Indenylidene Complexes of Ruthenium: Optimized Synthesis, Structure Elucidation, and Performance as Catalysts for Olefin Metathesis—Application to the Synthesis of the ADE-Ring System of Nakadomarin A

Abstract

An optimized and large scale adaptable synthesis of the ruthenium phenylindenylidene complex 3 is described which employs commercially available diphenyl propargyl alcohol 5 as a stable and convenient carbene source. Previous ambiguities as to the actual structure of the complex have been ruled out by a full analysis of its NMR spectra. A series of applications to ring closing metathesis (RCM) reactions shows that complex 3 is as good as or even superior to the classical Grubbs carbene 1 in terms of yield, reaction rate, and tolerance towards polar functional groups. Complex 3 turns out to be the catalyst of choice for the synthesis of the enantiopure core segment 77 of the marine alkaloid nakadomarin A 60 comprising the ADE rings of this target. Together with a series of other examples, this particular application illustrates that catalyst 3 is particularly well suited for the cyclization of medium-sized rings by RCM. Other key steps en route to nakadomarin A are a highly selective intramolecular Michael addition setting the quaternary center at the juncture of the A and D rings and a Takai-Nozaki olefination of aldehyde 73 with CH2I2, Ti(OiPr)4 and activated zinc dust.

A Catalytic Approach to (R)‐(+)‐Muscopyridine with Integrated “Self‐Clearance”

“…In the PES study, the AuX 2 À ions (X ¼ Cl, Br, I) are generated by electrospray ionization of diluted AuX solutions in water/methanol. [11] In the sector experiments, [12,13] fastatom bombardment (FAB) of aqueous slurries of AuX 3 is used to generate AuX 2 À ions; this method does not work for X ¼ I, because reduction of AuI 3 to metallic gold occurs upon contact of the metallic probe tip with the sample. Likewise, no gold-fluoride ions could be generated by FAB of an AuF 3 slurry, because of the rapid hydrolysis of gold fluorides.…”

“…Conversion of the product mixture of 11 and 10 to the corresponding hydrochloride salts [12] followed by treatment with the readily available ruthenium±indenylidene complex 13 (10 mol %) [13,14] under high dilution conditions leads to the selective cyclization of diene 11 to the meta-pyridinophane 12 (E,Z % 1.8:1), while the hydrochloride of compound 10 remains unchanged. This reflects the greater ease of formation of the 13-membered ring as compared to the kinetically and thermodynamically handicapped 11-membered analogue that would derive from 10 by ring-closing metathesis (RCM).…”

Ring closing metathesis employing organometallic substrates and the templated synthesis of macrocycles

“…As well, olefin metathesis is now firmly entrenched in polymer chemistry [1,10]. In addition to the original catalysts, a number of research groups have actively ଝ A portion of this contribution was presented as a lecture at the 16th Interna- pursued the development of either derivative or novel systems that have opened new areas in this chemistry by improving activity, chemo-, regio-and stereo-selectivity as well as addressing important factors such as catalyst stability, ease of synthesis, recycling and functional group tolerance; [1][2][3][4][5][6][7][8][9][11][12][13][14][15][16] see Fig. 1 for a small selection of metathesis catalysts with some selected properties.…”

Catalysis-based enantioselective total synthesis of the macrocyclic spermidine alkaloid isooncinotine

“…In line with our expectations, this key transformation proceeded smoothly in the presence of the ruthenium indenylidene catalyst 14 (36)(37)(38), previously developed in our laboratory as a cheap, stable, and practical alternative to the classical Grubbs catalyst Cl 2 (PCy 3 ) 2 RuACHPh (39). Protonation of the substrate is mandatory to avoid coordination of the amines to the metal center, which would result in loss of the catalytic activity of the ruthenium complex (40).…”

“…An equally highly integrated maneuver accounts for the end game of the synthesis in which the 22-membered ring is forged and saturated in another one-pot process comprising an RCM reaction followed by the hydrogenation of the resulting cycloalkene by using a single ruthenium precatalyst. The indenylidene complex 14 (36) described previously as a readily available and equipotent substitute for the classical Grubbs catalyst serves this twofold purpose very well. Together with the copper-catalyzed installation of the oxazolidin-2-one group (7 3 9) via a procedure recently outlined for the N-arylation of amides (31), all but one key steps of the chosen route rely on metal-catalyzed transformations.…”