Bronsted bases, chiral

CHIRAL BRONSTED BASE-LEWIS ACID BIFUNCTIONAL CATALYSIS... 

Studies of different cinchona alkaloids as the chiral Bronsted bases and a metal salt showed that hydrocinchonine lh (Scheme 10.13) and AgF were the most effective combination. The scope of the [3 + 2] cydoaddition of azomethine ylides and alkenes was investigated. Selected examples are shown in Scheme 10.14. High yields and moderate enantioselectivities were obtained from a variety of a-imino esters. It was worth mentioning that most of the pyrrolidine derivatives 11 obtained from tert-butyl acrylate were solids that could be enantiomerically enriched by crystallization. 

Scheme 6.15 Enantioselective vinylogous Michael reactions catalyzed by chiral Bronsted bases.

Two examples of hetero-Michael reactions have been reported using these kinds of bis-cinchona alkaloid-based chiral Bronsted bases as catalysts. One of them refers to a sulfa-Michael reaction and the other is a case of an aza-Michael reaction. 

Under a different manner of cinchona alkaloid activation, azodicarboxylates were utilized as substrates for enantioselective aUylic aminations. The electrophilic addition of nucleophiles to electron-withdrawing aUyUc C-H bonds (21) was feasible via activation by a chiral Bronsted base, DHQ(2PYR) (Scheme 13.6) [15]. This discovery, from Jorgensen s group, highUghts the first enantioselective, metal-free allylic amination using alkyUdene cyanoacetates with dialkyl azodicarboxylates. 

Figure 13,6 Basic scaffold of chiral Bronsted base derived thiourea catalysts.

Tetraaminophosphonium carboxylates and phenoxides have also been developed as chiral Bronsted base catalysts for asymmetric Mannich reachons and conjugate addihons [6c, 33]. These catalysts recognized and achvated the nucleophiles through the hydrogen-bonding network (Scheme 14.10). 

In addition, Palomo s group explored the use of chiral Bronsted bases such as 60 as an alternative approach for the addition of (phenylsulfonyl)acetonitrile to N-Boc-imines (Scheme 29.32). Only aromatic imines provide the desired final adducts in good yields, albeit with variable optical purities [69]. 

Chiral Bronsted base catalysis began with the recognition of a natural product class of compounds in the cinchona alkaloid family [2]. Cinchona alkaloids are templates for Bronsted bases when their quinuclidine nitrogen is protonated by nucleophilic substrates, resulting in a stabihzed chiral intermediate for stereochemical attack of an electrophile. Systematic evaluation of structural variants to the scaffold... 

The synthetic utility of the bifunctional catalysts in various organic transformations with chiral cyclohexane-diamine derived thioureas was established through the works of Jacobsen, Takemoto, Johnston, Li, Wang, and Tsogoeva. In the last decade, asymmetric conjugate-type reactions have become popular with cinchona alkaloid derived thioureas. The next section presents non-traditional asymmetric reactions of nitroolefins, enones, imines, and cycloadditions to highlight the role of chiral Bronsted base derived thiourea catalysts. 

---