Protonation catalysis

Copper is clearly the most selective metal-ion catalyst. Interestingly, proton catalysis also leads to high selectivities. This is a strong indication that selectivity in this catalysed Diels-Alder reaction does not result from steric interactions. 

According to a kinetic study which included (56), (56a) and some oxaziridines derived from aliphatic aldehydes, hydrolysis follows exactly first order kinetics in 4M HCIO4. Proton catalysis was observed, and there is a linear correlation with Hammett s Ho function. Since only protonated molecules are hydrolyzed, basicities of oxaziridines ranging from pii A = +0.13 to -1.81 were found from the acidity rate profile. Hydrolysis rates were 1.49X 10 min for (56) and 43.4x 10 min for (56a) (7UCS(B)778). O-Protonation is assumed to occur, followed by polar C—O bond cleavage. The question of the place of protonation is independent of the predominant IV-protonation observed spectroscopically under equilibrium conditions all protonated species are thermodynamically equivalent. 

Another application of this method is the synthesis of 5,10-epoxy[10]annulene (7) from 2,3.6,7-tetrabromo-4a,8a-epoxydecahydronaphthalene.152-154 The byproduct is 1-benzoxepin (8). The 5,10-cpoxyannulcnc (7) incorporates the oxepin structure. The annulene can be converted to 1-benzoxepin by proton catalysis.153154... 

Williams and Johnston have reported the first use of proton catalysis in the aziridination of imines by diazoesters (Scheme 4.30) [38]. A range of aryl and ali-... 

Kemkes256 assumes that the overall order relative to the esterification of terephthalic acid by 1,2-ethanediol in oligo(l,2-ethanediyl terephthalate) is two no mechanism has however been suggested. Mares257 considers that during the esterification of terephthalic acid with 1,2-ethanediol, two parallel kinetic paths take place, one corresponding to a reaction catalyzed by non-dissociated add and the other to a non-catalyzed process. In fact, Mares257 is reserved about the existence of protonic catalysis. Some other orders were found for the system terephthalic atid/l,2-ethanediol 0 (overall)318 2 (add) andO (alcohol)203 1 (add) and 1 (alcohol)181 1 (add)194 . These contradictory results could be partly due to the low solubility of terephthalic acid in 1,2-ethanediol. 

Two other theories as to the mechanism of the benzidine rearrangement have been advocated at various times. The first is the rc-complex mechanism first put forward and subsequently argued by Dewar (see ref. 1 pp 333-343). The theory is based on the heterolysis of the mono-protonated hydrazo compound to form a n-complex, i.e. the formation of a delocalised covalent it bond between the two rings which are held parallel to each other. The rings are free to rotate and product formation is thought of as occurring by formation of a localised a-bond between appropriate centres. Originally the mechanism was proposed for the one-proton catalysis but was later modified as in (18) to include two-protons, viz. 

Products of a so-called vinylogous Wolff rearrangement (see Sect. 9) rather than products of intramolecular cyclopropanation are generally obtained from P,y-unsaturated diazoketones I93), the formation of tricyclo[2,1.0.02 5]pentan-3-ones from 2-diazo-l-(cyclopropene-3-yl)-l-ethanones being a notable exception (see Table 10 and reference 12)). The use of Cu(OTf), does not change this situation for diazoketone 185 in the presence of an alcoholl93). With Cu(OTf)2 in nitromethane, on the other hand, A3-hydrinden-2-one 186 is formed 160). As 186 also results from the BF3 Et20-catalyzed reaction in similar yield, proton catalysis in the Cu(OTf)2-catalyzed reaction cannot be excluded, but electrophilic attack of the metal carbene on the double bond (Scheme 26) is also possible. That Rh2(OAc)4 is less efficient for the production of 186, would support the latter explanation, as the rhodium carbenes rank as less electrophilic than copper carbenes. 

Furans and some of its derivatives have been cyclopropanated with the ketocarbenoids derived from ethyl diazoacetate and copper catalysts. The 2-oxabicyclo[3.1.0]hex-3-enes thus formed are easily ring-opened to 1,4-diacylbutadienes thermally, thermo-catalytically or by proton catalysis 14,136). The method has been put to good use by Rh2(OAc)4-catalyzed cyclopropanation of furan with diazoketones 275 to bicyclic products 276. Even at room temperature, they undergo electrocyclic ring-opening and cis, trans-dienes 277a are obtained with fair selectivity 257,258). These compounds served as starting materials in the total syntheses 257 259) of some HETE s (mono-... 

