Acidic co-catalysts

Chiral Bronsted acid co-catalysts do not promote formation of optically enriched products in analogous couplings to pyruvates, although increased rate and conversion in response to the Bronsted acid co-catalyst is unmistakably apparent. For pyruvates, protonation likely occurs subsequent to the C-C... 

Scheme 11 Plausible role of Bronsted acid co-catalyst as supported by computational studies...

As corroborated by deuterium labeling studies, the catalytic mechanism likely involves oxidative dimerization of acetylene to form a rhodacyclopen-tadiene [113] followed by carbonyl insertion [114,115]. Protonolytic cleavage of the resulting oxarhodacycloheptadiene by the Bronsted acid co-catalyst gives rise to a vinyl rhodium carboxylate, which upon hydrogenolysis through a six-centered transition structure and subsequent C - H reductive elimina-... 

Scheme 77.8 Strategies to prepare cationic polymerization catalysts (a) using oxide supports that have high Bransted and Lewis acidity (b) the addition of a co-catalyst to a neutral supported species (c) modification of the surface with Lewis acid co-catalysts prior to the grafting of the organometallic species [91, 96, 98].

Finally, a few examples of the Morita-Baylis-Hilhnan reaction are provided, where a silyl species functions as a Lewis acid co-catalyst. These examples could have been presented in the previous section about silyl cation-based catalysts. Since the enantiomeric induction originated in the present examples from a Lewis base, we have listed these examples in this section. 

Overall second-order kinetics have been observed for catalysis by bases, alcohols or acids, and in the base-catalysed reactions the formation of ether groups is relatively insignificant46147). The base catalysis can be further activated by an acid co-catalyst, HA. For example any resident hydroxyl groups can act as internal co-catalysts. Tanaka and Kakiuchi48) proposed the following scheme for the reaction catalysed by base (B) with acid co-catalyst ... 

Bronsted acid (Scheme 2.42) [26-28]. (For experimental details see Chapter 14.9.4). These catalysts mediate the addition of ketones to nitroalkenes at room temperature in the presence of a weak acid co-catalyst, such as benzoic acid or n-butyric acid or acetic acid. The acid additive allows double alkylation to be avoided, and also increases the reaction kinetic. The Jacobsen catalyst 24 showed better enantio- and diastereoselectivity with higher n-alkyl-ethyl ketones or with branched substrates (66 = 86-99% dr = 6/1 to 15/1), and forms preferentially the anti isomer (Scheme 2.42). The selectivity is the consequence of the preferred Z-enamine formation in the transition state the catalyst also activates the acceptor, and orientates in the space. The regioselectively of the alkylation of non-symmetric ketones is the consequence of this orientation. Whilst with small substrates the regioselectivity of the alkylation follows similar patterns (as described in the preceding section), leading to products of thermodynamic control, this selectivity can also be biased by steric factors. 

Table 5.1 The effect of Bronsted acid co-catalysts on the rate of the MBH reaction.

The low reaction rates usually associated with the MBH reaction can be increased either by pressure [15a, 22, 34], by the use of ultrasound [35] and micro-wave radiation [14a], or by the addition of co-catalysts. Various intra- or inter-molecular Lewis acid co-catalysts have been tested [26, 36, 37] in particular, mild Bronsted acids such as methanol [36, 57d], formamide [38], diarylureas and thioureas [39] and water [27a, 40] were examined and found to provide an additional acceleration of the MBH reaction rate (Table 5.1). 

Considerable effort has been devoted to the development of enantiocatalytic MBH reactions, either with purely organic catalysts, or with metal complexes. Paradoxically, metal complex-mediated reactions were usually found to be more efficient in terms of enantioselectivity, reaction rates and scope of the substrates, than their organocatalytic counterparts [36, 56]. However, this picture is actually changing, and during the past few years the considerable advances made in organocatalytic MBH reactions have allowed the use of viable alternatives to the metal complex-mediated reactions. Today, most of the organocatalysts developed are bifunctional catalysts in which the chiral N- and P-based Lewis base is tethered with a Bronsted acid, such as (thio)urea and phenol derivatives. Alternatively, these acid co-catalysts can be used as additives with the nucleophile base. 

