TFA, Trifluoroacetic acid

Stereoselectivity in the condensation reaction of 2-arylethylamines with carbonyl compounds to give 1,2,3,4-tetrahydroisoquinoline derivatives was somewhat dependent on whether acid catalysis or superacid catalysis was invoked. Particularly in the cases of 2-alkyl-N-benzylidene-2-phenethylamines, an enhanced stereoselectivity was observed with trifluorosulfonic acid (TFSA) as compared with the weaker acid, trifluoroacetic acid (TFA). Compound 43 was cyclized in the presence of TFA to give modest to good transicis product ratios. The analogous compound 44 was cyclized in the presence of TFSA to give slightly improved transicis product ratios. 

The stage is now set for the crucial polycyclization event. Tertiary carbinol 8, derived from the action of methyllithium on enone 9, is a rather unstable substance, and it was submitted to the polycyclization reaction without purification. When intermediate 8 is treated with trifluoroacetic acid (TFA) and the vinyl cation trapping agent ethylene carbonate in 1,2-dichloroethane at 0°C, the desired... 

Finally, we tried to deprotect the amide nitrogen of the obtained pyridi-nones upon reflirx in neat trifluoroacetic acid (TFA) for 18 h [ 116]. Products were isolated in 73% and 79% yield, respectively. In contrast, upon microwave irradiation at 120 °C for only 20 min, a (1 2) TFA/DCM mixture sufficed to deprotect the pyridinones (isolated yields 75% and 73% respectively). Surprisingly, deprotection with either refluxing neat TFA (18 h) or microwave irradiation in neat TFA with a catalytic amount of methanesulfonic acid (20 min) did not work for dihydrofuropyridinone. 

The effect of the buffer on the efficiency of electrospray ionization was mentioned earlier in Section 4.7.1. This is a good example of the dramatic effect that this may have - good chromatographic separation and ionization efficiency with formic, acetic and propionic acids, and good separation, although with complete suppression of ionization, with trifluoroacetic acid (TFA), the additive used for the protein application described previously. Post-column addition of propionic acid to the mobile phase containing TFA has been shown to reduce, or even... 

In the Boc protection approach, benzyl groups are used to protect the reactive amino acid side-chain functionalities because they are more acid-stable than the Boc groups. Trifluoroacetic acid (TFA) is sufficient to remove the Boc groups while leaving the benzyl groups intact (Fig. 3). 

Trifluoroacetic acid (TFA) is strong enough to react with alkenes under relatively mild conditions.11 The addition is regioselective in the direction predicted by Markovnikov s rule. 

Further attempts to effect a one-step synthesis of the hasubanan skeleton via acid-catalyzed cyclization of urethane 28 and unsaturated amides 31 and 32 were explored, using trifluoroacetic acid (TFA) (Scheme 1). Treatment of... 

Electrochemistry and spectroscopy of the tt cation radical of meso-tetraalkylchlorin (tetra-methyl) and various porphyrins (tetramethyl, tetraethyl, and tetra-ra-propyl) indicate that these do not convert to Nim at low temperatures.280 Optical evidence reveals, however, that oxidation of the tt cation radical of [Ni(pEt2N)(TPP)] leads to a Ni111 cation radical which can be further oxidized to a Ni111 porphyrin dication. Similar studies have been carried out for various other derivatives of me.so-tetraarylporphyrins such as /V-oxides of TPP and 5,10,15,20-tetramesitylpro-phyrin (TMP). Addition of trifluoroacetic acid (TFA) to the /V-oxide of [NinTMP] at —25 °C in CH2C12 results in [Nim(TMP)]+ with a rhombic EPR spectrum, g = 2.40, 2.12, and 2.04.281... 

Protein applications are extremely sensitive to solvent pH, salt concentration, and small molecular weight additives such as trifluoroacetic acid (TFA), which affect solute equilibria. These effects are known and depending on the specific application, proteins are often run under denaturing conditions, which offer vastly different retention conditions than nondenaturing conditions. 

In order to investigate how HC1 affects the polyene sequences we (38) have investigated the effect of trifluoroacetic acid (TFA) on the polyenes introduced chemically into PVC using the method of Shindo (59). TFA was chosen since its concentration in solution can be controlled and set at higher levels than is possible with HC1 thus allowing the possibility of producing high concentration of intermediates which can be detected. 

An elimination/double Wagner-Meerwein rearrangement process has recently been developed by Langer and coworkers [39]. Treatment of compound 1-136, obtained by reaction of 1-134 and 1-135, with trifluoroacetic acid (TFA) led to the cationic species 1-137, which then underwent a twofold Wagner-Meerwein rearrangement to give the bicydic compound 1-139 via 1-138 (Scheme 1.34). 

