C Bond Formation Reactions

The formation of C-C bonds is of great importance for the synthesis of nonpepti-dic small molecules. For this, there is an increasing interest in the development of solid-phase methodology for this kind of transformation. Well-known liquid-phase reactions have been successfully transferred to solid-supported chemistry. 

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Trade et al. [56] used cationic bis(oxazoHne)-Cu(II) complexes, intercalated into lamellar clays by electrostatic interactions, as catalysts for C - C bond formation reactions. Interestingly, the heterogeneous catalysts led to higher conversions and selectivities than their homogeneous coimterparts. 

Near-critical water has been used as a medium for various C-C bond formation reactions including Friedel-Crafts alkylation and acylation (Eq. 7.12).30 In these reactions, near-critical water solubilizes the organics and acts as a source of both hydronium and hydroxide ions, thereby replacing the normally required hazardous solvents and catalysts that require subsequent neutralization and disposal. 

It should be noted that the Grob fragmentation reaction and the reductive cyclization (homoallylation) discussed in this section involve the same oxanickellacyclopentane 66 as a common intermediate (Scheme 17). The reversibility of these C - C bond cleavage reaction and C - C bond formation reaction is also supported by the isolation and characterization (by X-ray analysis) of an oxanickellacyclopentane-like 66 (without a tether), which is prepared from a stoichiometric amount of Ni(cod)2, a diene, an aldehyde, and a monodentate phosphine ligand [41]. 

Palladium catalyzed reaction of aryl halides and olefins provide a useful synthetic method for C-C bond formation reaction [171, 172], The commonly used catalyst is palladium acetate, although other palladium complexes have also been used. A sol-vent-free Heck reaction has been conducted in excellent yields using a household MW oven and palladium acetate as catalyst and triethylamine as base (Scheme 6.51) [173], A comparative study revealed that the longer reaction times and deployment of high pressures, typical of classical heating method, are avoided using this MW procedure. 

Chiral Hydrazone Systems. In 1976, Corey and Enders34 demonstrated the great synthetic potential of metalated dimethylhydrazones as highly reactive intermediates in regio- and diastereoselective C C bond formation reactions. The procedure for carrying out the electrophilic substitution reaction... 

Sultam 53 has proved to be an excellent chiral auxiliary in various asymmetric C-C bond formation reactions. One more example of using sultam 53 is the asymmetric induction of copper(I) chloride-catalyzed 1,4-addition of alkyl magnesium chlorides to a,/ -disubstituted (/ )-enesultams 60. Subsequent protonation of the reaction product gives compound 61c as the major product (Scheme 2-30 and Table 2-11).56... 

An example of an iron-catalyzed C-C bond formation reaction was reported in 2001 [89]. Treatment of propargyl sulfides 87 with trimethylsilyldiazomethane in the presence of 5 mol% FeCl2(dppb) gave substituted homoallenylsilanes 88 in good to moderate yields (Scheme 3.43). The silanes 88d and 88e, which bear two centers of chirality, were obtained as 1 1 mixtures of diastereomers. Slight diastereoselectivity (2 1) was seen for the formation 88f, which is an axially chiral allene with a sterogenic center. 

The simplest C-C bond formation reaction is the nucleophilic displacement of a halide ion from a haloalkane by the cyanide ion. This was one of the first reactions for which the kinetics under phase-transfer catalysed conditions was investigated and patented [l-3] and is widely used [e.g. 4-12], The reaction has been the subject of a large number of patents and it is frequently used as a standard reaction for the assessment of the effectiveness of the catalyst. Although the majority of reactions are conducted under liquiddiquid two-phase conditions, it has also been conducted under solidrliquid two-phase conditions [13] but, as with many other reactions carried out under such conditions, a trace of water is necessary for optimum success. Triphase catalysis [14] and use of the preformed quaternary ammonium cyanide [e.g. 15] have also been applied to the conversion of haloalkanes into the corresponding nitriles. Polymer-bound chloroalkanes react with sodium cyanide and cyanoalkanes under phase-transfer catalytic conditions [16],... 

In synthesis, the main screws that maintain the different pieces together are the C—C bonds. Therefore, C—C bond formation reactions can be considered the essence of organic synthesis [1]. 

Lemaire et al. have developed a efficient fructose-1,6-bisphosphate aldolase (FBPA)-mediated synthesis of aminocyclitol analogs of valiolamine [34], This one-pot route involves the formation of two C—C bonds where four stereocenters are created. The first C—C bond formation reaction is catalyzed by the aldolase, coupling DHAP to nitrobutyraldehydes the other one is the result of a highly stereoselective intramolecular Henry reaction occurring on the intermediate nitroketone under acidic conditions during the aldolase-catalyzed reaction and phytase-catalyzed phosphate hydrolysis coupled step (Scheme 4.13). 

Shimagaki et al. reported the synthesis of the C11-C16 fragment of the penta-mycin based in the stereoselechve C—C bond formation reaction catalyzed by FBPA [45]. Pentamycin is a polyene macrolide antibiotic, whose configurations at C15 and C14 would correspond to those of the C3 and C4 posihons of an aldol constructed from addihon of DHAP-derived from FBP by use of FBPA and TIM-to the corresponding aldehyde catalyzed by FBPA (Scheme 4.19). 

As the last example of C-C bond-formation reactions catalyzed by alkaline earth hydroxides, we mention the recently reported a-arylation of diethyl malonate in the presence of a palladium catalyst and a base in a separate phase 299). The arylation of carbonyl compounds is a carbon-carbon coupling reaction between an aryl halide and an enolate, which is usually catalyzed by palladium salts in the presence of an appropriate base (300,301). The arylation of diethyl malonate with bromobenzene (Scheme 48) was performed with tetrachloropalladate as the... 

During our investigations on asymmetric C—C bond formation reactions via conjugate addition of SAMP hydrazones to various a,(3-unsaturated Michael acceptors, it occurred to us to use the chiral hydrazine auxiliary S AM P as a nitrogen nucleophile and a chiral equivalent of ammonia in aza-Michael additions. Thus, we developed diastereo- and enantioselective 1,4-additions for the synthesis of P-amino acids and P-aminosulfonates [14, 15]. 

Scheme 2.2.7.22 Application of monomethoxy- and dimethoxyacetaldehyde in BAL-catalyzed C-C bond formation reactions.

The Pd-catalyzed alkynylation is one of the most widely used —C bond formation reactions. It has been thoroughly and extensively reviewed recently15-17. So only a brief overview and a discussion of some of the most recent advances will be presented in this section. As in the case of alkenyl-alkenyl coupling, Ni catalysts have rarely been used for alkynylation, even though Ni catalysts do affect the desired alkynylation in some cases. One main reason for disfavoring Ni is that Ni can readily react with alkynes to undergo alkyne cyclooligomerization represented by arene formation. The Pd-catalyzed alkynylation can, in principle, be performed in three discrete manners, as shown in Scheme 40. 

B. Giese, J. Dupuis, M. Leising, M. Nix, and H. J. Lindner, Synthesis of C-pento, -hexo, anc -heptulo-pyranosyl compounds via radical C-C bond-formation reaction, Carbohydr. Res 171 379 (1987). 

Type of reaction C-C bond formation Reaction condition solid-state... 

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