Vicinal Bisheterocyclizations of Alkynes via Nucleophilic Interception of a Catalytic Platinum Carbene

Abstract

A novel platinum-catalyzed double heterocyclization of propargylic ethers is described. The transformation exploits the intermediacy of a key α,β-unsaturated carbene. The reactivity of this carbene is such that systems can be developed which avoid a complicating 1,2-hydrogen migration, allowing remarkable versatility in the selective syntheses of oxygen- and nitrogen-containing vicinal bis-heterocyclic compounds.

Enantiospecific Total Syntheses of (+)‐Hapalindole H and (−)‐12‐epi‐Hapalindole U

“…This can be explained by the hydride ion, in taking the axial approach,h aving strong1 ,3 diaxial interactions with the cyclohexane ring hydrogens. This completes the first enantiospecific total synthesis of (+ +)-hapalindole-H (1) and (À)-12-epi-hapalindole U ( 13).S pec-tral data (IR, 1 H, 13 CNMR and HRMS) and opticalr otationo f synthesized 1 and 13 were identicalw ith those of isolated molecules. [1b, 7] We were also interested to showcase the utility of indoloterpene 19 a and ent-19 a for the synthesis of (+ +)-hapalindole Q and (+ +)-12-epi-fischerindoleUisothiocyanate.T owards this goal, nitrogen of indole terpenoid 19 a was protected using benzenesulfonyl chloride.…”

“…Our next focus was opening of b-epoxide by acetylide followed by Lindlarh ydrogenation of at riple bond to obtain the desired alcohol 30.A sp er our assumption, treating epoxide 24 with TMS-acetylenei nt he presenceo fA lMe 3 and BF 3 ·OEt 2 afforded the highly regio-and diastereoselective opening of the corresponding epoxide to furnish compound 28 in 75 %y ield (Scheme 3). [13] Excellent regioselectivity waso bserved for the openingo fe poxide 24,w hich is apparentlyd ue to preferential axial attack of alkynyl aluminate reagent on quaternary carbon Table 2. Substratess cope of the Friedel-Crafts reaction.…”

“…In summary,ahighly regio-and diastereoselective Friedel-Crafts reactionb etween as econdary allylic alcohol and an indole was developed. The potential of this methodology has Scheme3.Synthesis of (+ +)-hapalindole H( 1)a nd (À)-12-epi-hapalindole U ( 13).…”

“…Chem. Eur.J.2018, 24,8980 -8984 www.chemeurj.org been amply demonstrated by the total syntheses of (+ +)-hapalindole H( 1)a nd (À)-12-epi-hapalindole U ( 13), which involves 11 steps in the longest linear sequence startingf rom readily available R-(+ +)-limonene. This methodi sf airly general and amenable to synthesis of other naturalp roducts of this class as well as their analogues.…”

Highly Site Selective Formal [5+2] and [4+2] Annulations of Isoxazoles with Heterosubstituted Alkynes by Platinum Catalysis: Rapid Access to Functionalized 1,3‐Oxazepines and 2,5‐Dihydropyridines

“…[1] However, the generation of Pt carbenes has been explored relatively seldom as compared with the related Au carbenes, [1] and most studies have focused on vinyl Pt carbenes. [5] During the course of our recent studies on transitionmetal-catalyzed tandem reactions based on ynamides, [6,7] we disclosed a novel and atom-economical route to the generation of a-imino Au carbenes through a gold-catalyzed formal [3+2] annulation between ynamides and isoxazoles, thus providing ready access to various 2-aminopyrroles (Scheme 1 a). [3,4] Hence, access to novel Pt carbenes is highly desirable, not only for the enrichment of platinum chemistry, but also because it may result in a selectivity switch for the construction of diverse intricate scaffolds.…”