The sequence could even be prolonged by including a Pummerer reaction. Thus, treatment of 4-103 with trifluoroacetic acid (TFA) gave the furan 4-104, which underwent a cycloaddition to furnish 4-105 the erythryna skeleton 4-109 was obtained after subsequent addition of a Lewis acid such as BF3- Et20 (Scheme 4.23) [33]. It can be assumed that 4-106, 4-107 and 4-108 act as intermediates. In a more recent example, these authors also used the procedure for the synthesis of indole alkaloids of the Aspidosperma type [34]. 

The same starting compound 112 showed a totally different behavior when treated with trifluoroacetic acid (TFA), giving a rearrangement to 114 followed by spontaneous oxidation that afforded an equilibrium mixture of tautomeric compounds 115 and 116 (Scheme 15) <1999EJ03429>. 

A library of l,3,7-substituted-perhydropyrazino[l,2-f]pyrimidine-2,6,8-triones was built by preparation of functionalized ketopiperazines on the solid phase, followed by N-acylation with 2-bromoacetic acid, reaction with isocyanate and with concomitant cyclization using trifluoroacetic acid (TFA) <2003W02003/013740>. 

The protonation of thiadiazapentalenes 33 has been studied experimentally especially with regard to their weak and electron rich N-S-N bond <1996MOL142>. Recently it has been demonstrated that a doubly 1SN-Iabeled thiadiazapentalene (R1 = R2 = H) like 33 is protonated with trifluoroacetic acid (TFA) at N-l to N-5 maintaining the N-S-N bond with a ZJ coupling constant (N-l, N-9) of 3.5 Hz (Scheme 38). 

A solid-phase synthesis of pyrroloindolizines has been developed using this cycloaddition methodology, whereby an isoxazolopyrroloindolizine can be removed from the polymeric resin upon treatment with trifluoroacetic acid (TFA). This also results in ring opening of the isoxazole to give the isolated compound 210 (Scheme 58). A library of 96 such derivatives has been prepared in this way <1998TL5869>. 

The pyrrolonaphthyridines 208 and 209 can be prepared from rearrangement of the pentacycle 207 upon treatment with trifluoroacetic acid (TFA) (Scheme 52). These products are of interest as they have the same structural skeleton as the indole alkaloid (—)-goniomitine, isolated from the root bark of Gonioma Malagasy <1995JOC3282>. Compound 208 has since been used in the synthesis of further derivatives which show cytotoxic activity against leukemia cells <2001BML79>. 

Synthesis of a tricyclic core of marine alkaloid variolin B has been achieved in three steps. The key reaction involves tandem deoxygenation and cylization of a triarylmethanol 187 using a combination of trifluoroacetic acid (TFA) and triethylsilane (TES). The use of 4.3equiv of TFA and 8.1 equiv of TES minimizes the formation of side products 188, 189 and allows the formation of the desired product 190 in 34% yield (Scheme 5) <2005JOC6204>. 

Preparation of 0.1 % trifluoroacetic acid (TFA) solution from fractionated beeswax... 

Other electrophilic substitution reactions on aromatic and heteroaromatic systems are summarized in Scheme 6.143. Friedel-Crafts alkylation of N,N-dimethyl-aniline with squaric acid dichloride was accomplished by heating the two components in dichloromethane at 120 °C in the absence of a Lewis acid catalyst to provide a 23% yield of the 2-aryl-l-chlorocydobut-l-ene-3,4-dione product (Scheme 6.143 a) [281]. Hydrolysis of the monochloride provided a 2-aryl-l-hydroxycyclobut-l-ene-3,4-dione, an inhibitor of protein tyrosine phosphatases [281], Formylation of 4-chloro-3-nitrophenol with hexamethylenetetramine and trifluoroacetic acid (TFA) at 115 °C for 5 h furnished the corresponding benzaldehyde in 43% yield, which was further manipulated into a benzofuran derivative (Scheme 6.143b) [282]. 4-Chloro-5-bromo-pyrazolopyrimidine is an important intermediate in the synthesis of pyrazolopyrimi-dine derivatives showing activity against multiple kinase subfamilies (see also Scheme 6.20) and can be rapidly prepared from 4-chloropyrazolopyrimidine and N-bromosuccinimide (NBS) by microwave irradiation in acetonitrile (Scheme... 

THF) containing 10% (v/v) of trifluoroacetic acid (TFA). After microwave irradiation for 25 s at 60 °C, the mixture was concentrated to dryness, 5 equivalents each of N,N-diisopropylethy]amine (DIEA) and (S)-proline acid chloride in bdmimPF6/ THF were added, and the resulting mixture was stirred at room temperature for 3 min. Finally, after in situ deprotection with 20% piperidine (v/v) in bdmimPF6/ THF at 60 °C for 1 min in the microwave reactor, the target compounds were obtained as mixtures of diastereomers. 

Scheme 7.S Construction of peptoid sequences. Cleavage was carried out using trifluoroacetic acid (TFA) at room temperature.

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