Ruthenium‐Catalyzed Propargylic Substitution Reactions of Propargylic Alcohols with Oxygen‐, Nitrogen‐, and Phosphorus‐Centered Nucleophiles

Abstract

The scope and limitations of the ruthenium-catalyzed propargylic substitution reaction of propargylic alcohols with heteroatom-centered nucleophiles are presented. Oxygen-, nitrogen-, and phosphorus-centered nucleophiles such as alcohols, amines, amides, and phosphine oxide are available for this catalytic reaction. Only the thiolate-bridged diruthenium complexes can work as catalysts for this reaction. Results of some stoichiometric and catalytic reactions indicate that the catalytic propargylic substitution reaction proceeds via an allenylidene complex formed in situ, whereby the attack of nucleophiles to the allenylidene C(gamma) atom is a key step. Investigation of the relative rate constants for the reaction of propargylic alcohols with several para-substituted anilines reveals that the attack of anilines on the allenylidene C(gamma) atom is not involved in the rate-determining step and rather the acidity of conjugated anilines of an alkynyl complex, which is formed after the attack of aniline on the C(gamma) atom, is considered to be the most important factor to determine the rate of this catalytic reaction. The key point to promote this catalytic reaction by using the thiolate-bridged diruthenium complexes is considered to be the ease of the ligand exchange step between a vinylidene ligand on the diruthenium complexes and another propargylic alcohol in the catalytic cycle. The reason why only the thiolate-bridged diruthenium complexes promote the ligand exchange step more easily with respect to other monoruthenium complexes in this catalytic reaction should be that one Ru moiety, which is not involved in the allenylidene formation, works as an electron pool or a mobile ligand to another Ru site. The catalytic procedure presented here provides a versatile, direct, and one-step method for propargylic substitution of propargylic alcohols in contrast to the so far well-known stoichiometric and stepwise Nicholas reaction.

Brønsted Acid‐Catalyzed Nucleophilic Substitution of Alcohols

“…Recent advances in this field are based on the use of transition metal complexes as catalysts. Remarkable are the Ru-, [3] Re-, [4] and Au-catalyzed [5] propargylation of nucleophiles with propargylic alcohols, the Tsuji-Trost reaction of allylic alcohols with active methylene compounds, [6] the reaction of secondary benzylic alcohols with different nucleophiles catalyzed by La, Sc, or Hf salts, [7] and the Fe-, or Au-catalyzed arylation of benzylic alcohols.[8] In addition, InCl 3 has emerged as a powerful catalyst to perform direct nucleophilic substitution of allylic and benzylic alcohols. [9] Although the catalytic activation of alcohols is thought to be difficult due to the poor leaving ability of the OH group, we have recently found that simple Brønsted acids like p-toluenesulfonic acid monohydrate (PTS) catalyze the direct nucleophilic substitution of propargylic alcohols.…”

Lewis Acid-Catalyzed Propargylic Etherification and Sulfanylation from Alcohols in MeNO2-H2O

“…This is usually achieved by converting the hydroxyl group to a metal alkoxide. [23][24][25][26] Various other useful methods employing transition metals have been reported [27][28][29][30][31][32][33][34][35][36][37][38] ; however, these methods have limited applicability. To achieve one-pot etherification, the following four processes need to be performed: i) consider the alcohol as an electrophile and activate the hydroxyl group, ii) generate a carbocation, iii) consider the alcohol as a nucleophile and form an ether, and iv) control further reactions that lead to fission of the newly formed C-O bond.…”

Ruthenium‐katalysierte Reaktionen – eine Schatzkiste für atomökonomische Umwandlungen

“…(21)], [69] 1,3-Dicarbonylverbindungen [Gl. (22)] [70] sowie Amiden, Aminen, Phosphinoxiden, [67] Phenolen [71] und Olefinen. [72] [75] und Toste et al gelang die Rhenium-katalysierte Addition von Alkoholen, [76] Allylsilanen [77] und elektronenreichen Arylgruppen [78] an Alkine mit terminalen und internen Dreifachbindungen in hervorragenden Ausbeuten.…”

“…B. in 293) als ungesättigte Komponente agieren, was nach der Carbonylierung ungesättigte Lactone (wie 294) ergibt [Gl. (67)]. [210] 5.7.…”