American Chemical Society
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Highly Diastereoselective Hydrogenations Leading to β-Hydroxy δ-Lactones in Hydroxy-Protected Form. A Modified View of δ-Lactone Conformations

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journal contribution
posted on 2003-09-03, 00:00 authored by Svante Brandänge, Magnus Färnbäck, Hans Leijonmarck, Anders Sundin
Enol MEM ethers 4 and 15 and the corresponding enol acetates were hydrogenated over Pd/C with very high (>99%) diastereoselectivity to saturated δ-lactones. A stereochemical generalization can be formulated thus:  trans-5,6-disubstituted 1-oxa-3-cyclohexen-2-ones (e.g. 14 and 15) are hydrogenated over Pd with high selectivity from the side trans to the C(6)-substituent. A mechanistic rationalization of the stereochemical outcome in the Pd-catalyzed hydrogenation of this as well as other types of substituted α,β-unsaturated δ-lactones is presented. An analysis of X-ray crystallographic data for 67 compounds demonstrated a great conformational diversity of the saturated δ-lactone ring. Besides, ab initio calculations (HF/6-31G*) indicated a very high conformational mobility. Thus, the lowest calculated transition state for the conversion of the half-chair, most stable, conformer of δ-valerolactone to the boat-type conformer lies only 1.93 kcal/mol above the former. Beside these two conformers, also chair, envelope and skew conformations are accessible; all lie less than 2 kcal/mol above the half-chair. The previous conformational paradigm comprising only boat and half-chair types is incomplete.