Conjugate reduction, copper-catalyzed

Meerwein Arylation Reactions. Aryl diazonium ions can also be used to form certain types of carbon-carbon bonds. The copper-catalyzed reaction of diazonium ions with conjugated alkenes results in arylation of the alkene, known as the Meerwein arylation reaction.114 The reaction sequence is initiated by reduction of the diazonium ion by Cu(I). The aryl radical adds to the alkene to give a new (3-aryl radical. The final step is a ligand transfer that takes place in the copper coordination sphere. An alternative course is oxidation-deprotonation, which gives a styrene derivative. 

Many of the copper-mediated transformations summarized in the previous sections of this chapter can also be performed efficiently with catalytic amounts of copper salts or reagents. Indeed, some of the copper-catalyzed reactions have been discovered before the development of stoichiometric organocopper reagents. The focus of the last decade has been put on new copper-catalyzed transformations (e.g., conjugate reductions) and in particular on the discovery of chiral copper catalysts for highly enantioselective 1,4-addition and S -substitution reactions of prochiral substrates. 

Duan et al have synthesized a series of chiral alkylphosphonates (449) bearing a )5-stereogenic center in good enantioselectivities (up to 95% ee) via the CuH-catalyzed asymmetric, conjugate reduction of jS-substituted a,j8-unsaturated phosphonates (448) under optimal conditions using Cu(0Ac)2 H20 as the copper source, (R)-SEGPHOS as the ligand, polymethylhydrosiloxane as the siloxane, and /-BuOH as the additive (Scheme 111). 

Recently, extensive efforts have been made in the development of domino conjugate reduction/inter and intramolecular aldol reaction catalyzed by various metal complexes based on rhodium, iridium, cobalt, indium, nickel, and copper [22]. In 1999, Morken and Taylor [23] reported a rhodium-catalyzed conjugative reductive/aldol reaction between aldehyde and acrylate using QjMeSiH as reducing agent with a maximum diastereoselectivity of 23 1. 

S)-BINAP-, JOSIPHOS-, or (i ,S)-PPF-P(t-Bu)2-ligated copper hydride catalyzes conjugate reduction of o ,j8-unsaturated nitriles (319-321), dinitriles (322), ni-troalkenes (323,324), and sulfones (325,326) with phenylsilane or PMHS. 

Moritani Y, Appella DH, Jurkauskas V, Buchwald SL (2000) Synthesis of p-aUcyl cyclo-pentanones in high enantiomeric excess via copper-catalyzed asymmetric conjugate reduction. J Am Chem Soc 122 6797-6798. doi 10.1021/ja0009525... 

Buchwald reported asymmetric copper-catalyzed conjugate reductions of a variety of a,/i-unsaturated acceptors [175, 176]. The reactions were demonstrated to proceed with optimal enantioinduction in the presence of a chiral copper catalyst incorporating p-tol-BINAP (240, Scheme 12.20). A convenient feature of these reductions is the use of the inexpensive polymeric polymethyl-hydrosiloxane (PMHS) as the stoichiometric reductant. Unsaturated lactam 239 undergoes reduction in 90% yield and 90% ee to give 241, a key intermediate in a synthesis of the antidepressant (-)-paroxetine (242) [176]. 

In the conjugate addition of diethylzinc to enones catalyzed by copper reagent CuOTf or Cu(OTf)2 in the presence of 90, an ee of over 60% has been obtained. Study also shows that the actual catalyst in the reaction may be a Cu(I) species formed via in situ reduction of Cu(II) complexes. 

---