Protonated Amine Catalysts

I n this chapter, we wish to discuss the recent advancements in chiral Bronsted acid catalysis. We will focus chiefly on (i) thiourea catalysts [55], (ii) guanidium salts (protonated amine catalysts), (iii) diol catalysts, and (iv) phosphoric acids [56]. The first three catalysts are classified as neutral or weak Bronsted acids, which may be called hydrogen bond catalysts [57]. In contrast, phosphoric acids, being stronger acids, are Bronsted acid catalysts in a narrow sense (Figure 2.9). 

These reactions have been known for almost 100 years and they have been extensively studied. The reactions are catalyzed by the corresponding ammonium salt in each case, although other protonated amines function as catalysts. It appears that the function of the catalyst is to supply ff+, which helps to force an end of the ethylenediamine molecule away from the metal. 

Crampton24 has also demonstrated that for Meisenheimer complex formation, increased crowding at the reaction site caused by change from primary amines to piperidine results in rate reduction of proton transfer from the complex to the amine catalyst, and Hirst199... 

Baylis-Hillman reactions, the protonated amine was the governing factor in determining catalyst efficiency, thus making quinuclidine itself a better catalyst than 3-heteroatom substituted analogs, which are of reduced basicity/nucleophilic-ity and consequently give lower reaction rates. 

R3N could be an expensive chiral amine catalyst such as a chinchona alkaloid, whereas the proton sponge is used stoichiometrically. For achiral reactions, NEt3 can serve both functions. The subsequent reaction follows the pathway known from the reverse mode reactions, with the catalyst recovered unchanged ... 

R3N could be an expensive chiral amine catalyst such as a chinchona alkaloid, whereas the proton sponge is used... 

Figure 2.8 Catalysis by the protonated amine could explain the stereochemistry of threonine and 0/0-threonine synthesis by our catalyst 46 at low pH. (Reprinted from Ref. 47. Copyright 1994 American Chemical Society.)...

When a compound containing an activated methylene group is the proton-donating catalyst, the presence of a secondary amine is required for easy isolation of the desired ketose derivative in crystalline form. The conditions resemble those requisite for a Knoevenagel reaction. - A condensation of the Knoevenagel type evidently does not occur, as the dehydrated product would be too stable for practical reversibility. However, the addition compound which is an intermediate in the Knoevenagel reaction, such as V, couW be formed from IV. Splitting of V to yield the ketose de-... 

Hydrogenation of 25 was accomplished using Pearlman s catalyst to provide amino-ester 28 as a 10 1 mixture of diastereoisomers favoring the desired cis isomer.Excess acid (>1 equiv of p-toluensulfonic or sulfuric acid) was necessary to facilitate the hydrogenation by promoting relatively rapid nitrile reduction to protonated amine 26. This protocol prevents catalyst deactivation. Acid also catalyzes the subsequent benzylic alcohol dehydration and the final reduction to 28. The observed increase in diastereoselectivity during the hydrogenation is consistent with acid-catalyzed elimination of water to form intermediate indene 27 followed by reduction from the least hindered face of 27 to afford the cis isomer of 28 as the major product. We did not observe elimination of water prior to nitrile reduction. ... 

The Morita-Bayhs-Hillman (MBH) reaction involves the conversion of an a,p-imsaturated carbonyl compound into an aldol-like adduct. The reaction is catalysed by tertiary amines (7.155), which form an intermediate enolate (7.157) by conjugate addition (rather than by direct deprotonation of the a-proton). The enolate imdergoes an aldol reaction with an aldehyde (7.01), followed by loss of the amine catalyst to provide the Baylis-Hillman adduct (7.158), as shown in Figure 7.7. 

