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

Abstract

Enol MEM ethers 4 and 15 and the corresponding enol acetates were hydrogenated over Pd/C with very high (>99%) diastereoselectivity to saturated delta-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 alpha,beta-unsaturated delta-lactones is presented. An analysis of X-ray crystallographic data for 67 compounds demonstrated a great conformational diversity of the saturated delta-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 delta-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.

Integrated approaches to the configurational assignment of marine natural products

“…ccix The C4 S ,C5 S configurations established by NOESY correlations. ccx Only the 7 R ,11 R diastereomer was consistent with J coupling, NOESY data, and molecular modeling.…”

(−)‐R‐Mevalonolactone Studied by ROA and SERS Spectroscopy

“…However, the calculations predict that for mono‐ and disubstituted saturated δ‐lactones besides these two conformers, also chair, skew, and envelope conformations are possible to reach. For example, the δ‐valerolactone with the methoxy substituent in the same position in the six‐membered ring like substituents in the (−)‐R‐mevalonolactone molecule take chair, half‐chair, skew, and boat conformations . On the other hand, the calculations show that the compound with the methyl group in the same place exist in half‐chair and boat conformations only …”

“…Conformations of solitary saturated δ‐lactones determined by X‐ray crystallography are diverse as well. Moreover, the six‐membered ring of one compound can take two or even more conformations in the solid state …”

The Observation of the C–H···O Hydrogen Bond in Trisialic Acid Lactone and Its Implications for Cooperative Lactonization

“…[40] Furthermore, the binding energy of the C-H···O sp 3 hydrogen bond in the two-fragment model OLD 4 can be directly calculated by using a standard procedure to remove basis set superposition errors (BSSE), and the binding energy was estimated to be 1.61 kcal/mol at the MP2/6-31G* level of theory. The MP2 binding energy was further checked by using a mixed basis set in which extra sets of diffuse and polarized basis functions for the two atoms [41] the total energy of the S-type conformer is 1-1.5 kcal/mol higher than that of the half-chair conformer. In OSA/PSA lactones, the glycosidic oxygen O 8 as a hydrogen-bond acceptor contributes approximately 1.0-1.6 kcal/ mol of the binding energy of two lactone moieties.…”