Ru-catalyzed alkene-alkyne coupling. Total synthesis of amphidinolide P.
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, despite 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 E2 process using the azodicarboxylate-triphenylphosphine system is featured. Also featured is the first example of the use of a beta-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.
Trost
Barry M
BM
Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA. bmtrost@stanford.edu
Papillon
Julien P N
JP
Nussbaumer
Thomas
T
D000475:Alkenes / Q000737:chemistry*; D000480:Alkynes / Q000737:chemistry*; D002384:Catalysis; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D018942:Macrolides; D009942:Organometallic Compounds / Q000737:chemistry; D012428:Ruthenium / Q000737:chemistry; D000097442:Amphidinolides
D000475:Alkenes; D000480:Alkynes; D006571:Heterocyclic Compounds; D018942:Macrolides; D009942:Organometallic Compounds; D012428:Ruthenium; C407987:amphidinolide P; D000097442:Amphidinolides