TFA cleavage

Products of this type were not isolated, however, when the non-immobilised metathesis substrates were allyl esters or ethers. In these cases, the combined effect of metathesis and TFA cleavage was simply to remove the allyl group. A modified protodesilylation mechanism was proposed to account for these results (Scheme 3). 

C). In addition, cleavage efficiency was enhanced when the resins were dried under vacuum before exposure to the TFA cleavage solution. 

J Urban, T Vaisar, R Shen, MS Lee. Lability of JV-alkylated peptides towards TFA cleavage. Int J Pept Prot Res 47, 182, 1996. 

Tab. 12.3 l Resins studied in TFA cleavage reactions. Monitoring the Oeavage Completion 517... 

Fig. 12.15 Single bead IR spectra of resins (19) at various times during the TFA cleavage reaction (5% TFA).

Fig. 12.16 Time courses of TFA cleavage reactions for resin (19) obtained by integrations of the carbonyl bands. Lines represent the best fit obtained by PeakFit (Jandel Scientific, San Rafael, CA) analysis on a PC computer.

Resins (19) ( 30 mg each) reacted with 5% TFA in DCM. Droplet of suspension was taken at various time intervals for single bead FTIR (Fig. 12.15) and kinetics analysis (Fig. 12.16). The data was also fitted to a first order reaction rate equation and rate constants were determined to be 4.8x10 (5% TFA). Cleavage of carbamides (18), (20), (21), ureas (22-25), amides (26-29), and sulfonamides (30-33) were studied in the same way. 

Fig. 12.17 Kinetic comparison of TFA cleavage reactions of all 16 resin-bound compounds (18-33). The kinetics of cleavage reaction was analyzed as in Figures 12.15 and 12.16. The curves represent the best fit and are displayed for each reaction. The first order reaction rate constants (s ) determined for these reactions are resins (18) (1%), 1.2x10 (19) (5%), 4.8x10 (20) (0.5%), 6.5x10 (21) (1%),...

Solid-phase [2-i-2-i-2] cycloaddihon was also catalyzed by the Ir complex (Scheme 11.6) [14]. Here, the reachon of a resin-bound dipropargylamine and various monoalkynes proceeded under heating by microwave-irradiation, and isoindoline derivatives were obtained in moderate yield after trifluoracetic acid (TFA)-cleavage of the resin-bound intermediates. 

Numerous researchers have employed thiols as weak bases in the thioalkylation reaction to ligate unprotected peptides with a haloacetyl group to form thioethers at pH 7 8.5[90 91 131-133 or thioesters at acidic to basic conditions. 108"110 Of these two reactions, thioether formation is often the choice because thioesters suffer from instability in aqueous basic conditions. Haloacetyl derivatives, either as carboxylic acids or active esters, can be attached to either the N-terminal or side-chain amines during the stepwise solid-phase synthesis of either the peptide or the core and are stable to either HF or TFA cleavage conditions. Capping an amino group with a chloroacetyl group is compatible with Fmoc chemistry when used at a terminal step. 

The synthesis of 1,4-thiazepines from chalcones 184 is also possible on solid support. This has been shown by Lee etal. In an one-step bis-nucleophilic attack of 75, loaded on Wang or Rink amide resin, to the a,[)-unsaturated ketone 184, the seven-membered ring 192 is formed. TFA cleavage afforded more than 29% overall yield (Equation 14) <2001TL109>. 

The Suzuki coupling of arylboronic acids to the solid-supported arylha-lide 4 was initially performed by conventional heating methods, DMF at 85° in an oil bath for 16 h, to provide the desired products 6 after TFA cleavage. Due to the extended heating times necessary for the Suzuki reaction, full optimization of the reaction conditions were not investigated prior to compound library synthesis. Reaction conditions sufficient for the library synthesis were determined within a couple of weeks affording moderate yields of the desired oxazolidinones. Libraries of hundreds of... 

Fig. 1. Reversed-phase chromatogram of the crude unphosphorylated peptide H-CXVAVVRTPPKSPSSAK-NH2 (X = e-aminohexanoic acid) obtained after TFA cleavage and diethyl ether precipitation using the Jupiter Ci8-column and the gradient described in Subheading 2.4. Absorbance was recorded at 220 nm.

The two mainstays of modem mass spectrometry, electrospray MS and MALDI/ TOFMS, can both be used with adequate sensitivity for single-bead detection of molecular weight and structural information [37], Single-bead MS using TFA cleavage and MALDI/ TOF analysis is now a well-established technique [38 11], A Scripps group [42] reports... 

For the synthesis of C-terminal peptide amides, the commonly used resins are 1 to 3 (Fig. 4) (8-10). These resins are compatible with Fmoc chemistry and final TFA cleavage. For attachment of the first urethane A-protected residue, standard peptide coupling procedures (Protocol 5) can be used. These resins are usually supplied Fmoc-protected and should be deprotected before incorpora-... 

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