Another example of the use of Lewis acids in organic reactions in water is the lan-thanide(III) triflate catalysed aza-Diels-Alder reaction, exemplified in Scheme 14. In this reaction the hetero-dienophile is formed in situ from a primary ammonium hydrochloride and a carbonyl compound followed by the actual Diels-Alder reaction288,289. This type of reaction proceeds readily in aqueous media290-296, and a dramatic increase in the yield upon addition of lanthanide triflates was observed288,289. The exact role of the catalyst, however, is not entirely clear. Although it was suggested that the catalyst binds to the dienophile, other mechanisms, such as simple proton catalysis, are also plausible. Moreover, these reactions are further complicated since they are often heterogeneous. 

In order to exclude simple proton catalysis, this study also examined the catalytic activity of Brpnsted acids. It was noted that a 10 mM solution of hydrochloric acid has only a small catalytic effect (second-order rate constant k2 = 7.62 x 10-2M-1 s 1 compare Table 24). Another dienophile derivative also showed changes in rate (Table 25) and in the endo/exo selectivity (Table 26)302. A dramatic acceleration and an increase in the selectivity in 1,1,1-trifluoroethanol was observed in the presence of Cu2+ (Table 25). 

The term acid catalysis is often taken to mean proton catalysis ( specific acid catalysis ) in contrast to general acid catalysis. In this sense, acid-catalyzed hydrolysis begins with protonation of the carbonyl O-atom, which renders the carbonyl C-atom more susceptible to nucleophilic attack. The reaction continues as depicted in Fig. 7. l.a (Pathway a) with hydration of the car-bonium ion to form a tetrahedral intermediate. This is followed by acyl cleavage (heterolytic cleavage of the acyl-0 bond). Pathway b presents an mechanism that can be observed in the presence of concentrated inorganic acids, but which appears irrelevant to hydrolysis under physiological conditions. The same is true for another mechanism of alkyl cleavage not shown in Fig. 7.Fa. All mechanisms of proton-catalyzed ester hydrolysis are reversible. 

Fig. 7.1. a) Specific acid catalysis (proton catalysis) with acyl cleavage in ester hydrolysis. Pathway a is the common mechanism involving a tetrahedral intermediate. Pathway b is SN1 mechanism observed in the presence of concentrated inorganic acids. Not shown here is a mechanism of alkyl cleavage, which can also be observed in the presence of concentrated inorganic acids, b) Schematic mechanism of general acid catalysis in ester hydrolysis. 

Further studies that demonstrate that hydration of bay-region diol epoxides under acidic conditions can occur by general acid catalysis in addition to proton catalysis have expanded our understanding of their reactivity. General acid catalyzed hydration involves H-bonding of the epoxide O-atom by the acid catalyst, followed by nucleophilic attack of the distal C-atom by H20/H0 [108][109],... 

Similar results were obtained for tert-butyl hydroperoxide and perchloric acid in 2-propanol. Thus, it is evident from the decomposition of hydrogen peroxide into free radicals that both heterolytic and homolytic reactions may be catalyzed by hydrogen ions. Further research is needed to investigate proton catalysis in certain homolytic reactions. 

The /3-pinene fraction was used as a reference to determine the isomerization activity of the supports. Results given in Table 4 show that carbon VII is particularly inert with respect to /3-pinene. This behaviour is certainly related to the high content of this carbon in potassium (0.5 wt.-%). On the contrary, the CaO impurities present in carbon V seem to increase the isomerization activity of this carbon. It is well-known that the double bond shift isomerization of hydrocarbons can proceed via carbocation intermediates (protonic catalysis) or via allylic carbanion intermediates (acido-basic or purely basic catalysis) [Ref.7]. The results obtained with potassium-doped carbons show that in /3-pinene isomerization during HDS, the protonic mechanism predominates. 

Both glycosidases (61) and amylases (62) are inhibited by certain lactones, as is lysozyme, D-glucono-1,5-lactone, for example, is presumed to inhibit amylase by acting as a transition state analog because it closely approximates a half-chair conformation. However, as stated by Laszlo et al. (62), lactone inhibition cannot establish whether distortion of substrate occurs during binding, as in lysozyme, or after bond splitting to form the carbonium ion, as in proton catalysis. 

Proton catalysis which regenerates the radical cation ultimately leads to the thermodynamically most stable radical. This can even proceed in two well-separated steps [reactions (47) and (48)]. Here, the second step is much slower and hence only observed at lower pH (Behrens et al. 1982). 

To study the effect of a phosphate group at C(5 )> D-ribose-5-phosphate has been investigated in some detail as a model system (Stelter et al. 1974,1975a,b, 1976). The phosphate group is a much better leaving group than the OH group, and its elimination does not require proton catalysis. The data compiled in Table 10.29... 

This reaction involves the formation of an imine, requiring proton catalysis and liberation of a molecule of water. Therefore, this procedure may not be applied directly in an aprotic solvent, such as toluene. With the addition of a small amount of diethylether, however, the reaction was found to reach equilibrium after one hour... 

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