Catalytic, Enantioselective [4 + 2]-Cycloadditions of Ketene Enolates and o-Quinones:  Efficient Entry to Chiral, α-Oxygenated Carboxylic Acid Derivatives

Abstract

We report catalytic, enantioselective [4 + 2]-cycloadditions of o-quinones with ketene enolates (derived from readily available acid chlorides) using cinchona alkaloid derivatives as catalysts to produce products in high enantiomeric excess (ee) and good to excellent yields. The thermodynamic driving force for these reactions is due in part to the restoration of aromaticity to the products. The resulting chiral, bicycloadducts can be synthetically manipulated in a variety of useful ways, for example to provide a flexible synthesis of alpha-oxygenated carboxylic acid derivatives.

Lewis Base Catalysis in Organic Synthesis

“…[90] Lewis base catalysis has also made possible the first [4+2] cycloaddition of a ketene with an oquinone 58, again through the intermediacy of a similar amidonium enolate. [91] Cleavage of 59 affords high yields of enantioenriched a-hydroxycarboxylic acid derivatives. The reactions of ketenes are not broadly representative of n-p* type activation because the n-p* interaction need not necessarily lead to both enhanced electrophilic and nucleophilic character of the intermediate.…”

Lewis‐Base‐Katalyse in der organischen Synthese

“…[90] Unter Lewis-Base-Katalyse gelang auch die erste [4+2]-Cycloaddition eines Ketens mit einem ortho-Chinon, 58, die wieder über ein ähnliches Amidoniumenolat als Zwischenstufe verlief. [91] Die Spaltung von 59 führte mit hohen Ausbeuten zu enantiomerenangereicherten a-Hydroxycarbonsäure-Derivaten. [94] Dennoch verlaufen diese Reaktionen langsam, sodass brauchbare Umsätze oft erst nach Tagen erreicht werden.…”

N‐Heterocyclic Carbene‐Catalyzed Cyclization of Unsaturated Acyl Chlorides and Ketones

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Abstract: A straightforward synthesis of optically active trifluoromethyl dihydropyranones and spirocyclic oxindole-dihydropyranones has been realized by the chiral N-heterocyclic carbenes-catalyzed cy-A C H T U N G T R E N N U N G clization of a,b-unsaturated b-methylacyl chlorides with activated trifluoromethyl ketones or isatin derivatives.Keywords: asymmetric catalysis; cyclization; dihy-A C H T U N G T R E N N U N G dropyranones; N-heterocyclic carbenes; organocatalysis; vinylketenes Since Staudingers discovery of ketenes and the cycloaddition of ketene with imines to form b-lactams in early 1900s, [1] the cycloaddition reactions of ketene have become one of the powerful methodologies for construction of cyclic compounds.[2] In last decades, the catalytic enantioselective [2 + 2] or [2 + 4] cycloaddition of ketenes with aldehydes, [3] imines, [4] azo compounds, [5] nitro compounds, [6] oxadienes, [7] and azadienes [8] had been well established. In 2008 and later, we, [9] independently with Smith et al, [10] have demonstrated that N-heterocyclic carbenes (NHCs) [11] were efficient catalysts for the formal cycloaddition reactions of ketenes.

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