Metal-catalyzed carbonyl addition

The lanthanides are congeners of the Group IIIA metals scandium and yttrium, with the +3 oxidation state usually being the most stable. These ions are strong oxyphilic Lewis acids and catalyze carbonyl addition reactions by a number of nucleophiles. Recent years have seen the development of synthetic procedures involving lanthanide metals, especially cerium.195 In the synthetic context, organocerium... 

Among the catalytic asymmetric alkyne additions to the sp carbon center, such as carbonyl, imines, and iminiums, truly metal-catalyzed alkyne addition to alkenes is rare. By using a PINAP derivative (Figure 5.4), Cu-catalyzed Michael addition... 

Rare earth metal-catalyzed Michael additions of a-nitro esters or y9-keto esters with af-nn-saturated carbonyl compounds were investigated by Feringa and co-workers [7]. According to these authors, the use of Yb(OTf)3 enables addition products 5 to be isolated in higher yields and greater purities than those obtained in organic solvents (Scheme 1). 

The RuH2(PPh3)4-catalyzed addition of active methylene compounds can also be applied to conjugate additions to a,/3-unsaturated carbonyl compounds (Michael additions). In 1989, Murahashi reported the first example of the transition metal-catalyzed Michael addition of active methylene compounds [74]. One of the notable advances of this catalytic reaction is that the addition of C-H bonds to a,/3-unsaturat-ed carbonyl compounds give Michael adducts without contamination by the corresponding aldol products (Eq. 9.56) [74]. Recently, Murahashi applied their aldol and Michael addition reactions to a solid-phase synthesis using polymer-supported nitriles (Scheme 9.12) [76]. In this case, four component reactions took place with high diastereoselectivity. 

Section 8-6 presents two u.seful reduction processes. Carbonyl compounds such as ketones and aldehydes arc useful precursors (starting materials) for the synthesis of alcohols. Either metal-catalyzed Ht addition or reaction with the hydride reagents NaBH and LiAIH converts aldehydes to primary alcohols. The same processes convert ketones to secondary alcohols. The.se hydride reductions are the lirst of many examples that you will. see of nucleophilic additions to the electrophilic carbons of carbonyl groups. This is one of the most important clas.ses of reactions in organic chemistry. 

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. 

In the last six chapters we discussed the transition metal catalyzed carbonylative activation of organohalogen (C-X, X = I, Br, Cl, OTf, etc.) compounds. They all have one common point in their reaction mechanism taking a palladium catalyst, for example, the reactions start with Pd(0) and then go to Pd(II) after an oxidative addition. To summarize, the reactions all go through Pd(0) to Pd(II) and a Pd(0) cycle. But for oxidative carbonylation reactions, the reactions go through Pd(ll) to Pd(0) and a Pd(II) cycle. Clearly, oxidative carbonylations need additional oxidants to reoxidize the Pd(0) to Pd(II), and various organic nucleophiles were applied as substrates in the presence of CO. One of the most obvious advantages for oxidative carbonylation reactions is the oxidative addition step can be avoid which is more reluctant under CO atmosphere. 

There are two distinct groups of aldolases. Type I aldolases, found in higher plants and animals, require no metal cofactor and catalyze aldol addition via Schiff base formation between the lysiae S-amino group of the enzyme and a carbonyl group of the substrate. Class II aldolases are found primarily ia microorganisms and utilize a divalent ziac to activate the electrophilic component of the reaction. The most studied aldolases are fmctose-1,6-diphosphate (FDP) enzymes from rabbit muscle, rabbit muscle adolase (RAMA), and a Zn " -containing aldolase from E. coli. In vivo these enzymes catalyze the reversible reaction of D-glyceraldehyde-3-phosphate [591-57-1] (G-3-P) and dihydroxyacetone phosphate [57-04-5] (DHAP). 

In addition to the applications reported in detail above, a number of other transition metal-catalyzed reactions in ionic liquids have been carried out with some success in recent years, illustrating the broad versatility of the methodology. Butadiene telomerization [34], olefin metathesis [110], carbonylation [111], allylic alkylation [112] and substitution [113], and Trost-Tsuji-coupling [114] are other examples of high value for synthetic chemists. 

Although considerable progress has been made in metal-catalyzed preparations of non-racemic cyanohydrins, the HNL-catalyzed reaction is still the most important method for the synthesis of chiral cyanohydrins, especially for large-scale reactions. The usefulness of HNLs as catalysts for the stereoselective addition of HCN to carbonyl compounds has increased substantially because (7 )-PaHNL... 

These reactions are covered in other chapters of Volume 11 (Chapters 11.06 and 11.07). This part deals only with examples which are in connection with other sections of this chapter. Additions of metallocarbenoids to unsaturated partners have been extensively studied. Most of the initial studies have involved the transition metal-catalyzed decomposition of cr-carbonyl diazo compounds.163,164 Three main reaction modes of metallocarbenoids derived from a-carbonyl diazo precursor are (i) addition to an unsaturated C-C bond (olefin or alkyne), (ii) C-H insertion, and (iii) formation of an ylid (carbonyl or onium).1 5 These reactions have been applied to the total synthesis of natural... 

The carbon of complexed CO, i. e., M-CO, can appear at either a lower or higher frequency than CO itself depending on the metal. A useful list of CO chemical shifts can be found in a study describing mechanistic aspects of the Rh- and Ir-cat-alyzed carbonylation of methanol [59]. Additional C NMR data on Rh-acyl intermediates, derived from the Rh-catalyzed carbonylation of ethene, e. g., 60, have been reported [60]. 

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