Brpnsted acid-promoted reactions

There are many examples of Brpnsted acid-promoted reactions where highly polarized functional groups are the active electrophiles. For example, Olah and coworkers reported N-chlorosuccinimide to be a powerful chlorinating agent with superacidic BF —H O [11]. The active electrophile is likely the diprotonated (14) or triprotonated species (15, Eq. 1.3),... 

Xu, H., Zuend, S. J., Woll, M. G., Tao, Y., Jacobsen, E. N. (2010). Asymmetric cooperative catalysis of strong Brpnsted acid-promoted reactions using chiral ureas. Science, 327, 986-990. 

Dibenzyl Ether [Brpnsted Acid Promoted Reduction of an Aldehyde to a Symmetrical Ether].311 To a stirred solution of benzaldehyde (5.4 g, 0.05 mol) and TFA (11.4 g, 0.1 mol) under argon was added dropwise, with cooling, Et3SiH (8.1 g, 0.07 mol) at a rate such that the temperature of the reaction mixture did not exceed 40°. The solution turned a crimson color that gradually disappeared. Analysis by GLC showed the complete absence of the aldehyde immediately after addition of all of the silane. The products were separated by vacuum distillation at 20 Torr, collecting the fractions up to 125°. Dibenzyl ether was obtained from the residue by freezing out 4 g (0.02 mol, 80%) mp 3-6° nD25 1.5608. 

Ethyl Benzyl Ether [Brpnsted Acid Promoted Reduction of an Aldehyde to an Unsymmetrical Ether].327 To a cooled mixture of benzaldehyde (4.3 g, 41 mmol) and absolute ethanol (3.7 g, 80 mmol) was added trichloroacetic acid (18.2 g, 111 mmol). Et3SiH (6.96 g, 60 mmol) was then added dropwise with stirring while the mixture was maintained at 50-60°. After 4 hours, the reaction mixture was diluted with water, neutralized with aqueous NaHC03 solution, and extracted with Et20. The dried ether extract was distilled and the 170-190° fraction was collected. Distillation from sodium gave ethyl benzyl ether 4.8 g (90%) bp 187-189°. 

Dicyclohexyl Ether [Brpnsted Acid Promoted Reduction of a Ketone to a Symmetrical Ether].313 Cyclohexanone (3.92 g, 40 mmol) and tri(n-butyl) silane (1.78 g, 20 mmol) were placed in a round-bottomed flask. TFA (75 mmol) was added slowly over a one-hour period to the reaction mixture, which was held at —35°. After complete addition, the reaction flask was placed in a freezer at —15° for 70 hours. Direct distillation gave dicyclohexyl ether 2.91 g (16 mmol, 80%) bp 119-121718 Torr. 

A stereochemical study of the synthesis of unsaturated 1,4-aminoalcohols via the reaction of unsaturated 1,4-alkoxyalcohols with chorosulfonyl isocyanate revealed a competition between an retentive mechanism and an SnI racemization mechanism, with the latter having a greater proportion with systems where the carbocation intermediate is more stable.254 An interrupted Nazarov reaction was observed, in which a nonconjugated alkene held near the dienone nucleus undergoes intramolecular trapping of the Nazarov cyclopentenyl cation intermediate.255 Cholesterol couples to 6-chloropurine under the conditions of the Mitsunobu reaction the stereochemistry and structural diversity of the products indicate that a homoallylic carbocation derived from cholesterol is the key intermediate.256 l-Siloxy-l,5-diynes undergo a Brpnsted acid-promoted 5-endo-dig cyclization with a ketenium ion and a vinyl cation proposed as intermediates.257... 

In contrast with the above discussion, a radical itself (rather than a radical acceptor) can be activated by complexation with a Lewis acid. The aminyl radical cycliza-tion shown in Eq. (304) is a slow process and yields of the cyclic product are often low. It is, however, known that a Brpnsted acid promotes this cyclization [676], and by analogy the reaction proved to be promoted by the addition of a Lewis acid, which should coordinate with the nitrogen atom to increase the reactivity of the nitrogen radical. The effect of a series of titanium salts, Ti(0-i-Pr) CL , at a concentration of 0.025 M, is shown in Eq. (304). It is apparent that use of Ti(0-i-Pr)Cl3 resulted in significantly improved yield. 

