Carbon Bond Forming Reactions

The carbon-silicon bond to saturated alkyl groups is not very reactive because there are no high-energy electrons in the sp -sp bonds. Most of the valuable synthetic procedures based on organosilanes involve either alkenyl or allylic silicon substituents. The dominant reactivity pattern involves attack by an electrophilic carbon intermediate at the double bond. 

CHAPTER 9 CARBON-CARBON BOND-FORMING REACTIONS OF COMPOUNDS OF BORON, SILICON, AND TIN 

Attack on alkenylsilanes takes place at the a carbon and results in replacement of the silicon substituent by the electrophile. Attack on allylic groups is at the y carbon and results in replacement of the silicon substituent and an allylic shift of the double bond. The crucial influence on the reactivity pattern in both cases is the very high stabilization which silicon provides for carhocationic character at the -carbon atom. This stabilization is attributed primarily to a hyperconjugation with the C-Si bond.  

The most useful electrophiles from a synthetic standpoint are carbonyl compounds, iminium ions, and electrophilic alkenes. 

Most reactions of alkenylsilanes require strong carbon electrophiles, and Lewis acid catalysts are often involved. Reaction with acyl chlorides is catalyzed by aluminum chloride or stannic chloride. 

The BiCls-Al system is applicable to the Reformatsky-type reaction of aldehydes 

BiOClO4 %l l O is also used in fhe rearrangement of epoxides, although the cata- 

The electrophilic center is sometimes generated from the Lewis base by formation of the adduct. 

Unsymmetrical ketones can be made by using either thexylborane or thexychloroborane. Thexylborane works well when one of the desired carbonyl substituents is derived from a moderately hindered alkene. Under these circumstances, a clean monoalkylation of thexylborane can be accomplished. This is followed by reaction with a second alkene and carbonylation. 

An efficient process for one-carbon homologation to aldehydes is based on cyclic boronate esters. These can be prepared by hydroboration of an alkene with dibromoborane, followed by displacement of the labile bromines. The homologation 

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Carbon-Carbon Bond-Forming Reactions of Organometallic Reagents... 

Like other carbon-carbon bond forming reactions organocuprate addition to enones is a powerful tool m organic synthesis... 

Silicon—Carbon Bond-Forming Reactions. After the Rochow-MbUer direct process, the hydro silylation reaction (139),... 

Heck reaction, palladium-catalyzed cross-coupling reactions between organohalides or triflates with olefins (72JOC2320), can take place inter- or intra-molecularly. It is a powerful carbon-carbon bond forming reaction for the preparation of alkenyl- and aryl-substituted alkenes in which only a catalytic amount of a palladium(O) complex is required. 

An important variant is the rearrangement of silylketene acetals like 10 and 11 which are easily accessible from allyl esters 9. This so-called Ireland-Claisen rearrangement is a valuable carbon-carbon bond forming reaction that takes advantage of the fact that the reactants are first connected to each other by an ester linkage as in allyl esters 9, that are easy prepare. 

Together with reactions named after Heck and Suzuki, the Stille reac-tion belongs to a class of modern, palladium-catalyzed carbon-carbon bond forming reactions. The palladium-catalyzed reaction of an organotin compound 2 with a carbon electrophile 1 is called Stille coupling. 

Palladium-catalyzed carbon-carbon bond forming reactions like the Suzuki reac-tion as well as the Heck reaction and the Stille reaction, have in recent years gained increased importance in synthetic organic chemistry. In case of the Suzuki reaction, an organoboron compound—usually a boronic acid—is reacted with an aryl (or alkenyl, or alkynyl) halide in the presence of a palladium catalyst. 

Diborane reacts with unhindered olefins to form trialkylboranes (the so-called hydroboration reaction, cf. Chapter 4). In this Chapter, several of the recently discovered carbon-carbon bond forming reactions of trialkylboranes are presented. 

Step 5 of Figure 29.5 Condensation The key carbon-carbon bond-forming reaction that builds the fatty-acid chain occurs in step 5. This step is simply a Claisen condensation between acetyl synthase as the electrophilic acceptor and malonyl ACP as the nucleophilic donor. The mechanism of the condensation is thought to involve decarboxylation of malonyl ACP to give an enolate ion, followed by immediate addition of the enolate ion to the carbonyl group of acetyl... 

When 2-lithio-2-(trimethylsilyl)-l,3-dithiane,9 formed by deprotonation of 9 with an alkyllithium base, is combined with iodide 8, the desired carbon-carbon bond forming reaction takes place smoothly and gives intermediate 7 in 70-80% yield (Scheme 2). Treatment of 7 with lithium diisopropylamide (LDA) results in the formation of a lactam enolate which is subsequently employed in an intermolecular aldol condensation with acetaldehyde (6). The union of intermediates 6 and 7 in this manner provides a 1 1 mixture of diastereomeric trans aldol adducts 16 and 17, epimeric at C-8, in 97 % total yield. Although stereochemical assignments could be made for both aldol isomers, the development of an alternative, more stereoselective route for the synthesis of the desired aldol adduct (16) was pursued. Thus, enolization of /Mactam 7 with LDA, as before, followed by acylation of the lactam enolate carbon atom with A-acetylimidazole, provides intermediate 18 in 82% yield. Alternatively, intermediate 18 could be prepared in 88% yield, through oxidation of the 1 1 mixture of diastereomeric aldol adducts 16 and 17 with trifluoroacetic anhydride (TFAA) in... 

