Ru-Catalyzed Alkene−Alkyne Coupling. Total Synthesis of Amphidinolide P

Abstract

A coordinatively unsaturated ruthenium complex catalyzed the formation of a carbon-carbon bond between two judiciously chosen alkene and alkyne partners in good yield, and in a chemo-and regioselective fashion, in spite of the significant degree of unsaturation of the substrates. The resulting 1,4-diene forms the backbone of the cytotoxic marine natural product amphidinolide P. The alkene partner was rapidly assembled from (R)-glycidyl tosylate, which served as a linchpin in a one-flask, sequential three-components coupling process using vinyllithium and a vinyl cyanocuprate. The synthesis of the alkyne partner made use of an unusual anti-selective addition under chelation control conditions of an allyltin reagent derived from tiglic acid. In addition, a remarkably E-selective E 2 process using the azodicarboxylate-triphenylphosphine system is featured. Also featured is the first example of the use of a β-lactone as a thermodynamic spring to effect macrolactonization. The oxetanone ring was thus used as a productive protecting group that increased the overall efficiency of this total synthesis. This work was also an opportunity to further probe the scope of the ruthenium-catalyzed alkene-alkyne coupling, in particular using enynes, and studies using various functionalized substrates are described.

A novel mode of access to polyfunctional organotin compounds and their reactivity in Stille cross-coupling reaction

“…IR (M + ÀC 4 H 9 , 23), 327 (32), 223 (44), 197 (15), 121 (15); organic fragments 77 (16), 57 (14), 51 (14), 41 (100), 39 (27). 22 Hz), 128.9 ( 3 J Sn-C = 47 Hz, 6C), 129.2 ( 4 J Sn-C = 11 Hz, 3C), 137.5 ( 2 J Sn-C = 35 Hz, 3C), 139.6 ( 1 J Sn-C = 460-482 Hz, 3C); 119 Sn NMR d ppm (CDCl 3 ,149 MHz): À97.1; MS (70 eV) m/z: organotin fragments 351 (M + ÀC 4 H 9 , 55), 197 (52), 120 (47); organic fragments 77 (38), 57 (21), 51 (72), 41 (100), 39 (36).…”

Transition metals in organic synthesis: Highlights for the year 2005

“…Intermolecular alkene-alkyne couplings (Alderene reactions) to give 1,4-dienes, catalyzed by ruthenium were used in a synthesis of 21,22-diepimembrarollin [1480], of 1,4-dien-1-ylboronic esters [1481], (+)-amphidinolide A [1482,1483] and amphidinolide P (Eq. (357)) [1484]. A rhodium-catalyzed Alder-ene reaction-intramolecular Michael addition of propargyl alcohols with 3-enones was reported to give 4-methylene-2,6-dihydropyrans [499].…”

Acetylides from Alkyl Propiolates as Building Blocks for C3 Homologation

“…[10] Other electrophiles, such as nitrones, [11][12][13] acid chlorides, [14] Weinreb amides, [15,16] and acylpyridinium ions [17] are also accessible to these anions (Scheme 1). Less-active electrophiles require the use of coactivators or the replacement (transmetalation) of lithium with magnesium, [18] zinc, [19][20][21][22] cerium [23] or boron [24] ). The stereoselectivity of these C 3 homologations is substratecontrolled, and good diastereoselectivity can be achieved by convenient combinations of chiral auxiliary and metal.…”