accurate structural and conformational data are available, (iii) perform sufficiently good quantum mechanics calculations of the small molecular sys- tems, and, finally, (iv) make available reliable and fast, i.e. molecular mechanics, computational tools 0166.1280/97/$17.00 Copyright 0 1997 Elsevier Science B.V. All rights reserved P/I zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA SO 166.1280(96)04957-3