Coupling Reactions Mediated by Group

Multicomponent Coupling Reactions Mediated by Group 14 Radicals I 175... 

Typical mechanisms for pinacol couplings are shown in Scheme 2. In the first reduction step a ketyl radical is formed which can dimerize (path A) or add to a second carbonyl group, forming a C-C bond. In path B a second one-electron reduction must then follow. For pinacol coupling reactions mediated by transition metals the insertion of a carbonyl group into the metal-carbon bond of initially formed metal oxiranes has been proposed (path C). 

A formal iron-catalyzed [3 + 2]-cycloaddition of styrene derivatives with benzoqui-none was reported by Itoh s group [96]. The process is believed to proceed via electron-transfer reactions mediated by a proposed Fe3+/Fe2+ couple, which generates a styrene radical cation and a semiquinone. These intermediates undergo stepwise addition to yield the benzofuran product 51 (Scheme 9.38). The reaction seems to be limited to electron-rich alkoxy-functionalized styrenes, as the Fe3+/Fe2+ redox couple is otherwise unable to transfer the electrons from the styrene to the quinone. 

Unanticipated developments help to put known facts into place. Results from biochemistry drove home to organic chemists the message that it was not a chemical rarity for carbon-hydrogen bonds to be sources of hydride equivalents. Westheimer, Vennesland et al. established beyond doubt that in a redox reaction mediated by the coenzyme couple NAD(P)+/NAD(P)H the carbon-hydrogen bond of ethanol could serve directly as a hydride donor to an electron-deficient carbon of a pyridinium ion, and that this hydride equivalent could in turn be donated directly to the electropositive carbon of a carbonyl group. Thus the hydride donor capacities of carbon are also part and parcel of life. All this can occur under physiological conditions with the help of an enzyme, which somehow activates these reactants. The sequence is illustrated schematically in equation (1). In either direction hydride is transferred from carbon to carbon. 

In 2005, a group of researchers at Abbott turned their attention to the synthesis of a different regioisomer, the 1,2,4-oxadiazoles [75]. These heterocycles are normally prepared by reaction (mediated by a coupling reagent) of a carboxylic acid with an amidoxime, followed by based-catalyzed cyclization at high temperature (Scheme 11). 

The aldehyde function at C-85 in 25 is unmasked by oxidative hydrolysis of the thioacetal group (I2, NaHCOs) (98 % yield), and the resulting aldehyde 26 is coupled to Z-iodoolefin 10 by a NiCh/CrCH-mediated process to afford a ca. 3 2 mixture of diaste-reoisomeric allylic alcohols 27, epimeric at C-85 (90 % yield). The low stereoselectivity of this coupling reaction is, of course, inconsequential, since the next operation involves oxidation [pyridinium dichromate (PDC)] to the corresponding enone and. olefination with methylene triphenylphosphorane to furnish the desired diene system (70-75% overall yield from dithioacetal 9). Deprotection of the C-77 primary hydroxyl group by mild acid hydrolysis (PPTS, MeOH-ClHhCh), followed by Swem oxidation, then leads to the C77-C115 aldehyde 28 in excellent overall yield. 

The key to the success of the synthesis was the development of a novel method for enantioselective formation of a-arylpyrrolidines. In this method, (-)-sparteine-mediated, enantioselective lithiation of N-Boc-pyrrolidine 19 was followed by an in situ transmetallation to zinc and Pd-catalyzed coupling reaction with aryl bromide 3, which afforded 2-arylpyrrolidine in 63% isolated yield and 92% ee. Notably, the acidic aniline NH2 group was tolerated under the coupling reaction conditions. 

In 1991, Li and Chan reported the use of indium to mediate Barbier-Grignard-type reactions in water (Eq. 8.49).108 When the allylation was mediated by indium in water, the reaction went smoothly at room temperature without any promoter, whereas the use of zinc and tin usually requires acid catalysis, heat, or sonication. The mildness of the reaction conditions makes it possible to use the indium method to allylate a methyl ketone in the presence of an acid-sensitive acetal functional group (Eq. 8.50). Furthermore, the coupling of ethyl 2-(bromomethyl)acrylate with carbonyl compounds proceeds equally well under the same reaction conditions, giving ready access to various hydroxyl acids including, for example, sialic acids. 

The first examples of microwave-mediated solid-phase carbon-nitrogen cross-coupling reactions were reported in 1999 by the group of Combs [16], using a boronic... 

The redox and proton transfer reactions undergone by the flavin prosthetic group are summarized in Scheme 5.2. The vertical reactions are oxidations by Q regenerating P. From the standard potential values (V vs. SCE) of the four flavin redox couples that are involved in Scheme 5.2 and those of the mediators (Table 5.1), all four oxidation steps may be regarded as irreversible. The horizontal reactions are deprotonations by the bases present in the buffer. From the pA values of the various flavin acid-base couples indicated in Scheme 5.2 (over or below the horizontal arrows), reactions H2 and H4 may be regarded as irreversible and reactions HI and... 

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