The target scaffold is constructed by cyclopropanation by generating a rhodium carbenoid from a triazole.
The isomerization by inversion of the tertiary amine nitrogen lone pair leads to a possible conformation for cyclopropanation. This condition is explained by the DFT calculation that the Boc protection of the indole nitrogen is crucial.
The rhodium carbenoid forms an aziridinium ylide intermediate, which is the precursor for cyclopropanation. The intermediate came out of the calculation, but it is a reasonable result since ylide and carbene are related.
It will be useful to remember that cyclopropanation competes with the 1,2-H shift.
The convergent construction of the carbon skeleton by the Mukaiyama-Michael reaction is wonderful, and you will learn a lot from the difficulties and chemical considerations that followed.
The need to protect the phenol arose. Since southeastern cyclohexene is not prone to aromatization, they came up with the idea of protecting it with an intramolecular ether through the SN2 reaction. This leads to the final reaction to form a nitrogen-containing six-membered ring.
There were many unfamiliar reactions, but the reaction mechanisms, such as Michael and vinylogous substitution reactions, were quite understandable.
The [5+2] addition of o-quinone is the key step.
The double Michael was assumed, but the reaction did not work with most catalysts, and good results were obtained with a mixed primary amine derived from a cinchona alkaloid. I did not understand the reaction mechanism well, but it seems to be a stepwise [5+2] addition reaction, not a double Michael. This was deduced from isotope effects and other factors.
The aromatic ring is formed by the DA-reteroDA cascade invented by Dr. Danishefsky.
The asymmetric quaternary center containing oxygen is constructed by asymmetric cyanosilylation. Amazing that it is already a practical level.
(-)-Rauvomine B uploaded
https://www.ohira-sum.com/wp-content/uploads/2025/04/jacs24-22047.pdf
トリアゾールからロジウムカルベノイドを発生させてシクロプロパン化で目的骨格を構築します。
３級アミン窒素ローンペアの反転による異性化でシクロプロパン化の可能なコンフォーメーションになるのですが，その条件がインドール窒素のBoc保護ということで，DFT計算で説明してます。
ロジウムカルベノイドからアジリジウムイリド中間体ができそれがシクロプロパン化の前駆体となります。計算でその中間体が出てきたらしいですが，イリドとカルベンは親戚なのでごもっともな結果です。
シクロプロパン化と1,2-H shiftが競合するというのは覚えておきたい一般的知見です。
The target scaffold is constructed by cyclopropanation by generating a rhodium carbenoid from a triazole.
The isomerization by inversion of the tertiary amine nitrogen lone pair leads to a possible conformation for cyclopropanation. This condition is explained by the DFT calculation that the Boc protection of the indole nitrogen is crucial.
The rhodium carbenoid forms an aziridinium ylide intermediate, which is the precursor for cyclopropanation. The intermediate came out of the calculation, but it is a reasonable result since ylide and carbene are related.
It will be useful to remember that cyclopropanation competes with the 1,2-H shift.
Aleutianamine uploaded
https://www.ohira-sum.com/wp-content/uploads/2025/03/jacs25-5736.pdf
向山ーマイケルで炭素骨格を収束的につくるところもすばらしいですが，その後の苦労話ー化学的考察などが，いろいろ勉強になります。
フェノールを保護する必要が生じ，southeastのシクロヘキセンが，芳香化しにくいことから，SN2反応させて分子内エーテルで保護することを思いつきます。それが最後の含窒素6員環をつくる反応に繋がります。
馴染の少ない反応が多くありましたが，Michaelやvinylogousな置換反応など，反応機構はごもっともなものでした。
The convergent construction of the carbon skeleton by the Mukaiyama-Michael reaction is wonderful, and you will learn a lot from the difficulties and chemical considerations that followed.
The need to protect the phenol arose. Since southeastern cyclohexene is not prone to aromatization, they came up with the idea of protecting it with an intramolecular ether through the SN2 reaction. This leads to the final reaction to form a nitrogen-containing six-membered ring.
There were many unfamiliar reactions, but the reaction mechanisms, such as Michael and vinylogous substitution reactions, were quite understandable.
uploaded Asperones A and B
https://www.ohira-sum.com/wp-content/uploads/2025/03/jacs25-6739.pdf
o-キノンの[5+2]付加がキーステップとなります。
ダブルマイケルを想定していましたがほとんどの触媒でうまくいかず，結局シンコナアルカロイド由来の混み合った一級アミンで好結果が得られました。反応機構については，私はよく理解できなかったのですが，ダブルマイケルではなく，stepwiseな[5+2]付加反応らしい。同位体効果などから結論づけてます。
芳香環はDA−reteroDAカスケードで作っています。ダニシェフスキー先生考案の反応とのこと。
酸素を含む不斉４級中心は不斉シアノシリル化。実用レベルまで来てるんですね。
The [5+2] addition of o-quinone is the key step.
The double Michael was assumed, but the reaction did not work with most catalysts, and good results were obtained with a mixed primary amine derived from a cinchona alkaloid. I did not understand the reaction mechanism well, but it seems to be a stepwise [5+2] addition reaction, not a double Michael. This was deduced from isotope effects and other factors.
The aromatic ring is formed by the DA-reteroDA cascade invented by Dr. Danishefsky.
The asymmetric quaternary center containing oxygen is constructed by asymmetric cyanosilylation. Amazing that it is already a practical level.