Regiocontrol in Copper-Catalyzed Cross Coupling of Allylic Chlorides with Aryl Grignard Reagents

Abstract

The regioselectivity of copper-catalyzed reactions of allylic chlorides with aryl Grignard reagents was studied by variation of addition time of Grignard reagent, temperature, and amount of catalyst.It was found that slow addition of the Grignard reagent, increased temperature, and increased amount of catalyst favors formation of y-product. Investigation of preformed organocopper species "ArzCuMgBr" and "ArCu(X)MgBr" showed a striking difference in regioselectivity between the two reagents, the latter giving about 90% y-selectivity and the former being nonregioselective. It was found that for "ArCu(X)MgBr" the y-selectivity increased with the electronegativity of the halide X (I Br < Cl).Copper-catalyzed cross-coupling reactions constitute an important class of reactions for the creation of new carbon-carbon b0nds.l Apart from aryl-aryl, vinylvinyl, and aryl-vinyl couplings, copper-catalyzed couplings between an allylic halide or allylic alcohol derivative and an organometallic compound have attracted a lot of attention recently. The principle for these coupling reactions is shown in eq 1 and involves formation of an a X = CI, Br, OCR, S02Ph, OR, OP(O)(OR)a R =alkyl, aryl. vinyl, allyl M = -MgX, -Ti(OR)s, ZnX etc. organocopper intermediate from a transmetalation reaction.2 The most common type of these reactions in organic synthetic applications is the copper-catalyzed Grignard reaction with allylic but recently a number of copper-catalyzed reactions with other organometallics have been rep~rted.',~ An important issue in these reactions is the control of regiochemistry, i.e., whether the leaving group X is displaced a or y by the organometallic reagent. We recently reported a method @ Commercon, A.; Bourgain, M.; Delaumeny, M.; Normant, J. F.; Villieras, J. Tetrahedron Lett. 1975, 3837. (c) Barsantai, P.; Calo, V.; Lopez, L.; Marchese, G.; Naso, F.; Peace, G.

Copper‐Catalysed Allylic Substitution Using 2,8,14,20‐Tetrapentylresorcinarenyl‐Substituted Imidazolium Salts

“…[4] Notably, no significant differences were seen between runs using preformed complex 6 and tests carried out with the catalyst obtained from 1 in situ (entries 1 and 2); this observation justified the use of catalysts generated in situ. [4,6,[20][21][22][23][24][25][26][27][28] In these two possible pathways, a bulky ligand should accelerate the reductive elimination step leading to the γ-product. The proportion of branched product increased in the order 1Ͻ 2 Ͻ 3 Ͻ 4, with the b/l ratios varying from 22:78 for 1 to 78:22 for 4 (entries 1-4).…”

Synthesis and evaluation of 5-lipoxygenase translocation inhibitors from acylnitroso hetero-Diels–Alder cycloadducts

“…19, 20, 21, 22 Thus, benzylmagnesium bromide, was added to a solution of the copper catalyst and substrate at room temperature over 45 minutes (Table 1, entry 1). Consistent with our previous study, the reaction gave a 31% yield of the anti -1,2-product as determined by 2D NMR and X-ray crystallography.…”

The Copper-Catalyzed Asymmetric Allylic Substitution

“…The control of the regioselectivity depends on the nontransferable group R T . A halide or cyanide group usually allows high γ selectivity, whereas an alkyl group (as in R 2 CuLi) allows an equilibration, thus favoring the substitution at the least sterically hindered carbon [8][9][10][11][12][13][14].…”