The central pyrrolidine ring’s precursor is pyrrole. Introduction of a side chain via radical addition to its double bond causes dearomatization, resulting in an enamine. A cascade reaction of 5-endo-dig cyclization and aza-Prins occurred between the multiple bonds of the introduced side chain and the enamine (enamide) to construct the two rings at once. After adjusting the oxidation state, the final aldol reaction completes the synthesis of lycojapomine B and lycojapomine A through kinetic and thermodynamic control, respectively. The only difference in the reaction conditions is the temperature (34 degrees) and reaction time.
This demonstrates that radical-mediated dearomatization effectively shortens reaction steps. It appears that synthesizing optically active compounds may also be possible with the use of a chiral auxiliary.
Several reactions were optimized from 0% yield to practical yields, and I can imagine the student’s hard work. (Probably one of the two authors.)
最も複雑なbisdehydrostemoninineの合成は全１１段階で，そのうち６つは光化学反応です。もっとも，その中には，通常の”polar chemistry”でも問題なく実現できる反応もあります。
２つの五員環AB環を，ビニルアレンからタイプの異なるPRCCを連ねて，立体選択的に合成してしまうところがキモです。
linchpin化合物はラセミ体なのですが，これに対して試薬制御（光反応）で側鎖に不斉中心を導入し，ジアステレオマーを分離し，最大50%に対して15%の収率で，光学活性体を取り出しています。
筆者らの専門分野である9-メシチルアクリジニウム塩の機能とか，用いた光化学反応についてまとめて反応機構が示されており，いい勉強になります。
Bisdehydrostemoninine, the most complex molecule in this paper, was synthesized in 11 steps, six of which are photochemical reactions. However, some of these reactions can be easily achieved using conventional “polar chemistry.”
The key point is the stereoselective synthesis of two five-membered AB rings by linking PRCCs of different types from the vinyl allene.
The linchpin compound is a racemic mixture. However, after introducing an asymmetric center into the side chain via reagent control (a photochemical reaction), the diastereomers were separated and the optically active compound was isolated with a 15% yield relative to a maximum yield of 50%.
The reaction mechanism is summarized, including the functionality of 9-mesitylacridinium salts, which is the authors’ specialty, and the photochemical reactions employed there, making it a valuable learning resource.
All four chiral centers on the right half were introduced by reagent control, while the three on the left half were introduced by substrate control from chiral centers obtained by optical resolution.
The chiral sources used for the reagent control were three chiral phosphine ligands and an amine derived from proline. The metals were iridium and platinum.
Reactions such as the Carreira arylation, which diastereoselectively and enantioselectively constructs two chiral centers, or the Catellani reaction, which simultaneously forms two adjacent C-C bonds,
, are not widely used, but can be highly effective for specific skeletal constructions.
Optically active γ-butenoides of this type are frequently encountered. Since they cannot be synthesized via diastereoselective reactions, the Krische reaction may become the standard method.
It’s a five-step synthesis! The “ideality” is probably 100%.
Substituted decalin is constructed in one step using a Cope/Prins/Friedel-Crafts cascade based on biosynthesis.
To evolve it into an asymmetric synthesis, the initial Cope rearrangement must be made an asymmetric reaction. However, this has not yet been attempted.
The racemic synthetic intermediate was separated by liquid chromatography, and each enantiomer was converted into an optically active natural product.
Professor Lie has previously synthesized many related compounds, and this knowledge is fully utilized here.
Lycojapomine A and B uploaded
https://www.ohira-sum.com/wp-content/uploads/2025/07/jacs25-20200.pd
中央のピロリジン環の前駆体をピロールとし，その二重結合へのラジカル付加で側鎖を導入すると脱芳香化し，エナミンが残る。導入した側鎖の多重結合とエナミン(エンアミド）の５-endo-dig とアザプリンスのカスケード反応で２つの環を一挙に構築します。酸化状態を整えて，最後のアルドール反応では速度論制御でLycojapomine B，熱力学制御で Aの合成が完了です。(反応条件の違いは温度差（34度差）と反応時間のみ）
ラジカル反応による脱芳香化は短工程化に有効な手法になることを示しました。補助剤を使えば光学活性体の合成も可能なように思えます。
収率0%から初めて実用的収率まで最適化した反応がいくつかあり，一人の学生さん（多分）の苦労が思いやられました。
The central pyrrolidine ring’s precursor is pyrrole. Introduction of a side chain via radical addition to its double bond causes dearomatization, resulting in an enamine. A cascade reaction of 5-endo-dig cyclization and aza-Prins occurred between the multiple bonds of the introduced side chain and the enamine (enamide) to construct the two rings at once. After adjusting the oxidation state, the final aldol reaction completes the synthesis of lycojapomine B and lycojapomine A through kinetic and thermodynamic control, respectively. The only difference in the reaction conditions is the temperature (34 degrees) and reaction time.