In contrast to chiral amines, phosphorus-based chiral catalysts were less developed for asymmetric MBH transformations. As with amine-based reactions, the selectivity of the addition in phosphine-mediated reactions depends clearly on the nature of the complementary Bronsted acid co-catalysts used. 

Asymmetric organocatalytic Morita-Baylis-Hillman reactions offer synthetically viable alternatives to metal-complex-mediated reactions. The reaction is best mediated with a combination of nucleophilic tertiary amine/phosphine catalysts, and mild Bronsted acid co-catalysts usually, bifunctional chiral catalysts having both nucleophilic Lewis base and Bronsted acid site were seen to be the most efficient. Although many important factors governing the reactions were identified, our present understanding of the basic factors, and the control of reactivity and selectivity remains incomplete. Whilst substrate dependency is still considered to be an important issue, an increasing number of transformations are reaching the standards of current asymmetric reactions. 

These gold catalysts are a significant improvement on the mercury catalysts used previously and the reactions are conducted under mild conditions (293-323 K) in the presence of acid co-catalysts. 2-Propynol reacts with excess methanol at 328 K in the presence of 0.01 mol% CH3Au PPh3 and sulfuric acid to give the following dioxane derivative, f -2,5-dimethyl-2,5-dimethoxy-l,4-dioxane, in 93% yield after 20h at 328 K ... 

The yields and regioselectivity of the reactions of substituted methylenecyclopropanes with 2-cy-clopentenone are improved with the use of triethylborane as a Lewis acid co-catalyst (equations 95, 96). No reaction with cyclopentenone is observed in the case of (82) without this co-catalyst. ... 

In the first reported direct A -carbonylation of nitroaromatics to isocyanates, simple Pd- or Rh-based systems were used to catalyze the reaction of aromatic mononitro compounds with carbon monoxide [11, 12]. Later, it became possible to work without the drastic reaction conditions that had been required initially, by using Lewis acid co-catalysts [13], Various catalysts and catalyst mixtures, normally based on Ru, Rh, or Pd complexes with co-catalysts, were described in numerous patents and publications [1, 3, 14—16], The careful choice of the composition of the triad consisting of metal salt, co-catalysts and ligand (preferably aromatic amines) led to efficient catalyst systems [14a-e] for the direct reductive carbonylation process. A quite active Pd-phenanthroline-H system with noncoordinating carboxylic acids such as 2,4,6-trimethlybenzoic acid as proton source is worth mentioning [14 d]. 

Rather interestingly, radical cations have also been identified in styrene polymerizations catalysed by more conventional Lewis acid/co-catalyst systems [BF3/0(C2Hs)2, AlCla/PhOH, BFs/PhOH] by employing 2,4,6-tri-t-butyl-nitrosobenzene as a trap. One wonders once again therefore if the mechanisms which are generally accepted to operate do indeed represent a total picture. 

They were able to extend the scope of the direct arylation to simple, completely unactivated arenes, such as benzenes by development of a palladium-pivalic acid co-catalyst system (Scheme 28) [48]. 

Huser and Perron have extended this work to the isomerization of 2-methyl-3-butenenitrile (2M3 BN) to 3-PN (isomerization step Eq. (6) 92% yield) [17]. This patent mentions the use of iron and palladium catalysts but does not provide examples beyond nickel. In other work these same inventors discuss the use of other water-soluble ligands such as those containing carboxylate, phosphate, and alkyl-sulfonate substituents [18], while also exploring a wide range of Lewis acid co-catalysts for the addition of HCN to 3-pentenenitrile (Eq. 7) [19]. In general, the addi-... 

---