Metal-mediated conjugate addition reactions

In the 1970s, Hajos and Parrish and Wiechert and coworkers independently reported that the Michael addition of 2-methylcyclopentane-l,3-dione to vinyl ketone in water gives the corresponding conjugated addition product without the use of a basic catalyst. A similar 

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Copper has long played a dominant role in stoichiometric organometallic reactions in synthesis. Organocuprate mediated conjugate addition reactions are a cornerstone of carbon-carbon bond-forming reactions. Its preeminence has not been overlooked in the search for asymmetric versions of the reaction (134-136). However, the requirement for stoichiometric amounts of the metal has dampened efforts to introduce chirality into this process. 

Metal-catalyzed reactions have been of major importance in synthetic organic chemistry. Over the past decade, enantio- and diastereoselective metal-mediated domino catalysis has emerged as an effective tool to construct really highly complex molecules in one-pot processes [2, 4b,d]. Among them, enantioseletcive metal-catalyzed conjugate additions (in particular, Cu-catalyzed 1,4-addition to a,P-unsaturated carbonyl compounds) have been useful components of domino reactions [4d, 5]. The generated metal enolates 2 after the additions of nucleophiles readily react with a variety of electrophiles (Scheme 11.1). Enantioselectivity of 3 depends on the first addition of nucleophiles to the P-position of the unsaturated carbonyl compounds 1. 

Because of these interesting biological activities and the scarcity of materials from their natural sources through isolation, great emphasis has been placed on synthetic approaches toward the efficient construction of tetrahydropyrans. These approaches include the Prins and related cyclization reactions, the hetero-Diels-Alder cyclizations, radical cyclizations, transition metal mediated cyclizations, as well as more traditional methods such as epoxide-mediated cyclizations and oxa-conjugate addition reactions. 

Transition metal catalyzed asymmetric hydrocarboration reactions are addition reactions forming one C—C and one C—H bond. Prominent examples are hydrovinylation, hydroformylation, hydroacylation, hydrocarboxylation, and hydrocyanation. Various related conversions, such as hydroalkylation, hydroarylation, conjugate addition, reductive dimerization, and metal induced ene reactions are collected in Section 1.5.8.2.6. dealing with miscellaneous methods of this type. Some of these methods are not exclusively mediated by metal catalysts and therefore are also covered in other sections of this volume. 

A series of 1,2-diarylethane-l,2-diamines and/or their metal complexes are effective conjugate addition catalysts involving stabilized donors. In reaction of enamides with alky-lidenemalonic esters a Cu(II) complex of 119 is employed, whereas the strontium complex of the bis(sulfonamide) 120 mediates the addition of malonic esters to enones. ... 

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