Bronsted acid-catalyzed reactions with imines

The reactions of acylzirconocene chlorides with imines also proceed under Bronsted acid-catalyzed conditions, even with aqueous acids (Table 5.3) [23], 

Entry Bransted acid pKa Yield (%) a Entry Bransted acid pKa Yield (%) a 

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The appHcation of chiral Bronsted acids in asymmetric catalysis has increased in recent years [6], In 2006, Rueping et al. reported a double Bronsted acid catalyzed reaction of imine 1 and cyclohexenone 2, in which the electrophile was achvated by a chiral phosphoric acid 4 and the nucleophile was activated by an achiral Bronsted acid 5 (Scheme 43.1) (10). Various aromahc and heteroaromatic substituted isoquinuclidines with electron-withdrawing and electron-donating substituents could be isolated in good yields and high enantiomeric ratios (82-88% ee), with exo/endo ratios between 1 3 and 1 9. The reachvity of a broad range of achiral Bronsted adds was examined and the effect on the enantiomeric induchon was obvious (52% ee to 86% ee for the product 3). 

Bronsted-acid-catalyzed Diels-Alder reactions are not frequent because of the proton sensitivity of many dienes and cycloadducts, especially when long reaction times and high temperatures are required. Examples in aqueous medium involving imines activated by protonation as dienophiles and a proton-promoted Diels-Alder reaction of glyoxylic acid with cyclopentadiene are considered in Section 6.1. 

Classically, the acylzirconocene chlorides can be converted into aldehydes, carboxyhc acids, esters, and acyl halides. Recently, the usefulness of acylzirconocenes has been extended. In fact, these unmasked acyl anions directly add to aldehydes and imines affording a-hydroxy or a-amino ketones, respectively. The reaction of acylzirconocene chlorides with imines also proceeds under Bronsted acid-catalyzed conditions, even with aqneons acids. ... 

The catalytic, enantioselective, vinylogous Mannich reaction has recently emerged as a very powerful tool in organic synthesis for the assembly of highly functionalized and optically enriched 6 amino carbonyl compounds. Two distinctly different strategies have been developed. The first approach calls for the reaction of preformed silyl dienolates as latent metal dienolates that react in a chiral Lewis acid or Bronsted acid catalyzed Mukaiyama type reaction with imines. Alternatively, unmodified CH acidic substrates such as a,a dicyanoalkenes or 7 butenolides were used in vinylo gous Mannich reactions that upon deprotonation with a basic residue in the catalytic system generate chiral dienolates in situ. 

Allylations of aldehydes and imines also constitute important carbon-carbon bond-forming reactions [14]. A range of metal-based Lewis acid catalysts have been reported. Hall and co-workers described the Bronsted acid-catalyzed allylation of aldehydes with allyl boronate (Equation 10.8) [15]. 

It has also been shown that dimethylsilyl enolates can be activated by diisopropylamine and water and exhibit a high reactivity toward iV-tosyl imines to give Mannich-type reaction products in the absence of a Fewis acid or a Bronsted acid.51 For example, the reaction of [(1-cyclohexen-l-yl)oxy]dimethylsilane with 4-methyl-A -(phenylmethylene)benzene sulfonamide gave re/-4-methyl-N- (f )-[(15)-(2-oxocyclohexyl)phenyl-methyl] benzenesulfonamide (anti-isomer) in 91% yield stereoselectively (99 1 anti syn) (Eq. 11.30). On the other hand, Fi and co-workers reported a ruthenium-catalyzed tandem olefin migration/aldol and Mannich-type reactions by reacting allyl alcohol and imine in protic solvents.52... 

Recently, Liu has developed a Bronsted acid activated trifunctional organocatalyst, based on the BINAP scaffold, that was used for the first time to catalyze aza MBH reactions between N tosylimines and MVK with fast reaction rates and good enantioselectivity at room temperature. This trifunctional catalyst containing a Lewis base, a Bronsted base and a Bronsted acid, required add activation to confer its enantioselectivity and rate improvement for both electron rich and electron deficient imine substrates. The role of the amino Lewis base of 27 was investigated and found to be the activity switch in response to an acid additive. The counterion of the acid additive was found to influence not only the excess ratio but also the sense of asymmetric induction (Scheme 13.23) [36]. 

All of the reactions discussed till now have been catalyzed by zeolites functioning as Bronsted or Lewis acids. In a major new development, zeolites have also been tailored to act as base catalysts (Hathaway and Davis, 1988a,b,c Tsuji et al., 1991). A superbase catalyst of this type has now found application in the synthesis of the key intermediate, 4-methylthiazole, used in the preparation of the anthelmintic, thiabendazole. The existing industrial route for 4 methylthiazole (18) involves using several hazardous chemicals such as chloroacetone and carbon disulfide. The new zeolite-based route uses the base-catalyzed reaction of SO2 with the imine from acetone (reaction 6.12). 

While hundreds of Lewis acid catalysts have been developed for organic reactions, Brousted acid catalysts have been paid less attention until recently. Conventional Lewis acids, such as titanium chloride and aluminium chloride, are known to be incompatible with aqueous media. On the other hand, Bronsted acids are stable toward water and oxygen. Thus, they are potential candidates as activators of electrophilic substrates in water. It was found that among various Bronsted acids, HBF4 efficiently catalyzed Mannich -type reactions of silyl enol ethers with aromatic aldehydes derived from activated imines to afford the corresponding p-amino ketones (Scheme 3.1). ... 

The aza-Diels-Alder reaction of imines with diene of Danishefsky is an important route to 2,3-dihydro-4-pyridones. A number of Lewis acids have been used to catalyze the reaction in organic solvents. In water the reaction was realized by acid catalysis via iminium salts or by Bronsted acids. The montmorillonite K-10 catalyzed this cycloaddition in water or in aqueous acetonitrile in excellent yield. Recently Kobayashi has performed the reaction in water at room temperature under neutral conditions in two (imine - - diene) or three (aldehyde -b amine -b diene) component versions by using sodium triflate as catalyst. Imine intermediates from the indium-mediated reaction, in aqueous medium at 50° C, between aromatic nitro compounds and 2,3-dihydrofuran undergo aza-Diels-Alder cycloadditions to give tetrahydroquinoline derivatives in good overall yields. ... 

In 2006, Gong and coworkers reported the first chiral Bronsted add-catalyzed asymmetric direct aza-hetero-Diels-Alder reaction [70]. Phosphoric acid catalyst 160 exhibited excellent catalytic activity and selectivity for the reaction of cyclohex-enone (31) with a broad range of aldimines 159 to produce N-containing heterocycles 162 with up to 87% ee (Scheme 38.47). More recently, Carter and coworker developed the modified proline catalyst 161 for this reaction, and high levels of enantioselectivity and diastereoselectivity were obtained (Scheme 38.47) [71]. Interestingly, the aromatic imines favor exo products while the aliphatic imines favor endo products. 

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