“Designer Acids”: Combined Acid Catalysis for Asymmetric Synthesis

Abstract

Lewis and Brønsted acids can be utilized as more-effective tools for chemical reactions by sophisticated engineering ("designer acids"). The ultimate goal of such "designer acids" is to form a combination of acids with higher reactivity, selectivity, and versatility than the individual acid catalysts. One possible way to take advantage of such abilities may be to apply a "combined acids system" to the catalyst design. The concept of combined acids, which can be classified into Brønsted acid assisted Lewis acid (BLA), Lewis acid assisted Lewis acid (LLA), Lewis acid assisted Brønsted acid (LBA), and Brønsted acid assisted Brønsted acid (BBA), can be a particularly useful tool for the design of asymmetric catalysis, because combining such acids will bring out their inherent reactivity by associative interaction, and also provide more-organized structures that allow an effective asymmetric environment.

Development of Chiral Thiourea Catalysts and Its Application to Asymmetric Catalytic Reactions

“…Recently, hydrogen-bond donors such as ureas/thioureas, [10][11][12][13][14][15][16][17][18][19][20][21][22][23] BINOL/diols, [24][25][26][27][28][29][30][31][32] and phosphoric acids [33][34][35][36][37][38][39][40] have been also recognized as efficient organocatalysts. Novel urea and thiourea derivatives were developed as organocatalysts and their potential as a general acid has been successfully demonstrated by several groups.…”

Efficient Lewis acid-assisted Brønsted acid (LBA) catalysis in the iron-catalyzed Friedel-Crafts alkylation reaction of indoles

“…Based on our experimental results, a suggested and more practical mechanism of Lewis acid-assisted Brønsted acid (LBA) catalysis [21][22], is proposed in Scheme 1. The reasons for this proposal of LBA are given as follows: a) Only FeCl 3 or other iron salts catalyzed Friedel-Crafts alkylation of indoles with chalcones gave no desired product.…”

Development of Synthetic Transformations by Control of Acid-Catalyzed Reactions of Diazocarbonyl Compounds

“…Use of 2:1 ratio of aluminum source and BINOL was crucial for the successful implementation, in which each aluminum seems to be attached to each OH moiety of BINOL to form highly reactive aluminum Lewis acid-assisted aluminum Lewis acid (Scheme 26). 26 This reaction could also be applied to a simple α-unsubstituted diazoacetate (Scheme 27). Whereas the stereocenter formed at the α-position of the cyclic keto ester 31 easily disappeared by the facile enolization, desymmetrization of the 4-substitutent of the cyclohexanone secured the enantioselective process to give chiral 4-substituted cycloheptanone 32 with high enantioselectivity after the Krapcho decarboxylation.…”