Ester-directed couplings

This class of donor is activated by soft Lewis acids, such as copper triflate at room temperature, and despite their hydrolytic instability, they appear inert to conditions of sulfoxide activation, TMSOTf or Tf20 (Scheme 4.53). Activation is achieved with stoichiometric promoter in the presence of the acceptor alcohol, and although the mechanism has not been investigated, presumably it proceeds via coordination followed by collapse to a stabilized oxacarbenium ion. The method is compatible with standard glycosidation solvents such as dichloromethane, acetonitrile and diethyl ether, and ester-directed couplings do not lead to orthoesters, perhaps as a result of the presence of the Lewis acid promoter [303,304]. 

The chemiluminescence reaction of esters of oxalic acid can proceed within a wider pH range than for luminol. However, the most efficient oxalate derivatives are only soluble in organic solvents such as ethyl acetate, acetonitrile, dioxane or dimethoxyethane and dissolution problems of these solvents in aqueous media are encountered. This can limit the use of this chemiluminescence reaction for a direct coupling to an H202-generating enzymatic reaction. 

SADP, N-succinimidyl-(4-azidophenyl)l,3 -dithiopropionate, is a photoreactive heterobifunctional crosslinker that is cleavable by treatment with a disulfide reducing agent (Thermo Fisher). The crosslinker contains an amine-reactive NHS ester and a photoactivatable phenyl azide group, providing specific, directed coupling at one end and nonselective insertion capability at the other end. 

The preformed (BC) method is a one-step process used in this case to introduce high multiplicity of terminal hydroxy groups. The method involves direct coupling of branch cell reagents (i.e. tris(hydroxymethyl)aminomethane (Tris-)) by amidation of ester terminated PAMAM dendrimers. Advancement to the next generation of branch cells occurs in one step. 

Direct coupling of carbon nucleophiles with 1,3-dinitrobenzene is promoted by ultraviolet irradiation in the presence of quaternary ammonium fluorides, which can act not only as the base to generate the carbon nucleophile, but also as a proton transfer agent in the rearomatization step [83], The dinitrobenzene acts as the electron acceptor in the photochemical step. No reaction occurs in the absence of the fluoride and, surprisingly, although simple ketones, nitriles, esters and fl-kcto esters react, pentan-2,4-dione does not. 

A synthesis in solution of a protected K2K dendron and its functionalization by a dimeth-oxyacetyl derivative as a masked aldehyde185 is illustrated in Scheme 6. Synthesis of the tetravalent K2K dendron 29 was accomplished in three steps. The acetal derivative 30 was obtained from saponification of the commercially available methyl dimethoxyacetate ester and directly coupled to the tetravalent lysinyl dendron. Cleavage of the dimethoxy acetal requires an acid stronger than TFA and is removed successfully with cold concentrated HC1 because of the stabilization effect of the adjacent amide bond. Pallin and Tam 88 have found that a higher homologue with an extra methylene unit between the dimethoxy and acetyl moiety is susceptible to TFA conversion into the aldehyde unit for the same purpose. 

Coupling sodium tellurocarboxylates with R SiCl gives the unstable silyl derivative which isomerizes to the more thermodynamically stable RC(Te)OSiR 3 through a facile rearrangement that can be readily followed by 13C NMR spectroscopy. This contrasts with the reaction of alkali metal thiocarboxylates which give the O-silyl ester directly. There is no evidence for the S-silyl intermediate101. 

The coupling of carboxyl-containing compounds to amino groups of the polypeptide carrier is usually performed with an excess of carboxyl groups and an equivalent amount of the water-soluble carbodiimide around pH 5 at room temperature. In some cases where the hapten is not water soluble, it is usually dissolved in DMF or dioxane. In such cases it is also possible to prepare the hydroxysuccinimide ester using dicyclo-hexylcarbodiimide and couple this ester directly to the carrier. The experimental procedure will be demonstrated by two examples. 

More recently, a protocol was elucidated by Malezcka and Smith to produce aryl borate esters directly without first producing aryl halides.144 The reaction involves an Ir-catalyzed C-H activation (Section 7-2-1) to yield the aryl borate, which can then be used directly in Suzuki cross-coupling (equation 12.71). This new development adds another green aspect to Suzuki cross-coupling, which is already a relatively green synthesis tool. 

Direct coupling of two vinyl groups remains an important job for the Suzuki reaction. In their synthesis of the antibiotic (+)-fostriecin, Reddy and Falck46 coupled the Z-vinyl bromide 276 with the Z-boronic ester 277 to make the triene 278 with Z,Z, -alkenes. Free OH groups obviously do not interfere. 

The direct coupling of t-butyl thiazole-4-carboxylate at C-2 is successful with a wide range of (hetero) aryl halides, the hindered ester (rather than the methyl ester), together with the use of tri-o-tolylphosphine as ligand, giving optimum selectivity for C-2 vs. C-5 for iodoarenes and heteroarenes. Changing the ligand to JohnPhos allows extension to chloro- and bromo-heterocycles. ... 

---