Toward the Synthesis of Muironolide A: Synthesis and Structure of Heteroleptic Lanthanide–Terpyridine Complexes with 2‐Oxo Amides

Abstract

A lanthanide-catalyzed intramolecular Diels-Alder (IMDA) reaction en route to the synthesis of muironolide A is described, along with detailed crystallographic structural studies of lanthanide complexes between β-oxo amides and terpyridine. The X-ray crystallographic studies are first exam-

Total Synthesis and Structural Revision of (+)-Muironolide A

“…After careful optimization, we found that the final amide deprotection is ideally performed under oxidative conditions upon heating at 100 °C with DDQ in dioxane with a controlled water content of 0.09% (90% yield). 17 The 1 H and 13 C NMR data of the resulting compound did not match those reported for the natural product.…”

“…The IMDA reaction can be performed directly by thermal activation or under catalytic conditions. 13 We found that the thermal cycloaddition can be performed simply by heating the substrate at 110 °C in toluene, with no base additive required. It was also characterized by a very high level of diastereocontrol favoring the exo-IMDA product (>30:1).…”

“…Herein we report the enantioselective total synthesis of compound 1 with the originally assigned structure of muironolide A along with its C21,C22,C23-diastereomer 2 (Figure 1). Based on 1 H and 13 C NMR data from these two compounds, none of which matched those of the natural substance, we made a projection for the corrected structure. This structure was also accessed by total synthesis, and characterization data for this compound were found to be fully consistent with those of the natural product, resulting in the reassignment of stereochemistry at C21 and establishing the absolute stereochemistry as the enantiomer of 3.…”

“…As anticipated, such stabilized enolates could be generated catalytically via soft enolization, and a screen of Lewis acid additives revealed that lanthanide triflates or nitrates were effective catalysts. 13 In the event, when 3b was treated with 10 mol % of La(OTf) 3 , 12 mol % of PYBOX ligand 12, and triethylamine in ethyl acetate at 45 °C, exo-IMDA product 13 was obtained as an inseparable 3:1 mixture with its C4,C5,C8,C11-diastereomer in 61% combined yield (Scheme 4). Reduction of 13 with NaBH 4 afforded a mixture of two isomeric products which now could be readily separated by preparative HPLC.…”

β‐Keto Amides: A Jack‐of‐All‐Trades Building Block in Organic Chemistry

“…Some of these structures had been substantiated by X‐ray crystallography analysis. However, other lanthanides such as praseodymium (Pr), gadolinium (Gd), terbium (Tb), erbium (Er), ytterbium (Yb), lutetium (Lu) failed to give qualified single‐crystals for structure analysis [312] . It's worth to mention that most of the reported acetylacetonato complexes with lanthanides were supported by at least two such ligands, herein only one β ‐keto amide ligand was present.…”