Protic acids, addition

ARO reaction with phenols and alcohols as nucleophiles is a logical extension of HKR of epoxides to synthesize libraries of stereochemically defined ring-opened products in high optical purity. To this effect Annis and Jacobsen [69] used their polymer-supported Co(salen) complex 36 as catalyst for kinetic resolution of epoxides with phenols to give l-aiyloxy-2-alcohols in high yield, purity and ee (Scheme 17). Conducting the same reaction in the presence of tris(trifluoromethyl)methanol, a volatile, nonnucleophilic protic acid additive accelerates KR reaction with no compromise with enantioselectivity and yield. Presumably the additive helped in maintaining the Co(III) oxidation state of the catalyst. 

The reaction of 2,3-dibromopropene with racemic as well as enantiopure 4-oxoazeti-dine-2-carbaldehydes (1) in aqueous media was promoted by tin in the presence of catalytic amounts of different Lewis or protic acids (additives) to afford the corresponding bromo homoallylic alcohols (2) in high diastereoselectivities. In terms of achieving good yields and stereoselectivities, BiCU was considered the most promising candidate for further reactions (Equation 1) [25a]. 

The first member of the series, CF SO H, has been extensively studied. Trifluoromethanesulfonic acid [1493-13-6] is a stable, hydroscopic Hquid which fumes in air. Addition of an equimolar amount of water to the acid results in a stable, distillable monohydrate, mp 34°C, bp 96°C at 0.13 kPa (1 mm Hg) (18). Measurement of conductivity of strong acids in acetic acid has shown the acid to be one of the strongest protic acids known, similar to fluorosulfonic and perchloric acid (19). 

Fluorobenzene is readily alkylated with alkenes in the presence of protic acids, however, the isomenc purity of the product is poor, and polysubstitution can result Thus, propene and sulfuric acid alkylate fluorobenzene at 20 C to yield a 45 55 ortho/para ratio of the inonoalkyl product m addition to di- and triiso propylfluorobenzene [i5] The reaction of benzene and trifluoropropene at 25 °C in HF-BF3 gives a mixture of mono-, bis-, and tns(3,3,3-trifluoropropyl)ben zene [72, 75] (equation 12)... 

Since the revised Biginelli mechanism was reported in 1997, numerous papers have appeared addressing improvements and variations of this reaction. The improvements include Lewis acid catalysis, protic acid catalysis, non-catalytic conditions, and heterogeneous catalysis. In addition, microwave irradiation (MWI) has been exploited to increase the reaction rates and yields. 

Anhydrides are reduced with relative ease. McAlees and McCrindle 20) established the following increasing order of difficulty for various carbonyls acid chlorides > aldehydes, ketones > anhydrides > esters > carboxylic acids > amides. Reduction may proceed by 1,2-addilion of hydrogen or by cleavage of an oxygen-carbonyl bond. If 1,2-addition to the carbonyl occurs, as in the presence of strong protic acids over palladium, 1,1-diesters are formed by acylation 26). 

Cyanohydrin formation is somewhat unusual because it is one of the few examples of the addition of a protic acid (H—Y) to a carbonyl group. As noted in the previous section, protic adds such as H20, HBr, HC1, and H2S04 don t normally yield carbonyl addition products because the equilibrium constants ate unfavorable. With HCN, however, the equilibrium favors the cyanohydrin adduct. 

The authors used a synthesis of 9,9-spirobitluorenes 32 which was developed by Clarksen and Gomberg [60] and which includes the addition of biphenyl-2-yl-magnesium iodide to fluorenone and subsequent cyclization with protic acids. To obtain 2,2,, 7,7 -arylated 9,9-spirobifluorenes 33, 9,9-spirobifluorene (32) was tetrabrominated [58] to yield 34 followed by a Suzuki-type aryl-aryl cross-coupling with various oligoaryl and oligoheteroaryl boronic acids to obtain the 2,2, 7,7 -tetraarylated derivatives 33. 

Hydroboration is highly regioselective and stereospecific. The boron becomes bonded primarily to the less-substituted carbon atom of the alkene. A combination of steric and electronic effects works to favor this orientation. Borane is an electrophilic reagent. The reaction with substituted styrenes exhibits a weakly negative p value (-0.5).156 Compared with bromination (p+ = -4.3),157 this is a small substituent effect, but it does favor addition of the electrophilic boron at the less-substituted end of the double bond. In contrast to the case of addition of protic acids to alkenes, it is the boron, not the hydrogen, that is the more electrophilic atom. This electronic effect is reinforced by steric factors. Hydroboration is usually done under conditions in which the borane eventually reacts with three alkene molecules to give a trialkylborane. The... 

