Biomimetic catalytic enantioselective decarboxylative aldol reaction of β-ketoacids with trifluoromethyl ketones

Abstract

We disclose an organocatalyzed enantioselective decarboxylative ketone aldol reaction of β-ketoacids with trifluoromethyl ketones in the presence of biscinchona alkaloid (DHQD)(2)AQN, affording chiral tertiary alcohols in up to 98% yield and 90% ee.

Asymmetric organocatalytic decarboxylative Mannich reaction using β-keto acids: A new protocol for the synthesis of chiral β-amino ketones

“…The proposed addition–decarboxylation sequence is consistent with current mechanistic understanding [31,35,37–38]. However, we cannot exclude an alternative decarboxylation–addition pathway at this stage.…”

“…However, we cannot exclude an alternative decarboxylation–addition pathway at this stage. In fact, in sharp contrast to the popular use of malonic acid half thioesters (MAHTs) as an ester enolate equivalent in enantioselective decarboxylative additions [39], the employment of β-keto acids as a reaction partner in decarboxylative processes has rarely been explored [37]. Herein, we reported the first decarboxylative Mannich reaction between the β-keto acids and sulfonylimines, affording chiral β-amino ketones in excellent yields and good enantioselectivities.…”

Organocatalytic Decarboxylative Cyanomethylation of Difluoromethyl and Trifluoromethyl Ketones

“…[2] In addition, decarboxylative cyanomethylation and superbase catalyzed acetonitrile additions have emerged as a practical alternative. [3,4] …”

Catalytic Enantioselective Formal (4+2) Cycloaddition by Aldol–Aldol Annulation of Pyruvate Derivatives with Cyclohexane‐1,3‐Diones to Afford Functionalized Decalins

“…[1] Decalin derivatives often have antiinflammatory,a nti-bacterial, and anti-tumor activities. For enantioselective versions of the reaction, the use of (DHQD) 2 AQN [9] with tetraethylammonium bromide (TEAB) as additive in toluene-N-methyl-2-pyrrolidone (NMP) resulted in the formation of 3a in ag ood yield as as ingle diastereomer with high enantioselectivity (er 93:7, entry 4). [2][3][4][5] Construction of the decalin ring system has been performed using cycloadditions, [2] cross coupling, [3] polyene cyclizations and related ene-involved annulations, [4] Robinson annulations [2c,d, 5] and related Michael-aldol reactions, [6] in which the reactions start from Michael additions to a,b-unsaturated ketones.H ere we report organocatalytic enantioselective aldol-aldol annulation cascade reactions to afford functionalized decalin derivatives (Scheme 1).…”