ABSTRACT
[reaction: see text] Intramolecular Heck and ring-closing metathesis reactions on key intermediates 10 and 15, respectively, provide efficient entries into seco-C/D ring analogues of Ergot alkaloids 12 and 16, compounds of potential synthetic and biological interest.
Subject(s)
Ergot Alkaloids/chemical synthesis , Adrenergic alpha-Agonists/chemical synthesis , Cyclization , Ergolines/chemical synthesis , Heterocyclic Compounds, Bridged-Ring/chemistry , Molecular Structure , StereoisomerismABSTRACT
New constrained heterocyclic analogues, 2a,b and 3, of Raloxifene (1) have been prepared by complementary Directed remote Metalation (DreM)/Friedel-Crafts cyclization approaches. Utilization of a benzylidene-thiolactone rearrangement was successfully implemented to construct benzothiophenes 13a-c in good yields. Selective deprotection of 13a and 13b induced by complexation followed by triflation gave 18 and 23, thereby allowing efficient Suzuki-Miyaura cross coupling with borolane 16 to give biaryls 19 and 24. Treatment of 19 with BCl(3) induced an intramolecular para Fridel-Crafts cyclization and concomitant double deprotection to furnish analogue 2a, a new 5,6,6,6-(C(4)S-C(6)-C(6)-C(6)) sulfur-containing heterocycle. Exposure of 25 with excess LDA induced a DreM cyclization delivering the ortho-substituted 5,6,6,6-(C(4)S-C(6)-C(6)-C(6)) heterocylic analogue 26 in 70% yield. Similar treatment of 13c and 27 afforded 30, representing the novel 5,5,6,6-(C(4)S-C(5)-C(6)-C(6)) ring system, which was subjected to Suzuki-Miyaura cross coupling with 16 to give the biaryl 31 in 93% yield; deprotection furnished the final constrained analogue 3.
Subject(s)
Raloxifene Hydrochloride/analogs & derivatives , Raloxifene Hydrochloride/chemical synthesis , Selective Estrogen Receptor Modulators/chemical synthesis , Cyclohexanes , Esters , Indicators and Reagents , Molecular Conformation , Raloxifene Hydrochloride/chemistry , Selective Estrogen Receptor Modulators/chemistry , TitaniumABSTRACT
The oxygen-rich heterocyclic compound 1-which was proposed to be the structure of plicadin, the alleged naturally occurring coumestan from the herb Psoralea plicata-was synthesized by the rational combinations of directed ortho and remote metalation reactions with cascades of Negishi, Sonogashira, Castro-Stephens, and carbamoyl Baker-Venkataraman reactions.