A synthetically useful virtue of enol triflates is that they are amenable to palladium-catalyzed carbon-carbon bond-forming reactions under mild conditions. When a solution of enol triflate 21 and tetrakis(triphenylphosphine)palladium(o) in benzene is treated with a mixture of terminal alkyne 17, n-propylamine, and cuprous iodide,17 intermediate 22 is formed in 76-84% yield. Although a partial hydrogenation of the alkyne in 22 could conceivably secure the formation of the cis C1-C2 olefin, a chemoselective hydrobora-tion/protonation sequence was found to be a much more reliable and suitable alternative. Thus, sequential hydroboration of the alkyne 22 with dicyclohexylborane, protonolysis, oxidative workup, and hydrolysis of the oxabicyclo[2.2.2]octyl ester protecting group gives dienic carboxylic acid 15 in a yield of 86% from 22. 

Vinyl triflates derived from lactone enolates are also viable coupling partners In Ni(ll)/Cr(ll)-mediated carbon-carbon bond forming reactions... 

P. Magnus, Organosilicon reagents for carbon-carbon bond-forming reactions, Aldrichimica Acta 13,43 (1980). 

Engberts J. B. F. N., Feringa B. L., Keller E., Otto D. Lewis-Acid Catalysis of Carhon-Carbon Bond Forming Reactions in Water Reel Trav. Chim. Pays-Bas 1996 115 457 64... 

Mikami K. Asymmetric Catalysis of Carbonyl-Ene Reactions and Related Carbon-Carbon Bond Forming Reactions Pure Appl. Chem. 1996 68 639 644 Keywords hefero-Diels-Alder reactions, asymmetric catalysis... 

Pd-catalyzed asymmetric allylic alkylation is a typical catalytic carbon-carbon bond forming reaction [ 126 -128]. The Pd-complex of the ligand (R)-3b bearing methyl, 2-biphenyl and cyclohexyl groups as the three substituents attached to the P-chirogenic phosphorus atom was found to be in situ an efficient catalyst in the asymmetric allylic alkylation of l-acetoxy-l,3-diphenylprop-2-en (4) with malonate derivatives in the presence of AT,0-bis(trimethylsilyl)acetamide (BSA) and potassium acetate, affording enantioselectivity up to 96% and quantitative... 

Kobayashi S (1999) Lanthanide Triflate-Catalyzed Carbon-Carbon Bond-Forming Reactions in Organic Synthesis. 2 63-118... 

Compendium of Organic Synthetic Methods, Vo/ume 9 contains both functional group transformations and carbon-carbon bond forming reactions from the literature appearing in the years 1993,1994 and 1995. The classification schemes used for volumes 6-8 have been continued. Difunctional compounds appear in Chapter 16. The experienced user of the Compendium will require no special insructions for the use of Volume 9. Author citations and the Author Index have been continued as in Volumes 6-8. 

Lipases are the enzymes for which a number of examples of a promiscuous activity have been reported. Thus, in addition to their original activity comprising hydrolysis of lipids and, generally, catalysis of the hydrolysis or formation of carboxylic esters [107], lipases have been found to catalyze not only the carbon-nitrogen bond hydrolysis/formation (in this case, acting as proteases) but also the carbon-carbon bond-forming reactions. The first example of a lipase-catalyzed Michael addition to 2-(trifluoromethyl)propenoic acid was described as early as in 1986 [108]. Michael addition of secondary amines to acrylonitrile is up to 100-fold faster in the presence of various preparations of the hpase from Candida antariica (CAL-B) than in the absence of a biocatalyst (Scheme 5.20) [109]. 

Shey J, CM McGinley, KM McCauley, AS Dearth, BT Young, WA van der Donk (2002) Mechanistic investigation of a novel vitamin Bjj-catalyzed carbon-carbon bond forming reaction, the reductive dimerization of arylalkenes. J Org Chem 67 837-846. 

Carbon-carbon and non-carbon-carbon bond-forming reactions Atom economy increases as the molecular weights of the combining fragments increases... 

The nitroaldol reaction or Henry reaction is a powerful and highly versatile carbon-carbon bond-forming reaction, allowing a plethora of key molecular frameworks, such as p-hydroxynitroalkanes, 1,2-amino alcohols or a-hydroxy carboxylic acids to be synthesised in a straightforward manner. Therefore, the development of practical catalytic asymmetric versions of this reaction is still largely desirable. The first catalytic asymmetric nitroaldol reaction was reported in 1992, " but despite its long history, relatively few chiral ligands have... 

Other kinds of nucleophiles such as amines, alkoxides, and sulfide anions also react with electrophilic alkenes, but we focus on the carbon-carbon bond forming reactions. 

Examples of these transformations are discussed in Chapter 9, where carbon-carbon bond-forming reactions of organoboranes are covered. 

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