This demonstrates that radical-mediated dearomatization effectively shortens reaction steps. It appears that synthesizing optically active compounds may also be possible with the use of a chiral auxiliary.
Several reactions were optimized from 0% yield to practical yields, and I can imagine the student’s hard work. (Probably one of the two authors.)
Stemoamide Alkaloids uploaded
https://www.ohira-sum.com/wp-content/uploads/2025/07/jacs25-15482.pdf
最も複雑なbisdehydrostemoninineの合成は全１１段階で，そのうち６つは光化学反応です。もっとも，その中には，通常の”polar chemistry”でも問題なく実現できる反応もあります。
２つの五員環AB環を，ビニルアレンからタイプの異なるPRCCを連ねて，立体選択的に合成してしまうところがキモです。
linchpin化合物はラセミ体なのですが，これに対して試薬制御（光反応）で側鎖に不斉中心を導入し，ジアステレオマーを分離し，最大50%に対して15%の収率で，光学活性体を取り出しています。
筆者らの専門分野である9-メシチルアクリジニウム塩の機能とか，用いた光化学反応についてまとめて反応機構が示されており，いい勉強になります。
Bisdehydrostemoninine, the most complex molecule in this paper, was synthesized in 11 steps, six of which are photochemical reactions. However, some of these reactions can be easily achieved using conventional “polar chemistry.”
The key point is the stereoselective synthesis of two five-membered AB rings by linking PRCCs of different types from the vinyl allene.
The linchpin compound is a racemic mixture. However, after introducing an asymmetric center into the side chain via reagent control (a photochemical reaction), the diastereomers were separated and the optically active compound was isolated with a 15% yield relative to a maximum yield of 50%.
The reaction mechanism is summarized, including the functionality of 9-mesitylacridinium salts, which is the authors’ specialty, and the photochemical reactions employed there, making it a valuable learning resource.
(+)-Rubriflordilactone A uploaded
https://www.ohira-sum.com/wp-content/uploads/2025/06/jacs25-16792.pdf
右半分の４つの不斉中心はすべて試薬制御で導入，左半分の３つは，光学分割で得た不斉中心から基質制御で導入しています。
試薬制御に使われた不斉源は３つのキラルホスフィンリガンドとプロリン由来のアミンです。金属はイリジウムと白金。
２つの不斉中心をジアステレオ選択的かつエナンチオ選択的に構築するカレイラのアリル化とか，隣り合った２つのC-C結合を同時に作るカテラーニ反応とか，
広範に使われる反応ではないでしょうが，特定の骨格については強力に有効な骨格構築法となることがわかります。
この手の光学活性γ-ブテノライドはちょくちょく見かけますが，ジアステレオ選択的反応では合成できそうにないので，Krische反応は定番になるかもしれません。
All four chiral centers on the right half were introduced by reagent control, while the three on the left half were introduced by substrate control from chiral centers obtained by optical resolution.
The chiral sources used for the reagent control were three chiral phosphine ligands and an amine derived from proline. The metals were iridium and platinum.
Reactions such as the Carreira arylation, which diastereoselectively and enantioselectively constructs two chiral centers, or the Catellani reaction, which simultaneously forms two adjacent C-C bonds,
, are not widely used, but can be highly effective for specific skeletal constructions.
Optically active γ-butenoides of this type are frequently encountered. Since they cannot be synthesized via diastereoselective reactions, the Krische reaction may become the standard method.
Ambiguine P uploaded.
https://www.ohira-sum.com/wp-content/uploads/2025/06/jacs25-18391.pdf
５段階合成です。多分idealityは100%.
生合成に準じたCope/Prins/Friedel-Crafts cascadeで置換デカリンを一挙に作ります。
不斉合成に進化させるにはするには，最初のCope転位を不斉反応にする必要がありますが，さすがに試みられておらず
ラセミの合成中間体を液クロ分離して光学活性天然物に導いています。
Lie先生は過去に多くの関連化合物の合成を達成しており，そこで得られた知識が生かされてます。
It’s a five-step synthesis! The “ideality” is probably 100%.
Substituted decalin is constructed in one step using a Cope/Prins/Friedel-Crafts cascade based on biosynthesis.
To evolve it into an asymmetric synthesis, the initial Cope rearrangement must be made an asymmetric reaction. However, this has not yet been attempted.
The racemic synthetic intermediate was separated by liquid chromatography, and each enantiomer was converted into an optically active natural product.
Professor Lie has previously synthesized many related compounds, and this knowledge is fully utilized here.