Stereoselective synthesis of 3(2H)-dihydrofuranones by addition of lithiated methoxyallene to chiral aldehydes

Abstract

Lithiated methoxyallene 2 adds to chiral aldehydes such as 2-phenylpropanal and .ZV/JV-dibenzylated -amino aldehydes 4-8 to give products 9-14 in good yields and with excellent anti-selectivity. The stereochemical outcome of these reactions can be explained by the Felkin-Anh model in a straightforward manner.The crude reaction products can either be transformed to enones by hydrolysis with acid or be converted into 2,5-dihydro-3-methoxyfuran derivatives 19-24 by treatment with potassium tert-butoxide in DMSO. The latter can be hydrolyzed to give 3 (2H)-dihydrofur anones 25-29. The diastereoselectivity of the initial addition step is transferred to the dihydrofuran derivative without a major change in the isomer ratio. Compounds derived from -amino aldehydes 5, 6, and 8 are assumed to be enantiomerically pure. Sodium borohydride reductions of and Grignard additions

Oxidative Cleavage of 3‐Alkoxy‐2,5‐dihydrofurans and its Application to the De Novo Synthesis of Rare Monosaccharides as Exemplified by L‐Cymarose

“…Treatment of these nucleophiles with various electrophiles such as aldehydes, ketones, nitriles, and imines generated primary adducts of the alkoxyallenes, which serve as convenient precursors for many functionalized heterocycles 2. As an example, the addition of lithiated alkoxyallenes to aldehydes and subsequent cyclization of the primary adducts lead to 3‐alkoxy‐2,5‐dihydrofurans 2a,b. Here we report the oxidative cleavage of these allene‐based heterocycles to provide β‐alkoxy‐substituted α,β‐unsaturated γ‐keto aldehydes.…”

Oxidative Spaltung von 3‐Alkoxy‐2,5‐dihydrofuranen und ihre Anwendung in der De‐novo‐Synthese seltener Monosaccharide am Beispiel von L‐Cymarose

“…Die Umsetzung dieser Nucleophile mit Elektrophilen wie Aldehyden, Ketonen, Nitrilen und Iminen liefert primäre Additionsprodukte, die ideale Vorstufen für zahlreiche funktionalisierte Heterocyclen sind 2. So führt die Addition von lithiierten Alkoxyallenen an Aldehyde und die nachfolgende Cyclisierung der Primäraddukte zu 3‐Alkoxy‐2,5‐dihydrofuranen 2a,b. Hier berichten wir von der oxidativen Spaltung dieser alkoxyallenbasierten Heterocyclen zu β‐Alkoxy‐substituierten α,β‐ungesättigten γ‐Ketoaldehyden.…”

Stereodivergent synthesis of jaspine B and its isomers using a carbohydrate-derived alkoxyallene as C3-building block

“…During our current studies on the synthesis of highly functionalized heterocycles utilizing alkoxyallenes as versatile C 3 -building blocks we chose jaspine B ( 1 ) as an attractive target [29–33]. Our approach to 1 is based on the addition of a lithiated alkoxyallene with a chiral auxiliary to pentadecanal as electrophile.…”