CC Bond Formation

The formation of CC bonds to prepare glycoconjugates has also gained some attention. For example, Diels-Alder cycloaddition has allowed the preparation of synthetic glycoproteins [144] and the construction of a synthetic vaccine candidate against Neisseria meningitidis A [145], These methods relied on a pretagging step to create suitable protein reactants. 

Similarly, Pd-mediated sp2-sp2 C—C (Suzuki-Miyaura) coupling has been enabled in biology through the development of an aqueous biologically compatible Suzuki catalyst system [152], This has now allowed the synthetic glycosylation of whole cell surfaces to create bacterial strains with a synthetic glycocalyx [153], 

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Particularly the step of CC-bond formation is of interest, and has been investigated thoroughly by use of organometallic model compounds a survey of this subject has been given by IV. A. Herrmann [6], In the following, some more recent results are discussed briefly. 

For the generation of several contiguous chiral centers, two alternative key step reactions can be applied (i) stereoselective CC-bond formation and (ii) stereoselective functionalization of compounds having already the required carbon skeleton. In the de novo-synthesis of carbohydrates and related natural products via inverse-type hetero-Diels-Alder reactions both of these principles are especially well documented as will be shown below (8-10). ... 

Recent work from Lipshutz [10] et al. even shows at least in CC-bond formations the replacement of the rather expensive palladium with nickel. Chloroarenes are coupled with organo zink compounds under nickel]0) catalysis. 

Oxidation of 56 to dication gives irreversible cyclic voltammetry, which was qualitatively similar to that found by Kochi and coworkers for the achiral tetra-arylene 75 [113]. The cyclic voltammetric data were consistent with the reversible CC bond formation. Dication 752+.2SbCl6 was isolated and its hexacyclic structure was unequivocally determined by X-ray crystallography (Fig. 15.28) [113]. 

Schafer HJ (1981) Anodic and cathodic CC-bond formation. Angew Chem Int Ed 20 911-934... 

Singlet oxygen oxidation of 3-substituted indoles in the presence of alcohols followed by treatment with sodium borohydride gives 2-alkoxy-3-hydroxyindolines in high yields. Further reaction with a nucleophile and a Lewis acid forms the basis of a synthesis of 2-substituted indoles (Scheme 70). This represents an alternative approach to CC bond formation at the 2-position of indoles to that involving the reaction of 2-lithioindoles with electrophiles. Isoindoles and indolizines are also preferentially oxidized in the five-membered ring to give phthalic acid and picolinic acid derivatives, e.g., 168, respectively. 

Synthesis of imidazoles, oxazoles, and thiazoles by CC bond formation or 1,3-dipolar addition 4-Aminoimidazoles 266 are formed on base treatment of the appropriate precursors 265 (Scheme 130) <1975HCA2192>. Similarly the 4-aminothiazole 268 is obtained from the cyanoamidine 267 (Scheme 131) <1973JPR497>. 

However, only three out of these four possibilities are realistic, since there is no carbonyl group orbital available for a perpendicular approach and formation of a CC bond. Formation of a C,0-biradical is therefore possible only through a parallel approach. 

Recent efforts pertaining to direct attachment of chiral sidechain to a heteroarene show that enantioselective Pictet-Spengler reaction is achievable in the presence of a multifunctional thiourea An interesting observation is that annulation of pyrroles by this method (with 17) can give different isomers from CC bond formation at an a- or 3-carbon ... 

Equation 14.99 shows how the Mizoroki-Heck reaction can be used in the last step of a synthesis of (—)-tubifolene. The conformation of the molecule sets the regiochemistiy—CC bond formation at C7—and the geometry—attack from the front as written. Subsequent p elimination, followed by isomerization provides the final product. 

M. Muller, G.A. Sprenger, M. Pohl, CC bond formation using ThDP-dep>endent lyases, Curr. Opin. Chem. Biol. 17 (2013) 261-270. 

Since then, several phanes have been prepared by photoirradiation as a key step for CC bond formation (Table 19.1)." " Until the mid-1980s, stilbene, vinyl ether, and cinnamic acid moieties were used for the [2 + 2] cycloaddition, avoiding the use of labile vinylarenes. Thus, the phanes formed had some additional substituents at the tethers. This sometimes made their characterization complex. Other techniques were developed for the photochemical transformation of the simplest starting materials with vinyl groups directly attached to arene nuclei. 

SCHEME 6 Reaction mechanism for the photo-induced CC bond formation of with ketene silyl acetals. 

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