Bond-forming processes

The mechanism of free radical polymerization of ethylene is outlined m Figure 6 17 Dissociation of a peroxide initiates the process m step 1 The resulting per oxy radical adds to the carbon-carbon double bond m step 2 giving a new radical which then adds to a second molecule of ethylene m step 3 The carbon-carbon bond forming process m step 3 can be repeated thousands of times to give long carbon chains... 

Aldol condensations are one of the fundamental carbon-carbon bond forming processes of synthetic organic chemistry Furthermore because the products of these aldol con densations contain functional groups capable of subsequent modification access to a host of useful materials is gamed... 

Use curved arrows to show the carbon-carbon bond forming processes that lead to the four aldol addition products just shown J... 

The higher terpenes are formed not by successive addition of C5 units but by the coupling of simpler terpenes Thus the triterpenes (C30) are derived from two mole cules of farnesyl pyrophosphate and the tetraterpenes (C40) from two molecules of ger anylgeranyl pyrophosphate These carbon-carbon bond forming processes involve tail to tail couplings and proceed by a more complicated mechanism than that just described... 

The influence of the Lewis acid catalyst can be understood from the FMO diagram to the right in Fig. 8.17. The Lewis acid catalyst enhances significantly the asynchronicity of the bond-forming process for the more favorable ortho transition state as the 0-C distance in the BH3-catalyzed reaction is 2.478 A compared to 2.284 A in the uncatalyzed reaction. For the use of AlMe3 as the catalyst the 0-C distance is calculated to be 2.581 A in the transition state. 

Intermediates 18 and 19 are comparable in complexity and complementary in reactivity. Treatment of a solution of phosphonium iodide 19 in DMSO at 25 °C with several equivalents of sodium hydride produces a deep red phosphorous ylide which couples smoothly with aldehyde 18 to give cis alkene 17 accompanied by 20 % of the undesired trans olefin (see Scheme 6a). This reaction is an example of the familiar Wittig reaction,17 a most powerful carbon-carbon bond forming process in organic synthesis. 

The utility of the Suzuki reaction in the challenging arena of natural product total synthesis has been explored. The constitution of bombykol (106) (see Scheme 26), a well-known pheromone, lends itself to a Suzuki coupling. Indeed, in a short stereospecific synthesis of 106, Suginome et al. demonstrated that ( )-vinylboronic acid ( )-104 can be smoothly cross-coupled with (Z)-l-pentenyl bromide [(Z)-105] 44 the configurations of both coupling partners are preserved in the C-C bond forming process. 

It will be recalled that lactone-derived enol triflate 102 was expected to serve as a substrate for a Murai coupling37 with the mixed cuprate reagent derived from iodo ortho ester 103 (see Scheme 17c). If successful, this C-C bond forming process would accomplish the introduction of the remaining carbon atoms needed for the annulation of the seven-membered D-ring lactone. 

The (TMS)3Si radical addition to terminal alkenes or alkynes, followed by radical cyclization to oxime ethers, were also studied (Reaction 50). The radical reactions proceeded effectively by the use of triethylborane as a radical initiator to provide the functionalized pyrrolidines via a carbon-carbon bond-forming process. Yields of 79 and 63% are obtained for oxime ethers connected with an olefin or propargyl group, respectively. 

Alternative conditions for reductive decyanations can be used. The allylic ether in compound 26, an intermediate in a total synthesis of (-)-roxaticin, was prone to reduction when treated with lithium in liquid ammonia. Addition of the substrate to an excess of lithium di-ferf-butylbiphenylide in THF at -78°C, and protonation of the alkyllithium intermediate provided the reduced product 27 in 63% yield, as a single diastereomer (Eq. 7). a-Alkoxylithium intermediates generated in this manner are configurationally stable at low temperature, and can serve as versatile synthons for carbon-carbon bond forming processes (see Sect. 4). 

TKase is a homodimeric protein with a subunit of about 70kDa. The X-ray structures of TKase of E. colif S. cerevisiaeX Leishmania mexicana and mize have been solved. In addition, the crystal structures of a number of site-directed mutants have been determined. Schneider and co-workers have reported a series of studies in which they have mutated important residues of active site of TKase to elucidate the reaction mechanism and explain the origin of the stereospecificity of the C—C bond-forming process (Table The conserved... 

Organozinc reagents are also used extensively in conjunction with palladium in a number of carbon-carbon bond-forming processes that are discussed in Section 8.2. 

Our interest here is particularly with carbon-phosphorus bond forming processes, and development of this aspect has been relatively recent. 

Pd-catalyzed intramolecular etherification reactions of aliphatic alcohols have also been practiced in tandem with other bond-forming processes, such as a Pd-catalyzed allyltin addition to an aldehyde (Equation (32)).160 Similarly, a tandem C-N and G-O bond formation sequence occurs (Equation (33)) during the reactions of /3-amino alcohols with biscarbonates in the presence of the N,O-acetal-derived ligand 43.161-163... 

When 1,3-dienes containing a tethered alcohol are subjected to Wacker-type reactions, the initial intramolecular oxypalladation event creates a 7r-allylpalladium species, which can then undergo an additional bond-forming process to effect an overall 1,4-difunctionalization of the diene with either cis- or // -stereochemistry (Scheme 18).399 An array of substrate types has been shown to participate in this reaction to generate both five- and six-membered fused or ro-oxacycles.435-437 Employing chiral benzoquinone ligands, progress toward the development of an asymmetric variant of this reaction has also been recorded, albeit with only modest levels of enantioselectivity (up to 55% ee).438... 

In a perfect world of balanced checkbooks, the bond breaking and bond forming processes are synchronized, as it happens (albeit not always perfectly) in concerted pericyclic reactions. Even when such synchronization is not perfect, unimolecular... 

In the Zr-catalyzed cyclic carbometallation discussed above, a tandem process consisting of (i) transmetallation and (ii) P-H abstraction provides the missing link in the catalytic cycle. In a series of recent examples reported by Takahashi [206—208] and Hoveyda [209—214], the missing link has been provided by a process consisting of (i) [5-elimination or deheterometallation (Pattern 10), (ii) transmetallation, and (iii) P-H abstraction (Scheme 1.62). Some of these reactions have been developed into enantioselective C—C bond-forming processes, as discussed below. 

An important observation in the area of Zr-catalyzed carboaluminations of alkenes is that made by Wipf and Ribe that addition of water leads to substantial acceleration of the C—C bond-forming process [35]. Thus, as illustrated in Scheme 6.14, whereas catalytic alkylation of the silylated alkene 41 does not afford any of the desired product, upon addition of one equivalent of water, 42 is formed in 85 % yield with 80 % ee. As is also depicted in Scheme 6.14, carboaluminations of unsaturated alcohols are less efficient (—> 43, but better than reactions without water), while those involving alkenes that bear an a-branched substituent are less selective (—> 44). Another impressive example of rate... 

Catalytic asymmetric aldol reactions provide one of the most powerful carbon-carbon bond-forming processes affording synthetically useful, optically... 

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