Total Synthesis of (S)-(+)-Imperanene. Effective Use of Regio- and Enantioselective Intramolecular Carbon−Hydrogen Insertion Reactions Catalyzed by Chiral Dirhodium(II) Carboxamidates

Abstract

The total synthesis of (S)-(+)-imperanene, a natural product found in Chinese medicine, has been completed in 12 steps from a commercially available cinnamic acid. The key step is highly enantioselective carbon-hydrogen insertion from a diazoacetate using a chiral dirhodium(II) carboxamidate catalyst. An elimination process essential to the construction has been optimized to avoid intramolecular Friedel-Crafts alkylation.

Human Tyrosinase Inhibitor in Rum Distillate Wastewater

“…The 100% methanol eluate contained the highest tyrosinase inhibitory activity, and was successively subjected to silica gel, Toyopearl ® HW-40C and LiChroprep ® RP-18 chromatography to afford biologically active compound . Isolated was determined to be (S)-(+)-imperanene by comparing its spectral data with data reported previously 20,21) . Imperanene is a lignan in the rhizomes of Imperata cylindrica (L.) Beauv.…”

Catalytic asymmetric C–H insertion reactions of α-diazocarbonyl compounds

“…Doyle's chiral rhodium(II) carboxamidates are reliable catalysts for highly enantioselective intramolecular lactone synthesis. The imidazolidinone catalyst Rh 2 (S-MPPIM) 4 has proved to be particularly effective for the carbenoid decomposition reactions of primary and secondary alkyl diazoacetates, 87,83,86,118 while the related compound Rh 2 (S-MACIM) 4 has found success in the C-H insertion reactions of tertiary alkyl diazoacetates. 78,120 For the generation of dihydrobenzofuran products, the choice of catalytic system may include both Hashimoto's phthalimide catalysts and Davies' prolinate-and adamantate-derived catalysts.…”

“…The imidazolidinone complex Rh 2 (MPPIM) 4 has emerged as the superior catalytic choice in many cases, outperforming alternative rhodium(II) carboxamidates in terms of both yield and enantioselectivity (Table 9, entries a-c). 83,86,87,118 It has been suggested that the success of Rh 2 (MPPIM) 4 may be attributed to its extended N-3 phenylpropanoyl chain which causes enhanced steric interactions between the catalyst ligands and the reacting carbene, thereby reducing the number of possible carbenoid orientations and resulting in increased enantioselectivity. Excellent regio-and diastereocontrol may also be achieved for Rh 2 (S-MPPIM) 4 -catalysed C-H insertions.…”

Functionalization of Carbon–Hydrogen Bonds Through Transition Metal Carbenoid Insertion

“…The Doyle group reported an intramolecular approach toward this natural product, with diazoester 198 as the cyclization precursor (Scheme 49, top) [140]. In the key event, Rh 2 (4 S-MPPIM) 4 -catalyzed carbenoid insertion led to lactone 199 in 68% yield and 93% ee.…”