Ramachary and coworkers developed an efficient domino reaction between alkyl cyclopentanone-2-carboxylates (109) and 2-(2-nitrovinyl)phenols (78) [61]. The reaction involved a quinine-NH-thiourea (XXX)-catalyzed Michael addition followed by a Brpnsted acid-promoted lactonization, which afforded the spirohydro-coumarins 110 in good to excellent yields (60-90%) and excellent stereoselectivities (up to >99% de up to >99% ee), as shown in Scheme 10.40. 

The highly enantioselective Morita-Baylis-Hillman reaction of cyclohexenone with aldehydes is catalyzed by a chiral BlNOL-derived Brpnsted acid 8 in the presence of triethylphosphine as the nucleophilic promoter (Scheme 12.6). ... 

The Pictet-Spengler reaction is the method of choice for the preparation of tetrahydro-P-carbolines, which represent structural elements of several natural products such as biologically active alkaloids. It proceeds via a condensation of a carbonyl compound with a tryptamine followed by a Friedel-Crafts-type cyclization. In 2004, Jacobsen et al. reported the first catalytic asymmetric variant [25]. This acyl-Pictet-Spengler reaction involves an N-acyliminium ion as intermediate and is promoted by a chiral thiourea (general Brpnsted acid catalysis). 

The same group expanded the scope of the aza-Diels-Alder reaction of electron-rich dienes to Brassard s diene 97 (Scheme 37) [60]. In contrast to Danishefsky s diene, it is more reactive, but less stable. Akiyama et al. found chiral BINOL phosphate (R)-3m (3 mol%, R = 9-anthryl) with 9-anthryl substituents to promote the [4 + 2] cycloaddition of A-arylated aldimines 94 and Brassard s diene 97. Subsequent treatment with benzoic acid led to the formation of piperidinones 98. Interestingly, the use of its pyridinium salt (3 mol%) resulted in a higher yield (87% instead of 72%) along with a comparable enantioselectivity (94% ee instead of 92% ee). This method furnished cycloadducts 98 derived from aromatic, heteroaromatic, a,P-unsaturated, and aliphatic precursors 94 in satisfactory yields (63-91%) and excellent enantioselectivities (92-99% ee). NMR studies revealed that Brassard s diene 97 is labile in the presence of phosphoric acid 3m (88% decomposition after 1 h), but comparatively stable in the presence of its pyridinium salt (25% decomposition after 1 h). This observation can be explained by the fact that the pyridinium salt is a weak Brpnsted acid compared to BINOL phosphate 3m. 

The acceleration of a reaction by a substance that is also consumed during the process. An example of such a phenomenon is the acceleration of a reaction by a Brpnsted acid present in large excess or maintained by a nearly constant concentration by a buffer. The acceleration of the hydrolysis of an amide by a certain Brpnsted acid is actually general acid promotion rather than general acid catalysis. The term promotion has been used as a synonym for pseudo catalysis. 

In conclusion, extensive research has revealed that the Lewis and Brpnsted acid sites on the promoted sulfated zirconia catalysts are not necessarily stronger acids than the corresponding sites in zeolites, but sulfated zirconia circumvents the energetically unfavorable monomolecular reaction path by following a bimolecular mechanism. The question of superacidity of sulfated zirconia, however, is still debated.312... 

The reaction of enyne with either an Au(I) or Au(III) catalytic promoter gave a 6-oxabicyclo[3.2.1]octane (Scheme 98).141 The use of Au(PPh3)Cl in combination with AgC104 is equally effective. The possible involvement of the conjugate Brpnsted acid in the alkyne activation of the alcohol was excluded since treatment with HC1 in the absence of AuC13 gave exclusively tetrahydrofuran. 

Electrophilic substitutions of alkenyl-, aryl-, and alkynylsilanes with heteroatom-stabilized cationic carbon species generated by the action of a Lewis or Brpnsted acid (acyl cation, oxocarbenium ion, etc.) provide powerful methods for carbon-carbon bond formation. Particularly, intramolecular reactions of alkenylsilanes with oxocarbenium and iminium ions are very valuable for stereoselective construction of cyclic ether and amine units.21-23 For example, the BFj OEt -promoted reaction of (E)- and (Z)-alkenylsilanes bearing an acetal moiety in the alkenyl ligand gives 2,6-disubstituted dihydropyrans in a stereospecific manner (Scheme l).23 Arylsilanes also can be utilized for a similar cyclization.24... 

