Abstract:We report herein our synthetic efforts towards the divergent syntheses of (À)-huperzine Q( 1), (+ +)-lycopladine B (2), (+ +)-lycopladine C( 3), and (À)-lycopladine D( 4). The 10-step total synthesis of (À)-huperzine Q( 1)a nd the first total syntheses of (+ +)-lycopladines B( 2)a nd C( 3)w ere accomplished through as eries of cascade reactions. Our approach involved aM ichael addition/aldol/intramolecular C-alkylation sequence to forge the 6/9 spirocycle ring, and this was followed by an ethylene-accelerated … Show more
“…We recently reported a distinct design principle for catalytic carbonyl-olefin ring-closing metathesis reactions for the synthesis of cyclic systems such as spirocyclic lactones, indenes, polyaromatic hydrocarbons and 3-pyrrolines. [11][12][13] Upon reaction with FeCl3 as a Lewis acid catalyst, aryl ketones bearing prenyl or styrenyl fragments undergo a concerted, asynchronous [2+2]-cycloaddition to form intermediate oxetanes. A subsequent Lewis acid-catalyzed retro [2+2]-cycloreversion results in the desired ring-closing metathesis product.…”
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<p>Herein, we describe the application of Lewis acid-catalyzed
carbonyl-olefin metathesis towards the synthesis of chiral, substituted
tetrahydropyridines from commercially available amino acids as chiral pool
reagents. This strategy relies on FeCl<sub>3</sub> as an inexpensive and
environmentally benign catalyst and enables access to a variety of substituted
tetrahydropyridines under mild reaction conditions. The reaction proceeds with
complete stereoretention and is viable for a variety of natural and unnatural
amino acids to provide the corresponding tetrahydropyridines in up to 99% yield.</p>
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“…We recently reported a distinct design principle for catalytic carbonyl-olefin ring-closing metathesis reactions for the synthesis of cyclic systems such as spirocyclic lactones, indenes, polyaromatic hydrocarbons and 3-pyrrolines. [11][12][13] Upon reaction with FeCl3 as a Lewis acid catalyst, aryl ketones bearing prenyl or styrenyl fragments undergo a concerted, asynchronous [2+2]-cycloaddition to form intermediate oxetanes. A subsequent Lewis acid-catalyzed retro [2+2]-cycloreversion results in the desired ring-closing metathesis product.…”
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<p>Herein, we describe the application of Lewis acid-catalyzed
carbonyl-olefin metathesis towards the synthesis of chiral, substituted
tetrahydropyridines from commercially available amino acids as chiral pool
reagents. This strategy relies on FeCl<sub>3</sub> as an inexpensive and
environmentally benign catalyst and enables access to a variety of substituted
tetrahydropyridines under mild reaction conditions. The reaction proceeds with
complete stereoretention and is viable for a variety of natural and unnatural
amino acids to provide the corresponding tetrahydropyridines in up to 99% yield.</p>
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“…A similar method was recently reported by the Lei group [121] who used an iminium-catalyzed Robinson annulation reaction to build up the required skeleton enone 174 of Lycopodium alkaloids, namely, (−)-huperzine Q, (+)-lycopladine B, (+)-lycopladine C, and (−)-4- epi -lycopladine D (Scheme 44) starting from the common precursor 175 .…”
Section: Asymmetric Total Synthesis Of Bioactive Natural Products mentioning
Chirality is one of the most important attributes for its presence in a vast majority of bioactive natural products and pharmaceuticals. Asymmetric organocatalysis methods have emerged as a powerful methodology for the construction of highly enantioenriched structural skeletons of the target molecules. Due to their extensive application of organocatalysis in the total synthesis of bioactive molecules and some of them have been used in the industrial synthesis of drugs have attracted increasing interests from chemists. Among the chiral organocatalysts, chiral secondary amines (MacMillan’s catalyst and Jorgensen’s catalyst) have been especially considered attractive strategies because of their impressive efficiency. Herein, we outline advances in the asymmetric total synthesis of natural products and relevant drugs by using the strategy of chiral secondary amine catalyzed reactions of α,β-unsaturated aldehydes in the last eighteen years.
“…Our group finished the second synthesis of (−)‐ 13 in 2015 . As shown in Scheme b, an organocatalytic annulation provided enantioenriched enone ( 143 ).…”
Section: Fawcettimine Alkaloids With Level 2 Oxidation State At C16mentioning
confidence: 99%
“…In 2017, our group also disclosed our synthetic efforts which ultimately accumulated into the synthesis of (−)‐4‐ epi ‐lycopladine D ( 181 ) . As shown in Scheme b, upon treatment with K 2 CO 3 /MeOH, diketo‐aldehyde ( 176 ) underwent tandem C 15 epimerization/intramolecular aldol reaction to generate tetracyclic intermediate ( 177 ).…”
Section: Fawcettimine Alkaloids With Level 4 Oxidation State At C16mentioning
confidence: 99%
“…Lycopladines B ( 18 ) and C ( 19 ) were also isolated from Lycopodium complanatum by Kobayashi group in 2006 . In 2015, our group finished the first total synthesis of (+)‐ 18 and (+)‐ 19 . As shown in Scheme , an ethylene‐accelerated, selective carbonyl‐olefin metathesis generated desired tricyclic product ( 146 ) in 48 % isolated yield.…”
Section: Fawcettimine Alkaloids With Level 4 Oxidation State At C16mentioning
Ever since the pioneering synthetic work reported by both Inubushi and Heathcock back in 1980s, the fawcettimine-type Lycopodium alkaloids have continuously served as a driving force for discoveries in organic synthesis. In this personal account, we summarized our recent synthetic efforts towards the total synthesis of fawcettimine-type Lycopodium alkaloids, along with a brief summary of relevant syntheses reported by others. Our discussions focus mainly on the key reactions applied during the synthesis of fawcettimine-type Lycopodium alkaloids.
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