Heteroaromatic aldehydes are excellent electrophiles in the MBH reaction because of their increased electrophilicity. The heteroatom also facilitates the proton transfers involved in the reaction (Scheme 1.53)/ In the presence of DABCO, pyridine-2-carboxaldehyde derivatives react rapidly with acrylates, methyl vinyl ketone and acrylonitrile to give excellent yields of the MBH adducts 112, which can be further transformed into indolizines 114 by thermal cyclization of their acetate derivatives 113 (Scheme 1.54)/ Notably, a small amount of indolizine 114 was formed along with normal MBH adduct 112 in the reaction of pyridine-2-carboxaldehyde with methyl vinyl ketone. Similarly, substituted 2-chloronicotin aldehydes 115 are reactive and efficient in the MBH reaction of methyl acrylates, acrylonitrile and cyclic enones catalyzed by various tertiary amine catalysts, such as DABCO, DBU, imidazole and 1-methylimidazole, to provide novel MBH adducts 116 and 117 for biological activity screening (Scheme 1.55). ... 

The Sharpless ligand (DHQD>2AQN 45 was introduced to the asymmetric BH reaction in combination with acetic acid as co-catalyst. The ammonium salt generated in situ was proposed as a bifunctional catalyst, where the protonated amine acted as Brpnsted acid and the nonprotonated one performed as nucleophilic catalyst [99]. Besides, a simple phosphine-sulfonamide 46, synthesized readily from L-threonine, was found to be an efficient catalyst for the reaction of 7V-sulfonyl imines and (3-naphthyl acrylate to give the product in excellent enantioselectivities [100]. 

In the case of silicon alkoxides, hydrolysis occurs by the nucleophilic attack of the oxygen contained in water on the silicon atom and is most rapid and complete when acid (e.g. HCl, CH3COOH, HF,. ..) or basic (e.g. NH3, KOH, amines,. ..) catalysts are employed. Under acidic conditions, it is likely that an alkoxide group is protonated in a rapid first step. Electron density is withdrawn from silicon, making it more electrophilic and thus more susceptible to be attacked by water. Under basic conditions it is likely that water dissociates to produce nucleophilic hydroxyl anions in a rapid first step. The hydroxyl anion then attacks the silicon atom. Polymerization... 

Dendrimers are branch-like polymers (see Chapter 5, Section 5.8) and have been used as nano-reactorsThese branched molecules have large voids in their structure that can incorporate a catalytic species into the inner nanoscale environment of the dendrimer. The dendrimer poly(propylene imine) (PPl) has been used as a nanoreactor for Heck reactions and alkyl aminations. 4-Dipheny Iphosphinobenzoic acid is fixed into the voids of the dendrimer via ionic contacts between the positive charges on protonated amine functional groups and the deprotonated benzoic acid and used to anchor the palladium catalyst (Figure 2.36). 

The first catalytic asymmetric Staudinger reaction to be described used chiral tertiary amines 14 and 15 derived from the Cinchona alkaloids as the nucleophile to activate the ketene via zwitterion formation. The ketene was conveniently generated in situ from the acid chloride. Because the HCl generated in the elimination would consume the chiral tertiary amine catalyst, a nonnucleophilic strong base (e.g.. Proton Sponge) was included to remove the HCl formed. Yields of -lactams were on the order of 60% in 99% ee. 

Poly(phenylene oxide) (PPO) is a thermoplastic, linear, noncrystalline polyether commercially produced by the oxidative polymerization of 2,6-dimethylphenol in the presence of a copper-amine catalyst. PPO has become one of the most important engineering plastics widely used for a broad range of applications due to its unique combination of mechanical properties, low moisture absorption, excellent electrical insulation property, dimension stability and inherent flame resistance. This chapter describes the recent development of this polymer, particularly on the production, application, compounding, properties of its alloys and their general process conditions. The polymerization mechanism and thermal degradation pathways are reviewed and new potential applications driven by the increasing environmental concerns in battery industry, gas permeability and proton-conducting membranes are discussed. 

Throughout this chapter catalysts wiU be written without regard to charges. The bonds made and broken in this transition state as well as in the ones which follow are not colinear as represented.) Equation (30) represents general acid-catalyzed assistance of the attack of a free amine on the carbonyl compound. The kinetically equivalent general base-catalyzed attack of a protonated amine upon the carbonyl compound may be ruled out by the chemical inertness of an amine without a free electron pair. 

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