Ruthenium‐ and Copper‐Catalyzed Propargylic Substitution Reactions of Propargylic Alcohol Derivatives with Hydrazones

Abstract

Ruthenium-and copper-catalyzed propargylic substitution reactions of propargylic alcohol derivatives with Nmonosubstituted hydrazones as ambident nucleophiles are achieved in which N-monosubstituted hydrazones exhibit impressive different reactivities depending on different catalytic systems, behaving as carbon-centered nucleophiles to give the corresponding propargylic alkylated products in ruthenium catalysis, or as nitrogen-centered nucleophiles to afford the corresponding propargylic aminated products in copper catalysis. DFT calculations were carried out to investigate the detailed reaction pathways of these two systems. Further transformation of propargylic substituted products affords the corresponding multisubstituted pyrazoles as cyclization products in good to high yields.

Enantiodivergent Chemoenzymatic Dynamic Kinetic Resolution: Conversion of Racemic Propargyl Alcohols into Both Enantiomers

“…( S )‐1‐(Benzo[ b ]thiophen‐3‐yl)prop‐2‐yn‐1‐ol [( S )‐1 c] : ( S )‐ 1 c was obtained by the general procedure and purified by flash column chromatography using hexane/EtOAc (4 : 1) as an eluant; 97 % yield (24 mg); a yellow solid; Mp 64–65 °C; its enantiomeric excess was determined by HPLC analysis at 20 °C using a CHIRALPAK IA‐3 column (hexane/propan‐2‐ol (90 : 10), 1 mL/min, UV detection 220 nm, t R =11.0 min ( S ), 9.5 min ( R )); [α]$${{{22\hfill \atop {\rm D}\hfill}}}$$ =+39 ( c 0.38, CHCl 3 ); 1 H NMR (500 MHz, CDCl 3 ): δ =8.03 (d, J =7.5 Hz, 1H), 7.87 (d, J =7.5 Hz, 1H), 7.68 (s, 1H), 7.43 (td, J =7.5, 1.0 Hz, 1H), 7.39 (td, J =7.5, 1.0 Hz, 1H), 5.80 (dd, J =7.0, 2.0 Hz, 1H), 2.72 (d, J =2.0 Hz, 1H), 2.25 (d, J =7.0 Hz, 1H); 13 C NMR (125 MHz, CDCl 3 ): δ =141.0, 136.6, 134.6, 125.0, 124.7, 124.3, 122.9, 122.5, 82.5, 74.6, 59.9. 1 H and 13 C NMR data of the product ( S )‐ 1 c were in agreement with (±)‐ 1 c in the literature [25] …”

“…1 H and 13 C NMR data of the product (S)-1 c were in agreement with (�)-1 c in the literature. [25] ( 9, 147.8, 134.0, 120.3, 108.2, 107.3, 101.2, 83.4, 74.8, 64.2. 1 H and 13 C NMR data of the product (S)-1 d were in agreement with (�)-1 d in the literature.…”

Recent Progress in Application of Propargylic Alcohols in Organic Syntheses

“…This radical coordinated with the metal to deliver radical-metal In 2021, Sakata and Nishibayashi et al employed ruthenium and copper catalysts in the reaction of propargylic alcohols 1' with N-monosubstituted hydrazones 152 (Scheme 65). [62] In the ruthenium catalysis system, hydrazone substrates acted as carbon-centered nucleophiles, whereas they showed nitrogen-centered nucleophilicity behavior in the presence of a copper catalyst. DFT calculations and study of Gibbs free energies of intermediates showed that in the Rucatalyzed reaction, [1,6]-H shift was preferred in the C-attack pathway and alkylated products were observed.…”

Base-catalyzed addition of silylacetylenes to ketones: a route to protected tertiary propargyl alcohols

“…Propargyl alcohols are ubiquitous building blocks in chemical synthesis, being highly valued for their widespread application as valuable synthetic intermediates or medicinally relevant molecules themselves. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] They participate in a diverse array of transformations, owing this to their multifunctionality, and thereby being the subject of numerous studies. Protected propargyl alcohols can be accessed via well-developed stoichiometric methods, including mainly the use of a combination of propargyl alcohol, chlorosilane and organolithium reagent (Fig.…”