Enantioselective Copper‐Catalyzed 1,4‐Addition of Grignard Reagents to α,β‐Unsaturated Carbonyl Compounds

Abstract

The enantioselective copper-catalyzed 1,4-addition of Grignard reagents to a$-unsaturated carbonyl compounds was studied with the following Cu' compounds as catalyst precursor and 1,2 : 5,6-di-0 -isopropylidene-3-thio-a -o-glucofuranose (Hsiig) as chiral ligand: CuI, iodo[bis(dibutylsulfide)]copper(I), [Cu(siig)], [Cu(siig)(pp)] (pp = 1,2-bis(diphenylphosphinoethene), and tetrakis[iodo(tributylphosphine)]copper(I). The addition of BuMg halides to cyclohex-2-en-1-one was tested under several reaction conditions. The chemical yields and regioselectivities for this reaction were, in all cases, larger than 90 and 98 YO, respectively, and independent of the experimental conditions. The enantioselectivity was strongly dependent on the reaction conditions and reached a maximum of 60%. Several other substrates were also tested in the above reaction. The X-ray crystal structure for [Cu(siig)(pp)] was determined by X-ray crystallography.

Asymmetric Organocopper Chemistry: Cu‐Catalyzed Conjugate Addition and Allylic Substitution

“…39 Later on, various copper thiolates gave moderate to good results on cyclic and acyclic enones. [40][41][42][43] The best results were however obtained with external ligands, by Tomioka 44 and Sammakia. 45 Since the late 90's all authors focused on the dialkylzinc procedure.…”

A recyclable nanosize aminoarenethiolato copper(I) catalyst for C–C coupling reactions

“…In particular the catalytic activity of aminoarenethiolato copper(I) 1a has been extensively studied, which appeared to have wide applicability as stable catalysts in, e.g. 1,4-additions [6][7][8][9], 1,6-additions [10] and allylic substitutions [11,12]. Although it is not the most active copper catalyst reported to date, recent studies showed that these aminoarenethiolato copper(I) catalysts are very robust, i.e.…”

Copper-catalyzed asymmetric conjugate addition of Grignard reagents to cyclic enones

“…Shortly after this seminal work was published, various catalytic systems were developed based on copper thiolates (24)(25)(26)(27)(28)(29)(30) and monophosphine ligands (31)(32)(33)(34), although in these systems, enantioselectivities rarely reached the 90% enantiomeric excess (ee) level. Notable exceptions are the two literature reports of 92% ee in the addition of BuMgCl to cyclic enones.…”

“…In principle, diphosphines do not match with the metal-differentiating coordination concept (32). It should be emphasized that until now, most successful ligands in the field of copper-catalyzed 1,4-addition of Grignard reagents fulfill the criteria of combining P, S, or Se with N or O donor atoms in their structure to coordinate selectively with Cu and Mg of the organometallic species, respectively (24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). Among the most important bidentate ligands in asymmetric catalysis are ferrocenyl diphosphine ligands, especially TaniaPhos (1; Fig.…”