Copper -catalyzed allylic substitution

It may be concluded from die different examples sliown here tiiat die enantio-selective copper-catalyzed allylic substitution reaction needs ftirdier improvemetiL High enantioselectivities can be obtained if diirality is present in tiie leaving group of die substrate, but widi external diiral ligands, enantioselectivities in excess of 9096 ee have only been obtained in one system, limited to die introduction of die sterically hindered neopeatyl group. 

The method was later extended to the synthesis of a number of meroter-penoids from epoxygeranyl carbonates or acetates in a two-step approach combining titanocene catalysis with Stifle reactions (carbonates) [108,109] or copper-catalyzed allylic substitutions (acetates) [110-112], The cyclizations... 

Scheme 6.42. Copper-catalyzed allylic substitution of mesylate 197 with an organozinc reagent.

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]. 

The moderate ees obtained with the copper arenethiolate ligands discussed above prompted a search for new chiral ligands for use in asymmetric allylic substitution reactions. The binaphthol-derived phosphoramidite ligand 32, used successfully by Feringa et al. in copper-catalyzed 1,4-addition reactions [37], was accordingly tested in the reaction between 21 and n-BuMgl. 

Allylic substitutions with nonstabilized C-nucleophiles are an important domain of organocopper chemistry [51]. However, on close inspection of the literature, it becomes apparent that regioselectivity in favor of the branched allylic alkylation products is only obtained with alkyl copper compounds, while aryl copper compounds mainly give the linear alkylation products. This observation was an incentive for Alexakis et al. [52] to probe the reactions of aryl zinc hahdes in the Ir-catalyzed allylic substitution (Scheme 9.18). 

SCHEME 13. Copper-catalyzed allylic substitution using an arenethiolate ligand... 

Propargylic mesylates such as fluorine-substituted derivative 265 react with PhZnCl in the presence of Pd(PPh3)4 (5 mol%) in THF at 0°C within 2 h to provide the anti-Si 2 product in excellent yield and complete transfer of the stereochemistry leading to the allene 266 (Scheme 78). Copper(I) catalyzed allylic substitutions with functionalized diorganozincs proceed with high 8 2 selectivity. Thus, the reaction of the chiral allylic phosphate 267 with 3-carbethoxypropylzinc iodide in the presence of CuCN 2LiCl (2 equivalents) furnishes the awf/-Sjv2 substitution product 268 in 68% yield. By the addition of w-BuLi (1.2 equivalents) and TMSCl (1.5 equivalents), the bicyclic enone 269 is obtained in 75% yield and 93% ee (Scheme 79) . 

The copper-catalyzed photobicyclization of acyclic 1,6-dienes to bicyclo[3.2,0]heptanes using the bis[copper(l) lrifluoromethanesulfonate]benzene complex has found general and synthetic utility in the conversion of diallyl and homoallyl vinyl ethers to 3- or 2-oxabicyclo[3.2.0]heptanes,5 6 of /V-allyl-A -2-methyl-2-propenecarbamates to iV-carboethoxy-3-azabicyclo[3.2.0]heptanes 7 and of allylic alcohols to the corresponding hydroxy-substituted bicyclo[3.2.0]heptanes.8 9 Examples of such reactions are summarized below. 

Allyl complexes with boron, 9, 194 with chromium(III), 5, 373 copper-catalyzed substitution, 9, 518 with gallium, 9, 723, 9, 735 with indium... 

A sequential process involving a copper catalyzed cycloaddition of the vinyl sulfone 34 to Af-methylpropargylamine (35), and a subsequent palladium meditated allylic substitution, provided a route to mixtures of the separable isomeric pyrrolines 36 and 37 <02EJO1493>. 

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