Fluorinated solid supports

More stable catalysts are obtained by using fluorinated graphite or fluorinated alumina as backbones and Lewis acid halides, such as SbFs, TaFs and NbFs, which have a relatively low vapor pressure. These Lewis acids are attached to the fluorinated solid supports through fluorine bridging. They show high reactivity in Friedel-Crafts reactions including the isomerization of straight chain alkanes such as n-hex-ane. 

Using related chemistry, we have found these repetitive couplings to be facile and have used aromatic diboronic acids83 to generate simple terphenyl structures on solid support.84 We used gel-phase fluorine NMR spectroscopy85 to observe the incorporation of the appropriate groups (Scheme 34) in repeated palladium-catalyzed reactions at slightly elevated temperature (55°C). This unoptimized two-step process was complete in essentially 24 h. 

Our approach was based on the observation that it is possible to perform SwAr reactions on solid support with amino acids using a solvent system comprised, in equal parts, of acetone and an aqueous 0.5 M NaHC03 solution at temperatures around 70-75°C. Application of this solvent system to the synthesis of quinoxalin-2-ones 6 from la and a-amino acids is described in Section 3.3.2. With respect to the synthesis of 1,5-ben-zodiazepin-2-ones 4, more than 40 examples of aliphatic and aromatic P-amino acids 35 were found to furnish the desired o-nitro anilines 36, about 80% of which were successfully carried on to eventually afford the ben-zodiazepinone products 4 (Scheme 6). In general, the anthranilic acids required slightly harsher conditions to drive the fluorine displacement to completion (75-80°C, 72 h vs. 70-75°C, 24 h for aliphatic P-amino acids). 

Gel-phase NMR spectroscopy is a very convenient technique for the spectroscopic characterization of functionalized solid supports.Optimal conditions for acquiring standard gel-phase NMR spectra from a variety of resins are well-established optimal conditions, i.e. maximum swelling, result in reasonably narrow lines for the pendant groups. This method has the additional advantage of not requiring any special instrumentation besides a conventional FTNMR spectrometer and a conventional probe. In addition to NMR spectroscopy, NMR l and NMRt l spectroscopy can also be used in those cases where fluorine or phosphorous is present in the handle or in the first amino acid. 

F makes an excellent probe to monitor solid phase reactions most solid supports do not contain fluorine, 19F NMR is almost as sensitive as proton NMR, the range of 19F chemical shifts is large, and the resonance can be monitored even when the fluorine atom is quite remote from the site of reaction. The buildup of the peptide chain could be monitored by incorporating 19F into a peptide-protecting group (18). 

The anodic oxidation of carboxylic acids has also been carried out using a solid-supported base in methanol. Non-Kolbe-type electrolysis takes place to give the corresponding methoxylated product (Equation 12.7). The acid-base reaction between a carboxylic acid and a solid-supported base seems to reduce the cell voltage and makes the electrochemical reaction possible. Kolbe-type carbon-carbon coupling using aliphatic and benzylic carboxylic acids has also been accomplished using this method [26]. Based on a similar concept, anodic fluorination by an alkali metal... 

Fluorinated solvents owing to their unique affinity properties fluorinated compounds may be used as solvents or solid supports, offering novel, simple and greener approaches for performing organic transformations and separations, including the efficient reuse of catalysts and chiral resolution. 

Very little work has been carried out on the fluorination of organic compounds using solid supports. However, Durrane et al. report the adsorption of various substrates onto molecular sieves, which restricts the access of fluorine and provides the reaction with a high degree of selectivity [165]. A much softer fluorination has been achieved by adsorbing xenon hexafluoride on graphite (e.g. equation 4.45) [166]. 

More recently, Llobet and coworkers reported the anodic electropolymerization of A -substituted pyrroles as a convenient method of anchoring a redox-active dinuclear ruthenium catalyst onto conducting solid supports, like vitreous carbon sponges (VCS) and fluorine-doped tin oxide (FTO). In the presence of Ce(IV) as the sacrificial oxidant, turnover numbers up to 76 have been achieved. A major improvement of the system is accomplished by the copolymerization with a robust non active redox species, able to further separate the catalytically active species on the solid support, obtaining up to 250 catalytic cycles. 

Becker, M. L., Liu, J., and Wooley, K. L. (2001). Preparation of tritrpticin block copolymer bio-conjugates by fluorinated nitroxide mediated radical polymerization on solid support. Abstracts of Papers, 222nd ACS National Meeting, Chicago, IL, United States, August 26-30, 2001, p. OLY-017. 

Doebele M, Vanderheiden S, Jung N, Braese S (2010) Synthesis of aryl fluorides on a solid support and in solution by utilizing a fluorinated solvent. Angew Chem Int Ed 49(34) 5986-5988... 

Carbonate linkers have been transformed into carbamates and alcohols via cleavage from the solid support. Alcohols 243 can be produced by the addition of TFA/thioanisole to the resin-bound substrates 242 (Scheme 36). They can also be obtained by photolytic cleavage from resins with general linker structure 238 or via cleavage with fluorine reagents from linkers like 239 in Fig. 11 [205,206]. 

The utility of a new fluorine supported chiral auxiliary was established in a series of catalyzed and uncatalyzed 1,3-dipolar cycloaddition reactions with diphenylnitrone (637b) (Scheme 2.281) (797). The yields and selectivities of the cycloadducts (645a—d) compare favorably with those obtained with conventional Evans-type auxiliaries (798). Purification of the products was greatly improved by using fluorous solid phase extraction (FSPE). 

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