Efficient Entry to the Hasubanan Alkaloids: First Enantioselective Total Syntheses of (−)‐Hasubanonine, (−)‐Runanine, (−)‐Delavayine, and (+)‐Periglaucine B

Abstract

Maximized divergence: The hasubanan alkaloids given in the scheme have been synthesized in eight or nine steps from the aryl azide 1. The utility of 5‐trimethylsilylcyclopentadiene as an easily removed, stabilizing stereocontrol element has been demonstrated.

Mn-, Fe-, and Co-Catalyzed Radical Hydrofunctionalizations of Olefins

“…194,195,196 Specifically, treatment of 67 with stoichiometric Co(acac) 2 in isopropanol at 75 °C hydrated the styrenyl alkene, and conjugate addition occured upon treatment with excess formic acid to yield (+)-periglaucine B ( 68 ) in 55% over 2 steps. The hydration reaction proceeded with 2.2:1 diastereoselectivity in favor of the desired isomer.…”

“…194,195,381 However, they had found only one method (using a [Rh] catalyst under a hydrogen gas atmosphere) which could give them their desired product, and this in only 17% yield (56% based on unreacted starting material). This underwhelming result prompted them to develop a better method.…”

Total Syntheses of (−)‐Acutumine and (−)‐Dechloroacutumine

“…[8,9] Central to the success of this earlier work was the stereoselective and site-selective addition of arylacetylide nucleophiles (represented by the generalized structure 5; Scheme 1 b) to the complex, thermally unstable iminium ion 4 (formed in situ by N-methylation of the corresponding imine at À60 8C). Our routes build on our syntheses of various hasubanan alkaloids, including (À)-hasubanonine (3).…”

“…[8] Treatment of 12 with methyl triflate (À30 8C) to form the N-methyliminium ion 4, followed by cooling to À90 8C and addition of the lithium acetylide 10·Li (generated by deprotonation of 10 with nbutyllithium at À78 8C) provided the 1,2-addition product 13 as a single diastereomer (85 %, 1 H NMR analysis). [8] Treatment of 12 with methyl triflate (À30 8C) to form the N-methyliminium ion 4, followed by cooling to À90 8C and addition of the lithium acetylide 10·Li (generated by deprotonation of 10 with nbutyllithium at À78 8C) provided the 1,2-addition product 13 as a single diastereomer (85 %, 1 H NMR analysis).…”

Synthetic Strategies toward Natural Products Containing Contiguous Stereogenic Quaternary Carbon Atoms

“…Intermolecular Diels–Alder reaction between quinone 63 and trimethylsilyl cyclopentadiene 64 in the presence of the triflate salt of the Corey-Bakshi-Shibata (CBS) oxazaborolidine reagent, [47] led to endo -product 65 in excellent enantioselectivity. [48] Conversion to an amine via a Staudinger reaction, followed by N -methylation, gave iminium intermediate 66 , which was allowed to react with lithium acetylide 67 (prepared from 61 in four steps) to give 1,2-adduct 68 in excellent yield as a single diastereomer. Thermal extrusion of silylcyclopentadiene provided the retro -Diels–Alder product 69 in a remarkable 98 % yield.…”