The Ruthenium‐Catalyzed Domino Cross Enyne Metathesis/Ring‐Closing Metathesis in the Synthesis of Enantioenriched Nitrogen‐Containing Heterocycles

Abstract

The tetrahydropyridine structure is present in a wide variety of natural and synthetic compounds with interesting pharmacological properties. Therefore, the search for new chemical routes capable of yielding this valuable nitrogen‐containing heterocycle is of utmost interest. Herein, we report the use of the ruthenium‐catalyzed ring‐closing enyne metathesis (RCEYM) and cross enyne metathesis/ring‐closing metathesis (CEYM/RCM) reactions of chiral nitrogen‐containing 1,7‐enynes as an efficient route to synthesize a variety of enantioenriched tetrahydropyridine‐based conjugated 1,3‐dienes. The RCEYM presented wide functional group tolerance and took place in moderate to high yields, with no significant differences when carried out on gram scale. These 1,3‐dienes were suitable for further transformations, such as the Diels–Alder reaction, effectively yielding more complex enantioenriched bicyclic structures.

Rh-Catalyzed diastereoselective addition of arylboronic acids to α-keto N-tert-butanesulfinyl aldimines: synthesis of α-amino ketones

“…The α-amino ketone 3h was oxidized with m -CPBA to form the chiral sulfonamide 4 in 90% yield and with 95% ee (Scheme 4A, left). 18 Using NaBH 4 as the reductant, α-amino ketone 3h was smoothly reduced to obtain the chiral amino alcohol 5 in 78% yield with >98 : 2 dr, 16 b which was further oxidized by m -CPBA to give 6 (Scheme 4A, right). 18 The protecting groups of 3r could be easily removed to deliver the hydrochloride of the chiral primary amine 7 , 16 b which could further undergo amidation to afford the antitumor agent 8 in 98% ee.…”

“…18 Using NaBH 4 as the reductant, α-amino ketone 3h was smoothly reduced to obtain the chiral amino alcohol 5 in 78% yield with >98 : 2 dr, 16 b which was further oxidized by m -CPBA to give 6 (Scheme 4A, right). 18 The protecting groups of 3r could be easily removed to deliver the hydrochloride of the chiral primary amine 7 , 16 b which could further undergo amidation to afford the antitumor agent 8 in 98% ee. 19,20 After the successive reduction and deprotection processes, the amino ketone 3r was converted into amino alcohol 10 (absolute configurations were determined by HPLC compared with the commercial (1 S ,2 R )-2-amino-1,2-diphenylethan-1-ol, see the ESI† for details), which is an intermediate for the synthesis of the antidiabetic agent 11 (Scheme 4B).…”

Fluorinated Imines in Tandem and Cycloaddition Reactions

“…In this context, our group reported quite recently the use of the ruthenium‐catalyzed ring‐closing enyne metathesis (RCEYM) and cross enyne metathesis/ring‐closing metathesis (CEYM/RCM) reactions of chiral fluorinated and non‐fluorinated nitrogen‐containing 1,7‐enynes for the preparation of a variety of enantioenriched tetrahydropyridine derivatives [105] …”

A Density Functional Theory Study on the Cobalt-Mediated Intramolecular Pauson–Khand Reaction of Enynes Containing a Vinyl Fluoride Moiety

“…10 Thereby, strategies for the incorporation of fluorine into organic molecules, and organic reactions involving substrates with fluorine substituents, have become a blossoming field in the last decade. 11 The use of complex building blocks such as enynes, 12 which are organic compounds having a C=C double bond (alkene) and a C≡C triple bond (alkyne), has given access to more sophisticated structures under transition-metal catalysis using Au, 13,14 Ag, 15 Rh, 16,17 Ru, 18 Mn, 19 Pd, 20 and Ir, 21,22 among others.…”