Alkaline Earth Metal Catalysts for Asymmetric Reactions

Abstract

The group 2 alkaline earth metals calcium (Ca), strontium (Sr), and barium (Ba) are among the most common elements on Earth, abundant in both the sea and the Earth's crust. Although they are familiar in our daily lives, their application to organic synthesis has, so far, been limited. Some particularly useful properties of these elements include (i) low electronegativity, (ii) a stable oxidation state of +2, meaning that they can potentially form two covalent bonds with anions, and (iii) the ability to occupy a variety of coordination sites due to their large ionic radius. Furthermore, the alkaline earth metals, found between the group 1 and group 3 elements, show mild but significant Lewis acidity, which can be harnessed to control coordinative molecules via a Lewis acid-base interaction. Taken together, these characteristics make the metals Ca, Sr, and Ba very promising components of highly functionalized acid-base catalysts. In this Account, we describe the development of chiral alkaline earth metal catalysts for asymmetric carbon-carbon bond-forming reactions. Recently prepared chiral alkaline earth metal complexes have shown high diastereo- and enantioselectivities in fundamental and important chemical transformations. We chose chiral bisoxazoline (Box) derivatives bearing a methylene tether as a ligand for chiral modification. These molecules are very useful because they can covalently coordinate to alkaline earth metals in a bidentate fashion through deprotonation of the tether portion. It was found that chiral calcium-Box complexes could successfully promote catalytic asymmetric 1,4-addition and [3 + 2] cycloaddition reactions with high diastereo- and enantioselectivities. Both the calcium-Box complexes and chiral strontium-bis-sulfonamide and chiral barium-BINOLate complexes could catalyze asymmetric 1,4-addition reactions with high enantioselectivities. Furthermore, we designed a calcium-neutral coordinative ligand complex as a new type of chiral alkaline earth metal catalyst. We found that pyridinebisoxazolines (Pybox) worked well: they served as excellent ligands for calcium compounds in 1,4-addition reactions and Mannich reactions. Moreover, they were successful in 1,4-additions in concert with enantioselective protonation, affording the desired products in good to high enantioselectivities. Our results demonstrate that alkaline earth metals are very useful and attractive catalysts in organic synthesis. Moreover, their ubiquity in the environment is a distinct advantage over rare metals for large-scale processes, and their minimal toxicity is beneficial in both handling and disposal.

Metal-dioxidoterephthalate MOFs of the MOF-74 type: Microporous basic catalysts with well-defined active sites

“…Kobayashi et al [66] or Hatano et al, [67] for barium and magnesium ions respectively. In the following subsections, molecular modeling will be used for (1) the characterization of the basic sites and the open metal sites in the M 2 dobdc materials, and (2) studying the initial steps in the reaction mechanism for the Knoevenagel condensation (experimental data in Table 1).…”

Chiral Ca-, Sr-, and Ba-Catalyzed Asymmetric Direct-Type Aldol, Michael, Mannich, and Related Reactions

“…However, besides the potential high utility of alkalineearth metal species, their use in synthetic organic chemistry, especially in asymmetric synthesis as a chiral catalyst, has been quite limited for a long time. (Reviews of asymmetric reactions using alkaline-earth metal catalysts are: [5][6][7][8][9]. )…”

“…Since the orbitals of the alkaline-earth elements are similar to those of the lanthanoid elements, although the stable valences of the ions are different [20], the chemical properties of the compounds containing alkaline-earth metals are similar to those reported for the lanthanoid metals. These natures are important and promising for preparation of chiral alkaline-earth metal compounds [5][6][7][8][9]. Each alkaline-earth metal also possesses interesting properties for preparation of active catalysts.…”

“…However, chiral modification of strontium and barium is challenging, because these metals have larger ionic radii than calcium, and there are many coordination sites to be controlled. Recently, some promising strategies for modification of these metals as chiral catalysts have been reported [5][6][7][8][9].…”

Using the same organocatalyst for asymmetric synthesis of both enantiomers of glutamic acid-derived Ni(II) complexes via 1,4-additions of achiral glycine and dehydroalanine Schiff base Ni(II) complexes

“…This was a reason why the methods of asymmetric synthesis of Glu and its derivatives were sought. Presently, several synthetic protocols have been elaborated based on both stoichiometric (Williams 1989;Duthaler 1994;Cativiela and de DÍaz Villegas 1998;Ma 2003) and catalytic versions (Maruoka and Ooi 2003;Corey et al 1998;Vyskočil et al 2002;Belokon et al 2003;Lygo et al 2001;Nájera and Sansano 2007;Tsubogo et al 2010;Kobayashi and Electronic supplementary material The online version of this article (doi:10.1007/s00726-011-1076-y) contains supplementary material, which is available to authorized users. Yamashita 2011) of Michael additions of chiral or achiral activated Gly derivatives to acrylic acid derivatives.…”