Asymmetric synthesis of δ-substituted-β-keto esters and β-substituted ketones via carboxyl-assisted site- and enantio-selective addition reactions

Abstract

Carboxyl-assisted site- and enantio-selective additions of polyfunctional nucleophiles to imines and carbonyls were developed, affording δ-substituted-β-keto esters and β-substituted ketones with good yields and enantioselectivities. Besides, short synthetic routes to...

Organocatalytic Enantioselective γ-Position-Selective Mannich Reactions of β-Ketocarbonyl Derivatives

“…To perform γ-position-selective reactions of acetoacetates, the formation of dianions, which are generated using two or more equivalents of strong base(s), is usually necessary. 4 Alternatively, preformed silyl dienol ether and alkyl dienol ether derivatives, 5 diketene, 6 and γ-carboxylic-acid-substituted β-ketoesters 7 have been used to afford the same type of products. 5 − 7 Methods that involve the use of dianions or dienol ether derivatives or decarboxylation usually require severe conditions and/or protection and deprotection steps or are not atom-economical.…”

“… 4 Alternatively, preformed silyl dienol ether and alkyl dienol ether derivatives, 5 diketene, 6 and γ-carboxylic-acid-substituted β-ketoesters 7 have been used to afford the same type of products. 5 − 7 Methods that involve the use of dianions or dienol ether derivatives or decarboxylation usually require severe conditions and/or protection and deprotection steps or are not atom-economical. 4 , 5 There have only been a small number of reports of catalytic γ-position-selective reactions of unmodified β-ketocarbonyl derivatives, 8 including catalytic enantioselective γ-position-selective reactions, 8d , 8e and they are all aldol reactions.…”

“… 8 δ-Amino β-ketocarbonyl derivatives are also versatile compounds used for the synthesis of δ-amino β-hydroxy acid derivatives, N -heterocycles (such as piperidines, pyrrolidines, and lactams), bioactive natural products, and related molecules. 4 , 5b , 5c , 7 , 9 To provide concise access to highly enantiomerically enriched δ-amino β-ketocarbonyl derivatives and to further enable the γ-position-selective reactions of β-ketocarbonyl derivatives, here we report direct catalytic asymmetric γ-position-selective Mannich reactions of β-ketocarbonyl derivatives that afford δ-amino β-ketocarbonyl derivatives ( Scheme 1 b).…”

“…To perform γ-position-selective reactions of acetoacetates, the formation of dianions, which are generated using two or more equivalents of strong base(s), is usually necessary . Alternatively, preformed silyl dienol ether and alkyl dienol ether derivatives, diketene, and γ-carboxylic-acid-substituted β-ketoesters have been used to afford the same type of products. − Methods that involve the use of dianions or dienol ether derivatives or decarboxylation usually require severe conditions and/or protection and deprotection steps or are not atom-economical. , There have only been a small number of reports of catalytic γ-position-selective reactions of unmodified β-ketocarbonyl derivatives, including catalytic enantioselective γ-position-selective reactions, , and they are all aldol reactions . δ-Amino β-ketocarbonyl derivatives are also versatile compounds used for the synthesis of δ-amino β-hydroxy acid derivatives, N -heterocycles (such as piperidines, pyrrolidines, and lactams), bioactive natural products, and related molecules. ,,,, To provide concise access to highly enantiomerically enriched δ-amino β-ketocarbonyl derivatives and to further enable the γ-position-selective reactions of β-ketocarbonyl derivatives, here we report direct catalytic asymmetric γ-position-selective Mannich reactions of β-ketocarbonyl derivatives that afford δ-amino β-ketocarbonyl derivatives (Scheme b).…”