Achari B, Mandal SB, Dutta PK, Chowdhury C (2004) Synlett 2004 2449 Aggarwal VK, Belfield AJ (2003) Catalytic asymmetric Nazarov reactions promoted by chiral Lewis acid complexes. Org Lett 5 5075-5078 Akiyama T, Itoh J, Fuchibe K (2006c) Adv Synth Catal 348 999 Akiyama T, Itoh J, Yokota K, Fuchibe K (2004) Enantioselective Mannich-type reaction catalyzed by a chiral Brpnsted acid. Angew Chem Int Ed Engl 43 1566-1568... 

The Brpnsted acid-assisted chiral Lewis acid (BLA) 28, prepared from a 1 2 molar ratio mixture of a trialkylborate and optically pure binaphthol, is also an excellent chiral promoter for the aza Diels-Alder reaction of imines with Danishefsky dienes (Eqs 44 and 45). Enantioselectivity and double diastereodifferentiation in reactions employing chiral 28 are slightly better than those using chiral 27 [41]. 

Several patents have recently appeared in which metals have been incorporated into zeolite MFI to promote pyridine-jS-picoline yields [21,23,30-32], lon-ex-change procedures were used to make MO MFI catalysts (M = Tl, Pb, or Co) which, in a fixed-bed reactor, resulted in yields superior to those from the parent MFI and related supports (Table 1) [18,23], The presence of the same metals also affects product selectivity, as shown by the 1/3 ratios. It is tempting to believe that the proximity of a Brpnsted acid site and the redox metal within the MFI channels act in concert to catalyze the sequence of reaction steps. Other MO MFI catalysts (M = Zn, Sn, or W) containing more environmentally benign metals have been investigated for fluid-bed reactor use [30], Yield promotion has also been observed for related MO BEA catalysts (M = Pb, Cd, Tl, Sn, Ga, or Co) [26],... 

Many chemical reactions involve a catalyst. A very general definition of a catalyst is a substance that makes a reaction path available with a lower energy of activation. Strictly speaking, a catalyst is not consumed by the reaction, but organic chemists frequently speak of acid-catalyzed or base-catalyzed mechanisms that do lead to overall consumption of the acid or base. Better phrases under these circumstances would be acid promoted or base promoted. Catalysts can also be described as electrophilic or nucleophilic, depending on the catalyst s electronic nature. Catalysis by Lewis acids and Lewis bases can be classified as electrophilic and nucleophilic, respectively. In free-radical reactions, the initiator often plays a key role. An initiator is a substance that can easily generate radical intermediates. Radical reactions often occur by chain mechanisms, and the role of the initiator is to provide the free radicals that start the chain reaction. In this section we discuss some fundamental examples of catalysis with emphasis on proton transfer (Brpnsted acid/base) and Lewis acid catalysis. 

It is also worthy to mention that aniline derivatives have been used as nucleophiles in the Michael addition to chalcones [351] and nitrooleflns [352]. Especially interesting has resulted the addition to nitrooleflns, reaction which is catalyzed by the heterochiral [7.7]-P-spirocyclic arylaminophosphonium barfate 196, a novel charged cationic Brpnsted acid catalyst which efflciently promotes the addition of electron-rich anilines to nitrostyrenes and P-alkyl substituted nitrooleflns in toluene at -15°C under very low loading conditions (Scheme 2.124). 

Most recent studies from this group have extended the substrate scope to include a-acetoxy-(3-enamino esters [44]. In order to perform the reaction on those substrates they developed a novel class of chiral Lewis base catalysts, prepared from readily available chiral source (Scheme 15.16). A wide variety of A-aryl (3-aryl and heteroaryl substrates were reduced in good yields (up to 98%) and selectivity (up to 99 1 syn anti and 99% ee). The generation of Brpnsted acid that promoted... 

The mechanism of this reaction may be similar to that of the classical Koch reaction (11) and promoting role of copper consists of coordination of CO by Cu(I) species (11,85,90). The promoting role of copper, however, suggests that a high density of acidic sites may be inimical to the carbonylation reaction, since metal exchange is known to reduce significantly the number of Brpnsted acid sites present in zeolites. 

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