Copper-catalyzed allylic substitution Grignard reagents

A procedure for the highly enantioselective synthesis of chiral chromenes and tetrahydroquinolines was achieved in 2012 by Feringa and co-workers. By combining asymmetric copper-catalyzed allylic substitution with Grignard reagents and an efficient palladium-catalyzed intramolecular Heck... 

Van der Molen NC, Tiemersma-Wegman TD, Fanands-Mastral M, Feringa BL (2015) Regio-and enantioselective copper-catalyzed allylic alkylation of ort/to-substituted cinnamyl bromides with Grignard reagents. J Org Chem 80 4981-4984... 

In the 1952 paper mentioned above [3], Gilman reported on the formation of lithium dimethylcuprate from polymeric methylcopper and methyllithium. These so-called Gilman cuprates were later used for substitution reactions on both saturated [6] and unsaturated [7, 8, 9] substrates. The first example of a cuprate substitution on an allylic acetate (allylic ester) was reported in 1969 [8], while Schlosser reported the corresponding copper-catalyzed reaction between an allylic acetate and a Grignard reagent (Eq. 2) a few years later [10]. 

Althou little studied, asymmetric copper-catalyzed substitution reactions of dialkylzinc [236] and Grignard reagents [237] vrith allylic substrates have been achieved vrith ferrocenylamidocopper and arenethiolatocopper catalysts, respec-tivdy. Good enantiosdectivity can be achieved vrith the zinc compounds (87% ee), but the method is limited to stericaUy hindered dialkylzinc reagents v/hile Grignard methodology gives only modest selectivities (18-50% ee). 

Copper-catalyzed substitution of allylic halides (and related cases) with Grignard reagents has been extensively studied (see Section III). To a lesser extent the use of other transition metal catalyst, such as Ni, Fe, Ti. Mn, Cr, remains anecdotally studied. 

Related to the copper-catalyzed Michael addition reaction, allyl phosphates furnish substitution products via the anti Sn2 mechanism when treated with an appropriate Grignard reagent in the presence of catalytic amount of CuCN and 1 equiv of TMSCI (eq 43). ... 

Karlstrom ASE, Huerta FF, Meuzelaar GJ, Backvall JE (2001) Ferrocenyl thiolates as ligands in the enantioselective copper-catalyzed substitution of allylic acetates with Grignard reagents. Synlett 923-926... 

Magrez M, Le Guen Y, Basle O, Crevisy C, Mauduit M (2013) Bidentate hydroxyalkyl NHC ligands for the copper-catalyzed asymmetric allylic substitution of allyl phosphates with Grignard reagents. Chem Eur J 19 1199-1203... 

In analogy with the Ir-catalyzed allylic alkylations described in the previous section, chiral phosphoramidite ligands derived from BINOL have shown excellent potential in copper-catalyzed asymmetric 8 2 substitutions [93], Alexakis recognized that ligand 86 in the presence of CuBr effects enantio-selective displacement with simple Grignard reagents (Scheme 14.16) [9]. Thus, the reaction between chloride 96 and MeMgBr in the presence of... 

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