Hydrogen Bond Catalysts

Wenzel and Jacobsen reported the thiourea 15b-catalyzed Mannich-type reaction of a ketene silyl acetal with an N-Boc-aldimine, furnishing (3-amino esters with excellent enantioselectivities (Equation 10.30) [59]. Subsequently, Jacobsen and co-workers reported the hydrophosphonylation of dialkyl phosphites with aldimines to yield a-amino phosphonates [60]. 

The bifunctional thiourea catalyst 16 was developed by Takemoto and co-workers in 2003 [61, 62], The Michael reaction of diethyl malonate with nitroalkenes proceeded with excellent enantioselectivities (Equation 10.31). 

Following the pioneering work of Jacobsen s and Takemoto s groups, a range of chiral thiourea catalysts were reported [63]. 

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Fig. 16.5 Some examples of supported hydrogen-bonded catalysts (as described by Bianchini).

The first two methods have the advantage that no modification of the homogeneous catalyst is needed. Surface hydrogen-bonded catalysts are limited to cationic complexes, while physical entrapment is more widely applicable. However, both methods are very sensitive to the solvent properties of the reaction medium. The chemical methods of immobilization require modification of the ligand, and this may be quite laborious. In the case of irreversible catalyst deacti-... 

Scheme 11 Enantioselective H-atom transfer reaction with hydrogen bonding catalyst... 

Momiyama and Yamamoto have recently demonstrated that acid cocatalysts can even influence the outcome of enamine-mediated reactions [63]. In their studies of the acid-catalyzed O- and A-nitroso aldol reaction, they found that the nature of the acid catalyst dictates the regioselectivity of the reaction between preformed enamine species A carboxylic acid catalyst promoted the 0-nitroso aldol reaction whereas a hydrogen bonding catalyst catalyzed the formation of an A-adduct, both in high enantioselectivities(Scheme 10). 

Br0nsted acids such as thioureas 2 represent hydrogen-bonding catalysts. Phosphoric acids 3, AT-triflyl phosphoramides 4, and dicarboxyUc acids 5 are examples of stronger specific Brpnsted acids (Fig. 1). 

Examples of the Bronsted-acid catalysts and hydrogen-bond catalysts are shown in Figure 2.1. We have recently reported the Mannich-type reaction of ketene silyl acetals with aldimines derived from aromatic aldehyde catalyzed by chiral phosphoric acid 7 (Figure 2.2, Scheme 2.6) [12]. The corresponding [5-amino esters were obtained with high syn-diastereoselectivities and excellent enantioselectivities. 

OH N hydrogen bond, which can lead to high levels of asymmetric induction. Therefore, incorporation of a BBA functionality into the appropriate chiral scaffold has tremendous potential to result in both a highly reactive and enantioselective hydrogen-bonding catalyst. 

Figure 6.8 Proposed modes of action of hydrogen-bonding catalyst 16 Bidentate hydrogen bonding coordination of the zwitterion derived from Michael-type DABCO attack to methyl acrylate (1) and Zimmerman-Traxler transition state for the reaction of methyl acrylate with benzaldehyde (2).

In 2008, Tang and co-workers reported the utilization of tertiary amine-functionalized saccharide-thiourea 211 as a bifunctional hydrogen-bonding catalyst for the enantioselective aza-Henry [224] (nitro-Mannich) addition [72] of... 

Scheme 6.178 Typical products provided from the asymmetric aza-Henry addition of nitromethane to N-Boc-protected aldimines in the presence of saccharide thiourea 211 as bifunctional hydrogen-bonding catalyst.

Hayashi. Although the applications of hydrogen bonding catalysts in natural product synthesis are still in their infancy, hydrogen bonding has been used many times as a driving force for desired selectivity in total synthesis. 

Sigman and co-workers developed a novel oxazoline-based hydrogen-bonding catalyst (122) for HDA reactions. The modular nature of the catalyst design al-... 

In contrast to covalent bond catalysts that form covalent substrate-catalyst adducts, hydrogen bond catalysts activate carbonyl compounds via weak interactions such as hydrogen bonding. Bronsted acid catalysts form ion pairs by protonating imines. The concept of counteranion catalysis has also been proposed. Phase-transfer catalysts also form ion pairs. 

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