The ligand group can be introduced either on the meso or on the /5-pyrrole position of the porphyrin ring, but the synthesis of the meso-functionalized derivatives is easier and has been more widely exploited. Balch (50-53) reported that the insertion of trivalent ions such as Fe(III) (32) and Mn(III) (33) into octaethyl porphyrins functionalized at one meso position with a hydroxy group (oxophlorins) leads to the formation of a dimeric head-to-tail complex in solution (Fig. 11a) (50,51). An X-ray crystal structure was obtained for the analogous In(III) complex (34), and this confirmed the head-to-tail geometry that the authors inferred for the other dimers in solution (53) (Fig. lib). The dimers are stable in chloroform but open on addition of protic acids or pyridine (52). The Fe(III) octaethyloxophlorin dimer (52) is easily oxidized by silver salts. The one-electron oxidation is more favorable than for the corresponding monomer or p-oxo dimer, presumably because of the close interaction of the 7r-systems in the self-assembled dimer. 

Another way to enhance 1 1 addition of amines to butadiene consists of the use of catalytic amounts of protic acids, which apparently give rise to 7r-crotyl groups (234). 

The reactions are faster in the presence of weak protic acids, which can quench the initial products under conditions where the stannylcuprate reagents are not affected. This is illustrated in Scheme 2. With no internal proton source, the thermodynamically more stable result of Irans-addition is favored, but, in the presence of a proton source, the initial adducts resulting from m-metallostannation are trapped.116,117,118... 

As indicated under section 2.2. the overall result is the same as that of an insertion reaction, the difference being that insertion gives rise to a yw-addition and nucleophilic attack to an anri-addition. Sometimes the two reaction types are called inner sphere and outer sphere attack. There is ample proof for the anti fashion the organic fragment can be freed from the complex by treatment with protic acids and the organic product can be analysed [19], Appropriately substituted alkenes will show the syn or anti fashion of the addition. The addition reaction of this type is the key-step in the Wacker-type processes catalysed by palladium. 

In the Diels-Alder reaction between Danishefsky s diene and N-aryl imines derived from o-hydroxyaniline catalyzed by Ih, Akiyama observed substantial increases in chemical yield and enantioselectivty by the addition of stoichiometric amounts of acetic acid (Scheme 5.14) [27]. The authors concede that the role of the protic acid is unclear. 

In addition to small amounts of methane, acetaldehyde or acetic anhydride can be generated in substantial quantities depending on conditions. However, they are not present simultaneously in any appreciable quantity. Acetic anhydride and acetaldehyde must be competitively formed (equation 6), and subsequently react with each other to form EDA (step C). This reaction (step C) is generally catalyzed by protic acids (2-4). The reaction solution for reductive carbonylation is quite acidic HI is an intermediate generated under reaction conditions of high alkyl iodide concentration and hydrogen pressure. The thermodynamic equilibrium of this condensation is quite favorable for diester formation existence of an abundance of either anhydride or aldehyde in the presence of the other is not found. Yields of stoichiometric preparations are in excess of 95%... 

Selectivity for each product formation may also be controlled by an effective catalyst system. After the discovery of the reaction by Heck, Stille applied the reaction to organic synthesis, as he observed the preferential formation of [3-methoxy esters under neutral conditions and 1,2-diesters in the presence of a base. As Bianchini reported in 2001, selective formation of a,/3-unsaturated ester product is established by an addition of protic acid such as y)-TsOH in bis-phosphine/Pd-catalyzed oxidative alkoxycarbonylation. ... 

In the presence of a protic acid, triazolium thiolates underwent 1,4-Michael addition to p-quinones, and formed the corresponding thioether-substituted hydroquinone salts, which could be oxidized to quinones (85JA6987 85JOC433). This addition is also possible with o-quinones. Since they are... 

Lewis and protic acids, usually AICI3 and H2SO4, are used in the liquid phase at temperatures of 40-70°C and at pressures of 5-15 atm. Phosphoric acid on kieselguhr promoted with BF3 (UOP process)309 319 is used in gas-phase alkylation (175-225°C, 30-40 atm). In addition to the large excess of benzene, propane as diluent is also used to ensure high (better than 94%) propylene conversion. This solid phosphoric acid technology accounts for 80-90% of the world s cumene production. 

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