Ring-chain equilibria of R-but-3-enoate esters — A quantum mechanical study of direct and indirect ring-closing reactions Michael B. Burt, Angela K. Crane, Ning Su, Nicole Rice, and Raymond A. Poirier Abstract: Macrocyclic structures can be synthesized through two simultaneous olefin metathesis reactions: either directly through ring-closing metathesis (RCM) or indirectly through an intermediate formed by acyclic diene metathesis (ADMET). The proclivity of a homologous series of 16 R-but-3-enoate esters to form lactones through one of these two processes is studied at the HF/6–31G(d), B3LYP/6–31G(d), and MP2(full)/6–31G(d) levels of theory. Computed Gibbs free energies are used to determine DGRCM, DGADMET, and DDG (DGRCM – DGADMET). DDG is evaluated to compare the relative favourability of the RCM and ADMET reactions for the various R-but-3-enoate esters, where each system is differentiated by the number of methylene groups (n) added to the ester chain. When n = 0, 1, 10, or 13, cyclic lactone formation by direct RCM is predicted to be thermodynamically favoured, and the indirect synthesis is preferred for all other heterocyclic structures. The same trend holds between 298.15 and 333.15 K, therefore, the gas-phase model is a rea- sonable approximation of the experimental reaction conditions. The theoretical model is sufficient for smaller systems, but molecules larger than the n = 6 case do not follow experimental results for similar saturated structures. Hence, the assump- tions pertaining to straight-chain and cis-ring conformations need to be re-evaluated. In particular, chain flexibility should be further examined. Key words: olefin metathesis, ring-chain equilibria, ring-closing metathesis, acyclic diene metathesis. Re ´sume ´: On a re ´alise ´ des synthe `ses de structures macrocycliques par le biais de re ´actions de me ´tathe `se simultane ´es d’ole ´- fines, soit directement par une me ´tathe `se avec fermeture de cycle (MFC) ou indirectement par un interme ´diaire forme ´ par une me ´tathe `se de die `ne acyclique (METDA). On a e ´tudie ´ d’un point de vue the ´orique la proclivite ´ d’une se ´rie homologue de seize esters de l’acide R-but-3-e ´noı ¨que a ` former des lactones par un de ces deux processus aux niveaux HF/6–31G(d), B3LYP/6–31G(d) et MP2(complet)/6–31G(d) de la the ´orie. On a utilise ´ les e ´nergies libres de Gibbs calcule ´es pour de ´ter- miner les valeurs de DG MFC , DG METDA et DDG (DG MFC – DG METDA ). La valeur de DDG ae ´te ´e ´value ´e afin de comparer le caracte `re favorable relatif des re ´actions de MFC et de METDA des divers esters de l’acide R-but-3-e ´noı ¨que dans les- quels chaque syste `me se distingue par le nombre de groupes me ´thyle `nes (n) ajoute ´a ` la chaı ˆne de l’ester. Quand n = 0, 1, 10 ou 13, il est pre ´dit que la formation de la lactone cyclique par une MFC est thermodynamiquement favorise ´e alors que la synthe `se indirecte est la re ´action pre ´fe ´re ´e pour toutes les autres structures he ´te ´rocycliques. La me ˆme tendance est obser- ve ´e pour 298,15 et 333,15 K; le mode `le en phase gazeuse est donc une approximation raisonnable des conditions re ´action- nelles expe ´rimentales. Le mode `le the ´orique est suffisant pour les syste `mes les plus petits, toutefois les mole ´cules dans lesquelles est supe ´rieure a ` 6 ne reproduisent pas les re ´sultats expe ´rimentaux pour des structures sature ´es similaires. Il est donc impe ´ratif de re ´e ´valuer les hypothe `ses concernant les chaı ˆnes droites et les conformations cis du cycle. On devrait re ´- examiner en particulier la question de la flexibilite ´ de la chaı ˆne. Mots-cle ´s : me ´tathe `se d’ole ´fine, e ´quilibre cycle-chaı ˆne, me ´tathe `se avec fermeture de cycle. Introduction The development of olefin metathesis, a transalkylidena- tion reaction involving the redistribution of alkene bonds, has opened a variety of novel pathways to challenging or pre- viously impossible syntheses. 1–16 In particular, ring-closing metathesis (RCM) has been used for decades to create func- tionalized macrocycles because of its excellent functional group tolerance and neutral reaction conditions. Since these cyclic products are found in many synthetic targets, it is not surprising that RCM has become a popular methodology among synthetic chemists. Furthermore, the advent of Grubbs’ highly reactive ruthenium catalyst has made RCM reactions quick and easily accessible; especially when the catalyst is modified by N-heterocyclic carbene derivatives. 17 Unfortunately, RCM is still impractical at the commercial level owing to the high dilution conditions (1  10 –3 mol/L) Received 27 January 2010. Accepted 20 April 2010. Published on the NRC Research Press Web site at canjchem.nrc.ca on 22 October 2010. This article is part of a Special Issue dedicated to Professor R. J. Boyd. M.B. Burt, 1 A.K. Crane, N. Su, N. Rice, and R.A. Poirier. Department of Chemistry, Memorial University of Newfoundland, St. John’s, NL A1B 3X7, Canada. 1 Corresponding author (e-mail: mburt@mun.ca). 1094 Can. J. Chem. 88: 1094–1103 (2010) doi:10.1139/V10-074 Published by NRC Research Press Can. J. Chem. Downloaded from www.nrcresearchpress.com by Memorial University of Newfoundland on 07/18/12 For personal use only.